Evaluating the Impact of a Lao Language Mobile Phone Antimicrobial Use Guideline Application on Antimicrobial Prescribing in Laos
Phase: NA
Conditions: Infectious Disease
Sponsor: Lao-Oxford-Mahosot Hospital Wellcome Trust Research Unit

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Evaluating the impact of a Lao language mobile phone antimicrobial use 
guideline application on antimicrobial prescribing in Laos 
Short title: LAMPA (Lao Anti-Microbial Prescribing App) 
Principal Investigator:  Vilada Chansamouth 
Co-investigators 
Elizabeth Ashley 
Paul Newton 
Paul Turner 
Rogier van Doorn 
Mayfong Mayxay 
Nicholas Day 
Yoel Lubell 
Pimnara Peerawaranun 
Mavuto Mukaka 
Manivanh Vongsouvath 
Andrew Simpson 
Dr Sommai Keomany 
Dr Khamla Silavanh  
Dr Nunthakone Sihapanya 
Dr Phouvieng Duangmala 
Dr Khamkeo Mivapadith  
Dr Khamsai Dethleuxay 
Dr Valy Keoluangkhot  
Dr Sommana Rattana 
 
Funder: Wellcome Trust 
Study sponsor: University of Oxford 
 

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Table of Contents 
TRIAL SYNOPSIS ..................................................................................................................................................... 4 
I. INTRODUCTION ................................................................................................................................................... 7 
ANTIMICROBIAL RESISTANCE - GLOBAL SITUATION ........................................................................................................... 7 
COUNTRY PROFILE OF LAOS .................................................................................................................................................... 8 
HEALTHCARE SYSTEM IN LAOS .............................................................................................................................................. 8 
ANTIMICROBIAL RESISTANCE IN LAOS ............................................................................................................................... 10 
HOSPITAL ANTIMICROBIAL USE IN LAOS ........................................................................................................................... 10 
THE NEED FOR ANTIMICROBIAL PRESCRIBING GUIDELINES ........................................................................................... 12 
STUDY RATIONALE ................................................................................................................................................................ 13 
II. STUDY OBJECTIVES AND HYPOTHESIS .................................................................................................... 13 
STUDY OBJECTIVES ................................................................................................................................................................ 13 
Primary objective .................................................................................................................................................................. 13 
Secondary objectives............................................................................................................................................................ 13 
III. METHODS ......................................................................................................................................................... 14 
3.1 STUDY DESIGN ................................................................................................................................................................. 14 
3.2 STUDY SITES .................................................................................................................................................................... 14 
3.3 SAMPLE SIZE AND POWER CALCULATION ................................................................................................................... 16 
3.4 RANDOMIZATION AND BLINDING ................................................................................................................................. 17 
3.5 STUDY INTERVENTION AND REFERENCE .................................................................................................................... 17 
a. 
Pre-study phase ........................................................................................................................................................... 18 
Lao antimicrobial prescribing guidelines .................................................................................................................. 18 
b. 
Reference phase .......................................................................................................................................................... 19 
c. 
Intervention phase ..................................................................................................................................................... 20 
3.6 ENDPOINTS ...................................................................................................................................................................... 23 
Primary endpoint .................................................................................................................................................................. 23 
Secondary endpoints ............................................................................................................................................................ 23 
Definitions of adherence to the guidelines ................................................................................................................ 24 
3.7 DATA COLLECTION METHOD ......................................................................................................................................... 24 
a. 
Point Prevalence Survey procedures ................................................................................................................. 26 
a.3 Antimicrobial stewardship (AMS) knowledge survey ................................................................................... 31 
Pre-prescribing guidelines survey ................................................................................................................................. 32 
Prescriber feedback survey on paper-based prescribing guidelines ............................................................. 32 
Prescriber feedback survey on mobile phone App prescribing guidelines ................................................. 33 
DATA MANAGEMENT AND MONITORING ............................................................................................................................ 33 
STATISTICAL ANALYSIS ......................................................................................................................................................... 33 
SAFETY CONSIDERATIONS/ADVERSE EVENTS.................................................................................................................. 34 
ETHICS ..................................................................................................................................................................................... 35 
BENEFITS ................................................................................................................................................................................ 35 
RISKS ....................................................................................................................................................................................... 35 
PATIENT AND DOCTOR CONFIDENTIALITY ........................................................................................................................ 36 
TRIAL INSURANCE .................................................................................................................................................................. 36 
DATA SHARING AND DISSEMINATION ................................................................................................................................. 36 
FINANCE .................................................................................................................................................................................. 37 
REFERENCES .......................................................................................................................................................... 38 
APPENDICES ........................................................................................................................................................... 42 
A1. IN-PATIENT PPS WARD FORM .................................................................................................................................... 42 

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A2. IN-PATIENT PPS PATIENT FORM ................................................................................................................................ 43 
A3. OUTPATIENT PPS FORM .............................................................................................................................................. 44 
A4. POINT PREVALENCE SURVEY (PPS) OF HOSPITAL ANTIMICROBIAL USE REPORT FORMAT ............................. 45 
A5. ANTIMICROBIAL STEWARDSHIP (AMS) KNOWLEDGE SURVEY ............................................................................. 51 
A6. INTRODUCTORY SESSION OF THERAPEUTIC AND PROPHYLACTIC ANTIMICROBIAL PRESCRIBING GUIDELINES
 .................................................................................................................................................................................................. 55 
A7. INTRODUCTORY SESSION OF ANTIMICROBIAL PRESCRIBING GUIDELINES MOBILE PHONE APPLICATION 
(MICROGUIDE) ...................................................................................................................................................................... 58 
A8. INTRODUCTORY (PAPER/APP GUIDELINES) SESSION REGISTRATION SHEET ................................................................... 59 
A9. PRE-PRESCRIBING GUIDELINE SURVEY ...................................................................................................................... 60 
A10. PRESCRIBER FEEDBACK SURVEY ON PAPER-BASED PRESCRIBING GUIDELINES ................................................ 61 
A11. PRESCRIBER FEEDBACK SURVEY ON MOBILE PHONE APP PRESCRIBING GUIDELINES ...................................... 63 
A12. ANTIMICROBIAL STEWARDSHIP (AMS) TRAINING ............................................................................................... 65 
A13. ANTIMICROBIAL STEWARDSHIP (AMS) TRAINING SESSION REGISTRATION SHEET ........................................ 66 
A14. TIMELINES AND MILESTONES .................................................................................................................................... 67 
 

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Trial synopsis 
 
Primary Objective 
To compare the proportion of antimicrobial prescriptions adherent with 
prescribing guidelines delivered by mobile phone application (app) versus paper-
based prescribing guidelines in both in- and outpatients in six general hospitals in 
Laos 
Secondary 
objectives 
1. To compare the change in antimicrobial defined daily doses (DDDs) after 
introduction of paper-based versus mobile phone app prescribing 
guidelines plus antimicrobial stewardship (AMS) training in both in- and 
out patients 
2. To compare the change in proportion of patients receiving antimicrobials 
by the intravenous route between paper-based and mobile phone app 
prescribing guidelines + AMS training in both in- and out patients 
3. To compare the AMS knowledge level of prescribers before and after 
prescribing guidelines delivered by mobile phone app and AMS training 
4. To compare the prescriber satisfaction with/acceptability of paper-based 
prescribing guidelines versus mobile phone app prescribing guidelines 
5. To compare antimicrobial costs before and after prescribing guidelines 
delivered by mobile phone app and AMS training in both in- and 
outpatient departments 
6. To compare the proportion of patients admitted to hospital receiving an 
antimicrobial prescription before and after introduction of the paper-
based prescribing guidelines; and the mobile phone app prescribing 
guidelines + AMS training 
Methodology 
 
Study design 
An open cohort stepped-wedge cluster randomized controlled trial 3-step trial (4-
month intervals at each step) with a four-month pre-intervention period) 
Study sites 
Six general hospitals in Laos (two in the north (Luang Namtha and Xiengkhuang 
Provincial Hospitals), two in the centre (Mahosot Hospital and Vientiane 
Provincial Hospital) and two in the south (Savannakhet and Salavan Provincial 
Hospitals) 
Study duration 
16 months (four months preintervention period and 4-month interval between 
each step (three steps)) 
Sample size and 
power calculation 
The sample size of six hospitals was estimated assuming 30% antimicrobial 
prescription adherence with the paper-based prescribing guidelines (reference), 
and assuming 0.05 intra-cluster correlation coefficient. This will have 80% power 
to be able to detect a 15% minimum difference in adherence after introduction of 
the mobile phone app prescribing guidelines (intervention) at a 0.05 significance 
level. 
Randomization and 
blinding 
Simple random sampling will be used to select the order (step) of interventions 
implementation for a group of hospitals (two hospitals per group and one group 
per step). Neither hospitals nor investigators will be blinded to the timing of 
intervention. 
Intervention 
A MicroGuide antimicrobial prescribing guideline mobile phone application and 

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AMS training 
Reference 
Paper-based antimicrobial prescribing guidelines 
Outcomes/Primary 
endpoint 
The proportion of antimicrobial prescriptions adherent with prescribing 
guidelines delivered by mobile phone app versus paper-based prescribing 
guidelines at month 16 (12 months’ exposure in each group) 
Secondary endpoints 
 
1. Total antimicrobial defined daily doses (DDDs) prescribed in mobile 
phone app versus paper-based groups after 12 months’ exposure in each 
group  
2. Proportion of patients prescribed antimicrobials by the oral route in 
mobile phone app versus paper-based groups after 12 months’ exposure 
in each group 
3. AMS knowledge level of prescribers prescribed in mobile phone app 
versus paper-based groups after 12 months’ exposure in each group 
4. Prescriber satisfaction/acceptability of the prescribing guidelines in 
mobile phone app versus paper-based groups after 4 months’ exposure in 
each group 
5. Total costs of antimicrobials prescribed in mobile phone app versus 
paper-based groups after 12 months’ exposure in each group 
6. Proportion of patients admitted to hospital receiving an antimicrobial 
prescription before and after introduction of the paper-based prescribing 
guidelines; and the mobile phone app prescribing guidelines + AMS 
training after 12 months’ exposure in each group 
Outcome 
measurement  
• 
Point prevalence surveys (PPS) of hospital antimicrobial use 
• 
Prescriber questionnaires 
• 
AMS knowledge surveys of prescribers 
Data management 
Open Data Kit (ODK) system will be used as data collection instrument. We will 
collect data on patients’ characteristics, antimicrobial prescription status, the 
frequency of use of the antimicrobial prescribing guidelines (both paper-based 
and mobile app), AMS knowledge level of prescribers, acceptability of the 
guidelines and the cost of antimicrobial prescriptions in both groups.  
All data will be kept securely, protected by password access with automatic daily 
backup. 
Statistical analysis 
A logistic mixed-effects regression model will be used to compare the proportion 
of antimicrobial prescription adherence measured cross-sectionally at month 0, 4, 
8, 12 and month 16 after introduction of prescribing guidelines delivered by 
mobile phone application versus paper-based. The model will compare all wedges 
in the intervention from month 4 to month 16 with all wedges in the reference 
arm from month 0 to month 12. The duration of exposure of each hospital to the 
reference or intervention arm will be included in the model as interaction term 
with the study arm in order to assess whether the duration of exposure is the 
effect modifier. The model will consider the correlation among the outcomes’ 
measurements from the same hospital (cluster) by adjusting for clustering in the 
model. Odds ratios and the corresponding confidence intervals will be obtained 
and reported. 
Ethics 
University of Health Sciences, Vientiane, Lao PDR and Oxford Tropical Ethics 
Committee (OxTREC), University of Oxford, United Kingdom 

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Trial insurance 
Provided by University of Oxford 
Dissemination 
1/ Quarterly and annual reports (PPS dashboard and paper report) to 
participating hospitals, Lao Ministry of Health 
2/ Publication in national and international journals 
3/Oral presentation/poster in both national and international levels 
Sponsor 
University of Oxford 
Funder 
Wellcome Trust of Great Britain 
 
 
 

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I. Introduction 
 
Antimicrobial resistance (AMR) is the ability of microorganisms, including bacteria, fungi, viruses 
and parasites, to withstand exposure to antimicrobial medicines, such as antibacterial, antifungal, 
antiviral, anti-protozoal and anti-helminthic, so that the treatment becomes ineffective (1). 
Resistance can be acquired or intrinsic. Intrinsic resistance is the innate ability of bacteria to 
withstand the activity of some antimicrobial compounds whilst acquired resistance is the ability of 
bacteria to resist a particular antimicrobial compound which it was originally susceptible to. In a 
clinical setting, treating infections caused by bacteria having acquired novel resistance mechanisms 
is the main problem of AMR (2).  
 
Antimicrobial Resistance - global situation  
 
AMR is a major global public health concern with rising frequencies of AMR in key pathogens to key 
antimicrobials. The evidence suggests that this increase is accelerated by  use, misuse or overuse of 
antimicrobials (3). AMR results in both direct consequences, such as longer duration of illness, 
increased mortality and prolonged stay in hospital, and indirect consequences such as reduced 
productivity caused by sickness and increased family, community and health system economic 
burden (4). O’Neill estimated that ~700,000 people die every year from drug resistant pathogens, 
including bacterial infections, HIV and malaria. If AMR continues to increase with no appropriate 
action being taken, this could contribute 10 million excess deaths and a cost of 100 trillion USD 
worldwide by 2050 (5). In 2019, Limmathurotsakul et al. argued that the estimation of the AMR 
global burden may have been distorted because of limitations in the methodological approaches (6). 
Since 2000, the number of antibiotics in development has fallen sharply. Many pharmaceutical 
companies have left the antibiotics market, stopping production and engagement in research and 
development (R&D), as the returns in profit of drugs given as short courses and with a short 
therapeutic life are far lower than those from drugs intended for lifelong use such as anti-
hypertensive, or cholesterol-lowering drugs that do not fall to resistance (7), With drug-resistant 
infections potentially causing global economic damage on a par with the 2008 financial crisis, low-
income countries could lose more than 5% of their GDP. AMR could push up to 28 million people 
into poverty, mostly in developing countries. Healthcare costs may increase by $300 billion to more 
than $1 trillion per year. A decline in global livestock production could range from 2.6% to 7.5% per 
year (8).   
In order to address this major threat to global public health, there have been a number of 

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international initiatives. The Global Action Plan (GAP) to combat AMR was established by WHO in 
2015, which consists of five strategies: 1) improving awareness and understanding of antimicrobial 
resistance; 2) strengthening knowledge through surveillance and research; 3) reducing the 
incidence of infection; 4) optimizing the use of antimicrobial agents; and 5) ensuring sustainable 
investment in countering antimicrobial resistance. The GAP mainly focuses on antibiotic resistance 
and provides a framework for National Action Plans to combat antimicrobial resistance over the 
next 5 to 10 years (9). In the same year, the global antimicrobial resistance surveillance system 
(GLASS) was established to support GAP. GLASS focuses on some specific microorganisms in specific 
samples such as: Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Staphylococcus 
aureus, Streptococcus pneumoniae and Salmonella spp. in blood; Escherichia coli and Klebsiella 
pneumoniae in urine; Salmonella spp. and Shigella spp. in faeces; and Neisseria gonorrhoeae from 
urethral and cervical swabs (10). In February 2017, three global priority tiers of antibiotic-resistant 
bacteria were proposed by WHO to guide research, discovery and development of new antibiotics, 
including critical, high and medium priority pathogens (11).  
Country profile of Laos 
 
Lao PDR (Laos) is a land-linked country in Southeast Asia and bordered by China, Myanmar, 
Thailand, Cambodia and Vietnam. The majority (63%) of the population of ~6.77 million people live 
in rural areas and are predominantly dependent on farming. In 2013 the Gross National Income per 
capita was US$ 4,570/year and life expectancy was 66 years. The World Bank reclassified Laos as a 
lower middle-income country in 2013 (9). From 2005 to 2015 Laos had one of the fastest growing 
economies in the world, with an average GDP growth rate of 7.8% per annum (12). Total health 
expenditure per capita increased from US$29 in 2010-2011 to $59 in 2015-2016 but total health 
expenditure as a proportion of GDP ranged from 2.4% to 3% during 2010 and 2016 (13). This is low 
compared to surrounding countries where the GDP expenditure is 6.5% in Thailand, 5.7% in 
Cambodia, and 7% in Vietnam, but is similar to that of Myanmar (2.3% of GDP) (12). 
Healthcare system in Laos 
The governmental healthcare system in Laos comprises three main administrative levels, including 
the Ministry of Health (MoH), Provincial Health Offices and District Health Offices. Based on data 
from the Curative and Healthcare Department in 2017, there are five central hospitals in Vientiane 
City and 17 provincial hospitals, 135 district hospitals (29 with ability of performing surgery and 
106 unable to perform surgery) and 1,020 health centers (866 with ability to perform normal 

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vaginal delivery and 154 unable to perform normal vaginal delivery), country-wide (Curative and 
Healthcare Department, unpublished data 2017). There were 0.8-hospital beds per 1,000 
population in 2010-2011. The most common issues found in the service delivery system are 
overcrowding of patients at central and provincial levels and underuse of district and community-
level facilities (14). There are also a number of private international medical facilities in Vientiane, 
with links to Vietnam, China, France and the United Nations. There are also Thai government and 
private hospitals within easy reach of Vientiane and other towns in the Mekong Valley in Thailand. 
An Infection Prevention Control (IPC) committee was formed by MoH in 2008 and guidance on IPC 
at central and provincial hospitals was released in the same year. In 2014, IPC guidance for all 
healthcare levels was released. There are IPC committees in all central and provincial hospitals in 
Laos, as well as in some district hospitals. 
In 2016, there were 20,484 health workers for the whole country (6,758,000 population) or 
3/1,000 population. There were 2,716 physicians or 0.4/1,000 and 913 pharmacists or 0.13/1,000 
population, and one medical school and one-degree level pharmacy programme within the 
University of Health Sciences in Vientiane (Ministry of Health, unpublished data 2016). 
Limitations of laboratory services and clinical research infrastructure and capacity challenge the 
development of effective and evidence-based clinical and public health management strategies. In 
rural Laos, most treatment of infections is empirical, with basic laboratory testing such as Gram 
staining available at some provincial hospitals (15).  
The national laboratory network structure in Laos is in line with the overall five-tiered organization 
of the national health system. Of these five laboratories, only two laboratories (National Center for 
Laboratory and Epidemiology (NCLE) and Microbiology Laboratory/Lao-Oxford-Mahosot Hospital 
Wellcome Trust Research Unit (LOMWRU) routinely culture bacteria and perform antimicrobial 
susceptibility testing. Some laboratories in central (Sethathirad Hospital and Mittaphab Hospital) 
and provincial hospitals are able to culture and identify some bacteria. The National TB Laboratory 
and Centre d’Infectiologie Christophe Mérieux of Laos (CICML) perform GeneXpert TB assays (16). 
Until mid-2019, both Mahosot Hospital and NCLE laboratories used disk diffusion according to 
Clinical & laboratory Standards Institute (CLSI) guidelines for most of their antibiotic susceptibility 
testing and before changing to European Committee on Antimicrobial Susceptibility Testing 
(EUCAST).   

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Antimicrobial resistance in Laos 
 
Awareness of AMR is relatively recent in Laos and it is becoming a major public health concern. The 
main 
current 
concerns 
are 
Extended 
Spectrum 
Beta-Lactamase 
(ESBL) 
producing 
Enterobacteriaceae. ESBL producing K. pneumoniae and E. coli were first identified from the 
Mahosot Hospital Laboratory in clinical samples in 2000 and 2004, respectively. The frequency of 
ESBL-producing E. coli bacteraemia during 2004-2016 was 135/693 (19%), but the proportion of 
isolates producing ESBL increased 5-fold from 2004 2/28 (7%) to 2016 – 27/78 (35%). Whilst the 
proportion of K. pneumoniae producing ESBL was 39/284 (14%) between 2000-2016 in patients at 
Mahosot Hospital, there was no clear trend for an increase in ESBL producing K. pneumoniae, with 
levels varying from 3% to 41% over this period (Microbiology Laboratory/LOMWRU, unpublished 
data). Carbapenem resistance in E. coli was first identified in Laos in 2015 from a pus specimen 
from a patient admitted to Mahosot Hospital. Since then there have been three further isolates with 
the first carbapenem resistant E. coli isolated from blood in 2016 and 2017. All four isolates carried 
a New Delhi metallo-β-lactamase (NDM) gene (17). An analysis of 18 years of Salmonella Typhi 
bacteraemia data (2000-2018) in Laos showed 79% (712/898) were susceptible to all tested 
antimicrobials, 6.5% were multidrug-resistant and only 1% was fluoroquinolone resistant (18). 
Methicillin-resistant Staphylococcus aureus (MRSA) was also infrequent but it requires close 
monitoring; 18 years of bacteraemia data from Mahosot Hospital (2000-2018) only showed 2 
patients with invasive MRSA infection. However, of concern, during 2017 and 2018, 71/426 (17%) 
Staphylococcus aureus isolates cultured from pus from clinical specimens at Mahosot Hospital were 
MRSA (Microbiology Laboratory/LOMWRU, unpublished data). There is scattered information on 
other GLASS pathogens available in Laos.  
Hospital antimicrobial use in Laos 
 
The Lao Food and Drug Department (FDD) is responsible for drug registration, licensing of 
pharmacies/drug companies/drug industries, and overseeing their distribution, import, drug 
quality control, domestic manufacture and also monitoring the supply chain. In 2016, 218 antibiotic 
active pharmaceutical ingredients (APIs) and combination APIs were registered by the Lao FDD; of 
these 38 (17%) were produced in Laos. The main sources of packaged antibiotics are from 
neighbouring 
countries 
such 
as 
Thailand 
and 
China 
(http://www.fdd.gov.la/showContent.php?contID=48). 
 In 2006, Keohavong et al. described that nearly half (47%) of Lao outpatients within 30 health 

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facilities investigated throughout the entire country were prescribed antibiotics for mild diseases 
such as simple diarrhoea or common colds (19). Few data on hospital antimicrobial use exist in 
Laos; at one northern provincial hospital, 51% of 1,095 patients (2008-2010) received antibiotics 
but only 7% of these received appropriate antibiotics (20). Nearly 70% of Lao doctors prescribed 
antibiotics at least once daily and stated that they had not received much information on 
appropriate antibiotic use during their careers. The doctors stated that they mainly prescribed 
antibiotics according to the National Standard Treatment Guidelines, advice from their peers, more 
experienced colleagues, pharmaceutical companies or the Internet. Doctors indicated a preference 
for local antibiotic guidelines written in Lao language to international ones in other languages (21).  
The first hospital antibiotic use survey in Laos was conducted in 2017 using the Global Point 
Prevalence Survey methodology (LOMWRU, unpublished data). In 2018, five general hospitals 
across Laos participated in this survey, including two from the north, two from the centre and one 
from the south of Laos. Of 1,981 in-patient hospitals chart screened, 72% documented an 
antimicrobial (s) prescription, 43% patients received more than one antimicrobial, 98% were 
prescribed empirically and nearly half of them received antimicrobials for prophylaxis (LOMWRU, 
unpublished data). These hospital antimicrobial prescribing rates were much higher than rates 
(47%) reported in 2006 by Keohavong et al. (2006) (19). 
Keohavong et al. (2019) interviewed 54 healthcare providers at outpatient departments (OPD) in 
five health facilities in Savannakhet Province, Laos, finding that 98% prescribed antibiotics based on 
patients’ symptoms. The majority of them (91%) had heard about antimicrobial resistance but only 
46.3% had been trained in the rational use of drugs. Medical records of 576 OPD patients under 5 
years-old with upper respiratory tract infection (URTI) or common cold were screened for 
antibiotic prescription, 96% of URTI patients received antibiotic (s) and 5% for common cold 
patients. Of 405 patients given antibiotics, 395 (97.5%) received first line antibiotics (amoxicillin, 
ampicillin, erythromycin and penicillin V) based on Lao National Standard Treatment Guidelines. 
However, only a few of them used correct doses and durations based on these Guidelines (22).  
There is evidence that multi-activity antimicrobial stewardship (AMS) programs could significantly 
reduce the proportion of therapeutic and prophylactic antibiotic prescriptions in both in- and 
outpatients from a study of a large patient population in China during 2010 and 2016 (23). Scheetz 
et al. (2009) also showed that combining antimicrobial stewardship with standard treatment of 
bloodstream infections had favourable cost-effectiveness compared to many other standard 
treatments of care (24). AMS programs have only been recently established in Laos. The first 

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training session on AMS to improve the rational use of antibiotic of Lao doctors, will be held in 
Vientiane City by Ministry of Health in mid-2020 with some pilot hospitals. 
The need for antimicrobial prescribing guidelines 
 
Lao Standard Treatment Guidelines (STG) were first established in 1998 and the latest edition was 
published in 2012. The guidelines are broad and cover a variety of issues such as medicines, surgery, 
and emergency medicines for both adults and children but do not include AMS or guidelines for 
treatment of many common infections. There are no approved Lao evidence-based infectious 
disease treatment guidelines, except for some specific diseases, e.g. malaria, TB, Sexually 
Transmitted Diseases (STDs) and HIV. LOMWRU conducted a small survey on the need for 
antimicrobial prescribing guidelines in Laos during November and December 2019; 70 Lao doctors 
from either central or provincial hospitals reported the main challenges to making decisions on the 
choice of antimicrobials were lack of access to a microbiology laboratory 31/70 (44%), no suitable 
antimicrobial prescribing guidelines 30/70 (43%) and poor availability of some antimicrobial 
agents 30/70 (43%). The majority of doctors used Lao treatment guidelines 58/70 (83%) and 
guidelines from neighboring countries 40/70 (57%) with a small proportion using European or US 
treatment guidelines 16/70 (23%). Only 17/70 (24%) had used any antimicrobial prescribing 
guideline/treatment guidelines delivered by a mobile application. Of these, 41% used the Medscape 
App (LOMWRU, unpublished data). 
Antimicrobial prescribing guidelines have now been developed in country and are being adapted 
with the Ministry of Health based on AMR data from Laos, existing guidelines and international 
antimicrobial prescribing/treatment guidelines (e.g. WHO, CDC, NICE, Infectious Diseases Society of 
America (IDSA), Sanford). No antimicrobial use applications (apps) for the Lao PDR are available in 
English or Lao. Some 90% of Lao doctors from three provincial hospitals have smartphones 
(unpublished data) and apps are likely to be more attractive to physicians than bulky handbooks. 
Antimicrobial prescribing guidelines delivered by mobile phone app are now widespread in the 
world. Some evidence has suggested that antibiotic guidelines on a mobile phone app increased 
guideline adherence by prescribers, reduced unnecessary antibiotic use in hospital, reduced poor 
outcomes, improved quality of care and reduced antimicrobial consumption cost (25-27). Panesar et 
al. (2016) reported a survey on the use of MicroGuide smartphone application compared to pocket 
antimicrobial prescribing guidelines during a 3-month period at the University College London 
Hospital NHS Trust. Of 116 responses from pre-app survey questionnaires and 112 responses from 

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post-app survey questionnaires, the prescribing app was used more than pocket prescribing guides 
(p<0.01). The majority of responses (>90%) agreed that the app was easy to navigate and it was the 
most appropriate means to access hospital guidelines. The app also improved their antimicrobial 
stewardship awareness (RR 6.8 (CI 2.1-21.7) (28). A study in three main hospitals of Imperial 
College Healthcare Trust, London demonstrated that when introducing mobile health to the setting 
with an existing antimicrobial stewardship program, the proportion of antimicrobial prescriptions 
adherence with the prescribing policy was significantly increased but there was no significant effect 
on antimicrobial prescription trends (29). 
Study rationale 
Although the severity of the AMR situation in Laos remains lower than elsewhere in Asia, misuse of 
antimicrobials is a major driver of resistance. This is a therefore an important opportunity for 
implementation of a simple technology, which may help reduce further worsening of the AMR 
situation. Antimicrobial prescribing apps are a promising tool to improve prescribing. However, 
there has been no evidence from trials to support whether the antimicrobial prescribing guidelines 
in the format of a mobile phone application are superior to conventional means (i.e. paper–based) in 
low- and middle-income countries (LMIC). This trial could have a significant impact in Laos and in 
other LMICs, and inform policy globally, by improving prescribing and hence reducing AMR.  
II. Study objectives and hypothesis 
 
Study objectives 
Primary objective 
To compare the proportion of antimicrobial prescriptions adherent with prescribing guidelines 
delivered by mobile phone application (app) versus paper-based prescribing guidelines in both in- 
and outpatients in six general hospitals in Laos 
Secondary objectives  
 
1. To compare the change in antimicrobial defined daily doses (DDDs) after introduction of 
paper-based versus mobile phone app prescribing guidelines plus antimicrobial 
stewardship (AMS) training in both in- and out patients 

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14 
2. To compare the change in proportion of patients receiving intravenous antimicrobials route 
between paper-based and mobile phone app prescribing guidelines + AMS training in both 
in- and out patients 
3. To compare the AMS knowledge level of the prescribers before and after prescribing 
guidelines delivered by mobile phone app and AMS training 
4. To compare the prescriber satisfaction with/acceptability of paper-based prescribing 
guidelines versus mobile phone app prescribing guidelines 
5. To compare antimicrobial costs before and after prescribing guidelines delivered by mobile 
phone app and AMS training in both in- and outpatient departments 
6. To compare the proportion of patients admitted to hospital receiving an antimicrobial 
prescription before and after introduction of the paper-based prescribing guidelines; and 
the mobile phone app prescribing guidelines + AMS training 
III. Methods 
 
3.1 Study design 
  
The study design will be an open cohort stepped wedge cluster randomized controlled trial (SW-
CRT) in six central/provincial hospitals across Laos. SW-CRT is appropriate in the Lao context 
because it requires fewer sites than a parallel cluster trial, but has similar observational periods for 
reference and intervention phases. As the interventions will be delivered by one team travelling to 
each cluster in turn, implementing in stages will be more practical. In addition, all participating 
hospitals will have access to the novel interventions at the end of the study. Prescribers are allowed 
to move in and out of clusters during the trial. 
3.2 Study sites 
 
Six hospitals (two referral (200-450 beds) and four provincial hospitals (60-100 beds) have been 
purposively selected based on their capacity, location, previous participation in our PPS program 
with available hospital antimicrobial use and antimicrobial susceptibility data. 
Mahosot Hospital (MS) has 450 beds and is a central referral hospital situated in Vientiane City in 
Laos (17o95’N 102o 61’E, 268m above mean sea level). There are 968 staff, including 222 physicians, 

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414 nurses, 19 dentists, 46 pharmacists, 11 radiologists and 147 non-health worker staff.  There are 
18 in-patient wards and one main out-patient and small number of OPDs within in-patient wards. 
Vientiane Provincial Hospital (VTP) has 100 beds. There are 211 staff, including 30 physicians, 99 
nurses, 6 dentists and 9 pharmacists (data from 2018). There are six in-patients wards and one 
outpatient ward. The hospital is ~70km from Vientiane City (18o47’N 102o 48’E 497m above mean 
sea level). 
Xiengkhuang Provincial Hospital (XK) has 150 beds. There are 305 staff, including 66 physicians, 
117 nurses, 6 dentists and 24 pharmacists (data from 2019). There are 11 in-patient wards and one 
main out-patient units and a small number of OPDs within in-patient wards. It is in a broad valley in 
the northeast highlands (19° 27’N 103°10’E, 1,150m above mean sea level). 
Luang Namtha Provincial Hospital (LNT) has 50 beds. There are 117 staff, including 18 
physicians, 36 nurses, 3 dentists and 10 pharmacists (data from 2018). There are 6 in-patients 
wards and OPDs within in-patient wards. It is in the highlands on the China and Myanmar borders 
in the far NW of Laos (21° 00’N 101° 24’ E; 570m above mean sea level) 
Savannakhet Provincial Hospital (SVK) has 200 beds. There are 293 staff, including 60 physicians, 
139 nurses, 7 dentists and 13 pharmacists (data from 2019). There are 9 in-patient wards and one 
main out-patient and small number of OPDs within in-patient wards. It is located in the southern 
part of the country in the largest province in Laos (16o 55’N 104o 74’E; 726 m above mean sea level) 
Salavan Provincial Hospital (SV) has 70 beds. There are 191 staff, including 30 physicians, 50 
nurses, 3 dentists and 11 pharmacists (data from 2018). There are 7 in-patients wards and OPDs 
within in-patient wards outpatient. It is on the western slopes of Annamite mountains in southern 
Laos (15o43’N 106o25’ E; 184m above mean sea level). 
 
 

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16 
Figure 1.  SW-CRCT study sites 
 
 
3.3 Sample size and power calculation  
 
A PPS of hospital antimicrobial use in four general hospitals in Laos in 2017 showed 13% 
compliance to Lao treatment guidelines (LOMWRU unpublished data) but previous guidelines did 
not contain much information on antibiotic prescribing, therefore reliable baseline data are lacking.  
The sample size of 6 hospitals was estimated assuming 30% of antimicrobial prescription 
adherence with the paper-based prescribing guideline (reference), and assuming 0.05 intra-cluster 
correlation coefficient. This will have 80% of power of the test to be able to detect 15% minimum 
difference after introduction of the mobile phone app prescribing guidelines at 0.05 significant level. 
This will be a 3-step trial with one baseline measurement after introduction of the paper-based 
prescribing guidelines. The outcomes will be measured every four months. These will give four 
outcomes measurements in total (excluding baseline measurement at start), until the trial 

Version 1.0_13 June 2020  
17 
completes at month 16.  
3.4 Randomization and blinding 
 
Six participating hospitals have been divided into 3 pairs based on the geographical location and 
convenience for conducting the surveys.  The first paired hospitals include two provincial hospitals 
from the north of Laos (Luang Namtha and Xiengkhuang), the second pair includes hospitals in the 
center (Mahosot Hospital-central referral hospital and Vientiane provincial hospital which is 80 km 
from the center of the capital to the north). The third pair includes two provincial hospitals from the 
south of Laos (Savannakhet and Salavan).  
As there are only 3 orders to be assigned, clusters will be randomly assigned to one of three start 
dates using a simple random sampling, to have access to the study intervention. Three paired 
hospitals (LNT+XK, MS+VTP and SVK+SV) will be written on three different paper slips (similar 
paper size and paper texture). All slips will be folded to the same size and put in the non-
transparent container, covered firmly and mixed well. A person who is not related to the study will 
be asked to pick up the paper slip one by one and read out to the PI and a co-investigator. Simple 
random sampling processes will be performed before the start of the project and the order of each 
paired hospital to intervention introduction will be recorded. At month 4 after the start of the 
project, the intervention will be introduced to the first selected paired hospital, then every four 
months each pair of hospitals will be rolled out from the reference phase to the intervention phase 
until all have started the intervention. This will give 1:1 ratio of intervention vs reference period of 
observation (figure 2). We will therefore be able to compare the effects of the reference and 
intervention over a reasonable period of time. Neither hospitals nor investigators will be blinded to 
the introduction of the intervention. 
3.5 Study intervention and reference 
 
Before starting the project, PI, co-investigators and research team will visit each participating 
hospital to discuss about the project’s objectives and how we would like to conduct this project 
during 16 months to the directors of the hospitals. These six hospitals have already participated in 
Global PPS, led by the PI and research team of this project. Hospital staff will be informed about the 
study by the PI and a director of hospital (also co-investigator) before starting the project and all 
prescribers in participating hospitals will be encouraged to participate in the training and surveys. 

Version 1.0_13 June 2020  
18 
a. Pre-study phase 
 
Four participating hospitals (MS, XK, LNT and SV) in this study have already participated in Global-
PPS since 2017, whilst VTP participated in 2018 and SVK in 2019. Antimicrobial prescription data of 
all six hospitals are available for the whole of 2019. This is the period when there were no available 
Lao therapeutic and prophylactic antimicrobial prescribing guidelines. These data will be used in 
this project to compare the change in proportion of antimicrobial prescriptions and the change in 
administration route before and after the introduction of the prescribing guidelines (both paper-
based and mobile phone app versions). To be able to answer our study question, Lao therapeutic 
and prophylactic antimicrobial prescribing guidelines were developed to be introduced at month 0 
of the project. Details of Lao therapeutic and prophylactic antimicrobial prescribing guidelines are 
described below. 
 
 Lao antimicrobial prescribing guidelines 
 
Lao National antimicrobial prescribing guidelines are based on existing Lao treatment guidelines, 
current data on infectious disease pathogens and antimicrobial susceptibility patterns in Laos and 
international antimicrobial prescribing/treatment guidelines (e.g. WHO, CDC, NICE, ISID, Sanford). 
The guidelines are separated into paediatric and adult guidelines for ease of use. These guidelines 
include recommendation for therapy, prevention and antibiotic stewardship. 
Most recommendations are for empiric treatment. For pathogens and syndromes for which Lao data 
are available, common causative pathogens and their antimicrobial susceptibilities are provided as a 
guide. This guideline also refers to some specific Lao treatment guidelines (e.g. Dengue guideline for 
diagnosis and treatment, Lao PDR or National Guidelines for the Use of Antiretroviral Therapy in 
Adults and Children) to avoid duplication.  
Common and important infectious diseases are arranged by involved organ systems. Each infectious 
disease section includes causative pathogen (s) of the diseases, choices of antimicrobial regimen 
(primary and alternative), doses, duration and important notes on allergy or toxicity or to help 
guide treatment. 
 

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19 
b. Reference phase 
Study duration will be divided into two parts, reference and intervention phases. At the start 
(month 0), a point prevalence survey (PPS) on hospital antimicrobial use will be performed (more 
details on conduct of PPS are given in following section) to collect baseline data before introducing 
paper-based guidelines. The participating hospitals will receive a report of the PPS findings within 
one month of the survey (Appendix A4). 
After PPS, all medical doctors of each participating hospital will be asked to complete an AMS 
knowledge survey (Appendix A5) and pre-prescribing guidelines survey (Appendix A9). Then, 
paper-based prescribing guidelines in both adult and paediatric versions (one adult guideline and 
one paediatric guideline) will be distributed to all doctors at participating hospitals, followed by 
guideline introductory session of the guidelines (Appendix A6). This session will not cover how to 
diagnose infectious diseases or prescribe antimicrobials but how to use these guidelines. 
After introduction of the paper-based guidelines, all six hospitals will be formally included in the 
reference period.  PI and research team will not become involved with any antimicrobial prescribing 
decisions of local prescribers at participating hospitals for individual patients. There will be contact 
details of the PI in the guidelines in case any prescribers need more clarification on the guidelines. A 
prescriber feedback survey on the paper-based version will be performed just before each paired 
hospital enters to the intervention phase (month 4, month 8 and month 12 after introduction of the 
paper-based prescribing guidelines).  
After the first paired hospital is randomly selected to have access to the mobile phone app 
prescribing guidelines at month 4, the second pair of hospitals will be randomly selected to have to 
access to the mobile phone app at month 8, and the last pair of hospitals will have access to a mobile 
phone app at month 12 (Figure 2). 
The order of activities at the start of the project are listed below (these activities will be applied to 
all six hospitals, one by one): 
1. PPS on hospital antimicrobial use for all 6 hospitals (Appendix A1, A2 and A3) 
2. AMS knowledge survey (Appendix A5) 
3. Pre-prescribing guidelines survey (Appendix A9) 
4. Access to paper prescribing guidelines for all 6 hospitals 
5. Introductory session to paper prescribing guidelines (Appendix A6) 
6. PPS reports (Appendix A4) 

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20 
Activities in the reference phase after the start of the project (month 0) until the last paired hospital 
is assigned to the intervention (month 12) are listed below: 
1. PPS on hospital antimicrobial use (Appendix A1, A2 and A3) 
2. PPS reports (Appendix A4) 
c. Intervention phase 
c.1 Antimicrobial Prescribing guidelines mobile phone application (MicroGuide) 
 
Both paediatric and adult antimicrobial prescribing guidelines will be transferred to MicroGuide; 
which is a medical guideline application. MicroGuide was launched in 2013 and has been adopted by 
114 medical organizations, with more than 100,000 users in 173 countries. MicroGuide is an offline 
application, free-of-charge for the individual users. The app can monitor the number of users and 
which guidelines are being accessed.  
The app will be installed to the personal smart phones of local physicians by the PI. The project will 
not provide a smart phone to any physician without one (approximately <10% of physicians in 
provincial hospitals– unpublished data). The contents of the mobile app guidelines will be the same 
as the paper version but using hyperlinks to information, rather than displaying it as in paper 
guidelines. Both mobile app and paper guidelines will be available in Lao and English languages.  
c.2 Antimicrobial stewardship (AMS) training 
 
The aim of AMS training is to increase knowledge and awareness of rational antimicrobial 
prescriptions of Lao prescribers. AMS training sessions will be given to all prescribers in 
participating hospitals when they firstly enter to the intervention phase. This session will be given 
alongside an introduction of mobile phone app prescribing guideline. The training details will be 
based on the existing information in the paper-based therapeutic and prophylactic antimicrobial 
prescribing guidelines. The main part of the training will focus on good practices of antimicrobial 
prescription. Prescribers can also access information on AMS in both paper-based and mobile phone 
app prescribing guidelines by themselves. Providing training after introducing treatment guidelines 
is not routine practice in many hospitals in Laos. The combination of the AMS training and easy 
access to prescribing guidelines could be a new strategy to improve rational use of antimicrobial of 
Lao prescribers. For more details on how the training will be conducted see Appendix A12. 
Antimicrobial Stewardship Training. 

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21 
c.3 Intervention delivery  
 
The intervention period will start at month 4 after introducing the paper-based prescribing 
guidelines. This intervention will be introduced in one pair of hospitals at a time. The process will be 
repeated every 4 months until all six hospitals have access to the intervention. The order of the 
activities during intervention phase of each step (paired hospitals) are listed below: 
1. PPS on hospital antimicrobial use (Appendix A1, A2 and A3) 
2. AMS knowledge survey (Appendix A5) 
3. Prescriber feedback survey on paper-based prescribing guidelines (Appendix A10) 
4. Access to MicroGuide mobile phone app prescribing guidelines 
5. Introductory session on MicroGuide mobile phone app prescribing guidelines (Appendix 
A7) 
6. AMS training session (Appendix A12) 
7. PPS reports (Appendix A4) 
Note:  
a. A survey on the mobile phone app prescribing guidelines (Appendix A11) will be performed 
at the end of the project only when all participating hospitals have access to the mobile 
phone app prescribing guidelines (month 16). 
b. During the intervention period, prescribers in participating hospitals still have access to 
paper-based prescribing guidelines distributed at the start of the study. Mobile phone 
prescribing guidelines surveys (Appendix A11) will be used as a tool to access the use of the 
mobile phone app prescribing guidelines and the paper prescribing guidelines at the end of 
the study 

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22 
Figure 2: Study procedures of SW-CRT on Evaluation of Lao-language antimicrobial use guidelines mobile app 
 
Pre-study phase 
Study phase 
Hospital 6 
PPS+Report 
PPS+Report+Paper-based 
PPS+Report+Paper-based 
PPS+Report+Paper-based 
PPS+Report+App+AMS 
Hospital 5 
PPS+Report 
PPS+Report+Paper-based 
PPS+Report+Paper-based 
PPS+Report+Paper-based 
PPS+Report+App+AMS 
Hospital 4 
PPS+Report 
PPS+Report+Paper-based 
PPS+Report+Paper-based 
PPS+Report+App+AMS 
PPS+Report+App+AMS 
Hospital 3 
PPS+Report 
PPS+Report+Paper-based 
PPS+Report+Paper-based 
PPS+Report+App+AMS 
PPS+Report+App+AMS 
Hospital 2 
PPS+Report 
PPS+Report+Paper-based 
PPS+Report+App+AMS 
PPS+Report+App+AMS 
PPS+Report+App+AMS 
Hospital 1 
PPS+Report 
PPS+Report+Paper-based 
PPS+Report+App+AMS 
PPS+Report+App+AMS 
PPS+Report+App+AMS 
Month 0 
Month 4 
Month 8 
Month 12 
Month 16 
Activity at month 0 
Activity at month 4 
Activity at month 8 
Activity at month 12 
Activity at month 16 
 
AMS survey for all sites 
AMS survey* 
AMS survey* 
AMS survey* 
AMS survey for all sites 
Pre-prescribing survey 
AMS training* 
AMS training* 
AMS training* 
Prescriber feedback survey 
on the App guideline**  
 
Introduce paper-based 
guideline 
Introduce App guideline* 
Introduce App guideline* 
Introduce App guideline* 
 
Prescriber feedback survey 
on paper-based guideline* 
Prescriber feedback survey 
on paper-based guideline* 
Prescriber feedback survey 
on paper-based guideline* 
Prescriber feedback survey 
on the App guideline** 
Prescriber feedback survey 
on the App guideline** 
* This activity will only be performed in a new selected paired hospital 
** This activity will only be performed 4 months after introducing App guideline in each paired hospital 
 
 

Version 1.0_13 June 2020  
23 
 
c.4 Contamination prevention 
 
Although the clusters are geographically quite remote from each other, travel and communications 
between doctors in Laos is quite frequent. There is a possibility of contamination of the app to the 
reference group (however this is judged to be unlikely). The research team will record this if it 
occurs. Examples of how this could happen are: 
• 
Doctors from the intervention group move to the reference group for any possible reason 
(training or changing workplace) 
• 
Doctors from the intervention group give their smart phones to other doctors in the 
reference group (unlikely) 
• 
Doctors from the intervention group lose their smart phones that are subsequently found 
and used by doctors in a reference group (unlikely) 
To avoid or reduce the problem of contamination, at the start of the intervention phase, all 
participating hospitals will be requested to avoid sharing the mobile app prescribing guidelines to 
anybody outside their hospitals while they are still under evaluation. The app guidelines will be 
installed by the PI. This prescribing guidelines App will not be publicly available on the internet to 
download by users without the approval from the PI. Transferring the App from one phone to other 
device will be prevented by informatic code provided by the MicroGuide team. The functional 
system, security and app maintenance will be controlled by the MicroGuide team and PI of the 
project. 
3.6 Endpoints 
Primary endpoint 
The proportion of antimicrobial prescriptions adherent with prescribing guidelines delivered by 
mobile phone app versus paper-based prescribing guidelines at month 16 (12 months’ exposure in 
each group) 
Secondary endpoints  
1. Total antimicrobial defined daily doses (DDDs) prescribed in mobile phone app versus 
paper-based groups of 12 months’ exposure in each group  

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2. Proportion of patients prescribed antimicrobials by the intravenous route in mobile phone 
app versus paper-based groups of 12 months’ exposure in each group 
3. AMS knowledge level of prescribers prescribed in mobile phone app versus paper-based 
groups of 12 months’ exposure in each group 
4. Prescriber satisfaction/acceptability of the prescribing guidelines in mobile phone app 
versus paper-based groups of 4 months’ exposure in each group 
5. Total costs of antimicrobial prescribed in mobile phone app versus paper-based groups of 
12 months’ exposure in each group 
6. Proportion of patients admitted to hospital receiving an antimicrobial prescription before 
and after introduction of the paper-based prescribing guidelines; and the mobile phone app 
prescribing guidelines + AMS training of 12 months’ exposure in each group 
Definitions of adherence to the guidelines 
1. Full adherence with the guidelines = using correct antimicrobial agent (s) and correct dose 
based on the provided antimicrobial prescribing guidelines 
2. Partial adherence with the guidelines = using correct antimicrobial agent (s) with incorrect 
dose based on provided antimicrobial prescribing guidelines 
3. Non-adherence with the guidelines = using a different antimicrobial agent (s) compared to 
that suggested in provided antimicrobial prescribing guidelines 
 
3.7 Data collection method 
 
Open Data Kit (ODK) system will be used as the data collection tool for PPS. Outcomes will be 
measured by regular PPS of hospital antimicrobial prescribing in both in- and outpatients (details as 
below) at all six hospitals during 4 monthly visits (five visits including one baseline data collection). 
Data will be collected using separate electronic questionnaires for in- and outpatients.  
Paper case report forms (CRF) will be used for the prescriber surveys (Appendix A9.  Pre-
prescribing guideline survey; A10. Prescriber feedback survey on paper-based prescribing guidelines, 
A11. Prescriber feedback survey on mobile phone app prescribing guidelines and A5. Antimicrobial 
stewardship knowledge survey) will be distributed to all doctors in each study hospital in different 
time periods (Figure 2).  

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Each data collector will be trained on the study purpose/processes and the use of the data collection 
instruments before starting the project. IPD and OPD PPS data will be collected in ODK on patients’ 
characteristics and treatment status, including age, sex, body weight, wards, antimicrobial agent (s), 
administration, dosage, unit, diagnoses, prescribing indication and antimicrobial start date. IPD PPS 
data will be collected directly from hospital charts and OPD PPS data will be obtained from the 
scanned prescription sheets. Data on the frequency of use of the mobile app can also be downloaded 
from the MicroGuide App. 
Basic information (age, sex, specialty, departments, graduated year) of prescribers and their 
prescribing behaviors will be collected via survey forms (either prescriber feedback survey or AMS 
survey). All complete survey forms by prescribers will be returned to study team on the same day as 
the survey day. All data will be entered to MACRO system.  
We will only consider antibiotic costs. Name of antimicrobials, dose, dosage form, manufacturing 
country of antibiotics will also be collected from each pharmacy hospital.  
 

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26 
a. Point Prevalence Survey procedures 
a.1 In-patient point prevalence survey 
 
Design – Point prevalence survey 
Survey site - All in-patient wards from all 6 participating hospitals: 
1. Mahosot Hospital - 16 wards, including infectious disease paediatrics, general paediatrics, 
neonatal-paediatric intensive care unit (ICU), ICU adult, general medicine, gastro-intestinal, 
cardiovascular, infectious disease adult, lung, psychology, ear-nose-throat (ENT), abdominal 
surgery, uro-surgery, plastic surgery, general surgery, post operation room, obstetrics and 
gynaecology (OBGY) 
2.  LNT provincial hospital - 7 wards, including medicine, surgery, paediatrics, OBGY, intensive 
care unit, ENT  
3. XK provincial hospital - 11 wards, including cardiology, infectious disease, OBGY, ICU adult, 
ICU paediatrics, surgery, post operation, medicine, eyes, and specialty ward (mixture of 
medicine, surgery, OBGY or paediatric patients – this ward is for patients who need private 
and more comfortable room)  
4. VTP provincial hospital - 5 wards, including paediatrics, OBGY, medicine, surgery and ICU 
5. SVK provincial hospital - 9 wards, including medicine 1, medicine 2, lung, infectious diseases 
(HIV/AIDs ward), surgery, OBGY, ICU and specialty ward 
6. SV provincial hospital - 7 wards, including medicine 1 (general medicine), medicine 2 
(mostly infectious disease patients), lung, paediatrics, surgery, OBGY and ICU 
Survey dates and times – PPS will be conducted every four months throughout the year. There will 
be 5 PPS in total from the start of the project (month 0) until the finish date of the project (month 
16) (Figure 2). 
PPS must be completed within a maximum of 5 consecutive working days from the start date of 
collecting data in hospital of that PPS round. All hospital charts of all admitted patients on a ward 
must be screened at 8 o’clock in the morning on the day of the survey. Survey days will be from 
Monday to Friday, excluding public holidays. 
Survey staff 
• 
Research staff, OR 

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27 
• 
Local doctor who is familiar with their own local hospital charts and has been trained on 
data collection for this project 
Inclusion and exclusion criteria 
Inclusion criteria  
1. All patient hospital charts from all in-patient wards at 8:00 o’clock in the morning of a 
survey day will be counted as the denominator 
2. All patient hospital charts from all in-patient wards with any kind of antimicrobial agent (s) 
prescribed at 8 o’clock in the morning of a survey day will be counted as numerator. 
Definition for IPD surveys 
• 
Denominator: all in-patients admitted on a ward on the survey day at 8:00 o’clock in the 
morning. Patients who are admitted on a ward after 8:00 am (8:01 am onward) of the 
survey day will be excluded from the survey 
• 
Numerator: all in-patients admitted on a ward on the survey day at 8:00 o’clock in the 
morning who are prescribed an antimicrobial agent (s). Patients who are admitted on a 
ward after 8:00 am (8:01 am onward) of the survey day will be excluded from the survey, 
even if s/he is on antimicrobial agent (s) 
• 
On antimicrobial agent (s):  
o Documented antimicrobial agent (s) on a hospital chart on the survey day. This 
antimicrobial agent must be prescribed by 8:00am of the survey day 
o No antimicrobial agent is documented on the hospital chart on the survey day but 
the patient received an antimicrobial agent (s) within the previous 24 hours, or 
every 48 hours or once a week (any ongoing antimicrobial therapy or prophylaxis) 
 
• 
Surgical prophylaxis: check 24 hours before surgical date to define surgical prophylaxis 
status as below: 
o Single dose prophylaxis (SP1) – patient received only single dose of antimicrobial 
agent before surgical procedure 
o One-day prophylaxis (SP2) – patient receives multiple doses of an antimicrobial 
agent within 24 hours. There are no further doses of prophylaxis after 24 hours 
o > One day prophylaxis (SP3) - patient received an antimicrobial agent as surgical 
prophylaxis for more than 24 hours (one day), regardless of how many doses a day 

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28 
o If a patient receives antimicrobial prophylaxis 48 hours before (or earlier) the 
survey day but no antimicrobial agent in the 24 hours before survey date or on 
survey day, this patient will be defined as “no antimicrobial agent” 
 
• 
Number of beds = total number of beds in the ward (occupied + empty). Note: number of 
beds should usually be more than the number of inpatients at 8 o’clock. In case, there is an 
epidemic of some disease and the number of patients is more than the usual number of beds, 
count those extra beds (occupied beds + extra beds)  
 
• 
Antimicrobial start date: this should be stated in the patient hospital chart before the 
survey start. Patients should be prescribed before 8:00am of the survey day. It is required 
the surveyor to check the previous record in the patient hospital chart 
 
Exclusion criteria  
o Patients who are admitted to a ward after 8:00 o’clock (8:01am) in the morning of the 
survey day 
o Patients who are on topical antimicrobial agent(s) alone will be excluded from numerator 
but they will still be in the denominator 
Survey setting  
Research team will inform the hospital directors three days before starting each PPS (both IPD and 
OPD). Research staff will start collecting data on the ward at 8:00 o’clock in the morning of the 
survey day with permission of the hospital director few days before starting survey (both at IPD and 
OPD). The ward doctors and nurses will be informed about the survey on the same day as the 
survey day. Research staff will work on hospital charts only without interviewing any patients or 
ward staff, unless the number of charts and number of patients are not consistent or there is unclear 
handwriting of doctors or nurses. Research staff must complete the survey of a ward within a day. 
Research staff must finish a survey of one ward before moving to another ward.  
If research staff cannot start the survey at 8:00 o’clock in the morning of the survey day for all 
wards, starting a new ward after 8:00am is acceptable with the condition of excluding all patients 
who are admitted to hospital after 8:00am (8:01am) of the survey day. 

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If some hospital charts are not available at the wards during the survey time (i.e. consulting with 
other medical specialties at other wards), the survey team can come back to that ward in the same 
day for that hospital chart but excluding all information after 8:00am of that survey day. 
For more details of in-patient PPS data collection form, see Appendix A1. In-patient PPS Ward Form 
and Appendix A2. In-patient PPS Patient Form. 
 
a.2 Out-patient point prevalence survey 
 
Design – Point prevalence survey 
Survey site – In most hospitals, many wards have their own OPD within their wards. In this study, 
we will focus on three main wards (Paediatrics, Medicine and Surgery) where we would expect that 
the most antimicrobial prescribing would occur.  
Survey dates and times – PPS will be conducted every four months throughout the year or three 
times a year with 4-month intervals between each survey. There will be 5 surveys in total. PPS in 
OPD will be performed for 5 consecutive working days in total from the start date of collecting data 
in the hospital in that PPS round. 
All outpatient prescriptions will be screened between 8:00 o’clock in the morning and 4:00 o’clock 
in the afternoon on the day of survey. Survey days should be from Monday to Friday, excluding 
public holiday and weekends. 
Surveyor qualification  
• 
Research staff, OR 
• 
Local doctor who received training for data collection for this project 
 
Inclusion and exclusion criteria 
Inclusion criteria   
1. All patients consulting at OPD of paediatrics, medicine and surgical wards of all 
participating hospitals during 8:00am and 4:00pm of a survey day will be counted as the 
denominator  

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30 
2. All patients consult at OPD of these three wards of all participating hospitals who are 
prescribed antimicrobial (s) between 8:00am and 4:00pm on a survey day will be 
counted as the numerator  
3. If the same outpatient comes back for consultation during the same survey period (same 
round, any day during these five days) this patient will also be included in the survey 
and be defined as a new consultation. 
 
Definitions for OPD surveys 
• 
Denominator: all outpatients who consult at paediatrics, medicine and surgical OPDs on the 
survey day between 8:00am and 4:00pm for 5 consecutive working days. Patients who come 
outside this period of time will be excluded from the survey 
• 
Numerator: all outpatients who consult at paediatrics, medicine and surgical OPDs and are 
prescribed antimicrobial (s) on the survey day between 8:00am and 4:00pm for 5 
consecutive working days. Patients who come outside this period of time will be excluded 
from the survey, even if they are prescribed any antimicrobial (s). 
 
Exclusion criteria  
o Patients who come for consultation outside the survey time (before 8:00am or after 
4:00pm) of the survey day 
o Patient who are prescribed topical antimicrobial (s) only will be excluded from numerator 
but they will still be in the denominator 
Study setting  
OPD PPS will be conducted for 5 consecutive working days. Hospital directors of each hospital will 
be informed three days before the survey. Head of OPD will be informed about the survey on the 
same day as they survey day. Data will be collected from an OPD prescription sheet at the OPD 
pharmacy. There will not be any private discussion or interview of patients or doctors.  
The OPD prescription sheet from patients will be scanned and saved as an electronic file for data 
entry by research staff on the same day. The reason for scanning OPD prescription sheets is to avoid 
disrupting the OPD workflow of the rush hours of each participating hospital. The total number of 
OPD patients (denominator) will be collected from the OPD logbook at the end of each survey day. 

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31 
There are different systems of OPD data recording in each hospital. This project will not create a 
new system for the hospital but follow the existing routine systems of each hospital, ensuring that 
we can capture all antimicrobial prescription data and the denominators. Scanned prescription files 
will be securely kept and discarded one month after the scanned date. 
For more details of outpatient PPS data collection form, see Appendix A3. Outpatient PPS Form. 
Point prevalence survey report 
 
PPS reports of IPD and OPD survey will be available within one month after each survey. With the 
agreement of MoH, these PPS will support antimicrobial use surveillance in the country. The reports 
will be in the format of computer dashboard (AMU-Laos App) which will be published on the MoH 
website. Access to AMU-Laos App will be publicly available. Everybody can view the results of the 
survey but not access the raw data.  AMU-Lao App will be managed and operated by the PI and a 
dashboard programmer only. AMU-Laos App will display prevalence of antimicrobial prescriptions 
of each time points in different participating hospitals, as well as the overview of antimicrobial 
prescriptions (e.g. classes, agents, route and indications) and pattern of the prescription by age, by 
specialty in both IPD and OPD. Paper reports will be also available via this AMU-Laos App (Appendix 
A4. Point Prevalence Survey (PPS) of hospital antimicrobial use report format). However, paper 
reports will be also provided by the research team to the participating wards/doctors as there is 
limited access to computers and internet in some areas of Laos.  
a.3 Antimicrobial stewardship (AMS) knowledge survey 
 
This survey will be performed before introduction of the paper version of the therapeutic and 
prophylactic antimicrobial prescribing guidelines (at month 0) and every 4 months before the 
implementation of the mobile phone app guidelines and AMS training in the paired hospitals 
starting the intervention. The survey will be performed again in month 16 in all study hospitals 
before the study ends. Therefore, each hospital will participate this AMS knowledge survey 3 times 
during the whole study period (1st time= at the start of the project, 2nd time= before entering to the 
intervention period and 3rd time= at the end of the project) 
This survey questionnaires will be in Lao language. The survey will provide information on the level 
of knowledge of rational antibiotic prescribing of prescribers before and after having access to 
paper prescribing guidelines and the app prescribing guidelines at different time points. For more 
details on what questions will be asked, see Appendix A5.  Antibiotic stewardship knowledge survey. 

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32 
Each survey will include 8 questions in total. The 8 questions will be randomly selected (simple 
random sampling – using a computer-generated random allocation sequence) from a set of 
questions in Appendix A5. The answers to all questions are in the guidelines.  
Maximum 10 minutes will be requested to complete 8 questionnaires. The questionnaires will be 
multiple answers. There is no need to put the name of responders to the survey form but age, 
graduated year, department and speciality are needed. The survey will be conducted in the same 
day as introduction to the guidelines (paper (month 0)/app), introductory session of the guidelines 
(paper (month 0)/app), pre-prescribing guidelines survey (month 0), AMS training (only for those 
firstly enter to intervention period). Complete survey forms will be collected by the research team 
before starting the introductory session of the guidelines (paper (month 0)/app). 
Pre-prescribing guidelines survey 
 
The aim of conducting a pre-prescribing guidelines survey is to understand how prescribers 
prescribe antimicrobials and how much they use any prescribing guidelines in their routine work. 
This will provide some explanation as to what prescribers think about the provided prescribing 
guidelines. The survey will be performed once at the beginning of the study (month 0) after the first 
round of PPS and before introduction of the paper prescribing guidelines. Survey form (Appendix 
A9. Pre-prescribing guidelines survey) will be distributed to all prescribers at each study hospital and 
collecting back by the research team in the same day. The survey form contains 6 questions and it 
will take 5 minutes maximum to complete the survey. 
Prescriber feedback survey on paper-based prescribing guidelines  
 
Each participating hospital will participate this survey only once before they enter to the 
intervention period. The aim of the survey is to get feedback on the provided paper-based 
prescribing guidelines from the prescribers as well as self-reported use of the guidelines. Survey 
form (Appendix A10. Prescriber feedback survey on paper-based prescribing guidelines) will include 
questionnaires on the frequency of the use of paper-based guidelines and Likert scale 
questionnaires on prescribers’ opinions on the paper-based prescribing guidelines. The survey 
forms will be distributed to all prescribers after PPS and before introduction of the mobile phone 
app prescribing guidelines. By doing this, we will obtain different opinions about the paper 
prescribing guidelines at different time points. This will also provide feedback on  the guidelines 
and the change in prescribing behaviours in in participating hospitals exposed to paper and app 

Version 1.0_13 June 2020  
33 
prescribing guidelines for the same duration. Complete survey forms will be collected from all 
prescribers at each study hospital in the same days as the survey day.  
Prescriber feedback survey on mobile phone App prescribing guidelines  
 
This survey will be conducted at the end of the study (month 16) when all participating hospitals 
having access to the mobile phone app at least for 4 months. The aim of the survey is to get feedback 
on the mobile phone app prescribing guidelines from prescribers, as well as how prescribers find 
this app compared to the paper version of the prescribing guidelines. The survey forms include 
questionnaires on the frequency of the use of paper-based guidelines after introducing mobile 
phone app guidelines, as well as the frequency of the use of the mobile phone app guidelines use 
and Likert scale questionnaires on prescribers’ opinions of the mobile phone app prescribing 
guidelines. Complete survey forms will be collected from all prescribers at each study hospital on 
the same days as the survey day. The same survey form will be used for all participating hospitals 
(Appendix A11.  Prescriber feedback survey on mobile phone app prescribing guidelines).  
Data management and monitoring  
 
All data will be entered by PI and trained research staff. All complete survey forms will be kept 
securely in a locked filling cabinet.  Only the PI of the project and project data management team 
will have access to the raw data. All electronic data will be kept securely, protected by password 
access with automatic daily backup on the server at Lao-Oxford-Mahosot Hospital-Wellcome Trust 
Research Unit (LOMWRU) office and regular offsite tape backups. All scanned OPD prescription 
sheets will be appropriately destroyed within one month after the scanned date. Anonymized data 
from PPS will be fed back to the participating hospitals and Ministry of Health through a project-
generated computer dashboard and reports one month after each PPS in each hospital. Data 
checking and cleaning will be done by the PI after each survey. Data inconsistency will be discussed 
with the research team immediately. 
Statistical analysis 
 
Normally distributed continuous baseline characteristics will be summarized with means and 
standard deviations. Skewed continuous data will be summarized using median and inter-quartile 
range. Categorical data will be presented as frequency and percentages. A logistic mixed effects 
regression model will be used to compare the proportion of antimicrobial prescriptions adherence 

Version 1.0_13 June 2020  
34 
measured cross-sectionally at month 0, 4, 8, 12 until month 16 after introduction of prescribing 
guidelines by mobile phone application versus paper-based (30). The model will compare all 
wedges in the intervention from month 4 to month 16 with all wedges in the reference arm from 
month 0 to month 12. The duration of exposure of each hospital to the reference or intervention 
arm will be included in the model as interaction term with the study arm in order to assess whether 
the duration of exposure is the effect modifier. The model will consider the correlation among the 
outcome’s measurements from the same hospital (cluster) by adjusting for clustering in the model. 
Odds ratios and the corresponding confidence intervals will be obtained and reported. Tests of 
significance will be performed at 5% level. Analyses will be done using Stata 15.0 or higher. Likert 
scale analysis will be used to evaluate prescriber satisfaction with/ acceptability of paper-based 
compared 
to 
mobile 
phone 
app 
delivered 
antimicrobial 
prescribing 
guidelines. 
The 
satisfaction/acceptability scale will be assigned in six categories, including strongly agree=5, 
agree=4, neutral=3, disagree=2 and strongly disagree=1, no opinion/not use=0. Mann-Whitney test 
will be used to assess the differences between paper-based population and mobile phone app 
population. AMS knowledge level of prescribers will be assessed using questionnaires based on 
information in the prescribing guidelines. The overall proportion of correct answers in each time 
point will be compared (baseline, after paper-based guidelines (before AMS training and 
introduction of mobile phone app guidelines) and after AMS training and introduction of mobile 
phone app guidelines). Other factors such as extra AMR training program from hospital/MoH/other 
organizations, level of education and specialties of prescribers will also be taken into account. 
Cost of antibiotic therapy will be calculated from the start date of treatment to the survey day. The 
unit costs for the antibiotics will be obtained from the International Medical Product Price Guide. 
Antibiotic defined daily dose (DDD) will be calculated using data (antibiotic agent, start date, dose 
and DDD of each antibiotic from www.whocc.no ) from PPS in both IPD and OPD. Antimicrobial cost 
data from participating hospitals will also be collected each hospital pharmacy for comparison with 
international cost. 
The results will be reported in accordance with the Consolidated Standards of Reporting Trials 
(CONSORT) extension for the stepped wedge cluster randomised trial (SWCRT) (30). 
 
Safety considerations/Adverse Events  
 
 

Version 1.0_13 June 2020  
35 
The intervention is the introduction of antimicrobial prescribing guidelines delivered by a mobile 
app in line with national and international recommendations. Therefore, no adverse event 
monitoring is planned. 
Ethics 
 
Ethical approval will be requested from both the University of Health Sciences Ethics Committee, 
Ministry of Health, Lao PDR and the Oxford Tropical Research Ethics Committee (OxTREC), 
University of Oxford, United Kingdom to conduct this project. Verbal consent to participate to the 
study will be asked from the director of each participating hospitals. 
Benefits 
This study describes the introduction of the first therapeutic and prophylactic antimicrobial 
prescribing guidelines in Laos. The guidelines will encourage the rational use of antimicrobials. 
Prescribing guidelines in the format of mobile phone application will allow clinicians to access 
guidelines easier. This will help to improve clinical decision of doctors and consistency of care. This 
will give the potential to improve health outcomes of patients, reduce morbidity and mortality and 
give value for money.  
Risks 
Guidelines have been developed based on existing national treatment guidelines, current data on 
infectious diseases, antimicrobial susceptibility patterns in Laos, as well as international 
recommendations. Availability of antimicrobials in Laos is also considered. The guidelines will be 
transformed to a mobile phone App which will make it easier for the clinicians to access. This would 
be more likely to benefit than harm patients or clinicians. However, this App and paper prescribing 
guidelines will be introduced to 6 general hospitals across Laos for 16 months before the 
prescribing guidelines mobile phone App will be adapted and distributed nationwide. There might 
be some risk that MoH would like to introduce the guidelines and the App before the study finishes 
if the results are very positive. In addition, it could be challenging to manage and control the travel 
of Lao doctors from one hospital to another as many trainings, workshops or conferences (not 
related to this project) are conducted across the country throughout the whole year. In addition, 
some doctors may have to leave their local hospital for further education. Apart from this project, 
another 18-month AMR program (supported by the Fleming fund) is also conducted in three 
participating hospitals (SV, XK and LNT) to improve the quality of infectious diagnosis in these three 
hospitals. This program plans to start at the same time as this project. This AMR program could have 

Version 1.0_13 June 2020  
36 
some positive effect on antimicrobial stewardship knowledge of Lao doctors. In this case, the 
number of trainings and training materials (if applicable) provided by this AMR program will be 
recorded by our study team. There are also another three participating hospitals (MS, SVK and VTP) 
not included in the Fleming Fund project, this could allow us to compare MS knowledge level 
between hospitals with and without another AMR program in the analyzing stage.  
Patient and doctor confidentiality 
There will not be any record of patients’ personal details to be able to identify any individual. Only 
patients’ age, gender, weight and some information on antimicrobial prescription will be collected 
from hospital charts. There will not be any direct interaction between the research team and 
patients. 
This study targets the behaviour of all prescribers rather than individuals. We will therefore focus 
on cluster information rather than individual data. Only prescribers’ age, speciality, and the year of 
graduation will be collected as their personal details. Nobody (including research team and the PI of 
the study) will be able to identify the person who fills the survey form from a completed survey CRF 
or who prescribe antimicrobial (s) from ODK systems or database. All complete survey forms will be 
kept secured in the locked filing cabinet and all electronic data will be protected by password access. 
Trial insurance 
 
The University of Oxford has a specialist insurance policy in place: Newline Underwriting 
Management Ltd, at Lloyd’s of London, which would operate in the event of any participant 
suffering harm as a result of their involvement in the research. 
Data sharing and dissemination 
 
This stepped wedge cluster randomized controlled trial will generate valuable data for healthcare 
sectors and for diverse further research projects in AMR field in Laos. This trial will provide data of 
hospital antimicrobial use across Laos, which have never been reported before. It will introduce a 
Lao language antimicrobial prescribing guidelines mobile app for the first time. This project will 
also provide data on cost of antibiotics use comparing between the paper-based and the mobile 
phone app prescribing guidelines. The study will also have global impact as an evaluation of an 
increasingly popular intervention that lacks a strong evidence base. 
AMU-Laos App (computer dashboard) will be used to demonstrate real time results of the point 

Version 1.0_13 June 2020  
37 
prevalence survey on hospital antimicrobial use at each stage to local authorities, the MoH and 
policy makers. AMU-Laos App can generate the report to the users with just one click. 
Information on each PPS on hospital antimicrobial use will be shared with participating hospital 
staff and authorities and public health departments of each participating provinces, as well as MoH 
and funder one month after each survey. 
The Lao-language antimicrobial use guidelines mobile application will be discussed with the MoH 
before starting the trial and only shared with doctors in participating hospitals during the trial 
period.  
Preliminary results will be shared with the Lao Ministry of Health and the Wellcome Trust. Final 
results of the trial will be publicly available on the computer dashboard. Paper reports will be 
shared with participating hospitals, local public health offices, and the MoH. Oral presentation and 
posters will be used as tools to deliver progress updates and the results of the study in national, 
regional and international conferences. Results will also be published in open access peer reviewed 
medical journals.  
Finance 
 
This research is supported by the Wellcome Trust of Great Britain, UK. No funding sources have any 
role in study design, data collection, or preparation of the protocol.

Version 1.0_13 June 2020  
38 
References 
 
1. 
WHO. Action Agenda for Antimicrobial Resistance in the Western Pacific Region: 
http://www.wpro.who.int/entity/drug_resistance/documents/action_agenda.pdf; 2015 [Available 
from: http://www.wpro.who.int/entity/drug_resistance/documents/action_agenda.pdf. 
2. 
Munita JM AC. Mechanisms of Antibiotic Resistance. Microbiol Spectr. 2016;4(2). 
3. 
Holmes A ML, Sundsfjord A, Steinbakk M, Regmi S, Karkey A, Guerin P, Piddock L. 
Understanding the mechanisms and drivers of antimicrobial resistance. The Lancet. 2015:387. 
4. 
WHO. Global Action Plan on Antimicrobial Resistance: 
http://www.wpro.who.int/entity/drug_resistance/resources/global_action_plan_eng.pdf; 2015 
[Available from: 
http://www.wpro.who.int/entity/drug_resistance/resources/global_action_plan_eng.pdf. 
5. 
J ON. Tacking drug-resistant infections globally: Final report and recommendations. The 
review on antimicrobial resistance https://amr-
review.org/sites/default/files/160518_Final%20paper_with%20cover.pdf2016 [Available from: 
https://amr-review.org/sites/default/files/160518_Final%20paper_with%20cover.pdf. 
6. 
Limmathurotsakul D DS, Fukuda K, Feasey NA, Okeke IN, Holmes AH, Moore CE, Dolecek C, 
van Doorn HR, Shetty N, Lopez AD, Peacock SJ. Surveillance and Epidemiology of Drug Resistant 
Infections Consortium (SEDRIC). Improving the estimation of the global burden of antimicrobial 
resistant infections. Lancet Infect Dis. 2019;19(11):e392-e8. 
7. 
M M. We Need Antibiotics. They’re Not Profitable To Make. Who Pays? 
http://phenomena.nation-algeographic.com/2015/05/23/oneill-amr-3/: 
http://phenomena.nation-algeographic.com/2015/05/23/oneill-amr-3/; 2015 [Available from: 
http://phenomena.nation-algeographic.com/2015/05/23/oneill-amr-3/. 
8. 
World-Bank-Group. Drug-Resistant Infections: A Threat to Our Economic Future [Discussion 
Draft]: http://pubdocs.worldbank.org/en/527731474225046104/AMR-Discussion-Draft-
Sept18updated.pdf; 2016 [Available from: 
http://pubdocs.worldbank.org/en/527731474225046104/AMR-Discussion-Draft-
Sept18updated.pdf. 
9. 
WHO. Lao People’s Democratic Republic: WHO statistical profile: 
https://www.who.int/countries/lao/en/; 2015 [Available from: 
https://www.who.int/countries/lao/en/. 

Version 1.0_13 June 2020  
39 
10. 
WHO. Global Antimicrobial Surveillance System: Manual for early implementation: 
https://apps.who.int/iris/bitstream/handle/10665/188783/9789241549400_eng.pdf?sequence=1
; 2015 [Available from: 
https://apps.who.int/iris/bitstream/handle/10665/188783/9789241549400_eng.pdf?sequence=1. 
11. 
WHO. Global Priority of antibiotic-resistant bacteria to guide research, discovery, and 
development of new antibiotics: https://www.who.int/medicines/publications/WHO-PPL-
Short_Summary_25Feb-ET_NM_WHO.pdf?ua=1; 2017 [Available from: 
https://www.who.int/medicines/publications/WHO-PPL-Short_Summary_25Feb-
ET_NM_WHO.pdf?ua=1. 
12. 
World-Bank-Group. Managing Transition, Reaching the vulnerable while pursuing universal 
health coverage: 
http://documents.worldbank.org/curated/en/160201512147494228/pdf/121809-REVISED-v1-
Executive-Summary-07-12-17.pdf 2017 [Available from: 
http://documents.worldbank.org/curated/en/160201512147494228/pdf/121809-REVISED-v1-
Executive-Summary-07-12-17.pdf  
13. 
Lao-MoH. National Health Account Report, fiscal years 2012-2013, 2013-2014, 2014-2015 
and 2015-2016 https://thinkwell.global/wp-content/uploads/2018/04/Lao-NHA-2013-2016-
report-_Final-Eng.pdf: Ministry of Health (MoH); 2017 [1-33]. Available from: 
https://thinkwell.global/wp-content/uploads/2018/04/Lao-NHA-2013-2016-report-_Final-
Eng.pdf. 
14. 
WHO. The Lao People’s Democratic Republic health system review 
https://iris.wpro.who.int/bitstream/handle/10665.1/10448/9789290616481_eng.pdf; 2014 
[Available from: 
https://iris.wpro.who.int/bitstream/handle/10665.1/10448/9789290616481_eng.pdf. 
15. 
Peacock SJ NP. Public health impact of establishing the cause of bacterial infections in rural 
Asia. Trans R Soc Trop Med Hyg. 2008;102(1):5-6. 
16. 
Lao-MoH. Structure of th national laboratory network.  Operational guidelines for health 
laboratories networking in Lao PDR (version 1). 1 ed: Lao-Ministry of Health; 2015. p. 4. 
17. 
Cusack TP PV, Duangmala K, Phoumin P, Turton J, Hopkins KL, Woodford N, Shetty N, 
Stoesser N, Phan HTT, Dance DAB. Molecular characterizationof carbapenem-resistant Escherichia 
coli and Acinetobacter baumannii in the Lao People's Democratic Republic. 2019;74(9):2810-21. 
18. 
Roberts TR, Sayaphet & Phommasone, Koukeo & Chansamouth, Vilada & Davong, Viengmon 
& Valy, Keoluangkhot & Hongsakhone, Sitthivone & Bounsavath, Naly & Mayxay, Mayfong & 

Version 1.0_13 June 2020  
40 
Vongsouvath, Manivanh & Dance, David & Newton, Paul. Typhoid in Laos: An 18-Year Perspective. 
The American Journal of Tropical Medicine and Hygiene. 2020;102(4):749. 
19. 
Keohavong B SL, Sengaloundeth S, Nishimura A, Ito K. Rational use of drugs: prescribing and 
dispensing practices at public health facilities in Lao PDR. Pharmacoepidemiol Drug Saf. 
2006;15(5):344-7. 
20. 
Mayxay M C-VJ, Chansamouth V, Dubot-Pérès A, Paris DH, Phetsouvanh R, 
Tangkhabuanbutra J, Douangdala P, Inthalath S, Souvannasing P, Slesak G, Tongyoo N, 
Chanthongthip A, Panyanouvong P, Sibounheuang B, Phommasone K, Dohnt M, Phonekeo D, 
Hongvanthong B, Xayadeth S, Ketmayoon P, Blacksell SD, Moore CE, Craig SB, Burns MA, von 
Sonnenburg F, Corwin A, de Lamballerie X, González IJ, Christophel EM, Cawthorne A, Bell D, 
Newton PN. Causes of non-malarial fever in Laos: a prospective study. Lancet Glob Health. 
2013;1(1):e46-54. 
21. 
Quet F VE, Leyer C, Buisson Y, Newton PN, Naphayvong P, Keoluangkhot V, Chomarat M, 
Longuet C, Steenkeste N, Jacobs J. Antibiotic prescription behaviours in Lao People's Democratic 
Republic: a knowledge, attitude and practice survey. Bull World Health Organ. 2015;93(4):219-27. 
22. 
Keohavong B VM, Phoummalaysith B, Louangpradith V, Inthaphatha S, Kariya T, et al. 
Antibiotic prescription for under-fives with common cold or upper respiratory tract infection in 
Savannakhet Province, Lao PDR. Tropical medicine and health. 2019;47(1):16. 
23. 
Wang H WH, Yu X, Zhou H, Li B, Chen G, Ye Z, Wang Y, Cui X, Zheng Y, Zhao, R YH, Wang Z, 
Wang P, Yang C, Liu L. Impact of antimicrobial stewardship managed by clinical pharmacists on 
antibiotic use and drug resistance in a 
Chinese hospital, 2010-2016: a retrospective observational study. BMJ Open. 2019;9(8):e026072. 
24. 
Scheetz MH BM, Postelnick M, Noskin GA, Lee TA Cost-effectiveness analysis of an 
antimicrobial stewardship team on bloodstream infections: a probabilistic analysis. J Antimicrob 
Chemother. 2009;63(4):816-25. 
25. 
Tuon FF GJ, Wollmann LC, Moraes TP. Mobile health application to assist doctors in 
antibiotic prescription - an approach for antibiotic stewardship. Braz J Infect Dis. 2017;21(6):660-4. 
26. 
Yoon CH RS, Duffy EJ, Thomas MG, McBride S, Read K, Chen R, Humphrey G. Impact of a 
smartphone app on prescriber adherence to antibiotic guidelines in adult patients with community 
acquired pneumonia or urinary tract infections. PLoS One. 2019;14(1):e0211157. 
27. 
Antonello VS CM, Rosin ET, Castilhos JX, Beduschi FG, Bumaguin DB, Antonello ICF, Jimenez 
MF. The Use of Mobile Educational Tools to Improve Antimicrobial Prescription for the Treatment of 

Version 1.0_13 June 2020  
41 
Acute Pyelonephritis in Pregnancy: A Retrospective Cross-sectional Study. Rev Bras Ginecol Obstet. 
2019;41(2):97-101. 
28. 
Panesar P JA, Aldous A, Kranzer K, Halpin E, Fifer H, Macrae B, Curtis C, Pollara G. Attitudes 
and Behaviours to Antimicrobial Prescribing following Introduction of a Smartphone App. PLoS One. 
2016;11(4):e0154202. 
29. 
Charani E GM, Moore LSP, Castro-Sanchéz E, Lawson W, Gilchrist M, Holmes AH. Effect of 
adding a mobile health intervention to a multimodal antimicrobial stewardship programme across 
three teaching hospitals: an interrupted time series study. J Antimicrob Chemother. 
2017;72(6):1825-31. 
30. 
Hemming K, Taljaard, M., & Forbes, A. Analysis of cluster randomised stepped wedge trials 
with repeated cross-sectional samples. 2017;18(1):101. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Appendices 
A1. In-patient PPS Ward form 
Evaluating the impact of a Lao-language antimicrobial prescribing guidelines on antimicrobial prescribing in Laos 
 
Hospital Antimicrobial Prescribing Survey Form 
 
Ward Form 
 
Date of Survey 
Surveyor name 
☐ Vilada 
☐ Danoy 
☐ ___________ 
(dd-mmm-yyyy) 
Hospital name 
☐ Mahosot 
☐ VTP 
☐ SVK 
☐ SV 
☐ XK 
☐ LNT 
OPD/IPD 
☐ OPD 
☐ IPD 
Ward name 
Department type 
☐ 
Medicine 
☐ 
Surgery 
☐ 
Paediatrics 
☐ 
OBGY 
☐ 
ICU 
Total number of admitted patients by 8:00am on the day of survey 
Numeric 
Total number of bed (including extra bed) 
Numeric  
 
 
 
 

Version 1.0_13 June 2020  
43 
A2. In-patient PPS Patient Form 
Evaluating the impact of a Lao-language antimicrobial prescribing guidelines on antimicrobial prescribing in Laos  
Hospital Antimicrobial Prescribing Survey Form 
In-Patient Form 
Survey number 
Activity 
Age (≥2years) 
Age   
(1-23m) 
Age (<30days) 
Weight (kg) 
Gender 
(M/F)  
  
M   S   IC 
  
  
  
  
  
Antimicrobial 
1  
Antimicrobial 
2  
Antimicrobial 
3 
Antimicrobial 
4  
Antimicrobial 
5  
Antimicrobial name 
  
  
  
  
  
Antimicrobial start date 
  
  
  
  
  
Single Unit Dose 
  
  
  
  
  
Unit (g, mg, IU) 
  
  
  
  
  
Doses/day 
  
  
  
  
  
Route (P, O, R)* 
  
  
  
  
  
Diagnosis 
  
  
  
  
  
Diagnosis site 
  
  
  
  
  
Type of Indication  
  
  
  
  
  
Reason in Note (yes/no) 
  
  
  
  
  
Is a stop/review date documented? (yes/no) 
  
  
  
Treatment (empiric/targeted) 
  
  
  
  
  
The next section is to be filled in only if the treatment choice is based on microbiology data (Treatment=targeted) AND the organism is one of the following  
MRSA (yes/no) 
  
  
  
  
  
VRE (yes/no) 
  
  
  
  
  
ESBL-producing Enterobacteriaceae  (yes/no) 
  
  
  
  
  
3rd generation cephalosporin resistant Enterobacteriaceae non-ESBL producing or 
ESBL status unknown  (yes/no) 
  
  
  
  
  
Carbapenem-resistant Enterobacteriaceae  (yes/no) 
  
  
  
  
  
ESBL-producing non-fermenter Gram-negative bacilli  (yes/no) 
  
  
  
  
  
Carbapenem-resistant non-fermenter Gram- negative bacilli  (yes/no) 
  
  
  
  
  
Targeted treatment against other MDR organisms  (yes/no) 
  
  
  
  
  
Targeted treatment against other confirmed laboratory results  (yes/no) 
 
 
 
 
 
 
Treatment based on biomarker data (yes/no) 
  
If yes, which biomarker (CRP, PCT or other)  
 
  
Value  
 
Unit (in μg/L, 
mg/L)  
  
Remark: One In-patient PPS Ward Form is for one ward. One In-patient PPS Patient Form is for one patient who is on antimicrobial agent (s). No In-patient PPS Patient 
Form will be filled for patients with any antimicrobial agent (s) as defined in this study. * P=Parenteral, O=Oral, R=Rectal. 
 

Version 1.0_13 June 2020  
44 
A3. Outpatient PPS Form 
Evaluating the impact of a Lao-language antimicrobial prescribing guidelines on antimicrobial prescribing in Laos 
Hospital Antimicrobial Prescribing Survey Form 
Outpatient Form 
Date of Survey 
Add calendar 
Surveyor name 
☐ Vilada 
☐ Danoy 
☐ ___________ 
(dd-mmm-yyyy) 
Hospital name 
☐ Mahosot 
☐ VTP 
☐ SVK 
☐ SV 
☐ XK 
☐ LNT 
OPD/IPD 
☐ OPD 
☐ IPD 
OPD type 
Drop down list 
Total number of consulted patients between 8:00 am and 4:00pm on the day of survey 
Numeric 
Survey number 
Activity 
Age (≥2years) 
Age (1-23m) 
Age (<30days) 
Weight (kg) 
Gender  
  
  
  
  
  
  
  
Antimicrobial 1 
Antimicrobial 2 
Antimicrobial 3 
Antimicrobial 4 
Antimicrobial 5 
Antimicrobial name 
  
  
  
  
  
Single Unit Dose 
  
  
  
  
  
Unit (g, mg, IU) 
  
  
  
  
  
Doses/day 
  
  
  
  
  
Route (P, O, R) 
  
  
  
  
  
Diagnosis 
  
  
  
  
  
Diagnosis site 
  
  
  
  
  
Type of Indication  
  
  
  
  
  
Reason in Note (yes/no) 
  
  
  
  
  
Is a stop/review date documented? (yes/no) 
  
  
  
  
  
Treatment (empiric/targeted) 
  
  
  
  
  
If targeted, specify: 
 
 
 
 
 
 
 
Antimicrobial stop date 
  
  
  
  
  

Version 1.0_13 June 2020  
45 
A4. Point Prevalence Survey (PPS) of hospital antimicrobial use Report Format 
All participant hospitals will receive PPS report in the same format with their own hospital 
antimicrobial use data. The report will be available in both Lao and English languages. Participating 
hospitals will have access to both current and previous reports via AMU-Laos App. We would like to 
keep this report in a friendly format for all doctors with and without statistical knowledge 
background. 
Lao People’s Democratic Republic 
Peace, independence, democracy, unity and prosperity 
********************** 
Ministry of Health 
Lao-Oxford Mahosot Hospital  
Wellcome Trust Research Unit (LOMWRU) 
 
Point Prevalence Survey (PPS) of hospital antimicrobial use, [name of hospital], [name of 
province], Lao PDR 
Survey date:  
[start date] to [stop date] 
Survey team:  
[name of surveyor] 
 
 
Editor: Vilada Chansamouth 
 
 
 
[name of surveyor] 
[name of surveyor] 
 
I. 
Background 
 
This Point-prevalence survey (PPS) on hospital antimicrobial use in Laos has been 
developed based on the Global-PPS (www.global-pps.com) which was developed in 
2006. Laos participated in Global-PPS in 2017 to provide the first data of hospital 
antimicrobial prescribing of Lao doctors to the country as a part of a project on 
surveillance of antimicrobial use and resistance in Laos. In 2017, four hospital 
participated in this survey (Mahosot Hospital, Xiengkhuang, Luang Namtha and Salavan 
Provincial Hospitals). Vientiane provincial Hospital joined the survey in 2018 and in 
2019 Savannakhet Provincial Hospital also participated. There are now six hospitals in 
across Laos who participate in this PPS on hospital antimicrobial use.  
 
II. 
Survey objectives 
To provide hospital antimicrobial use data to participating hospitals and the country 

Version 1.0_13 June 2020  
46 
To promote the rational use of antimicrobials in Laos 
To contribute to national antimicrobial use and resistance surveillance 
 
III. 
Survey methods 
1. Surveyed hospitals: this PPS on hospital antimicrobial use in Laos was conducted in 
six hospitals, including Mahosot Hospital, Vientiane, Xiengkhuang, Luang Namtha, 
Savannakhet and Salavan Provincial Hospitals.  
2. Survey wards: all in- and outpatient departments of each participant hospitals 
participated in this survey 
3. Survey date and time: PPS on hospital antimicrobial use was conducted every 4 
months. 
3.1. 
In- patient department (IPD): All patient hospital charts from each IPD 
were screened at 8:00 o’clock in the morning of the survey day. Survey days 
were from Monday to Friday, excluding weekends and public holidays 
3.2. 
Outpatient department (OPD): PPS in OPD (medicine, paediatrics and 
surgery) was conducted for 5 consecutive working days from 8:00am to 
4:00pm, excluding weekends and public holidays 
 
4. Inclusion criteria: all IPD and OPD patients (medicine, paediatrics and surgery) 
who were prescribed antimicrobial (s) during the defined survey period 
5. Data collection: basic data on patient characteristics (age, sex, weight), information 
on antimicrobial prescriptions (e.g. dose, route, duration and indication) were 
collected. Neither doctors/nurses nor patients were interviewed in this survey.  
 
IV. 
Survey findings 
This survey was conducted from [start date to stop date] in [hospital name]. The survey 
was performed by [number of surveyors] in [number of in-patient wards] IPD and one 
OPD. During [number of survey days] days of IPD survey, [number of screened hospital 
charts] hospital charts were screened, of these, [number of patients with prescribed 
antimicrobial (s)] ([%]) received some kinds of antimicrobial (s). During 5 consecutive 
working days of the OPD survey, [number of prescriptions] were screened, of these 
[number of patients with prescribed antimicrobial (s)] ([%]) received antimicrobial (s). 
More details of prescriptions can be found as below: 

Version 1.0_13 June 2020  
47 
 
Overall antimicrobial prescription by quarter at [name of hospital] 
 
 
Overview of Point Prevalence Survey of hospital antimicrobial prescription at 
[name of hospital] from [survey start date] to [survey stop date] 
Description 
Number of in-patients (%) 
Number of outpatients (%) 
Number of screened hospital charts 
 
 
Number of patients with antimicrobial (s) 
 
 
Department:  
 
 
OPD 
NA 
 
Medicine 
 
NA 
Surgery 
 
NA 
ICU 
 
NA 
Paediatrics 
 
NA 
OBGY 
 
NA 
Age: 
 
 
≤ 1 year 
 
 
>1- ≤ years 
 
 
>5 - ≤ 15 years 
 
 
>15 years 
 
 
Number of prescribed antimicrobials 
 
 
1 antimicrobial agent 
 
 
2 antimicrobial agents 
 
 
≥3 antimicrobial agents 
 
 
Total number of prescribed antimicrobial agents 
 
 
Administration route 
 
 
Parenteral 
 
 
Oral 
 
 
Rectal 
 
 
Prescribing indication 
 
 
Therapeutic 
 
 
Prophylactic 
 
 
Empirical treatment 
 
 
Documented reason for treatment (diagnosis) 
 
 
Documented stop/review date  
 
 
 

Version 1.0_13 June 2020  
48 
Overall proportion of patients receiving an antimicrobial prescription by 
antimicrobial class at [name of hospital] from [survey start date] to [survey stop 
date] 
 
 
Overall antimicrobial prescription by antimicrobial class and age at [name of 
hospital] from [survey start date] to [survey stop date] 
In- patients [not real data - example chart only] 
 
 
 
 

Version 1.0_13 June 2020  
49 
 
 
Outpatients [not real data - example chart only] 
 
 
 
Overall antimicrobial prescription by 5 most common involved organs or systems 
 
 
 
 
 

Version 1.0_13 June 2020  
50 
List of antimicrobial prescriptions at [name of hospital] from [survey start date] to [survey 
stop date] 
Antimicrobial classes 
Antimicrobial 
agent 
Number of in-patient 
prescription (%); n= [total 
number of prescriptions] 
Number of OPD 
prescription (%); n= 
[total number of 
prescriptions] 
Beta lactams 
Cephalosporins 
 
 
 
[agent list] 
 
 
 
Penicillin 
 
 
 
[agent list] 
 
 
 
Carbapenem 
 
 
 
[agent list] 
 
 
 
Beta-lactam 
inhibitors 
 
 
 
[agent list] 
 
 
Aminoglycosides 
[agent list] 
 
 
Quinolones 
[agent list] 
 
 
Macrolides 
[agent list] 
 
 
Sulfonamides 
[agent list] 
 
 
Nitroimidazoles 
[agent list] 
 
 
Tetracycline 
[agent list] 
 
 
Antiviral 
[agent list] 
 
 
Antifungals 
[agent list] 
 
 
Anti-TB 
[agent list] 
 
 
Antimalarial 
[agent list] 
 
 
Anti-helminthic 
[agent list] 
 
 
 
 
 
 
 

Version 1.0_13 June 2020  
51 
A5. Antimicrobial stewardship (AMS) Knowledge survey 
 
Antibiotic stewardship (AMS) knowledge survey 
(Multiple answers are possible. Please circle your answers) 
Date: _____/_____/_______, Graduation year from medical school: ________________ Speciality: ________________  
Department: __________________, Hospital: ________________ 
 
1. Facts of antimicrobial resistance (AMR): 
a. Overuse or misuse of antimicrobials is accelerating the process of AMR 
b. AMR can occur naturally 
c. AMR can spread between people, animals and environment 
d. Poor infection control encourages the spread of AMR 
 
2. Misuse or overuse of antibiotics include: 
a. Prescribing an oral narrow spectrum antibiotic (e.g. amoxicillin) to treat the common 
cold  
b. Always using broad spectrum antibiotics as first choice 
c. Completing an antibiotic treatment course even though the patient is feeling better 
3. Which of the following is/are NOT correct? 
a. Antibiotics kill both good and bad bacteria 
b. Antibiotics kill both viruses and bacteria 
c. Humans can become resistant to antibiotics 
d. Bacteria can become resistant to antibiotics 
4. What is considered as good practice in antibiotic prescribing in general practice? 
a. Prescribe antibiotics with a clear clinical justification where a bacterial infection is 
suspected or proven 
b. Prescribe according to local antimicrobial susceptibility patterns 
c. Only prescribe when culture results are available   
d. Collect specimens for culture before starting antimicrobial therapy (but not delay 
therapy) 
 

Version 1.0_13 June 2020  
52 
5. What should consider before prescribing antibiotics? 
a. Previous antibiotic history 
b. Previous infection with drug resistant organism 
c. Allergy to antibiotic 
d. Availability of antibiotic 
 
6. What should be consider when reviewing empiric antibiotic therapy? 
a. Change antibiotics based on culture result 
b. Always keep IV therapy until patients discharge from hospital, then switch to oral 
c. Stop antibiotic if no evidence of infection 
d. Change to broader spectrum antibiotics if patients do not feel better 
 
7. Which of the following phrases is correct for choice of IV or oral antibiotic therapy? 
a. Always start IV antibiotic first, then switch to oral antibiotic for all in-patients 
b. IV antibiotic needs to be kept for at least 3 days before switching to oral antibiotic 
c. Keep IV therapy for the whole course of bacterial meningitis treatment 
 
8. What should be considered before switching from IV to oral therapy? 
a. Equivalent treatment efficacy 
b. No malabsorption problem 
c. availability of suitable oral antimicrobial drug 
d. Signs and symptoms of infection improving 
 
9. Which of the following antimicrobials are well absorbed from the gut and have 
excellent penetration into cells and tissues? 
a. Co-amoxiclav (e.g augmentin) 
b. Metronidazole (e.g. flagyl) 
c. Ciprofloxacin 
d. Chloramphenicol 
 
10. What are clinical signs of severe penicillin allergy (type I)?  
a. Anaphylaxis 
b. Maculopapular rash 

Version 1.0_13 June 2020  
53 
c. Laryngeal oedema 
d. Usually occurs with 1 to 4 hours after exposure 
 
11. What medications are contradicted in patients with severe penicillin allergy? 
a. Co-amoxiclav (e.g augmentin) 
b. Metronidazole (e.g flagyl) 
c. Ciprofloxacin 
d. Cloxacillin 
 
12. Antibiotic prophylaxis for elective surgery should usually be given for: 
a. A maximum of 24 hours 
b. A maximum of 3 days  
c. A maximum of 7 days 
d. Until discharge from hospital 
 
13. Good practice for clean wound/surgery procedures regarding antibiotic prophylaxis 
is: 
a. No antibiotic prophylaxis is needed 
b. A single dose of IV combined antibiotic prophylaxis (e.g. ceftriaxone + metronidazole) is 
needed 
c. IV mono-antibiotic prophylaxis for a maximum of 3 days is enough 
d. A maximum of 5 days of oral antibiotic prophylaxis is needed 
 
14. Which phrases are correct relating to viral respiratory infection: 
a. Antibiotics should be given to prevent bacterial complications in seasonal flu patients 
b. Antibiotics have no effect on colds 
c. Empirical treatment of bacterial co-infection of seasonal flu, should be for highly 
suspected cases only 
 
15. A 3-year-old girl comes to you complaining of 4 days of fever, running nose, sneezing, 
sore throat, cough with normal vital signs, which antibiotic you recommend? 
a. Amoxicillin 
b. Penicillin 

Version 1.0_13 June 2020  
54 
c. Single dose of ceftriaxone 
d. No antibiotic is needed 
 
16. Which statements are correct relating to the use of gentamicin? 
a. Gentamicin can cause serious nephrotoxicity and ototoxicity 
b. Gentamicin is often used for serious Gram-negative bacterial infections 
c. Gentamicin is cleared by the kidney, it is important to assess renal function before 
starting and during treatment courses 
d. Creatinine clearance should be monitored if drug level monitoring is not available 
17. Which of the following is NOT effective in preventing the emergence or spread of 
antimicrobial resistant organisms?  
a. Good hand hygiene 
b. Treating infections for a longer period to prevent resistance  
c. Avoiding the use of antibiotics for treatment of colds and flu 
d. Vaccination  
 
18. A 35-year-old man comes to you complaining of 2 days watery stool (~4-5 times a 
day), no history of fever, which antibiotic will you recommend? 
a. Ciprofloxacin 
b. Co-trimoxazole 
c. Azithromycin 
d. No antibiotic is needed, oral rehydration only 
 
 
 

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55 
A6. Introductory session of therapeutic and prophylactic antimicrobial prescribing 
guidelines 
The propose of the session is to introduce paper versions of therapeutic and prophylactic 
antimicrobial prescribing guidelines in both adult and paediatric version to all doctors in study 
hospitals. This session will not cover how to diagnose infectious diseases or prescribe 
antimicrobials. 
Trainees: this session will be given to all hospital doctors in all study participant hospitals at the 
start of the study (month 0).  
Date, time and venue: the session will take a maximum of 30 minutes with 10 minutes of 
discussion/questions. Session date, time and venue will be informed to all doctors one week in 
advance and again 3 days before starting the session. The session will be run in each hospital 
separately after conducting point prevalence survey (PPS) of hospital antimicrobial use and after all 
doctors have completed survey form on AMS knowledge for baseline data. Verbal consent will be 
asked from participants to record participant’s names, age, sex, working positions, departments, 
years of work and phone number onto the session registration sheet. 
Instructor: The principal investigator of the study will be the session instructor. Training will be 
given in the format of a PowerPoint presentation, following by question and discussion. 
Session material: paper versions of both adult and paediatric prescribing guidelines will be 
distributed to doctors who participate to this session. A handout of the introductory session (the 
same standard session for all hospitals) will also be provided. 
Session details include introduction of the guidelines, objectives of guidelines, guidelines skeleton 
and how to use these guidelines, see details as below:  
1. Introduction to the guidelines 
This guideline is based on: 
• existing Lao treatment guidelines 
• current data on infectious disease pathogens and antimicrobial susceptibility patterns 
in Laos 
• international antimicrobial prescribing/treatment guidelines (e.g. WHO, CDC, NICE, 
IDSA, Sanford) 

Version 1.0_13 June 2020  
56 
• both Lao and international clinicians, international infectious diseases experts and 
microbiologists contributed to this guideline 
 
2. Giving the purpose of the having these guidelines: 
• To support therapeutic clinical decision-making of Lao clinicians 
• To guide the reasonable use of antimicrobials to optimize cure and control 
antimicrobial resistance in Laos  
• To promote the use of essential medicines registered with the Lao Food and Drug 
Department 
• To diminish the cost of care for infectious diseases whilst ensuring optimal 
treatment 
• To promote patient safety by diminishing risks of allergy or toxicity 
• To promote the use of microbiology laboratory techniques for infectious disease 
diagnoses and for guiding treatment 
 
3. Explanation of overall guideline skeleton 
• 
Therapeutic section 
• 
Prophylactic section 
• 
AMS section 
• 
References 
• 
Contact details  
4. How to use these guidelines 
• Guidelines provide the principal uses of antimicrobials. The antimicrobial prescribing 
guidelines are separated into paediatric and adult guidelines for ease of use. 
• These guidelines include recommendations for therapy, prevention and AMS 
• This guideline mostly suggests empiric treatment as facilities to microbiological diagnosis 
in Laos is limited 
Structure: 
• Common and important infectious diseases are arranged by involved organ systems 

Version 1.0_13 June 2020  
57 
• Each infectious disease section includes causative pathogen(s) of the diseases, choices of 
antimicrobial regimen (primary and alternative), doses, duration and important notes on 
allergy or toxicity or to help guide treatment 
• Sources of information and contact details of developers and coordinators are displayed at 
the end of the guidelines for users who need further information 
• This guideline also refers to some specific Lao treatment guidelines (e.g. Dengue 
guideline for diagnosis and treatment, Lao PDR or National Guidelines for the Use of 
Antiretroviral Therapy in Adults and Children) to avoid duplication 
 
 
 

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58 
A7. Introductory session of antimicrobial prescribing guidelines mobile phone 
application (MicroGuide) 
Introductory session of the antimicrobial prescribing guideline mobile phone App will be given to 
all doctors at study hospitals in different time periods.  
Training objective is to introduce MicroGuide mobile phone App of therapeutic and prophylactic 
antimicrobial prescribing guidelines in both adult and paediatric version to all doctors in study 
hospitals. This session will cover how to install, register, use and update the App. The session will 
not cover how to diagnose infectious diseases or prescribe antimicrobials. 
Trainees: this session will be given to all hospital doctors in all study hospitals at the start of the 
intervention period of each pair of hospitals (month 4, month 8 and month 12). 
Training date, time and venue: the session will take maximum 4±1 hours in total (including 
installation and registration step by step, also include discussion/questions). Training date, time 
and venue will be informed to all doctors one week in advance and again 3 days before starting the 
session. The session will be run in each hospital separately (2 hospitals on month 4, another 2 on 
month 8 and the last 2 hospitals on month 12) after conducting point prevalence survey (PPS) of 
hospital antimicrobial use. Verbal consent will be asked from participants to record each 
participant’s name, age, sex, working position, department, years of work and phone number onto 
the session registration sheet. 
Instructor: the principal investigator of the study will be the training instructor. Training will be 
given in the format of PowerPoint presentation and showing the real process of each step, followed 
by questions and discussion. 
Training material: A handout of the training will be provided to all participants (the same standard 
session for all hospitals).  
Training details: training session will include introduction to the MicroGuide, how to register, how 
to install, how to use step by step and how to update the App.  
 
 
 

Version 1.0_13 June 2020  
59 
A8. Introductory (paper/App guidelines) session registration sheet 
 
Introductory session of the use of therapeutic and prophylactic antimicrobial prescribing 
guidelines 
Date: ________________________________________, Time: _______________________________________ 
Venue: ______________________________________, Hospital: ____________________________________ 
Participants list: 
No. Name and 
Surname 
Age 
Sex position Department Year of 
graduation from 
medical school 
Phone 
number 
1 
 
 
 
 
 
 
 
2 
 
 
 
 
 
 
 
3 
 
 
 
 
 
 
 
4 
 
 
 
 
 
 
 
5 
 
 
 
 
 
 
 
6 
 
 
 
 
 
 
 
7 
 
 
 
 
 
 
 
8 
 
 
 
 
 
 
 
9 
 
 
 
 
 
 
 
10 
 
 
 
 
 
 
 
11 
 
 
 
 
 
 
 
12 
 
 
 
 
 
 
 
13 
 
 
 
 
 
 
 
14 
 
 
 
 
 
 
 
15 
 
 
 
 
 
 
 
16 
 
 
 
 
 
 
 
17 
 
 
 
 
 
 
 
18 
 
 
 
 
 
 
 
19 
 
 
 
 
 
 
 
20 
 
 
 
 
 
 
 
21 
 
 
 
 
 
 
 
22 
 
 
 
 
 
 
 
23 
 
 
 
 
 
 
 
24 
 
 
 
 
 
 
 
25 
 
 
 
 
 
 
 
26 
 
 
 
 
 
 
 
27 
 
 
 
 
 
 
 
28 
 
 
 
 
 
 
 
29 
 
 
 
 
 
 
 
30 
 
 
 
 
 
 
 
 

Version 1.0_13 June 2020  
60 
A9. Pre-prescribing guideline Survey 
 
Pre-prescribing guideline Survey 
Date: ____/____/_______, Year of graduation from medical school: ________, Speciality: ____________________________, 
Department: __________________________Hospital: _________________________ 
 
1. 
How frequently do you prescribe antimicrobial (s)? 
 
 Daily   
 Nearly every day 
  Weekly  
 Monthly  
 Never 
 
2. 
How often do you access any antimicrobial prescribing guidelines? 
 
 Daily   
 Nearly every day 
 Weekly  
 Monthly  
 Never 
 
3. 
Do you have a smart phone?  
 Yes 
  No 
  Sometimes; If answer is “No”, you do not have to 
answer question 4, 5 and 6 
 
4. 
Do you carry your smart phone with you at work?   Yes 
  No 
 
5. 
Do you have any antimicrobial prescribing guideline App installed on your smart phone? 
 
  Yes 
 
   No; If answer is “No”, you do not have to answer question 6 
 
6. 
How often do you access any antimicrobial prescribing mobile phone App? 
 
 Daily   
 Nearly every day 
 Weekly  
 Monthly  
 Never 
 

Version 1.0_13 June 2020  
61 
A10. Prescriber feedback survey on paper-based prescribing guidelines  
 
Prescriber feedback survey on paper-based prescribing guidelines  
Date: ____/____/_______, Year of graduation from medical school: ________, Speciality: ____________________________,  
Department: __________________________Hospital: _________________________ 
1. 
Have you ever seen these paper-based antimicrobial prescribing guidelines? 
 Yes 
  No 
; If answer is “No”, you do not have to continue this survey 
2. 
If yes, have you ever used it? 
 Yes 
  No 
; If answer is “No”, you do not have to continue this survey 
If the answer is “Yes”, please continue the survey 
 
3. 
Complete this table below: Instruction-please indicate your level of agreement with the statement listed below 
(by ticking the box: 
 
 
Strongly 
agree 
Agree 
Neutral 
Disagree 
Strongly 
disagree 
No 
opinion 
The name of the guidelines is appropriate 
 
 
 
 
 
 
The structure is well-organised and easy to follow 
 
 
 
 
 
 
The topics covered are relevant to my patient population 
 
 
 
 
 
 
I can find information which I look for in the guidelines easily 
 
 
 
 
 
 
Language used in the guidelines is easy to understand 
 
 
 
 
 
 
Prescribing instructions (antibiotic of choice, dose and duration) are easy to 
follow 
 
 
 
 
 
 
The recommended antibiotics are mostly available in my hospital 
 
 
 
 
 
 
I find these guidelines restrict my choice of antibiotics 
 
 
 
 
 
 
Extra information (data on antibiotic susceptibility pattern, causes of infections in 
Laos, international recommendation) is useful 
 
 
 
 
 
 
Extra information (data on antibiotic susceptibility pattern, causes of infections in 
Laos, international recommendation) is too detailed 
 
 
 
 
 
 
Prophylaxis section is useful 
 
 
 
 
 
 
I can get more information from provided references 
 
 
 
 
 
 
These paper-based guidelines are thick and difficult to carry for my routine work 
 
 
 
 
 
 
These paper-based guidelines encourage me to document the indication for 
antimicrobial on hospital charts 
 
 
 
 
 
 
These paper-based guidelines encourage me to document the duration for 
antimicrobial on hospital charts 
 
 
 
 
 
 
Antibiotic stewardship (AMS) section is useful and relevant to my work  
 
 
 
 
 
 
These paper-based guidelines have increased my knowledge of AMS 
 
 
 
 
 
 
 
 
 
4. 
How frequently do you prescribe antimicrobial (s)? 
 
 Daily   
 Nearly every day 
 Weekly  
 Monthly  
 Never  
 
5. 
How often do you access this provided paper-based prescribing guidelines? 
 
 Daily   
 Nearly every day 
 Weekly  
 Monthly  
 Never  

Version 1.0_13 June 2020  
62 
 
6. 
How often do you access other prescribing guidelines? 
 
 Daily   
 Nearly every day 
 Weekly  
 Monthly  
 Never  
 
7. 
How would you rate these paper-based prescribing guidelines overall?  
 Very good and fitting with Lao context   
 Good but need a bit more editing  
 Moderate and need more editing  
 
 Not good and need to review many sections 
 
Please give comments in the box below: 
 
 
 

Version 1.0_13 June 2020  
63 
A11. Prescriber feedback survey on mobile phone app prescribing guidelines  
 
Prescriber feedback survey on mobile phone app prescribing guidelines  
Date: ____/____/_______, Year of graduation from medical school: ________, Speciality: ____________________________, 
Department: __________________________Hospital: _________________________ 
1. 
Have you ever seen this antimicrobial prescribing guideline mobile phone application? 
 Yes 
  No 
; If answer is “No”, you do not have to continue this survey 
2. 
If yes, have you ever used it? 
 Yes 
  No 
; If answer is “No”, you do not have to continue this survey 
 If the answer is “Yes”, please continue the survey 
 
3. 
Complete this table below: Instruction: please indicate your level of agreement with the statement listed below 
(by ticking the box): 
 
Strongly 
agree 
Agree 
Neutral 
Disagree 
Strongly 
disagree 
No 
opinion 
The structure and design are easy to follow 
 
 
 
 
 
 
I can find information which I look for more easily than from paper-based 
guidelines 
 
 
 
 
 
 
Language font size and colour are easy to read 
 
 
 
 
 
 
Prescribing instructions (antibiotic of choice, dose and duration) are easy to 
follow 
 
 
 
 
 
 
Links to extra information (data on antibiotic susceptibility pattern, causes of 
infections in Laos, international recommendation) are useful 
 
 
 
 
 
 
The offline mode makes it easy for me to access the guidelines anywhere 
 
 
 
 
 
 
The App guideline encourages me to document the indication for antimicrobial 
on hospital charts 
 
 
 
 
 
 
The App guideline encourages me to document the duration of antimicrobial on 
hospital charts 
 
 
 
 
 
 
The App guideline has increased my knowledge of antimicrobial stewardship 
(AMS) 
 
 
 
 
 
 
Antimicrobial stewardship training increased my knowledge of AMS 
 
 
 
 
 
 
 
4.  How often do you prescribe antimicrobial (s)?  
 Daily   
 Nearly every day 
 Weekly  
 Monthly  
 Never  
 
5. 
How often do you access paper-based prescribing guidelines? 
 
 Daily   
 Nearly every day 
 Weekly  
 Monthly  
 Never  
 
6. 
Do you carry your smart phone (with this prescribing guideline App) with you at work?  
 
 Yes      No     Sometimes 
 
 
7. 
How often do you access the provided mobile phone app prescribing guideline? 

Version 1.0_13 June 2020  
64 
 
 Daily   
 Nearly every day 
 Weekly  
 Monthly  
 Never  
 
8. 
How often do you access other prescribing guidelines? 
 
 Daily   
 Nearly every day 
 Weekly  
 Monthly  
 Never  
 
9. 
How would you rate this app overall?  
 
 Very good and I will continue to use it  
 Good but needs a bit more editing and I will continue to use it 
 Good but I prefer paper-based version 
 moderate but I prefer paper-based version   
 Not good and I prefer paper-based version 
 Others ________________________________________ 
 
Please give comments to improve this app: 
 
 
 

Version 1.0_13 June 2020  
65 
A12. Antimicrobial stewardship (AMS) training  
 
Training objective: to raise awareness of antibiotic good prescribing practices 
Trainees: this session will be given to all hospital doctors in all study hospitals at the start of the 
intervention period of each paired hospital (month 4, month 8 and month 12). 
Training date, time and venue: the session will take a maximum of 30 minutes with 10 minutes of 
discussion/questions. Training date, time and venue will be informed to all doctors one week in 
advance and again 3 days before starting the session. The session will be run in each hospital 
separately (2 hospitals on month 4, another 2 on month 8 and the last 2 hospitals on month 12) 
after conducting point prevalence survey (PPS) of hospital antimicrobial use, completing prescriber 
feedback survey and after finished introductory session of the prescribing guideline mobile phone 
App. Verbal consent will be asked from participants to record participant’s names, age, sex, working 
positions, departments, years of work and phone number onto the session registration sheet. 
Instructor: the principal investigator of the study will be the training instructor. Training will be 
given in the format of PowerPoint presentation, followed by question and discussion. 
Training material: Handout of the training will be provided to all participants (the same standard 
session for all hospitals).  
Training details: All training details already exist in the prescribing guidelines. The majority of 
training will be on the section of AMS and some part of the training will be from the therapeutic and 
prophylaxis sections. This training session will include good practice of antibiotic prescriptions, the 
idea and benefits of intravenous therapy to oral therapy switch, choice of prescription when 
patients report penicillin allergy. 
Training evaluation: All participating hospitals will join AMS knowledge survey three times during 
the study period (1st time= at the start of the project, 2nd time= before entering to the intervention 
period and 3rd time= at the end of the project) 
 
 

Version 1.0_13 June 2020  
66 
A13. Antimicrobial stewardship (AMS) training session registration sheet 
 
Antimicrobial Stewardship (AMS) Training Session Registration Form 
Date: ________________________________________, Time: _______________________________________ 
Venue: ______________________________________, Hospital: ____________________________________ 
 
No. 
Name and Surname 
Age 
Sex 
position 
Department 
Years of work (year) 
Phone number 
1 
 
 
 
 
 
 
 
2 
 
 
 
 
 
 
 
3 
 
 
 
 
 
 
 
4 
 
 
 
 
 
 
 
5 
 
 
 
 
 
 
 
6 
 
 
 
 
 
 
 
7 
 
 
 
 
 
 
 
8 
 
 
 
 
 
 
 
9 
 
 
 
 
 
 
 
10 
 
 
 
 
 
 
 
11 
 
 
 
 
 
 
 
12 
 
 
 
 
 
 
 
13 
 
 
 
 
 
 
 
14 
 
 
 
 
 
 
 
15 
 
 
 
 
 
 
 
16 
 
 
 
 
 
 
 
17 
 
 
 
 
 
 
 
18 
 
 
 
 
 
 
 
19 
 
 
 
 
 
 
 
20 
 
 
 
 
 
 
 
21 
 
 
 
 
 
 
 
22 
 
 
 
 
 
 
 
23 
 
 
 
 
 
 
 
24 
 
 
 
 
 
 
 
25 
 
 
 
 
 
 
 
26 
 
 
 
 
 
 
 
27 
 
 
 
 
 
 
 
28 
 
 
 
 
 
 
 
29 
 
 
 
 
 
 
 
30 
 
 
 
 
 
 
 
 
 
 
 

Version 1.0_13 June 2020  
67 
A14. Timelines and milestones 
Activities 
2020 
2021 
2022 
20
23 
3 
4 
5 
6 
7 
8 
9 
1
0 
1
1 
1
2 
1 
2 
3 
4 
5 
6 
7 
8 
9 
1
0 
1
1 
1
2 
1 
2 
3 
4 
5 
6 
7 
8 
9 
1
0 
1
1 
1
2 
1 
Building App with MicroGuide and piloting the 
App 
x 
x 
x 
x 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Receiving ethical approval to conduct study 
(minimal risk) 
  
  
x 
x 
x 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Meeting with Ministry of Health and Lao 
Infectious Society to introduce the application, 
formally informing the start of project and 
target hospitals 
  
  
  
x 
x 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
PPS on hospital antimicrobial use in both 
outpatient and in-patient departments in 6 
hospitals 
  
  
  
  
  
x 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Reporting PPS results  
  
  
  
  
  
x 
  
  
  
x 
  
  
  
x 
  
  
  
x 
  
  
  
x 
  
  
  
  
  
  
  
  
  
  
  
  
  
Pre-prescribing guideline survey  
  
  
  
  
  
x 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Antibiotic stewardship survey 
  
  
  
  
  
x 
  
  
  
x 
  
  
  
x 
  
  
  
x 
  
  
  
x 
  
  
  
  
  
  
  
  
  
  
  
  
  
Introducing paper-based guidelines 
(paediatrics and adults) in 6 hospitals 
  
  
  
  
  
x 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Giving introductory session of paper-based 
guidelines in 6 hospitals 
  
  
  
  
  
x 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Prescriber feedback survey on paper-based 
guidelines* 
  
  
  
  
  
  
  
  
  
x 
  
  
  
x 
  
  
  
x 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Introduce the App to the first paired hospitals 
  
  
  
  
  
  
  
  
  
x 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Introduce the App to the second paired 
hospitals 
  
  
  
  
  
  
  
  
  
  
  
  
  
x 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Introduce the App to the third paired hospitals 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
x 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Giving introductory session of the App version 
of prescribing guidelines 
  
  
  
  
  
  
  
  
  
x 
  
  
  
x 
  
  
  
x 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Giving antibiotic stewardship training 
  
  
  
  
  
  
  
  
  
x 
  
  
  
x 
  
  
  
x 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Prescriber feedback survey on the App version 
of guidelines* 
  
  
  
  
  
  
  
  
  
  
  
  
  
x 
  
  
  
x 
  
  
  
x 
  
  
  
  
  
  
  
  
  
  
  
  
  
Updating Ministry of health and Lao Infectious 
Society about the progress of the study 
  
  
  
  
 
x 
  
  
  
  
x 
  
  
  
x 
  
  
  
x 
  
  
  
x 
  
  
  
  
  
  
  
  
  
  
  
  
Data cleaning 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
x 
x 
  
  
  
  
  
  
  
  
  
  
  
Analysing data 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
x 
x 
x 
  
  
  
  
  
  
  
  
  
  
Writing thesis 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
x 
x 
x 
x 
x 
x 
  
  
  
  
  
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Version 1.0_13 June 2020  
68 
Official DPhil start date: 29 April 2019; Transfer deadline date from PRS to DPhil is 24 April 2020; Complete confirmation DPhil status by the end of 9th term on 14th Jan 2022 (final term); Maximum 
submission date is 13 Jan 2023 
* Prescriber feedback survey on the App will be performed 
in a paired hospitals/time only  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
End of grant 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
Maximum submission 
date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
Complete confirmation DPhil 
status 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Version 1.0_13 June 2020  
69