Defining Adult Beta-lactam Antimicrobial Pharmacokinetics Across the Secondary Care Setting
Conditions: Pharmacokinetics, Beta Lactam Adverse Reaction, Penicillin Allergy
Sponsor: Imperial College London

 
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Study protocol 
 
 
 
 
 
 
Defining adult beta-lactam antimicrobial pharmacokinetics 
across the secondary care setting  
 
 
 
V6   31/01/2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SPONSOR: Imperial College London (DOCUMAS: 16HH3571) 
 
FUNDER:  
 
STUDY COORDINATION CENTRE: National Institute for Health Research Health Protection Research  
Unit in Healthcare Associated Infection and Antimicrobial Resistance at Imperial College London. 
 
IRAS REF: 207217  
 
 
 
 
 
 
 
Protocol authorised by: 
 
Name & Role 
Date 
Signature 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Principal Investigator:  
Prof Alison Holmes 
 
Co-investigators:  
Dr Timothy M Rawson, 
Dr Damien Ming, 
BRC Fellow, 
Ms Orla Geoghegan 
Mr Mark Gilchrist, 
Ms Esmita Charani,  
Dr Pau Herrero-Vinas, 
Dr Pantelis Georgiou, 
Dr Xinzhu Wang, 
Prof Myra McClure, 
 
Collaborators: 
Prof Jason Roberts 
Prof William Hope 
 
Study Management:  
National Institute for Health Research Health Protection Research Unit in Healthcare 
Associated Infection and Antimicrobial Resistance, Imperial College London (Hammersmith 
Campus), Du Cane Road. London. W12 0NN. 
 
Study Coordination Centre  
For general queries, supply of study documentation, and collection of data, please contact: 
 
National Institute for Health Research Health Protection Research Unit in Healthcare 
Associated Infection and Antimicrobial Resistance, Imperial College London (Hammersmith 
Campus), Du Cane Road. London. W12 0NN 
 
 
 
 
 
 
Tel: 020 33132732  
 
 
 
 
 
 
 
Fax:  020 8383 3394  
Email: head.ops@imperial.ac.uk 
 
 
 
 
 
 
 
Clinical Queries 
Clinical queries should be directed to Dr Timothy M Rawson (tmr07@ic.ac.uk ; 
02033132732) who will direct the query to the appropriate person 
 
Sponsor 
Imperial College London is the main research Sponsor for this study.  For further information 
regarding the sponsorship conditions, please contact the Head of Regulatory Compliance at: 
 
 
 
Joint Research Compliance Office, Imperial College London, Room 215, Level 2, Medical 
School Building, Norfolk Place, London, W2 1PG Tel: 0207 594 1872 
Fax:  
 
Funder 
National Institute for Health Research Invention for Innovation Product Development Award & Imperial College EMBRACE 
pump priming award 
This protocol describes the study and provides information about procedures for entering participants.  Every care was taken in 
its drafting, but corrections or amendments may be necessary. These will be circulated to investigators in the study. Problems 
relating to this study should be referred, in the first instance, to the Chief Investigator. This study will adhere to the principles 
outlined in the NHS Research Governance Framework for Health and Social Care (2nd edition). It will be conducted in 
compliance with the protocol, the Data Protection Act and other regulatory requirements as appropriate.  

 
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Table of Contents 
1. 
INTRODUCTION 
6 
2.  STUDY OBJECTIVES 
7 
3.  STUDY DESIGN 
8 
3.1 STUDY PARTICIPANTS 
8 
3.2 PHARMACOKINETIC SAMPLING 
8 
3.3 SAMPLE PREPARTION AND ANLYSIS 
8 
3.4 PHARMACOKINETIC – PHARMCOKINETIC MODELLING 
8 
4. 
PARTICIPANT ENTRY 
10 
4.1 
INCLUSION CRITERIA 
10 
4.2 
EXCLUSION CRITERIA 
10 
• 
CHILDREN UNDER 18 YEARS OLD 
10 
4.3 
WITHDRAWAL CRITERIA 
10 
5. 
ADVERSE EVENTS 
11 
5.1 
DEFINITIONS 
11 
5.2 
REPORTING PROCEDURES 
11 
6. 
ASSESSMENT AND FOLLOW-UP 
12 
7. 
STATISTICS AND DATA ANALYSIS 
12 
8. 
REGULATORY ISSUES 
13 
8.1 
ETHICS APPROVAL 
13 
8.2 
CONSENT 
13 
8.3 
CONFIDENTIALITY 
13 
8.4 
INDEMNITY 
13 
8.5 
SPONSOR 
13 
8.6 
FUNDING 
13 
8.7 
AUDITS 
13 
9. 
STUDY MANAGEMENT 
14 
10. 
PUBLICATION POLICY 
14 
11. 
REFERENCES 
ERROR! BOOKMARK NOT DEFINED. 
12. APPENDICES 
15 

 
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STUDY SUMMARY 
 
TITLE 
Defining adult beta-lactam antimicrobial pharmacokinetics across 
the secondary care setting  
DESIGN 
Prospective, observational study 
AIMS 
1. To investigate the role of therapeutic drug monitoring for 
optimising the use of beta-lactam agents in secondary care 
2. To identify areas across secondary care where we are 
currently failing to optimise beta-lactam therapy 
3. To explore potential pharmacodynamics indices that can be 
associated with treatment response across this cohort 
OUTCOME MEASURES 1. Justification for the use of therapeutic drug monitoring of 
beta-lactams within secondary care populations 
2. Identification of areas where rich data sampling and 
population pharmacokinetic modelling may be of benefit in 
future investigations 
3. Identification of a potential pharmacodynamic model to guide 
describe response to therapy with beta-lactams 
POPULATION 
Hospital in-patients receiving beta-lactam antimicrobials at 
Imperial College NHS Healthcare Trust. 
DURATION 
January 2017 to August 2019 
 
 

 
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PROJECT FLOW CHART 
 
 
Beta-lactam TDM “point prevalence survey” over 
secondary care pathways within ICHNT 
(General medicine, surgery, care of the elderly, 
renal medicine, haematology, and critical care) 
Identification of “high risk” populations within 
secondary care who may benefit from routine TDM 
/ individualisation of therapy 
Review of local and national guidelines & operating 
procedures against findings of point prevalence 
survey & rich data sampling exercise  

 
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1. 
INTRODUCTION  
 
Antimicrobial chemotherapeutic agents are drugs which kill or inhibit the growth of micro-
organisms. Whilst essential to modern medicine, the exposure of micro-organisms to 
antimicrobial agents also drives generation of resistant strains, termed antimicrobial 
resistance (AMR). This, combined with a paucity of new antimicrobial drug development, has 
led to AMR becoming a global threat to modern medicine and a leading patient safety issue 
(Holmes et al., 2015).  
 
To address the challenge of AMR, it is imperative that the current finite pool of antimicrobial 
agents is optimised, maximising therapeutic success whilst minimising emergence of 
resistance  (Mouton et al., 2011). One avenue to optimise the use of antimicrobials is to 
ensure correct dosing strategies. Population pharmacokinetic (PK) modelling was developed 
from the simple concept of dose-response relationships in the 1960’s (Csajka & Verotta, 
2006). More recently the idea of individualised dosing, which accounts for intra- and inter-
individual variability in PK parameters, has gained popularity and has been demonstrated to 
improve patient outcomes in secondary care settings (J. A. Roberts et al., 2014). In tandem 
to optimisation of therapy through individualising dosing, population PK modelling also 
allows for the consideration of individualised therapeutic drug monitoring (TDM) protocols to 
help provide robust and accurate data to drive individualised dosing regimens.  
 
Currently in the UK, TDM is routinely performed for aminoglycosides and glycopeptide 
antimicrobial agents, given fears over the narrow therapeutic window of these agents and 
the serious adverse events associated with toxicity. However, in critical care the role of TDM 
for optimisation of therapy has been demonstrated to help optimise dosing of patients who 
tend to have variable pharmacokinetic parameters (J. A. Roberts et al,). This is of growing 
importance given that low concentrations of antimicrobial agents, below a micro-organisms 
minimum inhibitory concentration (MIC) is believed to be a major driver of AMR.  
 
 
 
 
Moreover, in individuals managed with enhanced TDM protocols and individualised dosing 
protocols  there is evidence that this enhances patient outcomes and reduces the cost of 
care for these patients, reducing hospital stay and lengths of therapy (van Lent-Evers, 
Mathôt, Geus, van Hout, & Vinks, 1999). Whilst, most evidence in this field currently focuses 
primarily on critical care setting, there is evidence to suggest that optimisation of therapy in 
secondary care can impact significantly on AMR in crititical care. However, this must go 
beyond simply selecting the optimal antibiotic for the organism in question. We must also 
ensure that the optimal dose is selected to maximise micro-organism killing, whilst 
minimising the risk of toxicity or development of AMR. The observation of wide variability in 

 
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therapeutic levels of antimicrobials being delivered to patients across a number of settings 
(e.g. ICU, obese, paediatric) has promoted the idea of individualised dosing that accounts for 
intra- and inter-individual variability in PK parameters. This has been demonstrated to 
improve target attainment and outcomes in secondary care (J. A. Roberts et al., 2014). 
However, outside controlled trial environments implementation of individualised dosing using 
population PK models, plasma sampling, and pre-determined PK-PD indices has been 
challenging to implement for several reasons. These include difficulties in access to 
appropriate antimicrobial assays, poor integration of dosing software with electronic health 
records and decision support systems, challenges with taking and handling PK samples, and 
the centralised nature of population PK’s with very few qualified healthcare professionals.  
To address the challenges of AMR and rapidly improve the use of antimicrobials in clinical 
practice, urgent validation of novel methods for precision prescribing and delivery of 
antimicrobial agents is required. However, before steps can be taken to develop methods for 
improving the precision prescribing and delivery of antimicrobial agents the size and breadth 
of the problem must be clearly described. 
 
 
 
2.  STUDY OBJECTIVES 
 
Given the paucity of data to support the need for individualised TDM and dosing strategies 
outside of critical care we aim to:  
 
1. To describe the current level of success of beta-lactam dosing across secondary 
care pathways in terms of attainment of target drug levels 
2. To investigate the potential role of therapeutic drug monitoring for optimising the 
use of beta-lactam agents in secondary care 
3. To use data generated through this study to develop a concept for novel methods 
for the therapeutic drug monitoring and precision delivery of beta-lactam agents  
 
 
These aims will be achieved through addressing the following: 
 
1. Describing the current state of PK-PD target attainment for beta-lactam agents 
across secondary care to highlight populations most in need of intervention 
2. Evaluate the role of beta-lactam TDM in different secondary care settings including 
impact on the patient, prescriber, and hospital (economic evaluation).  
 

 
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3.  STUDY DESIGN 
 
 
3.1 STUDY PARTICIPANTS 
 
(Applicable for all objectives) 
Inclusion and exclusion criteria can be found below (section 4) 
• 
Participants receiving oral or intravenous therapy will be included in this study. 
• 
Drug level sampling will be undertaken once the participant is at steady state (after at 
least 4-5 doses have been administered to those on treatment).  
• 
All patients will be consented using the participation information leaflet and consent form 
provided in appendix 1. 
 
3.2 DRUG LEVEL SAMPLING 
 
• 
Patients will be identified for inclusion, and researchers will discuss inclusion in the study 
with the patient and provide clinical information for them to consider. Individuals will be 
recruited from all areas of secondary care (including, general medicine, general surgery, 
augmented care, and out-patient parenteral antimicrobial therapy (OPAT). 
• 
They will then be consented by researchers after being given at least 24 hours to 
consider this information and as long as the patient has expressed interest in 
participating to their treating physician. 
• 
This will include permission for basic, anonymized demographic and clinical data to be 
collected related to the patients infection, for which they are receiving antimicrobial 
therapy (appendix 2). 
• 
An extra 3mls of blood will be collected during the patient’s routine daily phlebotomy 
round following their consent. They will be enrolled for up to 72 hours or two days of 
routine blood tests (whichever is shorter). Up to 10 samples may be taken during the 2 
days the patient is enrolled, depending on the number of routine blood tests the patient 
receives during that day. No more than 3mls will be taken per each routine blood 
sample. For example, if the individuals will only have routine blood tests taken at 8am on 
day 1 and day 2. Then only two extra samples will be taken (3mls on D1 and 3mls on 
D2).   
• 
 
The time they received their dose of antimicrobials, the length of infusion time (if 
available), and time the sample was collected will all be recorded. 
• 
 
PK/PD indices for evaluation will be calculated post-hoc during pharmacokinetic-
pharmacodynamic analysis. TDM sampling can occur at any time during the dosing 
schedule (in line with routine blood testing). 
• 
A standard operating procedure for this study can be found in appendix 3. 
 
3.3 SAMPLE PREPARTION AND ANLYSIS 
 
• 
All blood samples will be allowed to clot and placed on ice. They will be centrifuged at 
2,400rpm for 10 minutes. Sera from each sample will be separated into three vials and 
stored at -800C. 
• 
Beta-lactam concentrations will be measured using validated high-performance liquid 
chromatography methods. 
• 
Samples will be stored for up to three years post completion of data collection. 
o Consent will be gained for samples to be used for calibration of electrochemical 
sensors in ex-vivo studies. This will be performed within 90 days of the samples 
being collected. 
 
 
3.4 PHARMCOKINETIC-PHARMACODYNAMIC MODELLING 
 

 
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• 
Data will be anonymized and analyzed using Pmetrics in R. 
• 
Different pharmacokinetic models will be explored using in built statistical analysis 
options and visual predictive checks.  
• 
Pharmacodynamic models will then be incorporated into the model using evidence 
identified in the literature for selection of parameters.  
• 
Monte Carlo simulation will then be used to for simulation of target attainments and 
analysis of pharmacodynamic outcomes   
 
 
 
 

 
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o 
 
4. 
PARTICIPANT ENTRY  
  
 
4.1 
INCLUSION CRITERIA 
• 
Adult subjects over 18 years old 
• 
Capacity to consent to participation 
• 
Receiving target antimicrobial for at least 5 doses prior to sampling. 
o Amoxicillin (oral / IV) 
o Co-amoxiclav (oral / IV) 
o Tazocin (IV) 
o Flucloxacillin (oral / IV) 
o Cefuroxime (oral / IV) 
o Ceftriaxone (oral / IV) 
o Meropenem (oral / IV) 
• 
Appropriate venous access (or for venous access to be gained) 
 
 
4.2 
EXCLUSION CRITERIA 
• 
Children under 18 years old 
• 
Lacking capacity or prisoner 
• 
Anaemia or bleeding disorder, deemed significant by the patients physician 
• 
Patients physicians deems that they are not suitable for inclusion in the study 
• 
Patient unlikely to be receiving agent for study period 
 
 
 
4.3 
WITHDRAWAL CRITERIA 
Subjects will be able to withdraw at any time point during the study with immediate 
effect.  
 
Researchers will be able to withdraw participants for any reason that may make the 
results of the study void or put the participant at risk of unacceptable harm or 
discomfort (including failure of cannula / poor venous access, alteration of the 
individuals antimicrobial treatment by the treating physician). 
 
 

 
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5. 
ADVERSE EVENTS 
 
5.1 
DEFINITIONS   
Adverse Event (AE): any untoward medical occurrence in a patient or clinical study subject.   
 
Serious Adverse Event (SAE): any untoward and unexpected medical occurrence or effect 
that: 
• 
Results in death 
• 
Is life-threatening – refers to an event in which the subject was at risk of death 
at the time of the event; it does not refer to an event which hypothetically might 
have caused death if it were more severe 
• 
Requires 
hospitalisation, 
or 
prolongation 
of 
existing 
inpatients’ 
hospitalisation 
• 
Results in persistent or significant disability or incapacity 
• 
Is a congenital anomaly or birth defect 
 
Medical judgement should be exercised in deciding whether an AE is serious in other 
situations.  Important AEs that are not immediately life-threatening or do not result in death 
or hospitalisation but may jeopardise the subject or may require intervention to prevent one 
of the other outcomes listed in the definition above, should also be considered serious. 
 
5.2 
REPORTING PROCEDURES 
All adverse events should be reported. Depending on the nature of the event the reporting 
procedures below should be followed. Any questions concerning adverse event reporting 
should be directed to the Chief Investigator in the first instance.   
 
5.2.1 Non serious AEs 
All such events, whether expected or not, should be recorded.   
 
5.2.2 Serious AEs 
An SAE form should be completed and faxed to the Chief Investigator within 24 hours.  
However, relapse and death due to non-infective consitions and hospitalisations for elective 
treatment of a pre-existing condition do not need reporting as SAEs. 
 
All SAEs should be reported to the Bromley - REC where in the opinion of the Chief 
Investigator, the event was: 
• 
‘related’, ie resulted from the administration of any of the research procedures; 
and 
• 
‘unexpected’, ie an event that is not listed in the protocol as an expected 
occurrence 
 
Reports of related and unexpected SAEs should be submitted within 15 days of the Chief 
Investigator becoming aware of the event, using the NRES SAE form for non-IMP studies.  
The Chief Investigator must also notify the Sponsor of all SAEs. 
 
Local investigators should report any SAEs as required by their Local Research Ethics 
Committee, Sponsor and/or Research & Development Office. 
 
Contact details for reporting SAEs 
Fax: 0208383394,  
Urgent attention Prof A Holmes 
Tel: 02033132732 (Mon to Fri 09.00 – 17.00) 

 
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6. 
ASSESSMENT AND FOLLOW-UP  
 
• 
All subjects will be consented and assessed by a GCP certified researcher before 
inclusion in the study (appendix 2). 
 
 
7. 
STATISTICS AND DATA ANALYSIS 
 
• 
On enrolment to the study participants will be given a study number, under which all data 
will be collected. Any identifiable data (such as enrolment list) will be kept within Imperial 
College Healthcare NHS Trust firewall on secure account. All anonymised data will be 
analysed and stored on a computer within Imperial College computer network. 
• 
Signed consent forms will be stored in a locked filing cabinet in a security card 
accessible room on either the North Admin Block, 2nd Floor, Room N205, MIC Research 
Nurse Offic3 or the 7th floor of the commonwealth building, Hammersmith Hospital 
campus. Only researchers will have access to this.  
• 
Plasma samples will be stored in a minus 80 freezer on the 8th floor of the 
Commonwealth Building, Hammersmith hospital, before being transported for analysis at 
the School of Medicine, St Mary’s hospital or Bristol Antimicrobial Assay laboratory. All 
samples will only contain patients study number (i.e. no identifiable information). 
• 
Statistical analysis will be performed using SPSS statistical software and Pmetrics in R, 
where appropriate. 
 
 

 
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8. 
REGULATORY ISSUES 
 
8.1 
ETHICS APPROVAL 
The Chief Investigator is obtaining approval from the Research Ethics Committee and the 
HRA.    The study will be conducted in accordance with the recommendations for physicians 
involved in research on human subjects adopted by the 18th World Medical Assembly, 
Helsinki 1964 and later revisions. 
 
This study protocol and SOP has been reviewed by the MHRA and deemed to not require 
registration as a Clinical Trial of an Investigational Medicinal Product (CTIMP) – Appendix 
4. 
 
8.2 
CONSENT  
Consent to enter the study must be sought from each participant only after a full explanation 
has been given, an information leaflet offered and at least 24 hours has been allowed to 
decide upon participation. Signed participant consent will be obtained.  The right of the 
participant to refuse to participate without giving reasons will be respected.  After the 
participant has entered the study the clinician remains free to give alternative treatment to 
that specified in the protocol at any stage if he/she feels it is in the participant’s best interest, 
but the reasons for doing so should be recorded.  In these cases the participants remain 
within the study for the purposes of follow-up and data analysis.  All participants are free to 
withdraw at any time from the protocol treatment without giving reasons and without 
prejudicing further treatment. If participants were to lose capacity at any point during the 
study they would be withdrawn. However, they will be consented for samples and data 
collected up to this time point to remain a part of the study.  
 
8.3 
CONFIDENTIALITY 
The Chief Investigator will preserve the confidentiality of participants taking part in the study 
and is registered under the Data Protection Act. 
 
Participants data will be anonymised and given a study number on enrolment. Participants 
will have the option to provide a contact address / email address to be contacted with 
updates of research outputs. This will be stored on an encrypted database on the lead 
researchers Trust account within the Imperial Healthcare NHS Trust firewall.  
 
8.4 
INDEMNITY 
Imperial College London holds negligent harm and non-negligent harm insurance policies 
which apply to this study. 
 
8.5 
SPONSOR 
Imperial College London will act as the main Sponsor for this study.  Delegated 
responsibilities will be assigned to the NHS trusts taking part in this study.   
 
8.6 
FUNDING 
National Institute for Health Research Invention for Innovation Product Development 
Award 
Imperial College EMBRACE pump priming award 
Imperial Biomedical Research Centre, Infection Theme 
Merieux Research Grants  
 
8.7 
AUDITS  
The study may be subject to inspection and audit by Imperial College London under their 
remit as sponsor and other regulatory bodies to ensure adherence to GCP and the NHS 
Research Governance Framework for Health and Social Care (2nd edition).  
 

 
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9. 
STUDY MANAGEMENT 
 
Project oversight meetings will be held once a quarter. This will consist of the principal 
investigators, the patient representatives, the project personnel as costed on the grant, the 
named individuals not costed but participating in the project.  
 
10. 
PUBLICATION POLICY 
The methods and results from this study will be presented at national and international 
conferences to both infection and patient safety specialists who are researchers and 
decision makers. Targeting of these specific groups in disseminating the research findings 
will allow not only engaged and productive feedback, but is also likely to generate further 
questions and raise awareness of the product as a resource for wider adoption.  
 
High impact peer reviewed publications will arise from this research evaluation, enabling 
wider engagement of researchers in this subject. Open-access fees have been included in 
the research costs requested, against four high impact journals to enable the widest possible 
dissemination of the findings. 
 
 

 
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12. APPENDICES 
 
APPENDIX 2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ADMINISTRATION: 
 
Photocopy consent form:   
File original consent form:   
 
Review performed by: 
 
 
PRINT NAME: .................................................................... 
 
 
 
SIGNATURE: .................................................................... 
 
 
 
DATE: .................................................................... 
 
 
FOR COMPLETION ONCE RESULTS ARE AVAILABLE: 
 
This subject meets all inclusion and exclusion criteria:  Yes 
No  
 
Eligibility confirmed by: 
 
 
PRINT NAME: .................................................................... 
 
 
 
SIGNATURE: .................................................................... 
 
 
 
DATE: .................................................................... 
 
 
 
 
 
 
 
 
 
MRN Number:  
 
 
 
Date: 
 
Issues: 
 
Enrolled Yes /No: 
 

 
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Occupation:   
 
 
 
 
 
 
 
E-mail address (optional): 
 
 
GP Name/Address/Telephone No (optional): 
 
 
 
Ethnicity: 
WHITE 
BLACK OR BLACK BRITISH 
 
British  
                                   
C
ibb
 
 
Irish  
                                   
Af i
 
 
Any other White background  
                              Any other Black 
b
k
d
 
 
  
 
ASIAN OR ASIAN BRITISH 
OTHER ETHNIC GROUPS 
 
Indian  
Chinese 
  
Pakistani  
Any other ethnic group 
  
Bangladeshi  
 
Please 
if
 
 
Any other Asian background  
 
  
    I do not wish to disclose my ethnic 
 
 
MIXED  
White & Black Caribbean  
 
White & Black African  
 
White & Asian  
 
Any other mixed background  
 
  
 
 
 
Previous research participation including dates? 
 
 
 
 
 
Donated blood during the preceding 3 months or intention to do so before the end of 
the study? 
 
 
 
 
 
 
 
 
 
 

 
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Current medical conditions:  
 
 
 
 
 
 
 
 
 
Past medical history: 
 
 
 
 
 
Drugs (inc. Prescription, OTC, vitamins,OCP): 
Allergies: 
 
 
 
 
 
 
 
 
Available microbiology / clinical information:  
 
 
 
 

 
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Height: 
 
......... metres  
 
 
 
Pulse:  
.........
 
bpm 
 
 
Weight: 
 
......... kg  
 
 
BP: 
 
......... mmHg 
 
 
BMI: 
 
......... kg/m2 
 
 
 
Temp:  
......... °C 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
URINE TESTS: 
Spec. gravity  
. 
 
 
 
 
 
 
 
pH  
. 
 
 
 
 
 
Glucose  
 
 
 
 
 
 
Protein  
 
 
 
 
 
 
Blood  
 
 
 
 
 
 
CrCL 
  
  
 
 
 
  
 
 
 
 
 
 
 
Central venous access available:   
Yes  
No 
 
Appropriate for use in study:  
Yes  
No 
 
Discussed with patient:  
 
 
Yes  
No 
Discussed with physician: 
 
Yes  
No 
 
 
VEINS (a pink cannula is required for this study) 
 
Antecubital fossae?        
  Right:  
 
 
 
 
Left: 
 
Dorsum of Hand? 
 
 
Right  
 
 
 
Left: 
Access will be (please delete): EASY / POSSIBLE / DIFFICULT 
 

 
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CLINICAL LABORATORY TESTS: 
WBC  
 
 
 
·  
 
 
 
Sodium   
 
 
  
 
 
Hb  
 
 
 
·  
 
 
 
Potassium   
 
 
·  
 
 
Haematocrit  
 
 
 
·  
 
 
 
Chloride   
 
 
  
 
 
Platelets  
 
 
 
  
 
 
 
Urea   
 
 
·  
 
 
Neutrophils  
 
 
 
·  
 
 
 
Creatinine   
 
 
  
 
 
Lymphocytes  
 
 
 
·  
 
 
 
Bicarbonate   
 
 
·  
 
 
Monocytes  
 
 
 
·  
 
 
 
ALT   
 
 
  
 
 
Eosinophils  
 
 
 
·  
 
 
 
ALP   
 
 
  
 
 
Basophils  
 
 
 
·  
 
 
 
Bilirubin   
 
 
  
 
 
HbA1c  
 
 
 
.  
 
 
 
CRP   
 
 
·  
 
 
  
 
 
 
  
 
 
 
Corr Calcium   
 
 
·  
 
 
  
 
 
 
  
 
 
 
Phosphate   
 
 
·  
 
 
  
 
 
 
  
 
 
 
Albumin   
 
 
  
 
 
  
 
 
 
  
 
 
 
Total Protein   
 
 
  
 
 
  
 
 
 
  
 
 
 
AST   
 
 
  
 
 
  
 
 
 
  
 
 
 
ALT   
 
 
  
 
 
  
 
 
 
  
 
 
 
Gamma GT   
 
 
  
 
 
  
 
 
 
  
 
 
 
   
 
 
·  
 
 
 Date:  
 
 
  
Time:  
 
Pip level 1   
 
 
·  
 
 Date:  
 
 
  
Time:  
 
Pip level 2   
 
 
·  
 
 
 Date:  
 
 
  
Time:  
 
Tazo level 1   
 
 
·  
 
 
 Date:  
 
 
  
Time:  
 
Tazo level 2    
 
 
.  
 
 
 
 
Swab taken: 
Time:  _________ 
 
 
 
For repeat:  
Time/date:   
Site:    _________ 
 
 
 
 
 
Person   
Post    
 
Swab taken: 
Time:  _________ 
 
 
 
For repeat:  
Time/date:   
Site:    _________ 
 
Swab taken: 
Time:  _________ 
 
 
 
For repeat:  
Time/date:   
Site:    _________ 
 
Swab taken: 
Time:  _________ 
 
 
 
For repeat:  
Time/date:   
Site:    _________ 
 

 
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APPENDIX 3 
Point Prevalence of Beta-lactam - SOP 
 
1. Give Participant Information Sheet allow up to 24 hours to read 
2. Discuss information sheet with patient, allow to ask questions, and if happy 
perform consent 
3. Complete page 2, 3 & 4 of study proforma 
4. Identify time for plasma sampling with medical team 
a. Liaise with medical team re. next scheduled time for routine plasma 
sampling  
b. Select co-ordinate with routine phlebotomy in conjunction with medical 
team 
Upon day of sampling  
5. Check weight, height and recorded observations on routine clinical 
observations chart.  
6. Briefly explain study, allow to ask questions 
7. If happy to proceed – proceed 
8. Go through page 3, 4 & 5 of medical screening proforma. 
9. Bloods collected during routine phlebotomy (see below): 
 
 
 
 
 
 
 
 
 
 
 
 
      
 
 
 All routine bottles should be sent by pod to the lab as per routine blood tests normally are.  
 
10. Gold top TDM sample should be left to clot and placed on ice until frozen 
 
Once gold top TDMsample has clotted 
11. Samples spun down at 2400 RPM for 10 minutes in the centrifuge 
12. Aliquot plasma into three  separate vials 
13. Freeze at minus 800C until shipment to laboratory for analysis 
 
Repeat on following day / dosing schedule that co-insides with routine 
sampling 
 
 
Tube 
required 
Test 
PRN 
Routine 
tests 
as 
required 
by 
clinical 
team 
Gold top 
Drug level sample 

 
Page 21 
Beta lactam TDM  
 
 
 
V6 IRAS: 207217 
31/01/2018 
APPENDIX 4