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## Complete Summary

#### GUIDELINE TITLE

Use of antibiotics in adults.

#### BIBLIOGRAPHIC SOURCE(S)

Singapore Ministry of Health. Use of antibiotics in adults. Singapore:
Singapore Ministry of Health; 2006 Feb. 180 p. \[320 references\]

#### GUIDELINE STATUS

This is the current release of the guideline.

### \*\* REGULATORY ALERT \*\*

#### FDA WARNING/REGULATORY ALERT

**Note from the National Guideline Clearinghouse (NGC)**: This guideline
references a drug(s) for which important revised regulatory and/or
warning information has been released.

-   [July 08, 2008, Fluoroquinolones (ciprofloxacin, norfloxacin,
    ofloxacin, levofloxacin, moxifloxacin,
    gemifloxacin)](http://www.fda.gov/medwatch/safety/2008/safety08.htm#Fluoroquinolone):
    A BOXED WARNING and Medication Guide are to be added to the
    prescribing information to strengthen existing warnings about the
    increased risk of developing tendinitis and tendon rupture in
    patients taking fluoroquinolones for systemic use.

-   [September 11, 2007, Rocephin (ceftriaxone
    sodium)](http://www.fda.gov/medwatch/safety/2007/safety07.htm#Rocephin):
    Roche informed healthcare professionals about revisions made to the
    prescribing information for Rocephin to clarify the potential risk
    associated with concomitant use of Rocephin with calcium or
    calcium-containing solutions or products.

### COMPLETE SUMMARY CONTENT

 \*\* REGULATORY ALERT \*\*\
 SCOPE\
 METHODOLOGY - including Rating Scheme and Cost Analysis\
 RECOMMENDATIONS\
 EVIDENCE SUPPORTING THE RECOMMENDATIONS\
 BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS\
 CONTRAINDICATIONS\
 QUALIFYING STATEMENTS\
 IMPLEMENTATION OF THE GUIDELINE\
 INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT
CATEGORIES\
 IDENTIFYING INFORMATION AND AVAILABILITY\
 DISCLAIMER

### SCOPE

#### DISEASE/CONDITION(S)

-   Acute upper respiratory tract infection

-   Acute bronchitis and exacerbation of chronic bronchitis

-   Community acquired pneumonia

-   Hospital acquired pneumonia

-   Acute infectious diarrhoea

-   Urinary tract infection

-   Acute bacterial meningitis

-   Infections in the elderly

#### GUIDELINE CATEGORY

Diagnosis\
Evaluation\
Management\
Risk Assessment\
Treatment

#### CLINICAL SPECIALTY

Family Practice\
Gastroenterology\
Geriatrics\
Infectious Diseases\
Internal Medicine\
Pulmonary Medicine\
Urology

#### INTENDED USERS

Physicians

#### GUIDELINE OBJECTIVE(S)

-   To promote the proper and appropriate use of antibiotics so as to
    slow the emergence of antimicrobial resistance

-   To ensure that patients receive the appropriate treatment

#### TARGET POPULATION

Adults, including the elderly, in Singapore with infections that might
need antibiotics for treatment

#### INTERVENTIONS AND PRACTICES CONSIDERED

**Management/Treatment of Acute Upper Respiratory Tract Infection
(URTI)**

1.  Penicillin V therapy for group A beta-haemolytic streptococcal
    (GABHS) pharyngitis

2.  Ceftriaxone or chloramphenicol therapy for acute epiglottis

3.  Amoxicillin or penicillin therapy for acute bacterial maxillary
    rhinosinusitis

4.  Neuraminidase inhibitors for prevention and treatment of influenza

5.  Influenza vaccination

**Management/Treatment of Exacerbation of Chronic Bronchitis**

1.  Risk stratification

2.  Use of macrolides (e.g., azithromycin, clarithromycin),
    cephalosporins (e.g.,cefuroxime), or doxycycline

3.  Alternative therapy for complicated cases

**Management/Treatment of Community Acquired Pneumonia**

1.  Risk stratification

2.  Use of Fine pneumonia severity index

3.  Microbiological, haematological, biochemical and serological testing

4.  Chest radiograph

5.  Empirical therapy for *Burkholderia pseudomallei*

6.  Empirical antibiotic therapy based on risk category and relative
    presence of major pathogens

7.  Use of oral or intravenous antibiotics

**Management/Treatment of Hospital Acquired Pneumonia**

Empirical antibiotic therapy based on risk factors for core pathogens,
severity of illness, and duration of hospitalization

**Management/Treatment of Acute Infectious Diarrhoea**

1.  Medical history and physical examination

2.  Screening tests and stool culture

3.  Rehydration and anti-motility agents

4.  Empirical antibiotic therapy or specific therapy according to
    pathogens isolated

**Management/Treatment of Urinary Tract Infection**

1.  History and physical examination

2.  Urine analysis and urine culture if appropriate

3.  Empirical antibiotic therapy or specific therapy based on results of
    culture and sensitivity

4.  Refraining from antibiotic therapy in asymptomatic bacteriuria,
    except in pregnant women

5.  Prophylactic therapy for recurrent infections

6.  Referral to urologist as appropriate

**Management/Treatment of Acute Bacterial Meningitis**

1.  Physical examination

2.  Lumbar puncture and cerebrospinal fluid (CSF) analysis

3.  Intravenous (IV) penicillin G in patients with meningococcal rash or
    IV ceftriaxone, or IV ceftriaxone plus ampicillin or vancomycin in
    patients with rash

4.  Treatment modification after identifying specific pathogens

5.  Adjunctive dexamethasone when appropriate

6.  Chemoprophylaxis for close contacts

**Use of Antibiotics in the Elderly**

1.  Empirical broad-spectrum antibiotic therapy (e.g., beta-lactam
    antibiotics)

2.  Reserving aminoglycosides for selected situations only

3.  Use of measures to avoid aspiration

4.  Monitoring for adverse effects and drug-drug interactions

5.  Systemic antibiotic therapy for pressure ulcers

#### MAJOR OUTCOMES CONSIDERED

-   Effectiveness of antibiotic treatment

-   Length of hospitalization

-   Mortality

-   Development and spread of antibiotic resistance

-   Cost-effectiveness of antibiotic use

### METHODOLOGY

#### METHODS USED TO COLLECT/SELECT EVIDENCE

Searches of Electronic Databases

#### DESCRIPTION OF METHODS USED TO COLLECT/SELECT THE EVIDENCE

Not stated

#### NUMBER OF SOURCE DOCUMENTS

Not stated

#### METHODS USED TO ASSESS THE QUALITY AND STRENGTH OF THE EVIDENCE

Weighting According to a Rating Scheme (Scheme Given)

#### RATING SCHEME FOR THE STRENGTH OF THE EVIDENCE

**Levels of Evidence**

**Level Ia**: Evidence obtained from meta-analysis of randomised
controlled trials

**Level Ib**: Evidence obtained from at least one randomised controlled
trial

**Level IIa**: Evidence obtained from at least one well-designed
controlled study without randomisation

**Level IIb**: Evidence obtained from at least one other type of
well-designed quasi-experimental study

**Level III**: Evidence obtained from well-designed nonexperimental
descriptive studies, such as comparative studies, correlation studies
and case studies

**Level IV**: Evidence obtained from expert committee reports or
opinions and/or clinical experiences of respected authorities

#### METHODS USED TO ANALYZE THE EVIDENCE

Review of Published Meta-Analyses\
Systematic Review

#### DESCRIPTION OF THE METHODS USED TO ANALYZE THE EVIDENCE

Not stated

#### METHODS USED TO FORMULATE THE RECOMMENDATIONS

Expert Consensus

#### DESCRIPTION OF METHODS USED TO FORMULATE THE RECOMMENDATIONS

These guidelines on antibiotic use have been developed based on the best
available evidence as well as expert opinion of the multidisciplinary
workgroup in areas where studies are lacking. In addition to tailoring
the evidence to suit the practice of medicine in Singapore, local
microbiology patterns and resistance trends were also taken into
consideration.

#### RATING SCHEME FOR THE STRENGTH OF THE RECOMMENDATIONS

**Grades of Recommendations**

**Grade A** (evidence levels Ia, Ib): Requires at least one randomised
controlled trial as part of the body of literature of overall good
quality and consistency addressing the specific recommendation.

**Grade B** (evidence levels IIa, IIb, III): Requires availability of
well conducted clinical studies but no randomised clinical trials on the
topic of recommendation.

**Grade C** (evidence level IV): Requires evidence obtained from expert
committee reports or opinions and/or clinical experiences of respected
authorities. Indicates absence of directly applicable clinical studies
of good quality.

**GPP** (good practice points): Recommended best practice based on the
clinical experience of the guideline development group.

#### COST ANALYSIS

The guideline developers reviewed published cost analyses.

**Decision on when or whether to start antibiotic treatment** should be
based on the cost-effectiveness of the different treatment strategies.
An example is illustrated in the section on recommendations for the
treatment of acute rhinosinusitis. A study comparing treatment
strategies for uncomplicated acute bacterial rhinosinusitis reported the
cost per symptom-free day as US\$3.09 for the clinical criteria-based
treatment, US\$3.95 for symptomatic treatment\* and US\$184.56 for
empirical treatment\*\*. Radiographic-guided treatment was found to be
more expensive and less effective than the other 3 strategies. Clinical
criteria-guided treatment was shown to be the most cost-effective
strategy, and treatment based on radiographic findings was shown to be
more expensive and less effective.

\* In which no patients were initially treated with antibiotics

\*\* In which all patients were initially treated with amoxicillin

**Appropriate antibiotic choice** takes into consideration effectiveness
(including the impact of antibiotic resistance and local antibiotic
resistance patterns), costs and adverse effects. In cases where a range
of antibiotic treatments exists, and a choice of the best antibiotic has
to be made, an important consideration is cost-effectiveness. An example
is in the choice of antibiotics for the treatment of acute exacerbation
of chronic obstructive pulmonary disease (COPD) and chronic bronchitis.
It was reported that the use of azithromycin, amoxycillin clavulanate,
ciprofloxacin, cefuroxime, cefactor, cephradine or cefprozil was the
dominant strategy, being more effective as well as cheaper, compared to
agents such as amoxycillin and erythromycin.

On the other hand, inappropriate or unnecessary antibiotic prescribing
can be harmful to patients as well as to the community. It can cause the
emergence and spread of resistant organisms, which would not only lead
to clinical consequences, but also increased costs of health care. It
was reported that antibiotic-resistant bacteria generated US\$4 billion
to US\$5 billion in costs to the US society and individuals yearly.

There are many elements of the economic impact of antibiotic resistance.
Apart from increased length of hospital stay, morbidity and mortality,
there are also direct costs (e.g. diagnostic investigations, costs of
administration of newer or more costly drugs), as well as indirect costs
(e.g. loss of productivity of patients, costs to the drug industry
resulting from diminishing marketability of their drugs).

#### METHOD OF GUIDELINE VALIDATION

Not stated

#### DESCRIPTION OF METHOD OF GUIDELINE VALIDATION

Not applicable

### RECOMMENDATIONS

#### MAJOR RECOMMENDATIONS

Each recommendation is rated based on the levels of the evidence and the
grades of recommendation. Definitions of the grades of the
recommendations (A, B, C, Good Practice Points) and level of the
evidence (Level I-Level IV) are presented at the end of the Major
Recommendations field.

**Principles of Antibiotic Use**

**GPP** - Antibiotics should be used only for treatment of patients with
confirmed or suspected bacterial infections. Antibiotics may be used for
prophylaxis where consequences of infection would be severe. **(GPP)**

**GPP** - Antibiotics should only be chosen after considering the
following questions:

1.  Is there an infection?

2.  What is the site of infection and the most likely causative
    organism?

3.  Will the antibiotic reach the site of infection?

4.  What side effects of drug interactions might this antibiotic have?

5.  What adjustments should be made for the individual patient (e.g.,
    the young infant, the elderly, patients with renal failure)?

6.  What is the appropriate dose and duration of treatment for the site
    and type of infection? **(GPP)**

**GPP** - Patients or their caregivers should be clearly instructed on
the dose and the necessity of finishing a course of treatment. **(GPP)**

**Use of Antibiotics in Acute Upper Respiratory Tract Infections (URTI)
in Adults**

**Antibiotic Use in URTI**

**B** - The use of antibiotics for a large portion of URTIs is not
recommended because these are viral infections, for which antibiotics do
not provide clinical benefit. (Radetsky et al., 1981; Belongia et al.,
2002; Gonzales et al., 2001) (**Grade B, Level IIa**)

**Non-Specific Respiratory Infections**

**A** - Antibiotic treatment of adults with non-specific upper
respiratory tract infection is not recommended. (Arrol & Kenealy, 2003)
(**Grade A, Level Ia**)

**A** - The use of antibiotics is not recommended when there is a
purulent secretion from the nares or throat, in patients with
uncomplicated URTI. (Kaiser et al., 1996; Heald et al., 1993; Evans,
1957; Walsh et al., 1975) (**Grade A, Level Ia**)

**Acute Pharyngitis (Sore Throat)**

**B** - Patients identified with Group A beta-haemolytic streptococcal
pharyngitis should be treated with antibiotics to prevent complications.
(Huovinen et al., 1989) (**Grade B, Level III**)

**A** - Group A beta-haemolytic streptococcal-positive patients should
be treated with penicillin V for seven days. (Dagnelie, van der Graaf, &
de Melker, 1996; Zwart et al., 2000) (**Grade A, Level Ib**)

**A** - Throat cultures are not recommended for the routine primary
evaluation of adults with pharyngitis. (Dagnelie et al., 1998; Cooper et
al., 2001; Dagnelie, van der Graaf, & de Melker, 1996) (**Grade A, Level
Ib**)

**C** - Administer appropriate analgesics, antipyretics, and supportive
care to all patients with pharyngitis. (McKerrow et al., 1999) (**Grade
C, Level IV**)

**Acute Epiglottitis**

**B** - The antibiotic of choice to treat acute epiglottitis is
cefriaxone or chloramphenicol. (Carey, 1996) (**Grade B, Level IIb**)

**Acute Rhinosinusitis**

**B** - Sinus radiography is not recommended for diagnosis in routine
cases. (**Grade B, Level IIb**)

**B** - Symptomatic treatment and reassurance are the preferred initial
management strategy for patients with mild symptoms of acute
rhinosinusitis. (Berg & Carenfelt, 1988; Williams et al., 1992; van
Duijn, Brouwer, & Lamberts, 1992) (**Grade B, Level IIb**)

**B** - Antibiotic therapy should be reserved for:

-   Patients with moderately severe symptoms who meet the criteria for
    the clinical diagnosis of acute bacterial rhinosinusitis (symptoms
    that last \>7 days and include maxillary pain in the face or teeth
    and purulent nasal secretions); and

-   Patients with severe rhinosinusitis symptoms, regardless of duration
    of illness. (Berg & Carenfelt, 1988; Williams et al., 1992; van
    Duijn, Brouwer, & Lamberts, 1992) (**Grade B, Level IIb**)

**A** - For the initial treatment of acute bacterial maxillary
rhinosinusitis, amoxicillin or penicillin for 7-14 days is recommended.
(Antimicrobial treatment guidelines for acute bacterial rhinosinusitis,
2000; Williams et al., 2003) (**Grade A, Level Ia**)

**B** - Isolated infection of a frontal or sphenoid sinus is a rare but
potentially dangerous condition, usually caused by bacteria, and should
be referred to hospital for treatment. (Hickner et al., 2001) (**Grade
B, Level IIb**)

**Acute Laryngitis**

**GPP** - If symptoms last for more than 3 weeks, the condition is
classified as chronic laryngitis, for which an underlying cause must be
further investigated. Underlying causes include laryngeal polyps,
cancer, laryngeal tuberculosis, and gastro-esophageal reflux. (**GPP**)

**B** - Antibiotic treatment for acute laryngitis currently should be
reserved for high-risk patients, patients with severe symptoms, or in
the presence of an identifiable organism on Gram stain and culture.
(Vaughan, 1982; Shah & Shapshay, 1996) (**Grade B, Level IIb**)

**Acute Otitis Media**

**B** - Antibiotics are unnecessary in acute otitis media. (Burke et
al., 1991; Browning, 1990; Lisby-Sutch et al., 1990) (**Grade B, Level
IIb**)

**B** - Avoid local treatment with antimicrobial eardrops in acute
otitis media. (Lisby-Sutch et al., 1990; \"Clinical uncertainty clouds
pharmacoeconomic assessment of otitis media therapy,\" 1995) (**Grade B,
Level III**)

**Common Cold**

**A** - Antibiotics should not be given for the common cold. (Rosenstein
et al., 1998) (**Grade A, Level Ib**)

**B** - Antibiotics should not be given for the common cold which is
accompanied by mucopurulent rhinitis. (Puhakka et al., 1998) (**Grade B,
Level III**)

**Influenza**

[Severe Acute Respiratory Syndrome (SARS)]{.underline}

A patient presenting with a fever and URTI symptoms needs to be asked
for a history of recent travel within the previous 14 days from onset of
symptoms, and possible contact with known SARS patients. If the history
is positive for any of these, the patient must be immediately
quarantined in hospital until a definitive diagnosis is clear. In SARS,
the fever may temporarily improve but eventually recur, and by around
day 6 of the illness, the fever may become persistently high (38 degrees
C or higher). By this time, the patient will be acutely ill. A complete
resolution of symptoms by day 6 is therefore a good confirmation that
the patient\'s illness is not SARS.

**A** - Neuraminidase inhibitors (NIs) are effective for the prevention
and treatment of influenza. (Jefferson et al., 2003) (**Grade A, Level
Ia**)

**B -** The adamantanes, rimantadine and amantadine, are not recommended
for influenza A because of increasing drug resistance. (Bright et al.,
2006) (**Grade B, Level III**)

**Acute Bronchitis and Exacerbation of Chronic Bronchitis**

**Acute Bronchitis**

**B** - In a patient with an acute cough illness lasting less than 3
weeks, pneumonia should be ruled out by history and clinical
examination. Chest X-ray for pneumonia is not necessary in the absence
of red flags. (Gonzales et al., 2001; Aagaard & Gonzales, 2004; Diehr et
al., 1984; Heckerling et al., 1990; Gennis et al., 1989; Singal, Hedges,
& Radack, 1989; Metlay, Kapoor, & Fine, 1997) (**Grade B, Level III**)

**A** - Routine antibiotic treatment of acute bronchitis is not
recommended, regardless of the duration of cough. (Gonzales et al.,
2001; Bent et al., 1999) (**Grade A, Level Ia**)

**B** - Antibiotic therapy in acute bronchitis should be considered if
the patient is [\>]{.underline}60 years or ill at the outset.
(Macfarlane et al., 1993) (**Grade B, Level III**)

**C** - Once a diagnosis of acute bronchitis has been made, the
physician should address symptomatic treatment and patient expectations
of the visit. (Aagaard & Gonzales, 2004) (**Grade C, Level IV**)

**B** - All cases of acute bronchitis should be followed up and
antibiotics considered if they are not recovering. (Macfarlane et al.,
1993) (**Grade B, Level III**)

**Acute Exacerbations of Chronic Bronchitis (AECB)**

**A** - Patients with acute exacerbation of severity of Anthonisen Type
I (having increased dyspnea, increased sputum production, and increased
sputum purulence) and Anthonisen Type II (two of the three symptoms)
should be given antibiotic therapy. (Anthonisen et al., 1987) (**Grade
A, Level Ib**)

**A** - Patients with one or more of the following risk factors should
be given antibiotic therapy: more than 4 exacerbations within the past
year; a co-morbid condition, such as diabetes, asthma, or a history of
coronary artery disease, or marked airway obstruction. (Grossman et al.,
1998) (**Grade A, Level Ib**)

**B** - Patients with exacerbations without an increase in purulent
sputum do not need antibiotic therapy unless there is a consolidation on
a chest radiograph or clinical signs of pneumonia.  (Stockley et al.,
2000) (**Grade B, Level IIa**)

**B** - Patients with purulent exacerbations but who have no risk
factors for treatment failure or no enhanced association with more
virulent or resistant bacterial pathogens can be treated with an
advanced macrolide (azithromycin, clarithromycin), a cephalosporin
(cefuroxime), or doxycycline. (Sethi & Murphy, 2004; Brunton et al.,
2004; Adams & Anzueto, 2000; Martinez & Anzueto, 2005; Akalin, 2001)
(**Grade B, Level IIa**)

*See Table 2 in the original guideline document for classifications of
patients with chronic bronchitis and antibiotic choice.*

**A** - Patients with purulent exacerbations and who have risk factors
that are associated with an increased likelihood of treatment failure or
infection with more virulent or resistant organisms should be given
antibiotics with enhanced antimicrobial coverage, namely the newer
fluroquinolones (moxifloxacin, gemifloxacin\*, gatifloxacin,
levofloxain) (Shams & Evans, 2005; Wilson et al., 1999; Chodosh et al.,
1998; Wilson et al., \"A comparison of gemifloxacin,\" 2002; Wilson et
al., \"A clinical and outcomes assessment,\" 2002; Martinez et al.,
2005) or amoxillin-clavulanate. (Sethi, Breton, & Wynne, 2005) (Grade A,
Level Ib)

\* Currently not available in Singapore.

**GPP** - In a patient with AECB requiring repeat antibiotic therapy
within 3 months, a new class of antibiotics should be used. (**GPP**)

**Use of Antibiotics in Community Acquired Pneumonia (CAP)**

**Risk Stratification**

**B** - Risk stratification is a key step in the management of community
acquired pneumonia. (Niederman et al., 2001; British Thoracic Society
Standards of Care Committee, 2001; Mandell & Niederman, 1993; Bartlett
et al., 1998; Fine et al., 1997; Marrie et al., 2000) (**Grade B, Level
IIa**)

**Risk Categories**

*Category I (Low Risk: Outpatient Treatment)*

Patients with clinically mild disease, and with no co-morbidly nor risk
factors (see Table 4 in the original guideline document) fall in the
low-risk category. They may be safely treated initially with oral
antibiotics and monitored at home. They should be reviewed in the clinic
within 24-48 hours to ensure that they have improved with initial
treatment.

*Category II (Low Risk: Consider Outpatient Treatment)*

Outpatient treatment may also be considered for patients with
co-morbidity or risk factors but are clinically stable. The choice of
empiric antibiotics should cover the suspected pathogens such as
multi-drug resistant pneumococci, Gram-negative Enterobacteriaceae or
*Psuedomnonas aeruginosa* (see Tables 5-8 in the original guideline
document).

*Category III (Intermediate Risk: Outpatient vs Hospital Ward
Treatment)*

Selected clinically stable patients in this category with Fine Pneumonia
Severity Index (PSI) ≤90 may be safely managed as outpatients. Hospital
admission is usually considered for elderly patients with PSI \>90 and
all patients who show physical and radiological signs of clinical
severity (Table 7 in the original guideline document). The pathogens are
similar to patients in category II but the recommended treatment should
be intravenous antibiotics for most patients unless they do not show
modifying risk factors (see Tables 5-8 in the original guideline
document).

*Category IV (High Risk: Intensive Care Treatment)*

The most practical way to define severe CAP is a case that requires
admission to the intensive care unit (ICU). All patients in Singapore
should receive empiric treatment for *Burkholderia pseudomallei*, and
those with specific risk factors should also be covered for *Pseudomonas
aeruginosa* (see Tables 5-8 in the original guideline document).

**B** - All patients with severe community acquired pneumonia (Category
IV) in the ICU should be treated empirically for *Burkholderia
pseudomallei*. (Lee et al., 1996; Tan et al., 1998) (**Grade B, Level
III**)

**Inpatient Investigations**

**C** - Microbiological, haematological, biochemical and serological
tests (see list below) are recommended for patients in high risk
categories III and IV upon presentation. (Niederman et al., 2001;
British Thoracic Society Standards of Care Committee, 2001; Mandell &
Niederman, 1993; Bartlett et al., 1998; Fine et al., 1997; Sanyal et
al., 1999; Theerthakarai et al., 2001; Waterer & Wunderink, 2001)

The following microbiological tests should be done before starting
antibiotics in patients with moderate to severe CAP (Categories III and
IV). Initial microbiological studies may have limited value in the
management of patients with low risk CAP (Categories I & II) (Sanyal et
al., 1999; Theerthakarai et al., 2001; Waterer & Wunderink, 2001):

-   Sputum Gram stain and aerobic culture (mycobacterial smear and
    culture where appropriate).

-   Blood aerobic culture.

-   Pleural fluid Gram stain and culture.

-   Urine for *Legionella* antigen.

The other investigations are:

-   Blood count with differentials, and smear for toxic granulations.

-   Biochemistry, including renal and liver function (blood gas where
    necessary).

-   Consider human immunodeficiency virus (HIV) testing and work-up for
    *Pneumocystis carinii*.

-   Optional serological testing for atypical agents.

(**Grade C, Level IV**)

**Empirical Antibiotic Therapy**

**A** - The initial choice for empirical antibiotic therapy should be
based on the risk category and relative prevalence of major pathogens.
(Fine et al., 1997; Marrie et al., 2000; Gleason et al., 1999; Stahl et
al., 1999; Gotfried et al., 2002; Petitpretz et al., 2001;
Contopoulos-Ioannidis et al., 2001) (**Grade A, Level Ib**)

**C** - Quinolones are not recommended for the outpatient treatment of
community acquired pneumonia in risk categories I & II. (Petitpretz et
al., 2001; Mills, Oehley, & Arrol, 2005) (**Grade C, Level IV**)

See Table 8 in the original guideline document for empirical antibiotic
for initial treatment of community acquired pneumonia.

**A** - A switch from intravenous (IV) to oral antimicrobials and prompt
hospital release is recommended for patients in low or intermediate risk
categories who respond promptly or become clinically stable after
receiving initial antimicrobial treatment. (Omidvari et al., 1998;
Ramirez et al., 1999; Ramirez & Bordan, 2001; Paladino et al., 2002;
Rhew et al., 2001; Vogel, 2002) (**Grade A, Level Ia**)

Table: **B** - Criteria for discharge from hospital

+-----------------------------------------------------------------------+
| -   Stable vital signs for 24 hours (i.e. temperature \<37.8 degrees  |
|     C, respiratory rate \<24/min, systolic BP [\>]{.underline}90      |
|     mmHg, O~2~ saturation [\>]{.underline}90% while breathing room    |
|     air).                                                             |
|                                                                       |
| -   Patient able to take diet.                                        |
|                                                                       |
| -   Patient able to take oral antibiotics.                            |
|                                                                       |
| -   No other active clinical or psycho-social problems requiring      |
|     hospital stay.                                                    |
+-----------------------------------------------------------------------+

(Omidvari et al., 1998; Ramirez et al., 1999; Ramirez & Bordan, 2001;
Paladino et al., 2002; Rhew et al., 2001; Vogel, 2002) (**Grade B, Level
III**)

**B** - In addition to the usual outcomes of mortality and hospital
length of stay, the time to the first dose of antibiotics in elderly
patients (\>65 years) should be a key indicator of the evaluation of the
quality of CAP management. (**Grade B, Level III**)

**Use of Antibiotics in Hospital Acquired Pneumonia (HAP)**

**Classification of HAP and Antibiotic Use**

**B** - It is recommended that the initial empirical therapy be based
upon targeting a core group of pathogens according to severity of
illness, duration of hospitalisation and risk factors for specific
pathogens. (American Thoracic Society and the Infectious Disease Society
of America, 2005; Chastre & Fagon, 2002; Ewig, Bauer, & Torres, 2002;
Bruchhaus, McEachern, & Campbell, 1998; Mandell & Campbell, 1998;
McEachern, & Campbell, 1998) (**Grade B, Level III**)

**A** - Piperacillin-tazobactam is as safe and effective as ceftazidime
in the empirical treatment of severe hospital acquired pneumonia,
hospital acquired pneumonia in the ICU and ventilator-associated
pneumonia. (Joshi et al., 1999; Alvares-Lerma et al., 2001; Brun-Buisson
et al., 1998) (**Grade A, Level Ib**)

Table: **C** - Antibiotics for patients with no risk factors; hospital
acquired pneumonia of mild to moderate severity, and of early onset
([\<]{.underline}5 days)

+---------------------------------------+------------------------------+
| **Core Pathogens**                    | **Core Antibiotics**         |
+=======================================+==============================+
| Enteric Gram-negative bacilli         | 3^rd^-generation             |
|                                       | cephalosporin                |
| -   *Klebsiella* species and\         |                              |
|     *Escherichia coli*                | e.g. intravenous             |
|                                       | ceftriaxone,                 |
|                                       |                              |
|                                       | or beta-lactam /             |
|                                       | beta-lactamase inhibitor     |
|                                       |                              |
|                                       | e.g. intravenous             |
|                                       | ampicillin-sulbactam or      |
|                                       |                              |
|                                       | amoxicillin-clavulanic acid, |
|                                       |                              |
|                                       | or quinolone                 |
|                                       |                              |
|                                       | e.g. ciproflaxin.            |
+---------------------------------------+------------------------------+
| Also,                                 | Consider adding cloxacillin  |
|                                       | or clindamycin.\             |
| -   *Staphylococcus aureus*           | \                            |
|                                       | Consider adding azithromycin |
| -   *Hemophilus influenzae* and       | or clarithromycin.\          |
|     *Streptococcus pneumoniae*        | \                            |
|                                       | Alternative to above: newer  |
|                                       | quinolone as monotherapy.    |
+---------------------------------------+------------------------------+
| If MRSA\* isolated                    | Consider adding vancomycin.  |
| [\>]{.underline}50% in ICU            |                              |
+---------------------------------------+------------------------------+

(**Grade C, Level IV**)

(Source: American Thoracic Society and the Infectious Diseases Society
of America. Guidelines for the management of adults with
hospital-acquired, ventilator-associated, and healthcare-associated
pneumonia, 2005)

\*MRCA, methicillin-resistant *Staphylococcus aureus*

Table: **C** - Antibiotics for patients with no risk factors, but late
onset (\>5 days) hospital acquired pneumonia, or severe hospital
acquired pneumonia onset at any time (definition of severe hospital
acquired pneumonia as for severe community acquired pneumonia)

  -----------------------------------------------------------------------
  **Core Pathogens**  **Core Antibiotics**
  ------------------- ---------------------------------------------------
  *Pseudomonas        Ciprofloxacin or amikacin\
  Aeruginosa*         \
                      *PLUS either*\
                      \
                      An anti-pseudomonal beta-lactam/beta-lactamase
                      inhibitor (piperacillin/tazobactam), *or*\
                      \
                      Ceftazidime or carbepenems (imipenem, meropenem)

  Resistant           Anti-pseudomonal cephalosporin (ceftazidime), or
  *Acinetobacter*     imipenem/meropenem, or amikacin
  species             

  MRSA\*              Add vancomycin
  -----------------------------------------------------------------------

(**Grade C, Level IV**)

(Source: American Thoracic Society and the Infectious Diseases Society
of America. Guidelines for the management of adults with
hospital-acquired, ventilator-associated, and healthcare-associated
pneumonia, 2005)

\*MRCA, methicillin-resistant *Staphylococcus aureus*

Table: **C** - Risk factors for specific pathogens and antibiotics to be
added

  ----------------------------------------------------------------------------
  **Pathogen**      **Risk Factor**  **Antibiotic**
  ----------------- ---------------- -----------------------------------------
  Anaerobic         Observed         Clindamycin, metronidazole, or
                    aspiration\      Beta-lactam/beta-lactamase inhibitor
                    \                
                    Abdominal        
                    surgery\         
                    \                
                    Putrid discharge 

  *Staphylococcus   Coma\            Vancomycin
  aureus*           \                
                    Head injury\     
                    \                
                    Diabetes\        
                    \                
                    Renal failure    

  MRSA\*            Outbreaks        Vancomycin

  *Legionella*      Corticosteroid   Erythromycin
  species           use\             
                    \                
                    Outbreaks        

  *Pseudomonas      Prolonged ICU    As in severe hospital acquired pneumonia
  aeruginosa*       stay\            (see Table: \"Antibiotics for patients
                    \                with no risk factors\" above)
                    Antibiotic       
                    exposure\        
                    \                
                    Chronic lung     
                    disease\         
                    \                
                    AIDS             
  ----------------------------------------------------------------------------

(**Grade C, Level IV**)

(Source: American Thoracic Society and the Infectious Diseases Society
of America. Guidelines for the management of adults with
hospital-acquired, ventilator-associated, and healthcare-associated
pneumonia, 2005)

\*MRCA, methicillin-resistant *Staphylococcus aureus*

**Use of Antibiotics in Acute Infectious Diarrhoea in Adults**

**GPP** - In any patient with diarrhoea, obtain the following history:

-   age

-   evidence of an immunocompromised state

-   previous use of antibiotics

-   history of travel

-   scale of outbreak

(**GPP**)

**GPP** - Perform a focused physical examination in a patient with
diarrhoea:

1.  Look for signs of dehydration: loss of skin turgor, postural
    hypotension, increased pulse rate.

2.  Record the temperature.

3.  Examine the abdomen for tenderness or distension.

4.  Perform a rectal examination to look for the presence of blood in
    the stool.

(**GPP**)

**GPP** - In a patient with diarrhoea, look for red flags

-   Profuse, watery diarrhoea with dehydration.

-   Passage of small volume stool, containing blood and mucus.

-   Temperature [\>]{.underline}38.5 degrees C.

-   Passage of [\>]{.underline}6 times unformed stool in 24 hours.

-   Duration of illness \>72 hours.

-   Severe abdominal pain, in a patient over the age of 50 years.

-   Diarrhoea in the elderly ([\>]{.underline}70 years of age).

-   Diarrhoea in the immuno-compromised.

The presence of one or more of the above symptoms/signs suggests the
diarrhoea is severe enough to warrant further evaluation and treatment.
(**GPP**)

**Investigations**

**B** - The faecal leucocyte, faecal lactoferrin, or Hemoccult™ test may
be useful screening tests in patients with moderate to severe acute
infectious diarrhoea. These tests may be used to differentiate
inflammatory and non-inflammatory diarrhoeal syndromes. (Stoll et al.,
1983; Siegel et al., 1987; Savola et al., 2001; Herbert, 2000) (**Grade
B, Level III**)

**A** - Stool cultures (for salmonella, shigella and campylobacter)
should be performed only in patients who have prolonged diarrhoea, or in
patients who have clinical or biochemical evidence of inflammatory
diarrhoea. (Stoll et al., 1983; Chan et al., 2002; Chitkara, McCasland,
& Kenefic, 1996; Koplan et al., 1980) (**Grade A, Level Ib**)

**A** - For patients with diarrhoea that develops after three days of
hospitalisation, or have recently received antibiotics or
anti-neoplastics, an effort should be made to look for *Clostridium
difficile* infection. (Guerrant et al., 2001; Chitkara, McCasland, &
Kenefic, 1996; Rohner et al., 1997; Siegel, Edelstein, & Nachamkin,
1990) (**Grade A, Level Ib**)

**C** - Exposure of a traveller or hiker to untreated water and
illnesses that persist for more than seven days should prompt
evaluations for protozoal pathogens, especially giardia and
cryptosporidium. (Thielman & Guerrant, 2004) (**Grade C, Level IV**)

**GPP** - Endoscopy should be reserved for the investigation of patients
with persistent or chronic diarrhoea. (**GPP**)

**General Management**

**A** - Fluid and electrolyte replacement plays a pivotal role in the
management of all patients with acute diarrhoea. Oral rehydration is the
treatment of choice. (Guerrant et al., 2001; Dupont, 1997; Dupont, 1994;
Goodman & Segreti, 1999; Ilnyckyj, 2001; Park & Giannella, 1993)
(**Grade A, Level Ia**)

**GPP** - If an anti-motility agent is required, loperamide may be used.
(Schiller et al., 1984; Dupont & Hornick, 1973) (**GPP**)

**B** - Anti-motility agents should not be given to patients who have
febrile dysentery. (Dupont & Hornick, 1973) (**Grade B,** **Level IIa**)

**A** - Anti-motility agents should not be given o patients who have
suspected *Escherichia coli* O157:H7 infection, Shiga toxin-producing
*Escherichia coli* infection, or frank bloody diarrhoea. (Siegel,
Edelstein, & Nachamkin, 1990; Dupont & Hornick, 1973; Cimolai et al.,
1990) (**Grade A, Level Ib**)

**A** - In patients with moderate to severe inflammatory diarrhoea, an
empirical course of quinolones can be given for 3-5 days. (Sanchez et
al., 1993; Goodman et al., 1990; Dryden, Gabb, & Wright, 1996; Wistrom
et al., 1992) (**Grade A, Level Ib**)

**A** - In patients with moderate to severe traveller\'s diarrhoea, an
empirical course of quinolones can be given for 3-5 days. (Petruccelli
et al., 1992; Chak & Banwell, 1993) (**Grade A, Level Ib**)

**GPP** - Elderly patients with moderate to severe diarrhoea may also be
started on empirical antibiotic therapy (with quinolones). (**GPP**)

**B** - All patients with moderate to severe infection with shigellosis
should be treated with antibiotics. Patients with mild infections in the
setting of good public health and hygiene can be observed. (Weissman et
al., 1974; Dupont et al., 1989) (**Grade B, Level IIa**)

**A** - Routine treatment with antimicrobials for patients with
non-typhoid salmonellosis is not recommended. (Guerrant et al., 2001;
Dupont, 1997; Dupont, 1994) (**Grade A, Level Ib**)

**C** - Certain patients with intestinal salmonellosis should be treated
-- those who have fever and systemic toxicity, those with dysentery, the
elderly, and patients who are immunocompromised or immunosuppressed.
(Dupont, 1997) (**Grade C, Level IV**)

**B** - Certain patients with proven *Campylobacter* infection should be
treated with antibiotics -- those who are immunocompromised, the
elderly, and healthy patients with moderate to severe dysentery or with
evidence suggestive of bacteraemia. (Guerrant et al., 2001; Dupont,
1997; Dupont, 1994) (**Grade B, Level IIa**)

**A** - Patients with enterotoxigenic *Escherichia coli* infections
should be treated with antibiotics. (Dupont, 1997; Dupont, 1994;
Petruccelli et al., 1992; Chak & Banwell, 1993) (**Grade A, Level Ib**)

**A** - Patients with suspected or proven entero-haemorrhagic
*Escherichia coli* (EHEC) infection, especially with *Escherichia coli*
O157:H7, should not be given antibiotics. (**Grade A, Level Ib**)
(Cimolai et al., 1990; Boyce, Swerdlow, & Griffin, 1995)

**A** - All patients with proven *Vibrio cholera* infection should be
treated with antibiotics. (Khan et al., 1996; Moolasart, Eampokalap, &
Supaswadikul, 1998) (**Grade A, Level Ib**)

**B** - Patients with mild *Clostridium difficile* infection can be
treated symptomatically and with withdrawal of the offending antibiotic.
(Fekety, 1997; Teasley et al., 1983) (**Grade B, Level IIa**)

**A** - Patients with moderate to severe Clostridium disease warrant
prompt antibiotic treatment, with either oral metronidazole or
vancomycin. (Fekety, 1997; Teasley, et al., 1983; Jobe et al., 1995)
(**Grade A, Level Ib**)

**Use of Antibiotics in Urinary Tract Infection (UTI)**

**B** - It is not necessary to perform urine cultures in the management
of uncomplicated cystitis in women. However, for the remainder of
patients, pre-treatment cultures should be performed.  (\"Managing
urinary tract infection in women,\" 1998; Urinary Tract Infection
Guideline Team, 1999; O\'Connor et al., 1996; Saint et al., 1999)
(**Grade B, Level IIb**)

**Management of Uncomplicated UTIs**

**A** - Antibiotic therapy is not recommended in the management of
patients with asymptomatic bacteriuria, except in pregnant women.
(Abrutyn et al., 1994; Harding et al., 2002; Smaill, 2003) (**Grade A,
Level Ib**)

**A** - The recommended 1^st^ line therapy for uncomplicated cystitis in
women is a 3-day course of trimethoprim-sulfamethoxazole. (Hooton et
al., 1995) (**Grade A, Level Ib**)

**A** - Alternative treatment options for uncomplicated cystitis in
women include the use of:

-   Nitrofurantoin

-   Fluoroquinolones

-   1^st^ and 2^nd^-generation cephalosporins

-   Trimethoprim

-   Beta-lactam-lactamase-inhibitor combinations

(Hooton et al., 1995; Warren et al., 1999; Trienekens et al., 1989; Fihn
et al., 1988; Christiaens et al., 2002; Iravani et al., 1995; McCarty et
al., 1999; Saginur & Nicolle, 1992; Gupta & Stamm, 2002) (**Grade A,
Level Ib**)

**A** - The recommended duration of treatment of uncomplicated cystitis
for various agents in women is:

-   For 3 days with fluoroquinolones

Or

-   For 7 Days, with nitrofurantoin, 1^st^ and 2^nd^-generation
    cephalosporins, trimethoprim or beta- lactam-lactamase inhibitor
    combinations. (Hooton et al., 1995; Warren et al., 1999; Trienekens
    et al., 1989; Christiaens et al., 2002; Iravani et al., 1995;
    McCarty et al., 1999; Gupta & Stamm, 2002; Iravani et al., 1999)
    (**Grade A, Level Ia**)

**A** - Single-dose regimens are not recommended for routine use in the
treatment of cystitis in women, as these regimens are less effective
than multi-day regimens. (Fihn et al., 1988; Saginur & Nicolle, 1992;
Gupta & Stamm, 2002; Leibovici & Wysenbeek, 1991) (**Grade A, Level
Ia**)

**A** - Women with recurrent UTI should be treated with low dose
antibiotic prophylaxis,using nitrofurantoin,
trimethoprim-sulfamethoxazole, trimethoprim or cephalosporins. (Brumfitt
& Hamilton-Miller, 1990; Stapleton & Stamm, 1997; Pfau & Sacks, 1989;
Brumfitt et al., 1992; Vahlensieck & Westenfelder, 1992; Brumfitt &
Hamilton- Miller, 1998; Nicolle et al., 1989; Stapleton et al., 1990)
(**Grade A, Level Ib**)

**C** - Initial therapy with intravenous cephalosporin and
aminoglycoside, as for severe pyelonephritis, is recommended for the
treatment of severe acute prostatitis. (National guideline for the
management of prostatitis, 1999) (**Grade C, Level IV**)

**C** - Following clinical improvement, severe acute prostatitis should
be treated with antibiotics, based on sensitivities, for a total
duration of 4 weeks. (National guideline for the management of
prostatitis, 1999) (**Grade C, Level IV**)

**C** - For patients with acute prostatitis of mild to moderate
severity, initial therapy with oral fluoroquinolones,
trimethoprim-sulfamethoxazole or trimethoprim is recommended. Treatment
with antibiotics based on sensitivities should be given for a total
duration of 4 weeks. (National guideline for the management of
prostatitis, 1999) (**Grade C, Level IV**)

**A** - The recommended treatment for chronic bacterial prostatitis is
fluoroquinolones for 4 weeks. (Bundrick et al., 2003) (**Grade A, Level
Ib**)

**B** - Trimethoprim-sulfamethoxazole for 12 weeks can also be used in
the treatment for chronic bacterial prostatitis. (Lipsky, 1999; Fowler,
2002) (**Grade B, Level III**)

**C** - For patients with recurrent chronic prostatitis, suppressive,
low-dose therapy with trimethoprim-sulfamethoxazole, trimethoprim or
nitrofurantoin can be administered for 6 months or longer. (Fowler,
2002) (**Grade C, Level IV**)

**A** - Antibiotic therapy is not indicated in the treatment of chronic
prostatitis/chronic pelvic pain syndrome. (Alexander et al., 2004)
(**Grade A, Level Ib**)

**GPP** - Patients with symptoms of chronic prostatitis, but with
negative urine or prostatic fluid cultures, should be referred to a
urologist for further management. (**GPP**)

*Pyelonephritis*

**A** - Treatment options for severe acute pyelonephritis include:
parenteral 3^rd^-generation cephalosporins, aminoglycosides,
fluoroquinolones, beta-lactams or beta-lactam-beta-lactamase-inhibitor
combinations. Antibiotics should be modified when urine culture results
become available. Oral antibiotic therapy can be started following
clinical improvement, with a treatment course of 14 days. (Jimenez-Crus
et al., 2002; Sanchez et al., 2002; Talan et al., 2000) (**Grade A,
Level Ib**)

**GPP** - Initial treatment with intravenous aminoglycoside, together
with a 1^st^ or 2^nd^-generation cephalosporin, is recommended for
hospitalized patients with acute pyelonephritis, because of the low
sensitivity of hospital-acquired Escherichia coli to ceftriaxone and
ciprofloxacin in the local context. (**GPP**)

**A** - Treatment options for mild acute pyelonephritis include: oral
fluoroquinolones, trimethoprim-sulfamethoxazole, beta-lactams or
beta-lactam-beta-lactamase-inhibitor combinations. Antibiotics should be
modified when results of urine culture become available. (Jimenez-Crus
et al., 2002; Sanchez et al., 2002; Talan et al., 2000; Bergeron, 1995)
(**Grade A, Level Ib**)

*UTI in Pregnancy*

**A** - Asymptomatic bacteriuria in pregnancy should be treated with
antibiotics, based on culture and sensitivity, to reduce the risk of
pyelonephritis and other complications. (Smaill, 2003; Romero et al.,
1989; Patterson & Andriole, 1997) (**Grade A, Level Ia**)

**B** - For acute cystitis in pregnancy, empirical therapy with 1^st^ or
2^nd^-generation cephalosporins, nitrofurantoin or
trimethoprim-sulfamethoxazole (caution in 3^rd^ trimester) is
recommended. Treatment should be modified based on culture results and
appropriate antibiotics should be administered for 7 days. (Bergeron,
1995) (**Grade B, Level III**)

**B** - For pyelonephritis in pregnancy, empirical therapy with a
3^rd^-generation cephalosporin is recommended. Treatment should be
modified based on culture results and appropriate antibiotics should be
administered for 14 days. (Bergeron, 1995) (**Grade B, Level III**)

**Management of Complicated UTIs**

**C** - Antibiotic treatment of complicated urinary tract infections
should be based on cultures and sensitivity. When symptoms warrant
initiation of empirical therapy, cultures must be obtained prior to
antibiotic therapy and therapy modified based on results. (Ronald &
Harding, 1997; Nicolle, 1997; Smyth & O\'Connell, 1998; Patterson &
Andriole, 1997) (**Grade C, Level IV**)

**C** -For ill, hospitalized patients with complicated urinary tract
infections, empirical treatment with intravenous 3^rd^-generation
cephalosporins, fluoroquinolones, beta-lactams or
beta-lactam-beta-lactamase-inhibitor combinations is recommended. An
alternative regimen using intravenous ampicillin together with an
aminoglycoside is also effective. (Stamm & Hooton, 1993; Smyth &
O\'Connell, 1998) (**Grade C, Level IV**)

**A** - For complicated urinary tract infections of mild to moderate
severity, initial therapy with oral fluoroquinolones or
trimethoprim-sulfamethoxazole is recommended. (Gottlieb, 1995) (**Grade
A, Level Ib**)

**C** - For complicated urinary tract infections of mild to moderate
severity, alternative regimens for empirical treatment include
2^nd^-generation cephalosporins, beta-lactams, or
beta-lactam-beta-lactamase-inhibitor combinations. (Stamm & Hooton,
1993; Smyth & O\'Connell, 1998) (**Grade C, Level IV**)

**GPP** - After the initiation of empirical antibiotic therapy,
culture-based appropriate therapy is administered for 14 days as a
minimum. (**GPP**)

**GPP** - Symptomatic UTIs occurring in patients with a short-term
indwelling urinary catheter should be treated by removing the catheter,
followed by a 7-day course of antibiotics. For patients with long-term
indwelling urinary catheters, symptomatic UTIs can be treated with a
7-day course of antibiotics. (**GPP**)

**GPP** - In patients with renal impairment, effective antibiotics
therapy requires the use of antibiotics which achieve therapeutic
concentrations in the urine and are appropriately dose-adjusted for the
level of renal failure. (**GPP**)

**Use of Antibiotics in Acute Bacterial Meningitis in Immunocompetent
Adults**

**Diagnosis of Acute Bacterial Meningitis**

**C** - Initial physical examination should include evaluation for:

-   level of consciousness

-   cranial nerve palsies

-   focal deficits

-   meningismus

-   increased intracranial pressure

-   critical trauma

(Griffin, 1998) (**Grade C, Level IV**)

**B** - A lumbar puncture is recommended in all adult patients with
suspected meningitis except when a clear contradiction exists.
(\"Bacterial meningitis,\" 1995; McCarron, Chaudhuri, & Todd, 1996)
(**Grade B, Level III**)

**Antibiotic Therapy**

**C** - If bacterial meningitis is suspected, antibiotic treatment must
be started immediately, regardless of any investigations undertaken.
(Begg et al., 1999; Aronin, Peduzzi, & Quagliarello, 1998) (**Grade C,
Level IV**)

**B** - In the treatment of meningitis with a typical meningococcal
rash, intravenous penicillin G, 20 to 24 million units daily, should be
given. (Tunkel, Wispelwey, & Scheld, 1990; Radetsky, 1992) (**Grade B,
Level III**)

**B** - For adults without a typical meningococcal rash, intravenous
ceftriaxone, 2 g 12 hourly, should be given. (Begg et al., 1999)
(**Grade B, Level III**)

**C** - If the patient comes from an area where penicillin-resistant
*Streptococcus pneumoniae* are common (minimum inhibitory concentration
\[MIC\] [\>]{.underline}0.1micrograms/ml) then add intravenous
vancomycin 1 g 12 hourly. (Begg et al., 1999) (**Grade C, Level IV**)

**C** & **GPP** - For adults over the age of 50 years with a history of
alcoholism, diabetes or pregnancy without a typical meningococcal rash,
consider adding intravenous ampicillin, 2 g 4 hourly, to ceftriaxone as
above. (Begg et al., 1999) (**Grade C, Level IV** & **GPP**)

**C** - If there is a clear history of anaphylaxis to beta-lactams, give
intravenous chloramphenicol 25 mg/kg (maximum 1 g) 6 hourly. Add
vancomycin, 1 g 12 hourly, because of the possibility of
penicillin-resistant *Streptococcus pneumoniae* and likely failure of
chloramphenicol in this group. (Begg et al., 1999) (**Grade C, Level
IV**)

**B** - If Gram-negative diplococci are visible on Gram stain of
cerebrospinal fluid (CSF), or if *Neisseria meningitidis* is isolated
from CSF or blood, continue with intravenous penicillin G, 24 million
units daily. (van Deuren, Brandtzaeg, & van d Meer, 2000; Rosenstein et
al., 2001) (**Grade B, Level III**)

**C** - For patients who do not have adequate response to penicillin,
the treatment should be changed to ceftriaxone. (Quagliarello & Scheld,
1997) (**Grade C, Level IV**)

**C** - If penicillin-sensitive *Streptococcus pneumoniae* is isolated
from CSF or blood, intravenous penicillin G 24 million units is
recommended. If cephalosporin-sensitive *Streptococcus pneumoniae* is
isolated, intravenous ceftriaxone 2 g 12 hourly should be given. Add on
intravenous vancomycin, 1 g 12 hourly, if penicillin-resistant and
cephalosporin-resistant *Streptococcus pneumoniae* is isolated from
blood or CSF. Continue intravenous therapy for 10-14 days. (Quagliarello
& Scheld, 1997; Kaplan & Manson, 1998) (**Grade C, Level IV**)

**B** - For *Haemophilus influenzae* meningitis, intravenous
ceftriaxone, 2 g 12 hourly, is recommended. (Tunkel, Wispelwey, &
Scheld, 1990) (**Grade B, Level IIb**)

**C** - If Gram-positive coccobacilli suggestive of *Listeria*
monocytogenes is visible on Gram stain of CSF, or if *Listeria
monocytogenes* is isolated from blood or CSF, intravenous ampicillin, 2
g 4 hourly, and gentamicin 5 mg/kg 24 hourly (single or divided 8 hourly
doses) for more than 21 days is recommended. (Tunkel, Wispelwey, &
Scheld, 1990; Quagliarello & Scheld, 1997) (**Grade C, Level IV**)

Table: Recommended duration of therapy according to the type of pathogen
causing meningitis

  ------------------------------------------------------------------------
  **Pathogen**              **Recommended Duration of       **Grade and
                            Therapy**                       Level of
                                                            Evidence**
  ------------------------- ------------------------------- --------------
  *Haemophilus influenzae*  7-10 days (Tunkel, Wispelwey, & **Grade B,
                            Scheld, 1990; Quagliarello &    Level IIb**
                            Scheld, 1997)                   

  *Neisseria meningitidis*  7-10 days (van Deuren,          **Grade B,
                            Brandtzaeg, & van d Meer, 2000) Level III**

  *Streptococcus            10-14 days (Tunkel et al.,      **Grade C,
  pneumoniae*               2004)                           Level IV**

  *Listeria monocytogenes*  [\>]{.underline}21 days (Tunkel **Grade C,
                            et al., 2004)                   Level IV**

  Gram-negative bacilli,    21 days (Tunkel et al., 2004)   **Grade C,
  other than *Haemophilus                                   Level IV**
  influenzae*                                               
  ------------------------------------------------------------------------

**C** - The duration of therapy should be tailored to the individual
patient on the basis of the clinical and microbiological response.
(Radetsly, 1990; O\'Neill, 1993) (**Grade C, Level IV**)

**Adjunctive Dexamethasone Therapy in Bacterial Meningitis**

**A** - In adults with suspected or proven pneumococcal meningitis,
dexamethasone 10 mg 6 hourly should be given for 4 days with the first
dose administered 15-20 min before, or at least concomitant with, the
first dose of antimicrobial therapy. (de Gans & van de Beek, 2002)
(**Grade A, Level Ib**)

**A** - Dexamethasone should only be continued if the CSF Gram stain
reveals Gram-positive diplococci or if blood or CSF cultures are
positive for *Streptococcus pneumoniae*. (de Gans & van de Beek, 2002)
(**Grade A, Level Ib**)

**A** - Adjunctive dexamethasone should not be given to adult patients
who have already received antimicrobial therapy as in this circumstance,
dexamethasone is unlikely to improve patient outcome. (de Gans & van de
Beek, 2002) (**Grade A, Level Ib**)

**Prevention of Meningococcal Meningitis**

**C** - Chemoprophylaxis should be offered to close contacts of cases,
irrespective of vaccination status, in those who have:

-   Prolonged close contact with the case in a household setting during
    the seven days before onset of illness.

-   Contact at a child-care centre.

-   Transient close contact with a case where there was exposure to the
    patient\'s secretions (e.g. through kissing, mouth-to-mouth
    resuscitation, endotracheal intubation or endotracheal tube
    management) around the time of admission to hospital.

(\"Control and prevention of serogroup C meningococcal disease:
evaluation and management of suspected outbreaks: recommendations of the
Advisory Committee on Immunization Practices \[ACIP\]\", 1997; Bilukha &
Rosenstein, 2005) (**Grade C, Level IV**)

**C** - Close contacts of patients with meningococcal infection should
receive one of the following regimens:

-   Rifampicin:

> Adults: 600 mg, 12 hourly for 2 days (4 doses).
>
> Children (1-6 years): 10 mg/kg, 12 hourly for 2 days (4 doses).
>
> Children (3-11 months): 5 mg/kg 12 hourly for 2 days (4 doses).

-   Ciprofloxacin:

> Adults: 500 mg as a single dose.
>
> Children: Use of ciprofloxacin is not recommended.

-   Ceftriaxone:

> Adults: 250 mg as a single intramuscular dose.
>
> Children (\<15 years): 125 mg as a single intramuscular dose.

(Bilukha & Rosenstein, 2005; Dworzack et al., 1988; Schwartz et al.,
1988) (**Grade C, Level IV**)

**C** - If other antibiotics have been used for treatment, the index
patient should receive prophylactic antibiotics for eradication of
nasopharyngeal carriage before being discharged from hospital. (Abramson
& Spika, 1985) (**Grade C, Level IV**)

**Use of Antibiotics in the Elderly**

**Unique Aspects of Infections in Older People**

**B** - An infectious aetiology should be sought when there is:

-   A change in functional status and the oral temperature is
    [\>]{.underline}37.2 degrees C, or

-   An increase in temperature of ≥1.3 degrees C over the baseline.

(Norman, 2000) (**Grade B, Level III**)

**C** - Infection should be considered in the differential diagnosis of
older people who present, within a short period of time:

-   With only non-specific symptoms, including functional decline; or

-   With atypical complaints.

(Yoshikawa, 1994) (**Grade C, Level IV**)

**C** - Doctors should be alert to a leucocytosis with left shift or
left shift alone, as these have good predictive value for diagnosing
bacterial infections in older people.

(Keating et al., 1984) (**Grade C, Level IV**)

**Treatment Recommendations**

**C** - Empirical antibiotic therapy for specific infections is a valid
and practical option in older persons, given the higher risk of adverse
outcomes, diverse infectious causes and increased difficulty in
obtaining diagnostic specimens. In general, this therapy should include
a broad-spectrum beta-lactam antibiotic. (**Grade C, Level IV**)

**C** - When culture results are not available yet, the choice of
antibiotic should be guided by knowledge of the likely pathogens
encountered in older people in different settings. (**Grade C, Level
IV**)

**C** - Aminoglycosides should be reserved for selected situations:
septic shock without a specific aetiological diagnosis, confirmed or
suspected *Pseudomonas aeruginosa* infections, or where the cultured
organism is only susceptible to an aminoglycoside. (**Grade C, Level
IV**)

**C** - The patient\'s renal function should always be considered when
prescribing antibiotics in older people, particularly if the antibiotics
are excreted primarily by the kidneys (e.g. aminoglycosides,
fluoroquinolones, and some cephalosporins such as ceftazidime).
Estimated creatinine clearance should be used to guide appropriate
dosing of such antibiotics. (Rajagopalan & Yoshikawa, 2001) (**Grade C,
Level IV**)

**C** - There should be monitoring for adverse effects of antibiotics
during therapy. In addition to specific adverse effects, geriatric
syndromes or functional decline should also be considered as possible
adverse effects of antibiotics. (**Grade C, Level IV**)

**Additional Antibiotic Consideration in the Elderly**

**GPP** - Awareness of potential drug-drug interactions should guide the
choice of antibiotics. (**GPP**)

**C** - Assistance from caregivers who can help administer medications
should be sought where necessary. Keeping the antibiotic regimen as
simple as possible is also useful in improving compliance. (Stalam &
Kaye, 2004) (**Grade C, Level IV**)

**Special Situations in the Elderly**

**C** - The choice of antibiotic is usually guided by the likely
spectrum of bacterial flora that might be encountered. Broad-spectrum
antibiotics that include Gram-negative cover are usually required. For
pneumonia in the setting of long-term care institutions, antibiotic
cover for anaerobes (e.g. amoxicillin-clavulanate) should be considered
if aspiration is a concern. (Torres et al., 1999)

(**Grade C, Level IV**)

The following measures to prevent aspiration are recommended:

**C** - Reduce the risk of aspiration by:

-   Avoiding sedative medication

-   Minimising the use of nasogastric tubes

-   Elevating the head of bed during and after feeding

(Cantrell & Norman, 1998; Finegold, 1995) (**Grade C, Level IV**)

**C** - Timely assessment of swallowing, at the bedside or by a speech
therapist, can be useful in guiding any modification of feeding (e.g.
consistency of fluids). (Cantrell & Norman, 1998)  (**Grade C, Level
IV**)

**C** - There should be proper treatment of periodontal disease and
gingivitis. (Finegold, 1995)

(**Grade C, Level IV**)

**C** - In treating aspiration pneumonia, use antibiotics that include
broad-spectrum ones with anaerobic cover (such as
amoxicillin-clavulanate), or the combination of a fluoroquinolone with
either metronidazole or clindamycin. (Leroy et al., 1997) (**Grade C,
Level IV**)

**C** - Patients with asymptomatic bacteriuria while on intermittent
catheterisation should not be treated with antibiotics. (Stalam & Kaye,
2000) The exception is the presence of possible \"atypical
presentation\" of infection. (**Grade C, Level IV**)

**C** - Systemic antibiotics should be used with more serious pressure
ulcer infections, including those with spreading cellulitis,
osteomyelitis and bacteraemia. (Livesley & Chow, 2002) (**Grade C, Level
IV**)

**C** - Empirical antibiotics that are effective against Gram-positive
and Gram-negative organisms as well as anaerobic organisms are needed.
Monotherapy with piperacillin-tazobactum or a carbapenem, or combination
therapy employing ciprofloxacin with either metronidazole or clindamycin
are useful options. (Stalam & Kaye, 2000; Livesley & Chow, 2002) As
tissue perfusion is usually poor in infected ulcers, intravenous
antibiotic therapy should be administered initially.  (Livesley & Chow,
2002) (**Grade C, Level IV**)

**Definitions**:

**Grades of Recommendations**

**Grade A** (evidence levels Ia, Ib): Requires at least one randomised
controlled trial as part of the body of literature of overall good
quality and consistency addressing the specific recommendation.

**Grade B** (evidence levels IIa, IIb, III): Requires availability of
well conducted clinical studies but no randomised clinical trials on the
topic of recommendation.

**Grade C** (evidence level IV): Requires evidence obtained from expert
committee reports or opinions and/or clinical experiences of respected
authorities. Indicates absence of directly applicable clinical studies
of good quality.

**GPP** (good practice points): Recommended best practice based on the
clinical experience of the guideline development group.

**Levels of Evidence**

**Level Ia**: Evidence obtained from meta-analysis of randomised
controlled trials

**Level Ib**: Evidence obtained from at least one randomised controlled
trial

**Level IIa**: Evidence obtained from at least one well-designed
controlled study without randomisation

**Level IIb**: Evidence obtained from at least one other type of
well-designed quasi-experimental study

**Level III**: Evidence obtained from well-designed nonexperimental
descriptive studies, such as comparative studies, correlation studies
and case studies

**Level IV**: Evidence obtained from expert committee reports or
opinions and/or clinical experiences of respected authorities

#### CLINICAL ALGORITHM(S)

Clinical algorithms are provided in the original guideline document for:

-   Risk-Stratification Approach to Antibacterial Therapy of Acute
    Exacerbation of Chronic Bronchitis

-   Management of Community Acquired Pneumonia

-   Management of Acute Diarrhoea

-   Approach to Management of Urinary Tract Infections in Adults

-   Initial Management of a Patient with Acute Meningitis

### EVIDENCE SUPPORTING THE RECOMMENDATIONS

#### REFERENCES SUPPORTING THE RECOMMENDATIONS

[References open in a new
window](http://www.guideline.gov/summary/select_ref.aspx?doc_id=9120)

#### TYPE OF EVIDENCE SUPPORTING THE RECOMMENDATIONS

The type of supporting evidence is identified and graded for each
recommendation (see \"Major Recommendations\")

### BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS

#### POTENTIAL BENEFITS

Appropriate use of antibiotics and appropriate treatment of patients

#### POTENTIAL HARMS

-   Local treatment with antimicrobial eardrops should generally be
    avoided in acute otitis media as there is a possibility of ototoxic
    adverse effects. They also contribute to the development of
    antibiotic resistance.

-   Adverse effects of antibiotic therapy, including drug-drug
    interactions. These effects are most problematic in the elderly who
    are taking multiple medications.

### CONTRAINDICATIONS

#### CONTRAINDICATIONS

-   Contradictions to lumbar puncture include presence of signs of
    raised intracranial pressure or focal neurological signs unless
    there is a normal brain computerised tomographic (CT) scan. Other
    contradictions include severe shock, severely depressed or
    fluctuating consciousness level or coagulation disorder.

-   Anti-motility agents (e.g., loperamide) should not be given to
    patients who have febrile dysentery, patients with suspected
    Escherichia coli 0157:H7 infection, or to patients under 2 years of
    age

-   Sulphonamides should be avoided in the third semester of pregnancy.

-   Fluoroquinolones are best avoided in pregnancy.

-   Gentamicin is best avoided in patients with underlying renal
    disease.

### QUALIFYING STATEMENTS

#### QUALIFYING STATEMENTS

-   These guidelines are not intended to serve as a standard of medical
    care. Standards of medical care are determined on the basis of all
    clinical data available for an individual case and are subject to
    change as scientific knowledge advances and patterns of care evolve.

-   The contents of this publication are guidelines to clinical
    practice, based on the best available evidence at the time of
    development. Adherence to these guidelines may not ensure a
    successful outcome in every case. These guidelines should neither be
    construed as including all proper methods of care, nor exclude other
    acceptable methods of care. Each physician is ultimately responsible
    for the management of his/her unique patient in the light of the
    clinical data presented by the patient and the diagnostic and
    treatment options available.

### IMPLEMENTATION OF THE GUIDELINE

#### DESCRIPTION OF IMPLEMENTATION STRATEGY

The following indicators for community acquired pneumonia are proposed:

-   Antibiotic timing: percentage of pneumonia patients who received
    first dose of antibiotics within 4 hours after hospital arrival

-   Initial antibiotic consistent with current recommendations

#### IMPLEMENTATION TOOLS

Audit Criteria/Indicators\
Clinical Algorithm\
Personal Digital Assistant (PDA) Downloads\
Quick Reference Guides/Physician Guides\
Slide Presentation\
Staff Training/Competency Material

For information about
[availability](#identifying-information-and-availability), see the
\"Availability of Companion Documents\" and \"Patient Resources\" fields
below.

### INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT CATEGORIES

#### IOM CARE NEED

Getting Better

#### IOM DOMAIN

Effectiveness

### IDENTIFYING INFORMATION AND AVAILABILITY

#### BIBLIOGRAPHIC SOURCE(S)

Singapore Ministry of Health. Use of antibiotics in adults. Singapore:
Singapore Ministry of Health; 2006 Feb. 180 p. \[320 references\]

#### ADAPTATION

Not applicable: The guideline was not adapted from another source.

#### DATE RELEASED

2006 Feb

#### GUIDELINE DEVELOPER(S)

Singapore Ministry of Health - National Government Agency \[Non-U.S.\]

#### SOURCE(S) OF FUNDING

Singapore Ministry of Health

#### GUIDELINE COMMITTEE

Workgroup on Use of Antibiotics in Adults

#### COMPOSITION OF GROUP THAT AUTHORED THE GUIDELINE

*Workgroup Members*: Dr Oh Helen, Senior Consultant, Medicine Dept,
Changi General Hospital (*Chairperson*); A/Prof Ananthraman Vathsala,
Senior Consultant, Dept of Renal Medicine, Singapore General Hospital;
A/Prof Goh Lee Gan, Dept of Community, Occupational & Family Medicine,
National University of Singapore; Dr Fatimah A Lateef, Consultant, Dept
of Emergency Medicine, Singapore General Hospital; Dr Leong Hoe Nam,
Registrar, Dept of Internal Medicine, Singapore General Hospital; Dr
Ling Moi Lin, Director & Senior Consultant, Dept of Quality Management,
Singapore General Hospital; Dr Ding Yew Yoong, Head, Senior Consultant
of Geriatric Medicine, Tan Tock Seng Hospital; Prof Lim Tow Keang,
Senior Consultant, Medicine Dept, National University Hospital; Dr Ee
Guan Liang, Adrian, Director, Clinical Services, SingHealth Polyclinics;
Dr Chong Siong Eng, Roland, Roland Chong Gastroenterology & Medical
Clinic Pte Ltd; Dr Koh Tse Hsien, Consultant, Dept of Pathology,
Singapore General Hospital; Dr Hia Kwee Yang, HIA Clinic; Mr Ian Wee,
Senior Pharmacist, Changi General Hospital

#### FINANCIAL DISCLOSURES/CONFLICTS OF INTEREST

Not stated

#### GUIDELINE STATUS

This is the current release of the guideline.

#### GUIDELINE AVAILABILITY

Electronic copies: Available in Portable Document Format (PDF) from the
[Singapore Ministry of Health Web
site](http://www.moh.gov.sg/mohcorp/publications.aspx?id=16428).

Print copies: Available from the Singapore Ministry of Health, College
of Medicine Building, Mezzanine Floor 16 College Rd, Singapore 169854.

#### AVAILABILITY OF COMPANION DOCUMENTS

The following is available:

-   Use of antibiotics in adults, slides & speeches. Mar 2006. Available
    from the [Singapore Ministry of Health Web
    site](http://www.hpp.moh.gov.sg/HPP/1164169557195.html).

The following is also available:

-   Audit criteria and a continuing medical education (CME) self
    assessment are available in the [original guideline
    document](http://www.hpp.moh.gov.sg/HPP/1130910778681.html).

-   The full text guideline and summary card are available for PDA
    download in ISilo and MSReader formats from the [Singapore Ministry
    of Health Web
    site](http://www.moh.gov.sg/mohcorp/publications.aspx?id=16428).

#### PATIENT RESOURCES

None available

#### NGC STATUS

This NGC summary was completed by ECRI on July 25, 2006. This summary
was updated by ECRI Institute on October 3, 2007 following the U.S. Food
and Drug Administration (FDA) advisory on Rocephin (ceftriaxone sodium).
This summary was updated by ECRI Institute on July 28, 2008 following
the U.S. Food and Drug Administration advisory on fluoroquinolone
antimicrobial drugs.

#### COPYRIGHT STATEMENT

This NGC summary is based on the original guideline, which is subject to
the guideline developer\'s copyright restrictions. Please contact the
Ministry of Health, Singapore by e-mail at <MOH_INFO@MOH.GOV.SG>.

### DISCLAIMER

#### NGC DISCLAIMER

The National Guideline Clearinghouse™ (NGC) does not develop, produce,
approve, or endorse the guidelines represented on this site.

All guidelines summarized by NGC and hosted on our site are produced
under the auspices of medical specialty societies, relevant professional
associations, public or private organizations, other government
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Guidelines represented on the NGC Web site are submitted by guideline
developers, and are screened solely to determine that they meet the NGC
Inclusion Criteria which may be found at
<http://www.guideline.gov/about/inclusion.aspx> .

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Date Modified: 11/10/2008