RATIONAL USE OF ANTIBIOTICS

EXPERT COMMITTEE ON RATIONAL USE OF ANTIBIOTICS

Chairman: V K E Lim
Members: O P Foo, R Jalleh, P Kandasami, E L Lee, J Mohan, T S Ng, S Rahman, T Essau

Contents

1. GENERAL PRINCIPLES IN THE USE OF ANTIBIOTIC
   Introduction
   Monitoring efficacy

2. ANTIBIOTICS GUIDELINES 1996
   2.1 Guidelines on antibiotic therapy

Table 1.    Respiratory Infections
Table 2.    Urinary Tract Infections
Table 3.    Skin and Soft Tissue Infections
Table 4.    Musculosketel Infections
Table 5.    Gastrointestinal Infections
Table 6.    Genitourinary Infections (Including Sexually Transmitted Diseases)
Table 7.    Central Nervous System Infections
Table 8.    Cardiovascular Infections
Table 9.    Bacteraemia And Septicaemia
Table 10.  Other Infections
Table 11.  Infections Associated With Pregnancy
Table 12.  Chemoprophylaxis For Selected Medical Condition

3. SURGICAL CHEMOPROPHYLAXIS

4. GUIDELINES FOR SURGICAL ANTIBIOTIC PROPHYLAXIS

• Gynaecologic Surgery
• General Surgery
• Vascular Surgery
• Cardiac Surgery
• Thoracic Surgery
• Orthopaedic Surgery
• ENT Surgery
• Neurosurgery
• Urological surgery
• Endoscopic procedures

5. ANTIBIOTIC DOSAGES FOR ADULTS

6. ANTIBIOTIC DOSAGES FOR NEONATES WITH SERIOUS INFECTIONS

7. ANTIBIOTIC DOSAGES OF ORAL ANTIBIOTICS FOR NEONATES

8. PARENTERAL ANTIBIOTIC DOSAGES FOR SERIOUS INFECTIONS IN INFANTS AND CHILDREN

9. ANTIBIOTIC DOSAGES OF ORAL ANTIBIOTICS FOR INFANTS AND CHILDREN

10. References

GENERAL PRINCIPLES IN THE USE OF ANTIBIOTICS

Introduction

Antibiotics are one of the most commonly prescribed drugs today. Rational use of antibiotics is extremely important as injudicious use can adversely affect the patient, cause emergence of antibiotic resistance and increase the cost of health care. Prescribing an antibiotic comprises several phases:

i) perception of need - is an antibiotic necessary ?
ii) choice of antibiotic - what is the most appropriate antibiotic ?
iii) choice of regimen : what dose, route, frequency and duration are needed ?
iv) monitoring efficacy : is the treatment effective ?

Is an antibiotic necessary?

Antibiotics are generally only useful for the treatment of bacterial infections. It is important to remember that not all fevers are due to infections and not all infections are caused by bacteria. The majority of infections seen in general practice are of viral origin and antibiotics can neither treat viral infections nor prevent secondary bacterial infections in these patients. Even where a bacterial aetiology is established, an antibiotic may not be always necessary. Many bacterial infections resolve spontaneously. Minor superficial skin infections may be more suitably treated with a local antiseptic. Collections of pus should be drained surgically and if drainage is adequate, antibiotics are often not required.
 
Choice of an antibiotic
The successful outcome of therapy would depend very much on the choice of the antibacterial agent. In the process of selecting an antibiotic, three main factors need to be considered; the aetiological agent, the patient and the antibiotic.
 
The aetiological agent
Determination of the aetiological agent depends on a combination of clinical acumen and laboratory support. In many instances an antibiotic prescription has to be made based on the clinical diagnosis (empirical therapy). Even where a bacteriology report is available it is necessary to interpret the report. Bacterial isolates from culture specimens may represent normal flora, colonisers or contaminants rather than true pathogens. Sensitivity results when available are at best only a guide to treatment. Laboratory reports should always be viewed in the light of clinical findings.
 
The patient
Several patient factors have to be considered in selecting an antibiotic. Age is an important factor. The very young and the very old tend to be more prone to the adverse effects of the antibiotics. Neonates have immature liver and renal functions which affect their ability to metabolise or excrete antibiotics. Antibiotics and their metabolites may adversely affect growing tissues and organs in children. Elderly patients are more likely to suffer from nephrotoxicity and allergic reactions. Dosage modifications would also have to be made in those patients with hepatic or renal impairment. Antibiotics can also give rise to severe toxic reactions in patients with certain genetic abnormalities eg sulphonamides in patients with glucose-6-phosphate dehydrogenase deficiency. Antibiotics should as far as possible be avoided in pregnancy and when it is necessary to use an antibiotic, betalactam antibiotics and erythromycin are probably the safest. A history of allergy to antibiotics should always be sought before administration. Routine intradermal test doses for penicillin allergy is of little value and may even be dangerous. If in doubt avoid betalactams and use a macrolide or tetracycline (in adults) instead. In serious infections like meningitis and bacteraemic shock the immediate institution of the best available antibiotic for the suspected pathogen(s) is imperative as delay in treatment will increase both mortality and morbidity. In less serious situations such as otitis media where spontaneous recovery is common, an antibiotic that covers for the predominant organisms is adequate.
 
The antibiotic
The clinician should have adequate knowledge of the pharmacokinetic properties of the antibiotic he uses. Antibiotics vary in their ability to be absorbed orally or to cross the blood brain barrier and these factors will affect their routes of administration. The ability of the antibiotic to achieve therapeutic concentrations at the site of infection is another important consideration thus antibiotics used for treating urinary infections should ideally be concentrated in urine. Some antibiotics have very severe toxic effects and are best avoided in certain conditions. The doctor should also be aware of drug-drug interactions since many antibiotics can interact with other non-antibiotic drugs. Finally the cost of the antibiotic is also of major concern. In calculating costs it is perhaps more reasonable to take into account the total cost of treatment rather than just the actual cost of antibiotic per dose. The route of administration, the necessity for monitoring antibiotic levels and the patient's length of stay in hospital can affect the cost of treatment as well. The patient's compliance to medication is an important factor for consideration in the choice of antibiotics.
 
Choice of regimen
Parenteral or oral
Whether the route of administration should be oral or parenteral would depend on whether the patient is able to take oral treatment reliably. In cases of severe sepsis where rigors, hyperthermia/hypothermia, tachycardia and hypotension are present, intravenous therapy should be instituted. When in doubt it would be safer to commence intravenous treatment and review the treatment daily.
 
Duration of treatment
Except for a few conditions, the optimum duration of antibiotic treatment is unknown. Many antibiotics are often presribed for a duration of 5-7 days. Nevertheless it is reasonable to discontinue therapy even after a shorter period if the patient's symptoms have resolved. There are however certain infections where prolonged treatment is necessary (Table I). In some conditions eg uncomplicated cystitis in women and gonococcal urethritis in males, single dose regimens have been shown to be effective.

Table I. Conditions where a minimum duration of treatment has been established.

Monitoring efficacy
Early review of response
A routine early review ( 3 days after commencing treatment) of the patient's response is important in order to ensure that the patient is receiving appropriate treatment. After review the doctor will have to decide whether to:

i) continue with the present regimen
ii) increase the level of treatment by changing from oral to parenteral; increasing the dose or
    changing   to a broader spectrum antibiotic
iii) decrease the level of treatment by changing from parenteral to oral, decreasing the dose or
     changing to a more specific narrow spectrum antibiotic
iv) stopping the antibiotic if the infection has resolved; the objective of treatment is achieved or
     the diagnosis has been changed.
 
Inconsistent microbiology reports
If the patient is responding there is no necessity to change antibiotic even when the laboratory reports a resistant organism. The isolate in question could have been a coloniser or a contaminant. Infections may resolve spontaneously and the antibiotic could have affected the bacteria in a way that makes it more susceptible to the host's immune defenses.

If the patient's condition fails to improve, a change in antibiotic may be necessary even when the laboratory reports a sensitive organism.
 
Causes of non-response to antibiotics
A patient may fail to respond to an antibiotic for a number of reasons which include:

i) the aetiological agent is resistant to the antibiotic
ii) the diagnosis is incorrect
iii) the choice of antibiotic is correct but the dose and/or route of administration is wrong
iv) the antibiotic cannot reach the site of infection
v) there is a colletion of pus that should be drained surgically or a foreign body/devitalised
    tissue that should be removed
vi) there is secondary infection
vii) antibiotic fever
viii) non-compliance of the host
 
Changing from intravenous to oral
Wherever feasible intravenous therapy should be changed to oral therapy. The oral antibiotic (not necessarily the oral preparation of the intravenous antibiotic) should be selected based on clinical and laboratory findings. Similarly one should not hesitate to revert to intravenous therapy if the patient's condition warrants it.
 
References:

ANTIBIOTIC GUIDELINES 1996

GUIDELINES ON ANTIBIOTIC THERAPY

The following guidelines are issued for the more common infections only. However even for common infections they may not apply to certain patients. When in doubt always seek a second opinion. The recommendations for first and second choice regimens are based on a global assessment of efficacy, adverse effects , prevailing sensitivity patterns and cost. It should also be noted that guidelines such as these have to be reviewed and updated from time to time.

NOTE :

Abbreviations:

1o : First generation
2o : Second generation
3o : Third generation

Table 1.    RESPIRATORY INFECTIONS

Table 2.    URINARY TRACT INFECTIONS

Table 3.    SKIN AND SOFT TISSUE INFECTIONS

Table 4.    MUSCULOSKELETAL INFECTIONS

Table 5.     GASTROINTESTINAL INFECTIONS

Table 6.    GENITOURINARY INFECTIONS (INCLUDING SEXUALLY TRANSMITTED DISEASES)
Note : For all sexually transmitted diseases every effort should be made for contact tracing and treatment of the sexual partners.

Table 7.    CENTRAL NERVOUS SYSTEM INFECTIONS

Table 8.    CARDIOVASCULAR INFECTIONS

Table 9.    BACTERAEMIA AND SEPTICAEMIA

Table 10.    OTHER INFECTIONS

Table 11.    INFECTIONS ASSOCIATED WITH PREGNANCY
Antibiotics should be used with care in pregnancy. Beta-lactam antibiotics and macrolides are probably the safest antibiotics to use in pregnancy.

 Table12.    CHEMOPROPHYLAXIS FOR SELECTED MEDICAL CONDITIONS

SURGICAL CHEMOPROPHYLAXIS
The use of antibiotic prophylaxis has been shown to prevent post-surgical wound infections. When employed rationally significant reductions in morbidity and mortality and savings in resources can be achieved. However when used excessively and in situations when its benefit has not been proven, perioperative antibiotics can lead to unjustifiably high costs of medical care. Single dose regimens or very short courses are unlikely to lead to emergence of bacterial resistance but routine prolonged courses have been clearly associated with increased rates of resistance.

Surgical operations can be divided into four broad categories :

• clean (eg breast, thyroid and hernia operations)
• clean contaminated (eg upper gastrointestinal and biliary)
• contaminated (eg colorectal and trauma surgery within 4 hours of injury)
• dirty (eg perforated intestinal viscus, trauma surgery after 4 hours of injury)

Prophylaxis is generally recommended for clean-contaminated and contaminated operations. In clean operations prophylaxis maybe justified if the consequence of infection is very serious eg in cardiac operations and orthopaedic implants.

Another factor which should be considered in determining probability of infection is the patient himself. Factors that reduce host defenses eg old age, malignancy, malnutrition, steroid therapy, etc will increase the risk of infection.
 
 In using antibiotics for surgical chemoprophylaxis the following principles should be adhered to:

GUIDELINES FOR SURGICAL ANTIBIOTIC PROPHYLAXIS

Gynaecologic surgery

 
General Surgery

Vascular Surgery

Cardiac Surgery

 
Thoracic Surgery

 
Orthopaedic Surgery

ENT Surgery

Neurosurgery

Urological surgery

   
Endoscopic procedures
Antibiotic prophylaxis for endoscopic procedures are given for 2 main reasons:
1) to prevent endocarditis (see table below for degree of risk)
2) to prevent infective complications
 

Estimated risk of endocarditis associated with preexisting cardiac disorders.
(From New Engl J Med 1995, 323:39)
 
 

   
ANTIBIOTIC DOSAGES FOR ADULTS

Note : The following dosing guidelines are the usually recommended regimens. They may not apply to all patients nor to all infections. When in doubt always consult a specialist.