Antimicrobials, like any other medicines, may be used inappropriately. A prescriber may choose an inappropriate type of antimicrobial, taking into account the clinical condition, resistance patterns and cost. Incorrect drugs, doses, dose-interval or duration may be prescribed, dispensed or administered. Continuing antimicrobial misuse leads not only to poor patient outcome, unnecessary adverse reactions and wasted resources, but also to emerging resistance of bacteria to antimicrobials. Antimicrobials can also be very expensive, and in most facilities they constitute a major portion of the drug budget. Thus, it is very important for the DTC to pay particular attention to the issue of antimicrobial use.

The phenomenon of resistance is seen not only in bacteria and mycobacteria (multidrug resistant TB, for example), but also in protozoal infections (resistance to chloroquine as an antimalarial) and viral infections (HIV and antiretrovirals). However, for most DTCs the main issue is the use of antimicrobials for bacterial infections.

8.1.1 Problems in the use of antimicrobials

Inappropriate use of antimicrobials is one of the most important types of drug misuse. Often misuse is due to uncertainty about the diagnosis or the identity and drug susceptibility of the organisms. Common areas of misuse particularly associated with antibiotics include:

• treatment of minor respiratory and gastrointestinal infections, viral infections and self-limiting bacterial diseases that do not benefit from use of antimicrobials

• incorrect choice of antimicrobial for common problems, for example the use of a broad-spectrum antimicrobial when a narrow-spectrum agent would be sufficient

• insufficient dose and duration dispensed or purchased because patients cannot afford the cost of the antimicrobial

• inappropriate choice of antimicrobial for surgical prophylaxis

• wrong dose and duration of appropriate antimicrobial prophylaxis and treatment

• the tendency to use newly introduced and expensive antimicrobials, when there is no evidence supporting better drug susceptibility of the newer drug over an older one.

The inappropriate use of antimicrobials is an important factor in the development of resistance. Every time an antimicrobial is used, the susceptible (sensitive) bacteria are killed leaving the resistant ones behind, i.e. the use of antimicrobials selects for resistant bacteria (selection pressure). Antimicrobial resistance is more prevalent in hospital settings than in the community, because of the selection pressure on organisms caused by the high intensity of antimicrobial use. Basic infection control procedures are often not practised, so the transfer of resistant organisms between patients, and between patients and staff, is common. Increasing resistance in the hospital setting contributes to increasing resistance in the community, which is of serious public health importance, since future generations may contract infections that are resistant to treatment.

8.1.2 Improving antimicrobial use and containing resistance

The need for the prudent use of antimicrobials cannot be overemphasized. All the strategies that are used to promote more rational use of medicines generally are also relevant for antimicrobials. Such strategies may be aimed at prescribers, dispensers, those who administer medicines, those responsible for the selection and purchase of medicines, and consumers.

Important strategies to improve antimicrobial use, so containing the development of resistant pathogenic organisms, include:

• An effective antimicrobial subcommittee of the DTC to set norms and monitor antimicrobial use in order to reduce misuse and contain the development of resistant organisms (section 8.1.3).

• Use of antimicrobial treatment guidelines (section 8.1.4) updated according to antimicrobial resistance surveillance data, together with sustained education and supervision on rational use of antimicrobials.

• Classification of antimicrobial prescribing in hospitals into non-restricted, restricted and very restricted to avoid indiscriminate use of antimicrobials of ‘last resort’ (section 8.1.5).

• Audit of antimicrobial use, by department or by drug, together with feedback and other appropriate measures in order to correct inappropriate use (sections 6.5 on drug use evaluation and 8.1.6).

• Improved diagnostic facilities (section 8.1.7) to aid clinicians not to prescribe antimicrobials unnecessarily, for example malaria blood smear, TB sputum smear.

• Antimicrobial resistance surveillance (section 8.1.10) in order to:

- inform clinicians about the susceptibility patterns of bacteria causing infections in individual patients so ensuring correct antimicrobial choice

- use the collated information when developing STGs and choosing which antimicrobials should be on the formulary list; this requires the disaggregation of resistance patterns in community-acquired and nosocomial infections

- where laboratory facilities are not available, it maybe necessary to rely on surveillance information from the nearest available laboratory in a similar hospital setting. Such information may be used to identify first-choice antimicrobials which can be used empirically, i.e. without information on the susceptibility patterns of individual patients.

Important strategies to improve infection control, thereby preventing the spread of resistant infections, include:

• An infection control committee (section 8.1.8) to monitor hygiene practices with a view to containing the spread of resistant organisms. The DTC should liaise closely with any existing infection control committee. If no such committee exists, the DTC should form one.

• Guidelines and procedures to prevent the transmission of infections, including those that are drug-resistant (section 8.1.9). There should be policies for hand washing by medical staff when transferring from one patient to another; for using sterile gloves, especially in intensive care wards; and for certain procedures involving the use of disinfectants and sterile equipment.

• Surveillance of infections and antimicrobial resistance (section 8.1.10) in order to detect, and therefore deal with, outbreaks of nosocomial (hospital-acquired) infection.

8.1.3 Antimicrobial subcommittee

The goal of an antimicrobial subcommittee is to assist the DTC in dealing with the management of antimicrobials, and in particular to ensure that:

• Safe, effective, cost-effective antimicrobials are made available.

• Antimicrobials are used only when clinically indicated, at the correct dose and for the appropriate duration of time.

• Correct information is given to patients and that, as far as possible, patients take antimicrobials correctly.

The functions of the antimicrobial subcommittee are similar to those of the DTC, but with an emphasis on antimicrobial drugs. Ideally such a subcommittee would:

• Advise the DTC and medical staff on all aspects of antimicrobial use and misuse.

• Assist in evaluating and selecting antimicrobials for the formulary and standard treatment guidelines.

• Develop policies concerning use of antimicrobials for approval by the DTC and medical staff. Policies should specifically include sections on methods to limit and restrict use of antimicrobials in the hospital and primary care clinics.

• Participate in prescribing quality assurance programmes and drug use evaluations to ensure use of effective antimicrobials of adequate quality only when clinically indicated, in the correct dose and for the appropriate length of time.

• Participate in the educational programmes for health-care staff.

• Liaise with the infection control committee with regard to assessment and use of data obtained from the monitoring of antimicrobial sensitivity and resistance patterns in hospitals and primary care clinics.

8.1.4 Antimicrobial treatment guidelines

Antimicrobial guidelines are a very useful adjunct to the more general STGs and formulary manual. The DTC should be able to develop and advocate the use of antimicrobial guidelines especially for treatment and prophylaxis in the common infections managed in the hospital.

A process similar to that described for STGs (section 3.4) can be used. It is important to emphasize the use of evidence-based information, and assess the local susceptibility patterns. In small hospitals, without laboratory and technical capability, this information should be obtained from the nearest hospitals that do have this capacity and/or are using evidenced-based antimicrobial guidelines. Education on rational use of antimicrobials should include advocacy on the use of the antimicrobial treatment guidelines information and on current antimicrobial susceptibility patterns. A good example of antimicrobial guidelines is contained in a booklet published and used in Australia (Therapeutic Guidelines Ltd 2000).

8.1.5 Classification of antimicrobials

It is important to classify antimicrobials according to the general criteria of efficacy, safety, quality and cost, and according to resistance patterns. Any classification should be country-specific and based on local conditions.

Antimicrobials for non-restricted use

These antimicrobials are safe, effective and reasonably priced (for example benzyl penicillin). All prescribers may prescribe these drugs without approval by senior prescribers or the antimicrobials and infection control subcommittees, but prescriptions should be compliant with STGs.

Restricted antimicrobials

These antimicrobials may be more expensive and/or have a wider spectrum of activity and should only be used for specified more serious clinical conditions (for example, ceftriaxone). Such conditions might include:

• specific infections known to be sensitive to the antimicrobial after culture and susceptibility testing

• empirical emergency treatment of suspected serious or life-threatening infections pending the result of culture and sensitivity testing.

• countersignature by a senior physician who has the approval of the DTC for such an activity.

Thus these antimicrobials are used only with the approval of clinicians who are experts on infectious diseases and familiar with local susceptibility patterns.

Very restricted

These antimicrobials should be reserved for life-threatening infections (for example, vancomycin). They should only be used when culture and sensitivity testing has indicated resistance to other effective and less expensive antimicrobials. Approval for use in each individual patient must be given by the clinical microbiologist or the DTC itself.

In hospitals without laboratories, it may not be possible to distinguish between ‘restricted’ and ‘very restricted’ and the two categories may be treated as one.

8.1.6 Antimicrobial use review

This is the same as drug utilization evaluation (DUE) or an audit and feedback programme where the drug being evaluated is an antimicrobial. The steps involved in conducting such a review are the same as for DUE, and are demonstrated in the country example shown in box 8.1. Antimicrobial use audit should be done at regular intervals to make sure that prescribers adhere to the hospital antimicrobial policy and guidelines. Medicines given during the discharge of inpatients and those prescribed to outpatients should be monitored in order to contain the spread of antimicrobial-resistant bacteria to the community.

8.1.7 Improved diagnostic facilities

Many antimicrobials are prescribed unnecessarily because the prescriber is unsure of the diagnosis. Diagnostic procedures can help to ensure that antimicrobials are prescribed only when needed. For example, using malaria blood smears in hospitals helps to ensure that patients with malaria are treated with antimalarials and not with unnecessary anti-microbials. Sputum microscopy for TB helps to ensure that those patients with TB are treated with antitubercular drugs and not with inappropriate antibiotics. As for any laboratory procedures, quality control for diagnostic procedures and microscopy is vital as otherwise false diagnoses will be made or true diagnoses missed (see section 8.1.10 on antimicrobial resistance surveillance).

8.1.8 Infection control committee

The goal of an infection control committee is to prevent the spread of infection within the hospital or facilities within its jurisdiction. This involves overseeing the hospital’s infection control, prevention, and monitoring programmes (Wenzel et al. 1998). An infection control committee usually operates independently of the DTC, but will frequently rely on the DTC’s advisory function. Where there is no such committee, the DTC should create a subcommittee that will specifically deal with all issues relating to infection control. If there are not sufficient professional staff in a hospital, the infection control committee could be combined with the antimicrobial subcommittee. In any case better coordination would be achieved by some overlap of membership between the infection control and antimicrobial subcommittees. If there are still fewer personnel, as is the case in many small hospitals in developing countries, coordination with bigger hospitals and professional groups specializing in infectious diseases will be necessary. What is crucial is that somebody is responsible for ensuring that infection control procedures and strategies to prevent unnecessary antimicrobial use are in place.

The functions of an infection control committee are concerned with environmental issues such as food handling, laundry handling, cleaning procedures, visitation policies and direct patient care practices, including hand washing and immunizations. An infection control committee should:

• Carry out active surveillance of infections and antimicrobial resistance, with data analysis and feedback (ideally monthly reports) to the appropriate departments, health-care staff, antimicrobial subcommittee and the DTC.

• Develop and recommend policies and procedures pertaining to infection control.

• Intervene directly to prevent infections.

• Recognize and investigate outbreaks or clusters of infections.

• Educate and train health-care workers, patients and non-medical care-givers.

Normally the infection control committee appoints a team, often just one nurse in small hospitals, to implement its policies. Where there are laboratory facilities a microbiologist is responsible for collating and assessing sensitivity and resistance patterns.

8.1.9 Preventing the transmission of infections

Preventing transmission of infections helps not only to prevent healthy individuals from becoming ill but also to contain resistance. Firstly, one can reduce the spread of resistant bacteria and, secondly, one can reduce the need to treat sensitive infections with antimicrobials, thereby reducing selection pressure for resistant organisms. The infection control committee is responsible for undertaking active surveillance of infections and antimicrobial resistance, and for developing policies to ensure implementation of the following activities to minimize the spread of infection:

• hand washing by staff between patients and before undertaking any procedures, for example injections

• use of barrier precautions, for example wearing gloves and gowns for certain agreed procedures

• adequate sterilization and disinfection of supplies and equipment

• use of sterile techniques, together with protocols, for medical and nursing procedures, for example bladder catheterization, administration of injections, insertion of intravenous cannulas, use of respirators, sterilization of equipment, and other surgical procedures

• maintenance of appropriate disinfection or sanitary control of the hospital environment, including:

- adequate ventilation
- cleaning of the wards, operating theatre, laundry, etc.
- provision of adequate water supply and sanitation
- safe food handling
- safe disposal of infectious equipment, for example dirty needles
- safe disposal of infectious body fluids, for example sputum

• isolation of infectious patients from other non-infected patients, for example separation of suspected and proven sputum-positive TB cases

• visitation policies, for example preventing visitors with coughs and colds visiting patients who may be immunocompromised, for example patients with AIDS or leukaemia, or premature babies

• training of health-care staff in appropriate sterile techniques and infection control procedures

• immunizations

- routine childhood vaccinations in the community, for example diptheria, tetanus, polio, pertussis, measles, BCG, Haemophilus influenzae

- vaccination of community members and staff in times of threatened epidemics, for example meningitis, typhoid, influenza

• patient education in hospitals or health facilities on topics that may help to reduce transmission of infections in the community, for example:

- hygiene, hand washing, safe water and sanitation - to prevent diarrhoeal disease
- immunization - to prevent diptheria, measles
- bednets - to prevent malaria
- condoms - to prevent sexually transmitted diseases and HIV.

8.1.10 Antimicrobial resistance surveillance

The extent of resistance discovered by laboratory culture and sensitivity testing is only the tip of the iceberg in terms of the total bacterial strains and antimicrobial resistance that may be present in the community. Of all the people exposed to resistant organisms, only some will become infected; of infected patients, only some will manifest disease; of diseased patients, only some will seek medical attention; of those seeking medical attention, only some will give a clinical specimen; in only some specimens will a pathogen be isolated; and only for some pathogens will resistance be tested.

Surveillance of bacterial resistance to antimicrobials is an essential component of any programme to contain the spread of resistance. Only by knowing the extent of the problem can appropriate choices be made and staff persuaded to change their use of medcines. Resistance data not only help in choosing the correct antimicrobial in individual patient care; they also, if collated, allow a DTC to be informed about sensitivity patterns when choosing antimicrobials for the formulary. Many hospital laboratories do not actually collate resistance data in order to inform the formulary process, but the DTC has a role in ensuring that such information is provided if possible.

Often resistance is reported in terms of the number of isolates. However, such data usually include multiple specimens from a few very sick patients and does not give an accurate picture of overall resistance in all patients. In order to inform the formulary process, resistance data should be representative of all likely patients, and therefore the data should be collated by case (or patient) not by isolate. If specimens for culture are taken from patients on arrival at a hospital, before they receive any antibiotics, the resulting data may be used to gain an impression of resistance patterns in the community.

Detailed discussion about resistance surveillance is beyond the scope of this manual. However, if surveillance is done, quality control within the laboratory is extremely important. It is worse to have inaccurate reports than none at all. Any good and reliable microbiology laboratory should be able to demonstrate to the DTC documented internal and external quality assurance:

• Internal quality assurance consists of regularly conducting and recording various internal checks to ensure that all laboratory equipment is functioning and that all specimen collection and processing is done in a reliable manner.

• External quality assurance is where the laboratory participates in an external scheme run by a reference laboratory. In such a scheme, the reference laboratory sends out test clinical specimens, and asks the participating laboratory to identify the organism and its sensitivity pattern. In this way the competence of the participating laboratory can be checked against that of the reference laboratory.

Box 8.2 shows a checklist of questions that a DTC may ask of a microbiology laboratory in order to make an assessment of its likely quality and reliability with regard to the isolation and identification of bacteria and sensitivity testing to antimicrobials.