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P A R T 2  Chemotherapeutic agents

may examine stool for ova and parasites. Microscopic examination of other samples is also used to detect fungal and protozoal infections. The correct identi- fication of the organism causing the infection is an important first step in determining which anti-infective drug should be used. Sensitivity of the pathogen In many situations, healthcare providers use a broad- spectrum anti-infective agent that has been shown likely to be most effective in treating an infection with certain presenting signs and symptoms. In other cases of severe infection, a broad-spectrum antibiotic is started after a culture is taken but before the exact causative organism has been identified. Again, experience influ- ences selection of the drug, based on the presenting signs and symptoms. In many cases, it is necessary to perform sensitivity testing on the cultured microbes to evaluate bacteria and determine which drugs are capable of controlling the particular microorganism. This testing is especially important with microorganisms that have known resistant strains. In these cases, culture and sen- sitivity testing identify the causal pathogen and the most appropriate drug for treating the infection. Combination therapy In some situations, a combination of two or more types of drugs effectively treats the infection. When the offending pathogen is known, combination drugs may be effective in interfering with its cellular structure in different areas or developmental phases. Combination therapy may be used for several reasons: • The healthcare provider may be encouraged to use a smaller dose of each drug, leading to fewer adverse effects but still having a therapeutic impact on the pathogen. • Some drugs are synergistic, which means that they are more powerful when given in combination. • Many microbial infections are caused by more than one organism, and each pathogen may react to a different anti-infective agent. • Sometimes, the combined effects of the different drugs delay the emergence of resistant strains. This is important in the treatment of tuberculosis (a mycobacterial infection), malaria (a protozoal infection), HIV infection (a viral infection) and some bacterial infections. Resistant strains may be more likely to emerge when fixed combinations are used over time; however, this may be prevented by individualising the combination. Prophylaxis Sometimes it is clinically useful to use anti-infectives as a means of prophylaxis to prevent infections before they occur. For example, when people anticipate travelling

to an area where malaria is endemic, they may begin taking antimalarial drugs before the journey and peri- odically during the trip. People who are undergoing gastrointestinal (GI) or genitourinary surgery, which might introduce bacteria from those areas into the system, often have antibiotics ordered immediately after the surgery and periodically thereafter, as appro- priate, to prevent infection. People with known cardiac valve disease, valve replacements and other conditions are especially prone to the development of subacute bacterial endocarditis because of the vulnerability of their heart valves. These people use prophylactic anti- biotic therapy as a precaution when undergoing invasive procedures, including dental work. Refer to the RHD Australia, National Heart Foundation of Australia and the Cardiac Society of Australia and New Zealand rec- ommended schedule for this prophylaxis. ■■ Resistance of a pathogen to an anti-infective agent can be natural (the pathogen does not use the process on which the anti-infective works) or acquired (the pathogen develops a process to oppose the anti-infective agent). ■■ The emergence of resistant strains is a serious public health problem. Healthcare providers need to be alert to prevent the emergence of resistant strains by not using antibiotics inappropriately, assure that the anti-infective is taken at a high enough dose for a long enough period of time, and avoid the use of newer, powerful anti-infectives if other drugs would be just as effective. Adverse reactions to anti-infective therapy Because anti-infective agents affect cells, it is always possible that the host cells will also be damaged (see Box 8.5). No anti-infective agent has been developed that is completely free of adverse effects. The most commonly encountered adverse effects associated with the use of anti-infective agents are direct toxic effects on the kidney, GI tract and nervous system. Hypersensitiv- ity reactions and superinfections can also occur. Kidney damage Kidney damage occurs most frequently with drugs that are metabolised by the kidney and then eliminated in the urine. Such drugs, which have a direct toxic effect on the fragile cells in the kidney, can cause conditions ranging from renal dysfunction to full-blown renal failure. When people are taking these drugs (e.g. amino- glycosides), they should be monitored closely for any sign of renal dysfunction. To prevent any accumulation of the drug in the kidney, people should be well hydrated throughout the course of the drug therapy. KEY POINTS KEY POINTS