Efficacy is the most important criterion in choosing among available regimens. STI therapy regimens should, ideally, cure at least 95% of those infected with a bacterial STI. Regimens yielding lower cure rates should be used only with great caution since in a setting of unstable susceptibility patterns, they may select for resistant strains and rapidly limit their own usefulness. Such caution should be applied to regimens yielding cure rates between 85% and 95%. Regimens with still lower cure rates are unacceptable.
In order to reduce the risk of development and transmission of resistant strains of sexually transmitted pathogens to the general population, special programmes for effective case management should be designed for groups at high risk, such as sex workers and their clients. Treatment regimens for these groups should be nearly 100% effective, and efforts should be made to promote health-seeking behaviour in these populations, preferably through the use of a participatory approach with peer educators and peer health care providers.
Efficacy data cannot be transferred reliably from one location (or in some situations, from one sub-population) to another. Thus, ideally, assessments should be based on well-designed studies conducted in the populations where the treatment will be applied. As a consequence of changes in the local epidemiology of resistant N. gonorrhoeae and H. ducreyi, therapeutic efficacy against these infections changes over time. Periodic surveillance of clinical efficacy, and/or in vitro sensitivity is recommended. If resistance levels and cure rates are not known in an area, the regimens used should be those which can reasonably be expected to produce acceptable cure rates under the most adverse ecological conditions. It is recognized that few comparative clinical trials are large enough to define small differences in efficacy between highly effective antimicrobial regimens.
In order to ensure efficacy, practitioners are cautioned not to use less than the recommended dosages.
Toxicity is a second major concern in STI treatments because of the frequency with which patients become reinfected and their consequent exposure to repeated courses of antimicrobials. In addition, treatment of resistant STI agents often requires achievement of relatively high serum levels of antimicrobials, in some cases for periods of 7 days or more. Combination regimens further increase the risk of adverse drug reactions. Pregnancy, relatively common in sexually active groups with a high incidence of STI, represents a special situation in which additional considerations of foetal safety become important. The safety of the fluoroquinolones in pregnancy and adolescence is uncertain and limits their use in groups with a high level of sexual activity. In some areas, doxycycline is not used because of the danger of photosensitization. Tetracyclines are contraindicated in pregnancy and children under 8 years of age.
The prominence of third-generation cephalosporins in the recommended regimens results from their combination of high efficacy, even against relatively resistant organisms and low toxicity.
Cost is a major limiting factor in all areas. Kanamycin is chosen in preference to spectinomycin for the treatment of gonorrhoea in many parts of the world because of its lower cost. It is assumed that local programmes will use the best regimens that each can afford. In calculating the total cost of various regimens, however, it is important to consider the costs associated with less effective therapies: repeat treatment, further spread, complications and selection for increased microbial resistance. Choosing the most appropriate regimen may be facilitated by the use of a formal decision analysis and sensitivity analyses can sometimes compensate for uncertainties in primary data.
COMPLIANCE AND ACCEPTABILITY
Patient compliance with STI treatment regimens is a continuing problem seriously limiting the effectiveness of multidose regimens such as those involving erythromycin and tetracyclines. Single-dose or very short course regimens should therefore be given preference. Appropriate counselling and health education have been shown to increase compliance and should be a part of clinical management.
Extra effort is required to achieve compliance amongst adolescents as they are often less tolerant of side-effects. They may also not want others to know that they are taking medication. Health workers must ensure that instructions are fully understood, especially if several regimens are involved, as well as the implications of failure to complete treatment.
In some societies, oral regimens are strongly preferred to injections, whereas among other groups injection may be seen as the only acceptable form of treatment. In view of the emergence and spread of HIV infection, preference should be given to oral regimens, in order to reduce risks associated with the reuse of non-sterilized injection equipment. Patient education on the efficacy of oral preparations must be part of STI management.
The geographical distribution and availability of drugs vary considerably. The regional availability of some excellent drugs could be improved by their inclusion on national essential drugs lists.
When several STI are prevalent in a population, co-infection may be a common occurrence. Unfortunately, the ability to treat common co-infections with single drugs has been reduced by the development of resistance to the tetracyclines among N. gonorrhoeae. In most cases, dual therapy is now required for simultaneous gonococcal and chlamydial infections. Coincident chancroid and syphilis require a multi-drug regimen. The severity of disease caused by several sexually transmitted pathogens (e.g. herpes simplex virus, H. ducreyi, T. pallidum) may be increased in HIV infection and AIDS, and treatment must be intensified and prolonged.
RISK OF REDUCING DRUG EFFICACY FOR OTHER INDICATIONS
More effective but expensive drugs should not be reserved for referral centres. Use of less effective regimens at the primary care level would quickly discourage patients from seeking the most readily and rapidly available care and would foster disease spread and selection of resistant organisms.
Simultaneous treatment with several agents has been used to prevent the emergence of resistance in individuals during therapy for tuberculosis. The efficacy of this technique in preventing emergence of resistance in STI populations is unknown. Unfortunately resistance to a number of antimicrobials is sometimes acquired simultaneously by N. gonorrhoeae. The use of multiple drugs to treat polymicrobial processes (e.g. pelvic inflammatory disease) or presumed simultaneous infection (e.g. tetracycline for chlamydial co-infection in cases of gonorrhoea), is widely practised and recommended.