Health and Prostate

In the Individual Patient

The use of two drugs in combination to delay the emergence of a drug-resistant strain is now a well established principle and is almost universally used in the treatment of tuberculosis. A change in the drug sensitivity of an infecting bacterium during a single short course of treatment does not in fact occur very frequently. On the bacterial side the only organisms likely to show such a change are staphylococci and conform bacilli. When antibiotics have to be given for long periods the danger is increased, and is particularly great in the case of tuberculosis, since tubercle bacilli are nearly as adaptable to antibacterial drugs as are staphylococci and coliform bacilli.

Although staphylococci appear to be able to develop resistance to almost any antibiotic, this usually only follows continued use of the antibiotic in a hospital where strains are spreading from patient to patient. With streptomycin, erythromycin, novobiocin and Fucidin, however, resistance develops so rapidly that a gross change in sensitivity of an infecting strain is not infrequent after antibiotic treatment of less than a week’s duration. For this reason streptomycin was long ago abandoned for staphylococcal infection. Since the discovery of the new penicillins, erythromycin, novobiocin and Fucidin are rarely used, but, if they are, there is a clear case for giving two of them together.

It is less certain to what extent double chemotherapy is desirable from this point of view for infections due to coliform bacilli. Undoubtedly they can develop resistance to streptomycin within a day or so of the onset of treatment. With other antibiotics the position has been less well studied than with staphylococci.

Another use of drug combinations is to prevent superinfection. In practice the only form of super-infection likely to be prevented in this way is that due to Candida, infection with this organism is liable to occur when broad-spectrum antibiotics, particularly tetracycline, are given, especially if treatment is continued for more than a week. When tetracyclines have to be administered for long periods the addition of nystatin is worth considering. Alternatively, a preparation of antibiotic-resistant lactobacilli administered orally helps to prevent superinfection. The practice of combining tetracycline with the highly toxic antibiotic amphotericin, in a single preparation, is to be deplored.

In a Hospital Community

In most large hospitals antibiotics are used extensively in wards where cross-infection is liable to take place, so that the emergence of drug-resistant strains is encouraged. The best way to deal with this situation is to prevent cross-infection and limit the use of antibiotics. But the first is difficult, if not impossible, in most existing hospital buildings and the use of antibiotics will almost certainly remain high, even if they are reserved for the treatment of patients likely to benefit directly from their administration.

In hospitals where drug-resistant staphylococci are a serious problem, universal double chemotherapy for all infections in the hospital has been suggested, at least as a temporary measure. But there are obvious objections. Double chemotherapy is bound to increase the total consumption of antibiotics in the hospital and, apart from cost, this increases the frequency with which hospital bacteria come into contact with each antibiotic. Moreover, the policy might favour the spread of Ps. pyocyanea in hospitals, since this organism tends to be resistant to nearly all the commonly used antibacterial drugs.

Conclusions

Combinations of two antibiotics showing bactericidal synergy are of great importance in the treatment of bacterial endocarditis and other infections where bactericidal therapy is necessary, when the infecting bacteria are not readily killed by a single drug. The most likely combination to be synergic is benzylpenicillin and streptomycin, but there are no absolute rules and double sensitivity tests should always be carried out with the microbe concerned. Bactericidal antibiotics, other than a polymyxin, are frequently antagonized by bacteristatic drugs, particularly tetracycline and chloramphenicol, so that such combinations should be avoided in conditions needing bactericidal therapy, unless tests have shown that there is no antagonism with the infecting organism.

Drug combinations may also help to delay the emergence of resistant strains and in this connexion should be considered in the treatment not only of tuberculosis, but also of infections due to staphylococci and coliform bacilli. The addition of nystatin may be useful for the prevention of candidiasis when long-term treatment with a broad-spectrum antibiotic is necessary.

Drug combinations may be preferable to the use of broad-spectrum antibiotics for the treatment of mixed infections. Finally, they may be essential for the blind treatment of fulminating infections pending bacteriological diagnosis.