Selection and Administration of Antibacterial Antimicrobics
This topic is largely beyond the scope of this book, but a few principles merit emphasis. Most bacterial infections are now potentially curable by chemotherapy alone or its use as an adjunct to surgical or other to physicians makes selection of the most appropriate agent(s) particularly challenging.Although the clinical indications for use vary widely, they usually fit into one of three categories: empiric, specific, or prophylactic.
The first decisions on selection of antimicrobic(s) are based on the physician’s assessment of the probable microbial etiology of the patient’s infection. The variables involved are the subject of much of this book and include the site of infection (eg, throat, lung, urine) and epidemiologic factors such as age, season, geography, and predisposing conditions. A mental list of probable etiologies must then be matched with their probable antimicrobial susceptibilities as shown in Table 13 – 1. Specific local “batting averages” for each antimi- crobic against the common organisms are available from hospital laboratories and infection control committees. Many astute clinicians carry statistics concerning bacterial effectiveness in a pocket.
This process may be as simple as selecting penicillin to treat a patient with suspected group A streptococcal pharyngitis, or as complex as resorting to a cocktail of broad-spec- trum antibacterial, antifungal, and antiviral agents to treat a febrile patient who has had a bone marrow transplant. In general, the risks of broad-spectrum treatment (superinfec- tion, overgrowth) become more tolerable as the severity of the infection increases. When the risk of not “covering” an improbable pathogen is death, it is difficult to be selective.This treatment selection based on clinical criteria alone must be coupled with appropri- ated diagnostic steps to determine the etiology, so the empiric therapy can be converted to specific therapy as quickly as possible.
Specific antimicrobial therapy is directed at the known agent of infection, usually a single species. It is unique to infectious diseases and is made possible by isolation and identifi-cation of the microorganism from the patient. In the case of bacterial diseases, it can even be made specific to the patient’s own isolate by the use of antimicrobial susceptibility tests. The ideal goal of specific therapy is to attack the infecting organism and nothing else — to be the mythical “silver bullet.” As the results of Gram smears, cultures, and susceptibility tests are gathered from the laboratory, unnecessary antimicrobics can be discontinued and the spectrum of therapy narrowed as much as possible. For example, a patient with suspect staphylococcal or streptococcal infection might be empirically started on a cephalosporin to cover both possibilities. The isolation of a S. aureus suscep-tible to a cephalosporin and oxacillin but resistant to penicillin requires reassessment of that regimen. Even though the cephalosporin is active, the oxacillin is the better choice, because its narrower spectrum carries less risk of complications for the patient and re-duces the selective pressure for emergence of resistance.
In general, the best specific therapy is a single antimicrobic, but there are exceptions. Two or more antimicrobics acting by different mechanisms may be combined to reduce the possibility that mutations to resistance can be expressed. This is particularly true for chronic infections such as tuberculosis, in which the microbial load is high and the treat-ment period is long. For example, if a lesion contains 109 organisms, and the frequency of resistant mutants is 10-6, the chance of relapse by selection of a resistant mutant is signif-icant. Adding a second drug with the same mutation rate but a different mechanism re-quires a double mutant for expression of the resistance in the patient. Because the chance of this event is to 10-12, the addition of a second antimicrobic should prevent develop-ment of resistance during therapy.
Another indication for antimicrobial combinations is the desire to achieve a greatly enhanced biologic effect called synergism. For example, relatively low concentrations of a β-lactamand an aminoglycoside may be bactericidal for Enterococcus faecalis when combined, but neither agent is lethal at clinically achievable levels. This occurs because inhibition of cell wall synthesis by penicillin allows passage of the aminoglycoside to its ribosomal target in the cell. Unfortunately, combinations may also be antagonistic. This happens when the action of one antimicrobic partially prevents the second from express-ing its activity. Examples include certain combinations of bacteriostatic antimicrobics with a β-lactamantimicrobic, such as penicillin. Penicillin exerts its bacterial effect only on dividing cells, and inhibition of growth by a bacteriostatic antimicrobic may prevent the lethal activity of penicillin. Although specific therapy is the ideal, it is not always pos-sible. Any degree of uncertainty about the etiologic diagnosis will broaden the therapeutic coverage, and in some instances an etiologic diagnosis may not even be attempted. Em-pirical treatment of acute otitis media usually stands, because reaching the middle ear to culture the specific etiology is judged to carry more risk and discomfort for the patient.
The use of antimicrobics to prevent infection is a tempting but potentially hazardous en-deavor. The risk for the individual patient is infection with a different, more resistant or-ganism. The risks for the population are in increasing the pressure for the selection and spread of resistance. After many years of experience, the indications for antimicrobial prophylaxis have now been narrowed to a limited number of situations in which antimi-crobics have been shown to decrease transmission during a period of high risk. Prophy-laxis can reduce the risk of endogenous infection associated with certain surgical and dental procedures if given during the procedure (a few hours at most). The transmission of highly infectious bacteria to close contacts can also be reduced by prophylaxis. This has been effective for some pathogens spread by the respiratory route, such as the etio-logic agents of meningitis, whooping cough, and plague. One of the outstanding suc-cesses of antimicrobial prophylaxis is the reduction of group B streptococcal sepsis and meningitis in neonates. In this instance, prophylactic penicillin is administered during la-bor to mothers with demonstrated vaginal group B streptococcal colonization.