Enhancement of antimicrobial agent uptake: Penicillins and other cell wall-active agents can increase the uptake of aminoglycosides by a number of bacteria, including staphylococci, enterococci, streptococci, and P aeruginosa. Enterococci are thought to be intrinsically resistant to aminoglycosides because of permeability barriers. Similarly, amphotericin B is thought to enhance the uptake of flucytosine by fungi.
Mechanisms of Antagonistic Action
There are few clinically relevant examples of antimicrobial antagonism. The most striking example was reported in a study of patients with pneumococcal meningitis. Patients who were treated with the combination of penicillin and chlortetracycline had a mortality rate of 79% compared with a mortality rate of 21% in patients who received penicillin monotherapy (illustrating the first mechanism set forth below).
The use of an antagonistic antimicrobial combination does not preclude other potential beneficial interactions. For example, rifampin may antagonize the action of anti-staphylococcal penicillins or vancomycin against staphylococci. However, the aforementioned antimicrobials may prevent the emergence of resistance to rifampin.
Two major mechanisms of antimicrobial antagonism have been established: 1. Inhibition of cidal activity by static agents: Bacteriostatic agents such as tetracyclines and chloramphenicol can * Pneumocystis jiroveci is a fungal organism found in humans (P carinii infects animals) that responds to antiprotozoal drugs. See Chapter 52.
antagonize the action of bactericidal cell wall-active agents because cell wall-active agents require that the bacteria be actively growing and dividing.
2. Induction of enzymatic inactivation: Some Gram-negative bacilli, including Enterobacter species, P aeruginosa, Serratia marcescens, and Citrobacter freundii, possess inducible β-lactamases. β-Lactam antibiotics such as imipenem, cefoxitin, and ampicillin are potent inducers of β-lactamase production. If an inducing agent is combined with an intrinsically active but hydrolyzable β-lactam such as piperacillin, antagonism may result.
Antimicrobial agents are effective in preventing infections in many settings. Antimicrobial prophylaxis should be used in circumstances in which efficacy has been demonstrated and benefits outweigh the risks of prophylaxis. Antimicrobial prophylaxis may be divided into surgical prophylaxis and nonsurgical prophylaxis.
Surgical wound infections are a major category of nosocomial infections. The estimated annual cost of surgical wound infections in the USA is more than $1.5 billion.
The National Research Council (NRC) Wound Classification Criteria have served as the basis for recommending antimicrobial prophylaxis. NRC criteria consist of four classes (see Box: National Research Council [NRC] Wound Classification Criteria).
The Study of the Efficacy of Nosocomial Infection Control (SENIC) identified four independent risk factors for postoperative wound infections: operations on the abdomen, operations lasting more than 2 hours, contaminated or dirty wound classification, and at least three medical diagnoses. Patients with at least two SENIC risk factors who undergo clean surgical procedures have an increased risk of developing surgical wound infections and should receive antimicrobial prophylaxis.
Surgical procedures that necessitate the use of antimicrobial prophylaxis include contaminated and clean-contaminated operations, selected operations in which postoperative infection may be catastrophic such as open heart surgery, clean procedures that involve placement of prosthetic materials, and any procedure in an immunocompromised host. The operation should carry a significant risk of postoperative site infection or cause significant bacterial contamination.
General principles of antimicrobial surgical prophylaxis include the following: 1.