Preventing antibiotic resistance through rapid genotypic identification of bacteria and of their antibiotic resistance genes in the clinical microbiology laboratory.

Abstract

The emergence of drug resistance in microorganisms is a serious problem, and several strategies have been proposed to try to tackle it. Prevention should be the ultimate solution, and vaccines have been suggested as a strategy that can be used to slow down the emergence of drug resistance by decreasing the infection rate and hence antibiotic usage (15). Unfortunately, we are far from this ideal. Broad surveillance programs (22) and education of clinicians, pharmacists, veterinarians, drug company representatives, and the public about the spread of antimicrobial resistance and the consequences of antibiotic misuse should also have a significant impact (21). Restrictive use of newer and broad-spectrum antibiotics has also been applied and advocated. Strict application of therapeutic guidelines might also be useful. Another strategy is to increase our understanding of the biochemical basis of antimicrobial resistance mechanisms which should suggest preventive and therapeutic strategies for overcoming resistance (17). The understanding of resistance mechanisms is also necessary for the development of the tools necessary to detect resistance by methods other than phenotypic testing, which now includes disc diffusion or dilution tests (MIC tests) to evaluate the susceptibilities of microbes to antibiotics. We advocate that rapid (≤1 h) identification of microorganisms should literally modify the habits of the prescribers and contribute to a reduction of the dissemination of antimicrobial resistance. While most DNA-based tests are presently used to identify viruses or bacteria whose identification is tedious, like Mycobacterium tuberculosis or chlamydia, we are suggesting that the time is ripe for the use of these tests to identify bacteria causing common and deadly bacterial diseases. We believe that the simultaneous rapid genotypic identification of bacteria and their antibiotic resistance genes will have a major impact on the treatment of infectious diseases while contributing to a better control of antimicrobial resistance (14). Speed is the essence when one deals with bacterial infections. Although the Gram stain can sometimes be helpful, presently, diagnosis in the clinical microbiology laboratory is only confirmatory because a clinical decision has been made long before (usually 48 h) the identity of the organism responsible for the infection and its susceptibility to antibiotics become available. With the actual state-of-the-art technology, which dates back to the last century, we cannot even tell accurately before 18 to 24 h whether a clinical sample has bacteria or not. This is of importance because no bacteria can be grown out of more than 80% of all normally sterile clinical samples sent to clinical microbiology laboratories (4). The lack of a timely response by the laboratory has consequences on antibiotic usage and prescription. Patients must be treated empirically. When severe or nosocomial infections are suspected, they are often treated with broad-spectrum antibiotics. The increased use of broad-spectrum antibiotics is not restricted to hospitalized patients in intensive care units or patients seen in emergency rooms, however. Indeed, a recent American survey has indicated that toxic and expensive broad-spectrum antibiotics are prescribed more frequently for the treatment of common infections by office-based physicians (14). Clearly, with 80% of normally sterile specimens received in the microbiology laboratory not growing any microorganism, several patients are receiving antibiotics even if they do not have a bacterial infection because there are no accurate ways of determining before the next day whether the clinical sample harbors bacteria. In line with this latter argument, a recent study in Spain has indicated that on any particular day, the number of antibiotic prescriptions exceeded by three times the number of bacterial infections diagnosed (3). Moreover, microbiologic results are available so slowly that physicians rarely consult them unless the patient is not responding to the given antibiotic. If physicians could have in hand the identity of the microorganism and its resistance profile from the microbiology laboratory at the same time that they have the biochemistry and hematology results, antibiotic prescription rates could go down dramatically, and when antibiotics are needed, more targeted and inexpensive antibiotics could be used. On the other hand, whether you are using phenotypic or genotypic identification systems, the presence of bacteria or even the absence of bacteria in the clinical specimens does not necessarily mean the presence or the absence of infection because clinical judgment should always prevail.