Antimicrobial agents are frequently used before the pathogen responsible for a particular illness or the susceptibility to a particular antimicrobial agent is known. This use of antimicrobial agents is called empiric (or presumptive) therapy and is based on experience with a particular clinical entity. The usual justification for empiric therapy is the hope that early intervention will improve the outcome; in the best cases, this has been established by placebo-controlled, double-blind, prospective clinical trials. For example, treatment of febrile episodes in neutropenic cancer patients with empiric antimicrobial therapy has been demonstrated to have impressive morbidity and mortality benefits even though the specific bacterial agent responsible for fever is determined for only a minority of such episodes.
Finally, there are many clinical entities, such as certain episodes of community-acquired pneumonia, in which it is difficult to identify a specific pathogen. In such cases, a clinical response to empiric therapy may be an important clue to the likely pathogen.
Frequently, the signs and symptoms of infection diminish as a result of empiric therapy, and microbiologic test results become available to establish a specific microbiologic diagnosis. At the time that the pathogenic organism responsible for the illness is identified, empiric therapy is optimally modified to definitive therapy, which is typically narrower in coverage and is given for an appropriate duration based on the results of clinical trials, or experience when clinical trial data are not available.
Approach to Empiric Therapy
Initiation of empiric therapy should follow a specific and systematic approach.
A. Formulate a Clinical Diagnosis of Microbial Infection
Using all available data, the clinician should determine that there is a clinical syndrome compatible with infection (eg, pneumonia, cellulitis, sinusitis).
B. Obtain Specimens for Laboratory Examination
Examination of stained specimens by microscopy or simple examination of an uncentrifuged sample of urine for white blood cells and bacteria may provide important immediate etiologic clues. Cultures of selected anatomic sites (blood, sputum, urine, cerebrospinal fluid, and stool) and nonculture methods (antigen testing, polymerase chain reaction, and serology) also may confirm specific etiologic agents.
C. Formulate a Microbiologic Diagnosis
The history, physical examination, and immediately available laboratory results (eg, Gram stain of urine or sputum) may provide highly specific information. For example, in a young man with urethritis and a Gram-stained smear from the urethral meatus demonstrating intracellular Gram-negative diplococci, the most likely pathogen is Neisseria gonorrhoeae. In the latter instance, however, the clinician should be aware that a significant number of patients with gonococcal urethritis have negative Gram stains for the organism and that a significant number of patients with gonococcal urethritis harbor concurrent chlamydial infection that is not demonstrated on the Gram-stained smear.
D. Determine the Necessity for Empiric Therapy
Whether to initiate empiric therapy is an important clinical decision based partly on experience and partly on data from clinical trials. Empiric therapy is indicated when there is a significant risk of serious morbidity or mortality if therapy is withheld until a specific pathogen is detected by the clinical laboratory.
In other settings, empiric therapy may be indicated for public health reasons rather than for demonstrated superior outcome of therapy in a specific patient. For example, urethritis in a young sexually active man usually requires treatment for N gonorrhoeae and Chlamydia trachomatis despite the absence of microbiologic confirmation at the time of diagnosis. Because the risk of noncompliance with follow-up visits in this patient population may lead to further transmission of these sexually transmitted pathogens, empiric therapy is warranted.
E. Institute Treatment