Selection of empiric therapy may be based on the microbiologic diagnosis or a clinical diagnosis without available microbiologic clues. If no microbiologic information is available, the antimicrobial spectrum of the agent or agents chosen must necessarily be broader, taking into account the most likely pathogens responsible for the patient’s illness.
Choice of Antimicrobial Agent
Selection from among several drugs depends on host factors that include the following: (1) concomitant disease states (eg, AIDS, neutropenia due to the use of cytotoxic chemotherapy, organ transplantation, severe chronic liver or kidney disease) or the use of immunosuppressive medications; (2) prior adverse drug effects; (3) impaired elimination or detoxification of the drug (may be genetically predetermined but more frequently is associated with impaired renal or hepatic function due to underlying disease); (4) age of the patient; (5) pregnancy status; and (6) epidemiologic exposure (eg, exposure to a sick family member or pet, recent hospitalization, recent travel, occupational exposure, or new sexual partner).
Pharmacologic factors include (1) the kinetics of absorption, distribution, and elimination; (2) the ability of the drug to be delivered to the site of infection; (3) the potential toxicity of an agent; and (4) pharmacokinetic or pharmacodynamic interactions with other drugs.
Knowledge of the susceptibility of an organism to a specific agent in a hospital or community setting is important in the selection of empiric therapy. Pharmacokinetic differences among agents with similar antimicrobial spectrums may be exploited to reduce the frequency of dosing (eg, ceftriaxone, ertapenem, or daptomycin may be conveniently given once every 24 hours). Finally, increasing consideration is being given to the cost of antimicrobial therapy, especially when multiple agents with comparable efficacy and toxicity are available for a specific infection. Changing from intravenous to oral antibiotics for prolonged administration can be particularly cost-effective.
Brief guides to empiric therapy based on presumptive microbial diagnosis and site of infection are given in Tables 51–1 and 51–2.
Properly obtained and processed specimens for culture frequently yield reliable information about the cause of infection. The lack of a confirmatory microbiologic diagnosis may be due to the following: 1.
Sample error, eg, obtaining cultures after antimicrobial agents have been administered, inadequate volume or quantity of specimen obtained, or contamination of specimens sent for culture 2.
Noncultivable or slow-growing organisms (Histoplasma capsulatum, Bartonella or Brucella species), in which cultures are often discarded before sufficient growth has occurred for detection 3.
Requesting bacterial cultures when infection is due to other organisms 4.
Not recognizing the need for special media or isolation techniques (eg, charcoal yeast extract agar for isolation of Legionella species, shell-vial tissue culture system for rapid isolation of cytomegalovirus)
Even in the setting of a classic infectious disease for which isolation techniques have been established for decades (eg, pneumococcal pneumonia, pulmonary tuberculosis, streptococcal pharyngitis), the sensitivity of the culture technique may be inadequate to identify all cases of the disease.
Testing bacterial pathogens in vitro for their susceptibility to antimicrobial agents is extremely valuable in confirming susceptibility, ideally to a narrow-spectrum nontoxic antimicrobial drug.