Tests measure the concentration of drug required to inhibit growth of the organism (minimal inhibitory concentration [MIC]) or to kill the organism (minimal bactericidal concentration [MBC]). The results of these tests can then be correlated with known drug concentrations in various body compartments. Only MICs are routinely measured in most infections, whereas in infections in which bactericidal therapy is required for eradication of infection (eg, meningitis, endocarditis, sepsis in the granulocytopenic host), MBC measurements occasionally may be useful.
A. Beta-Lactamase Assay
For some bacteria (eg, Haemophilus species), the susceptibility patterns of strains are similar except for the production of β lactamase. In these cases, extensive susceptibility testing may not be required, and a direct test for β lactamase using a chromogenic β-lactam substrate (nitrocefin disk) may be substituted.
B. Synergy Studies
Synergy studies are in vitro tests that attempt to measure synergistic, additive, indifferent, or antagonistic drug interactions. In general, these tests have not been standardized and have not correlated well with clinical outcome. (See section on Antimicrobial Drug Combinations for details.)
MONITORING THERAPEUTIC RESPONSE: DURATION OF THERAPY
The therapeutic response may be monitored microbiologically or clinically. Cultures of specimens taken from infected sites should eventually become sterile or demonstrate eradication of the pathogen and are useful for documenting recurrence or relapse. Follow-up cultures may also be useful for detecting superinfections or the development of resistance. Clinically, the patient’s systemic manifestations of infection (malaise, fever, leukocytosis) should abate, and the clinical findings should improve (eg, as shown by clearing of radiographic infiltrates or lessening hypoxemia in pneumonia).
The duration of definitive therapy required for cure depends on the pathogen, the site of infection, and host factors (immunocompromised patients generally require longer courses of treatment). Precise data on duration of therapy exist for some infections (eg, streptococcal pharyngitis, syphilis, gonorrhea, tuberculosis, and cryptococcal meningitis). In many other situations, duration of therapy is determined empirically. Minimizing duration of antimicrobial therapy for specific infections is an intervention that may help prevent the development of antimicrobial resistance. For many infections, a combined medical-surgical approach may be required for clinical cure.
Clinical Failure of Antimicrobial Therapy
When the patient has an inadequate clinical or microbiologic response to antimicrobial therapy selected by in vitro susceptibility testing, systematic investigation should be undertaken to
TABLE 51–1 Empiric antimicrobial therapy based on microbiologic etiology.
TABLE 51–1 Empiric antimicrobial therapy based on microbiologic etiology. (Continued)
Suspected or Proven Disease or Pathogen Drugs of First Choice Alternative Drugs 1Trimethoprim-sulfamethoxazole (TMP-SMZ) is a mixture of one part trimethoprim plus five parts sulfamethoxazole.