Antimicrobials

Antibiotic use. The yearly number of prescriptions for systemic antibiotics in the United States between 1992 and 1996 fluctuated between 266,752,000 and 291,215,000. (There were only approximately 240,000,000 Americans in the 1990 census; what is going on here?). (Abstract O-22.)

Adverse effects. A retrospective review of records of 5293 consecutive pediatric outpatients found that the incidence of oral antibiotic associated rash (9% overall) was highest with cefaclor (12.3% of recipients), followed by sulfonamides (8.5%), penicillins (7.4%), and other cephalosporins (2.7%). (Abstract MN-1.) The high rate of allergic reactions, including serum sickness, to cefaclor has been repeatedly described (J Clin Epidemiol 1992;45:1177). The reasons for the tremendous use of this antibiotic in the United States remain a mystery to me, given the rate of reactions and its rather poor performance against infections caused by beta-lactamase producing Haemophilus influenzae.

The dizziness associated with trovafloxacin administration can be significantly reduced by dosing with food or at bedtime. (Abstract A-86.)

Nephrotoxicity has been previously reported to occur with greater frequency when once daily aminoglycoside is administered during usual sleeping hours (12-7:30 a.m.) than during other times of the day (Clin Pharmacol Ther 1997;62:106-111). This occurs despite comparable peak and trough serum concentrations. A similar result was reported from a retrospective study of 65 patients. (Abstract A-87.)

In an attempt to evaluate the clinical relevance of antibiotic-induced endotoxin release from gram-negative bacilli, 66 patients with acute septicemic melioidosis were randomized to treatment with either imipenem or ceftazidime. Plasma endotoxin levels were significantly higher following the initial dose of ceftazidime than after imipenem (P < 0.0005). Furthermore, the mean time to defervescence was 124 hours in the ceftazidime group and only 77 hours in those treated with imipenem (P = 0.01). However, survival rates were almost identical (67.6% vs 66.3%, respectively). (Abstract MN-34.)

Drug interactions. Quinupristin and dalfopristin are primarily metabolized by the CYP3A4 pathway. Coadministration of this combination with nifedipine resulted in a median increase in AUC of the latter of 44%. The inhibition of nifedipine metabolism was, however, wildly variable with a range of AUC decrease of 1-169%, indicating a need for extreme caution in the use of these drugs together. (Abstract A-77.)

Coadministration of the leukotriene receptor antagonist, zafirlukast, does not affect the pharmacokinetics of clarithromycin or 14-OH clarithromycin. (Abstract A-79.)

Linezolid is a weak competitive inhibitor of human monoamine oxidase, but related adverse effects have not been observed in clinical trials to date. (Abstract A-85.)

Omeprazole, which is known to inhibit the NorA efflux pump, enhanced the bactericidal activity of ciprofloxacin but not norfloxacin, against Staphylococcus aureus. (Abstract A-39.)