The incidence of antimicrobial allergies in hospitalized patients: implications regarding prescribing patterns and emerging bacterial resistance.

BACKGROUND: The development of antimicrobial guidelines is one way in which institutions attempt to control emerging resistance, but the real challenge falls on promoting and ensuring adherence to these guidelines. Investigating reasons for the prescribing of alternative antimicrobial agents outside of these guidelines is crucial for modifying practices that may adversely impact institutional antimicrobial goals. METHODS: Retrospective cross-referencing of computerized pharmacy printouts and concurrent manual medical record review. RESULTS: Approximately 25% (470/1893) of the patients requiring antimicrobial therapy reported an allergy to at least 1 antimicrobial agent. The most commonly reported antimicrobial allergy was penicillin (295/1893 [15.6%]). Eighty-five patients (18.1%) reported having an allergy to 2 or more antimicrobial agents. Only 4% (27/601) of the reported antimicrobial allergies contained documentation as to the nature of the specific allergic reactions, while a manual medical record review revealed that 32% (23/73) of the antimicrobial allergies contained documentation of the specific allergic reaction. Ninety-eight (39. 7%) of 247 patients reporting an allergy only to penicillin and/or cephalosporin received vancomycin in comparison with 247 (17.4%) of 1423 patients without any antimicrobial allergies (P<.001). Similarly, 53 (21.5%) of 247 patients with reported penicillin and/or cephalosporin allergies received levofloxacin compared with 114 (8.0%) of 1423 patients without any antimicrobial allergy (P<. 001). CONCLUSION: The incidence of penicillin allergy at our institution exceeds population averages. This finding, in combination with limited documentation of drug allergies, appears to lead to the prescribing of alternative antimicrobial agents that do not fit into institutional antimicrobial guidelines and, in some instances, may put the patient at risk for infection and/or colonization with resistant organisms. Use of these alternative agents may adversely impact the ability to manage emerging antimicrobial resistance.

Synergistic effect of gentamicin plus ampicillin on enterococci with differing sensitivity to gentamicin: a phenotypic assessment of NCCLS guidelines.

Between December 1, 1993, and December 1, 1996, we tested 4,411 isolates of Enterococcus sp. at gentamicin concentrations of 500 micrograms/mL and 2000 micrograms/mL using agar dilution to phenotypically categorize them into 3 groups: those with a MIC < or = 500 micrograms/mL (n = 3,132; 71%); a MIC > 500, but < or = 2000 micrograms/mL (n = 441; 10%); and those with a MIC > 2000 micrograms/mL (n = 838; 19%). Ten unique strains of each phenotype were tested to determine which gentamicin concentration was the best in vitro predictor of synergy with ampicillin. Testing was done by a time-kill method using clinically achievable levels of ampicillin and gentamicin. We found that for the gentamicin MIC < or = 500 micrograms/mL group, 7 of 10 isolates demonstrated synergy with ampicillin as manifested by a > or = 2 log10 increase in killing versus the effect of ampicillin alone (at 1/2 the MIC for ampicillin). In the group sensitive to a gentamicin MIC range between > 500 and < or = 2,000 micrograms/mL, none of the 10 isolates demonstrated synergy. Absence of synergy was also found in the group resistant to 2,000 micrograms/mL of gentamicin. Assessment of eight additional enterococcal isolates with reduced sensitivity to ampicillin (MIC from 32-256 micrograms/mL) found no correlation between gentamicin sensitivity at 500 micrograms/mL and any in vitro test for synergy, nor with clinical therapeutic outcome. Gentamicin at 2 micrograms/mL combined with ampicillin was as effective in enhancing killing as a higher level of 4 micrograms/mL. These findings validate the current NCCLS guideline for predicting synergistic activity against enterococci in strains with usual susceptibility to ampicillin, and suggest that a therapeutic level less than maximal recommended dosing is sufficient when using gentamicin in this setting.

The utility of aminoglycosides in an era of emerging drug resistance.

As the problem of global antibiotic resistance continues to worsen, aminoglycosides have assumed increasing importance in clinical practice. Their broad antimicrobial spectrum, rapid bactericidal action, and ability to act synergistically with other drugs have made them especially useful in the treatment of serious nosocomial infections. However, as with other drugs, their overuse and misuse leads to the development of resistance in important microbial pathogens. The appropriate use of the aminoglycosides is essential to assure their continued efficacy. Therefore, physicians must familiarize themselves with both the clinical indications and the limitations of these drugs if they are to remain efficacious in the years to come.

Survey of vancomycin monitoring guidelines in Illinois hospitals.

Disparity exists in published recommendations for monitoring of vancomycin serum concentrations. To evaluate the degree of disparity of practice in Illinois, directors of pathology of 202 Illinois hospitals were surveyed to assess their vancomycin monitoring practices. Of the 202 surveys mailed, 82 were returned for a response rate of 41 percent. Most hospitals have 200-500 beds (60 percent) and are nonteaching institutions (72 percent). Two thirds of the hospitals sent vancomycin to an outside laboratory for analysis. Timing of postinfusion (peak) concentrations ranged from 0 minutes following end of infusion to 360 minutes. Approximately one half of the institutions reported a peak therapeutic range of 30-40 mg/L at 30 minutes following end of infusion. A great majority of institutions were consistent in recommended trough range, with 48 of 55 reporting 5-10 mg/L. Although there is some consistency among at least half of the hospitals, there is a great deal of variability among the other half in peak monitoring guidelines.

Rapid adjustment of theophylline: a kinetic model.

This study was designed to test the validity and applicability of basic kinetic equations to describe theophylline disposition. The method involves early determination of clearance from a nonsteady-state level, dosage adjustment on the basis of the estimated clearance, and measurement of serum theophylline concentration at a point very near steady state. To test the method, a 32-patient study group was examined. The results were encouraging, with the actual mean level 19-28 hours after dosage adjustment being 13.4 micrograms/ml (SD, 3.1) as compared with a projected level of 13.2 micrograms/ml (SD, 2.9). Although further investigation is necessary, these findings indicate that within the limitations of the population studied this approach is a reliable and rapid method to achieve therapeutic serum theophylline levels while at the same time avoiding toxicity and subtherapeutic responses.