Helen M. Crowe

Drug malabsorption and resistant tuberculosis in HIV-infected patients.

To the Editor: Directly observed therapy for tuberculosis has been advocated as a way to improve compliance and control the emergence of drug resistance.1,2 We recently cared for two patients with ...

Antibiotic formulary selection

Physicians worldwide are being forced to consider economics in the care of patients. In most hospitals, antibiotics are a steadily increasing segment of the pharmacy budget. This article discusses how the authors used drug pharmacokinetics, restriction policies, and cost benefit analysis to design a cost-effective antibiotic formulary.

Transitional Antibiotic Therapy

With all the fiscal restraints in healthcare systems. it is crucial to develop methods to treat infections that are both clinically sound and cost-effective. Of the various options available. the rapid transition from intravenous to oral therapy represents one of the most effective ways to attain these goals. Moreover, it has the further advantages of shortening hospital stay, reducing nosocomial bacteremia and avoiding the need to rely upon intravenous technicians and equipment. Although there is a need for more patient outcome studies with this approach, the early experience with transitional therapy appears promising.

Rifampin-Fluconazole Interaction in Critically ILL Patients:

Objective: To report the influence of rifampin coadministration on the pharmacokinetics of fluconazole in 2 critically ill patients. Case Summaries: The pharmacokinetics of fluconazole are reported in 5 patients in the intensive care unit (ICU), 2 of whom received rifampin and 3 who received only fluconazole. Patient 1 was a 52-year-old man with bilateral pneumonia who received rifampin for 9 days in addition to other antibiotics when fluconazole was added for suspected fungal superinfection. Patient 2, a 39-year-old man with steroid-dependent asthma was admitted to the ICU with a right middle lobe pneumonia and ventilatory insufficiency. Because of rapid clinical deterioration, intravenous rifampin 600 mg q12h and fluconazole 100 mg q24h were added to conventional antibacterial therapy. Patients 3–5 received intravenous fluconazole therapy, but were never administered rifampin prior to their antifungal therapy. Discussion: Fluconazole has gained wide use as an antifungal agent because of its efficacy, limited toxicity, and the paucity of reported drug interactions. In some clinical situations, however, the drug must be coadministered with rifampin. Limited data in healthy volunteers suggest that the coadministration of rifampin and fluconazole results in a 23% reduction in the fluconazole area under the concentration-time curve (AUC). In this report, we found a statistically significant lowering of the AUC (52%) and a 93% higher total body clearance of fluconazole in patients treated with rifampin. Conclusions: Although limited data are available describing the magnitude of the interaction between fluconazole and rifampin in patients, our data suggest a more significant interaction than previously reported. If the concurrent administration of the 2 drugs is unavoidable, the patients clinical response to treatment should be monitored closely, as the unexpectedly large reduction in fluconazole serum concentrations may lead to poor treatment outcomes.

Effect of Continuous Arteriovenous Hemodiafiltration on the Pharmacokinetics of Fluconazole

In critically ill patients with acute renal failure, continuous arteriovenous hemodiafiltration (CAVHD) has become an increasing popular supportive technique. An adult with acute renal failure during CAVHD therapy received fluconazole. Drug clearance by the hemodiafilter system and its total body clearance during the CAVHD period were 23–28 ml/minute and 22 ml/minute, respectively, indicating that the rate of systemic clearance was solely dependent on CAVHD in this patient. Total body clearance, area under the curve, and half‐life values for this patient closely resembled those in healthy subjects. These observations suggest that patients treated with fluconazole during CAVHD should receive standard maintenance dosages, and neither supplementation nor dosage adjustment is required.

ANTIBIOTIC USE IN THE CRITICAL CARE UNIT

The antimicrobial management of patients in the critical care unit is complex. Not only must the clinician be familiar with a number of clinical, microbiological, pharmacological, and epidemiological observations but also fundamental pharmacodynamic concepts. It is an understanding of these concepts that forms the basis for the design of dosing strategies that maximize clinical efficacy and minimize toxicity. Antimicrobial selection is further complicated by the plethora of new antimicrobial agents available with varying clinical utility. Nowhere is this more evident than in the quinolone class of antibiotics. To aid the clinician in differentiating between quinolones it now seems reasonable to create a classification system akin to the generation grouping applied to the cephalosporins. Our classification is based upon the pharmacodynamic principles discussed within this article.