Failure of current cefepime breakpoints to predict clinical outcomes of bacteremia caused by gram-negative organisms.

For commonly encountered gram-negative bacilli, a MIC of cefepime of 8 mug/ml or less was defined by the Clinical and Laboratory Standards Institute as "susceptible" prior to the commercial release of the antibiotic. We assessed 204 episodes of bacteremia caused by gram-negative organisms for which patients received cefepime (typically 1 to 2 g every 12 h) as the primary mode of therapy. The cefepime MIC breakpoint derived by classification and regression tree (CART) software analysis to delineate the risk of 28-day mortality was 8 microg/ml. Patients infected with gram-negative organisms treated with cefepime at a MIC of > or =8 microg/ml had a mortality rate of 54.8% (17/31 died), compared to 24.1% (35/145 died) for those treated with a cefepime MIC of <8 microg/ml. The rate of mortality for those treated with a cefepime MIC of 8 microg/ml was 56.3% (9/16 died), compared to 53.3% (8/15 died) for those treated with cefepime at a MIC of >8 microg/ml. A multivariable analysis including severity of illness indices showed that treating patients with bacteremia due to gram-negative organisms with a cefepime MIC of > or =8 microg/ml was an independent predictor of mortality (P < or = 0.001). There was no significant difference in outcome according to the dosage regimen utilized. Pharmacodynamic assessments that were presented previously would suggest that cefepime treatment (particularly a dosage of 1 g every 12 h) has a low probability of target attainment associated with successful in vivo outcome when the cefepime MIC is > or =8 microg/ml. It would appear reasonable, based on pharmacodynamic and clinical grounds, to lower the breakpoints for cefepime in countries where the cefepime dosage of 1 to 2 g every 12 h is the licensed therapy for serious infections, so that organisms with a cefepime MIC of 8 microg/ml are no longer regarded as susceptible to the antibiotic.

Scedosporium prolificans brain abscess in a patient with chronic granulomatous disease: successful combination therapy with voriconazole and terbinafine.

A patient with chronic granulomatous disease developed brain abscesses with Scedosporium prolificans. In vitro susceptibility revealed a synergistic effect of terbinafine and voriconazole. He received therapy with both these antifungals which resulted in disappearance of the brain abscesses. This is the first reported cure of a CNS S. prolificans infection in an immunocompromised host.

Acinetobacter baumannii bloodstream infection while receiving tigecycline: a cautionary report.

OBJECTIVES: Tigecycline has shown in vitro activity against Acinetobacter baumannii. Yet, published clinical experience with tigecycline use outside clinical trials is lacking. We describe, for the first time, bloodstream infection caused by tigecycline-non-susceptible A. baumannii occurring in patients receiving tigecycline for other indications. The possible mechanisms of resistance and pharmacokinetic limitations of the drug are addressed. METHODS: The clinical records of involved patients were systematically reviewed. Tigecycline susceptibility testing was initially performed using the Etest method and confirmed by agar dilution. Involved isolates underwent PFGE and exposure to phenyl-arginine-beta-naphthylamide (PAbetaN), an efflux pump inhibitor. RESULTS: Two patients developed A. baumannii bloodstream infection while receiving tigecycline. Tigecycline was administered for other indications for 9 and 16 days, respectively, before the onset of A. baumannii infection. Patient 1 died of overwhelming A. baumannii infection and Patient 2 recovered after a change in antibiotic therapy. The MICs of tigecycline were 4 and 16 mg/L, respectively. Both isolates had a multidrug-resistant phenotype and were genotypically unrelated. After exposure to PAbetaN, the MICs reduced to 1 and 4 mg/L, respectively. CONCLUSIONS: To our knowledge, this is the first clinical description of bloodstream infection caused by tigecycline-non-susceptible A. baumannii. Such resistance appears to be at least partly attributable to an efflux pump mechanism. Given the reported low serum tigecycline levels, we urge caution when using this drug for treatment of A. baumannii bloodstream infection.