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Carbapenem-resistant (CR) Acinetobacter baumannii is an important pathogen in ventilator-associated pneumonia (VAP), but therapeutic options are limited. We describe the clinical outcomes of the largest case series of CR-Acinetobacter VAP reported to date.A retrospective analysis of 55 participants with CR-Acinetobacter VAP from July 2004 to December 2007 was undertaken. The primary endpoint was clinical response or microbiological eradication. Secondary endpoint was treatment-associated nephrotoxicity defined as ≥50% increase in serum creatinine or an increase of ≥0.5 mg/dL during therapy.Forty-two (76.4%) participants achieved clinical response at the completion of therapy. Clinical responses were achieved in 60.0% of sulbactam-based, 66.7% of polymyxin-based, 77.8% of aminoglycoside-based, 80.6% of minocycline-based, and 90.0% of tigecycline-based regimens. Follow-up sputum cultures were available in 6 of 10 tigecycline-treated participants with 4 of 6 isolates developing intermediate resistance to tigecycline while on therapy. Ten (18.2%) participants without preexisting renal disease developed treatment-associated nephrotoxicity. Baseline serum creatinine was 0.9±0.1 mg/dL (range: 0.6-1.0 mg/dL) at the start of therapy and peaked at 1.9 ± 0.5 mg/dL (range: 1.6-3.0 mg/dL) during therapy. After excluding other potential concomitant renal toxic agents, nephrotoxicity developed in 6 of 30 (20.0%) and 4 of 7 (57.1%) participants treated with an aminoglycoside-or polymyxin-based regimen, respectively.Our results demonstrated that CR-Acinetobacter VAP can be effectively treated with second-line agents. However, colistin-related nephrotoxicity was much higher than recently reported and decreased susceptibility to tigecycline emerged on therapy demonstrating the limitations of alternative regimens.