Clinical Features and Risk Factors for Development of Breakthrough Gram-Negative Bacteremia during Carbapenem Therapy

Abstract

ABSTRACT With the increasing use of carbapenems, carbapenem-resistant Gram-negative bacteria have become a major concern in health care-associated infections. The present study was performed to evaluate the clinical and microbiological features of breakthrough Gram-negative bacteremia (GNB) during carbapenem therapy and to assess risk factors for development of breakthrough GNB. A case-control study was performed at a tertiary hospital from 2005 to 2014. Case patients were defined as individuals whose blood cultures grew Gram-negative bacteria while the patients were receiving carbapenems for at least 48 h before breakthrough GNB. Age-, sex-, and date-matched controls were selected from patients who received carbapenem for at least 48 h and did not develop breakthrough GNB during carbapenem treatment. A total of 101 cases of breakthrough GNB were identified and compared to 100 controls. The causative microorganisms for breakthrough GNB were Stenotrophomonas maltophilia ( n = 33), Acinetobacter baumannii ( n = 32), Pseudomonas aeruginosa ( n = 21), and others ( n = 15). Approximately 90% of S. maltophilia isolates were susceptible to levofloxacin and trimethoprim-sulfamethoxazole. The most common infection types were primary bacteremia (38.6%) and respiratory infections (35.6%). More than half of the patients died within a week after bacteremia, and the 30-day mortality rate was 70.3%. In a multivariate analysis, a longer hospital stay, hematologic malignancy, persistent neutropenia, immunosuppressant use, and previous colonization by causative microorganisms were significantly associated with breakthrough GNB. Our data suggest that S. maltophilia , A. baumannii , and P. aeruginosa are the major pathogens of breakthrough GNB during carbapenem therapy, in association with a longer hospital stay, hematologic malignancy, persistent neutropenia, immunosuppressant use, and previous colonization.