PURPOSE: Infections due to carbapenem resistant gram negative bacteria’s (CRGNB) are ubiquitous and are associated with an overall poor outcome. Synergistic effects of combination therapy with polymyxin, a carbapenem and rifampin (PCR) are observed in in-vitro studies. However, clinical data to support this is limited. We performed a prospective observational cohort study to further study risk factors and outcomes.
METHODS: A prospective observational cohort study was performed from September 2009 to April 2010. All patients older than 18 years with a CRGNB infection were included. All patients were treated with polymyxin B, a carbapenem with or without rifampin. All patients were followed until 1 year after discharge or expiration. Baseline characteristics, risk factors for infection, indices of severity of disease were collected. The outcomes measured were mortality, length of stay, clinical success, microbiological success and toxicity.
RESULTS: 107 patients were studied. The mean age was 77 years, 60% were male. The mean Charlson Index was 8.1, 73% were recently exposed to antibiotics, 67% were recently hospitalized and 48% lived in a subacute nursing facility. The main sites of infection were lungs 66%, urinary tract 43%, skin and bones 20% with multiple sites infected in 34% of the patients. The mean APACHE IV score was 73. Clinical success was achieved in 50% after a mean treatment of 21.3 days (median 14 days), 23% did not clear the organism from the cultures. In reverse, 28% of the patients cleared the cultures but did not clinically get better. Recurrence occurred in 48%. The mean hospital length of stay was 53.8 (median 41). The all cause mortality for the hospitalization was 48% and mortality at 1 year was 70%. Nephrotoxicity was observed in 8.7% with recovery in 33%. Combination therapy with PCR was associated with decreased mortality (59% vs 75%).
CONCLUSIONS: CRGNB infections are associated with a high comorbidity index, previous antibiotic and health care exposure. Triple therapy results in improved survival.
CLINICAL IMPLICATIONS: PCR treatment is recommended for CRGNB infections.
DISCLOSURE: The following authors have nothing to disclose: Robbert Crusio, Sriharsha Rao, Nisarg Changawala, Vishesh Paul, Ceres Tiu, Edward Chapnick, Yizhak Kupfer, Sidney Tessler
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