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Abstract
BackgroundWhile quantification of viral loads has been successfully employed in clinical medicine and has provided valuable insights and useful markers for several viral diseases, the potential of measuring bacterial DNA load to predict outcome or monitor therapeutic responses remains largely unexplored. We tested this possibility by investigating bacterial loads in Acinetobacter baumannii bacteremia, a rapidly increasing nosocomial infection characterized by high mortality, drug resistance, multiple and complicated risk factors, all of which urged the need of good markers to evaluate therapeutics.Methods and FindingsWe established a quantitative real-time PCR assay based on an A. baumannii-specific gene, Oxa-51, and conducted a prospective study to examine A. baumannii loads in 318 sequential blood samples from 51 adults patients (17 survivors, 34 nonsurvivors) with culture-proven A. baumannii bacteremia in the intensive care units. Oxa-51 DNA loads were significantly higher in the nonsurvivors than survivors on day 1, 2 and 3 (P = 0.03, 0.001 and 0.006, respectively). Compared with survivors, nonsurvivors had higher maximum Oxa-51 DNA load and a trend of increase from day 0 to day 3 (P<0.001), which together with Pitt bacteremia score were independent predictors for mortality by multivariate analysis (P = 0.014 and 0.016, for maximum Oxa-51 DNA and change of Oxa-51 DNA, respectively). Kaplan-Meier analysis revealed significantly different survival curves in patients with different maximum Oxa-51 DNA and change of Oxa-51 DNA from day 0 to day 3.ConclusionsHigh Oxa-51 DNA load and its initial increase could predict mortality. Moreover, monitoring Oxa-51 DNA load in blood may provide direct parameters for evaluating new regimens against A. baumannii in future clinical studies.
Highlights
The successful employment of quantitative PCR to measure viral load in clinical medicine has advanced our understanding of pathogenesis of many viral diseases and provided useful markers for predicting outcome and/or monitoring therapeutic responses [1]
Previous studies have identified multiple and complicated risk factors for the high mortality of A. baumannii bacteremia [5,6,10,11,12,13,14,15], but none has investigated the roles of bacterial load in the disease outcome
We reported previously that high levels of mecA DNA in blood after 3 and 7 days of antibiotic therapy were associated with mortality in methicillin-resistant Staphylococcus aureus (MRSA) bacteremia [21], suggesting sequential bacterial DNA load in blood can be used to evaluate therapeutic responses
Summary
The successful employment of quantitative PCR to measure viral load in clinical medicine has advanced our understanding of pathogenesis of many viral diseases and provided useful markers for predicting outcome and/or monitoring therapeutic responses [1]. While quantification of viral loads has been successfully employed in clinical medicine and has provided valuable insights and useful markers for several viral diseases, the potential of measuring bacterial DNA load to predict outcome or monitor therapeutic responses remains largely unexplored. We tested this possibility by investigating bacterial loads in Acinetobacter baumannii bacteremia, a rapidly increasing nosocomial infection characterized by high mortality, drug resistance, multiple and complicated risk factors, all of which urged the need of good markers to evaluate therapeutics
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