Bacterial quantitation in clinical infection: a systematic review

Pivotal clinical studies of new anti-infective drugs enrol patients with strictly defined clinical syndromes, with clinical and laboratory endpoints used to define treatment success. Assessing bacterial killing in the host by serial quantitation has potential as a more efficient pharmacometric approach to assess antibiotic efficacy. We conducted a systematic review of the use of bacterial quantitation in clinical infection. The main syndromes studied in the 222 included articles were bacteraemia, chronic respiratory disease, diarrhoea, pneumonia and sexually transmitted infections. Most reports (135 articles, 61%) quantified bacterial load in different specimen types using quantitative polymerase chain reaction (qPCR). For bacteraemias, bacterial DNA load measured in whole blood by qPCR at clinical presentation was typically 2-3 log10 copies ml-1, usually substantially higher than the estimates from quantitative culture. Higher bacterial loads were associated with increased mortality in 28 of 35 studies. Faster bacterial clearance was correlated with appropriate antibiotic therapy and improved outcome in the majority of studies. Most studies sampled too infrequently for accurate characterization of bacterial clearance rates. The rate of bacterial clearance from blood or other compartments is an informative pharmacodynamic endpoint in the assessment of antibacterial therapeutic effects, but standardized approaches to assessment are needed based on optimal study design. This article is part of the Theo Murphy meeting issue 'Evaluating anti-infective drugs'.