Draft Key Questions
Disposition of Comments Report
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To conduct a systematic review of the use of pharmacokinetic/pharmacodynamic (PK/PD) measures or strategies to dose and monitor intravenous (IV) antibiotics in the treatment of adults with hospital-acquired pneumonia (HAP).
MEDLINE® (via PubMed), Cochrane Library, International Pharmaceutical Abstracts, and ClinicalTrials.gov from January 1, 2004, to June 7, 2014.
Two investigators independently selected, extracted data from, and rated risk of bias of studies. We graded strength of evidence based on established guidance.
Ten studies (seven trials, three cohort studies) met inclusion criteria. Evidence is insufficient to conclude whether using PK/PD measures to inform decisions about dosing or monitoring IV antibiotic treatment improves either intermediate or health outcomes. One trial (rated high risk of bias) used PK/PD measures to study the impact of different antibiotic dosing levels on clinical responses, such as time on mechanical ventilation, treatment failure, and mortality.
Evidence is also insufficient to draw conclusions about the effect of continuous infusions of beta-lactam antibiotics compared with the effect of intermittent infusions on outcomes related to clinical response, mechanical ventilation, morbidity, mortality, or rates of antibiotic-related adverse events. Clinical response, duration of mechanical ventilation, superinfection, rates of antibiotic-related adverse events, and infusion-related adverse effects did not differ significantly in any study.
Despite the theoretical advantages of optimizing IV antibiotic dosing using PK/PD principles in patients with HAP, major gaps in the available evidence preclude our drawing conclusions or explaining clinical or policy implications. The near absence of strong evidence, particularly related to clinical applications, limits our ability to either support or oppose the adoption of various PK/PD strategies for this specific clinical purpose.