SYSTEMATIC REVIEW Continuous Infusion Versus Intermittent Bolus of Beta-Lactams in Critically Ill Patients with Respiratory Infections: A Systematic Review and Meta-analysis Young R. Lee 1 • Pamela D. Miller 1 • Saeed K. Alzghari 2 • Delilah D. Blanco 3 • Jackson D. Hager 1 • Kailey S. Kuntz 1 Ó Springer International Publishing AG 2017 Abstract Background Critically ill patients display altered pharma- cokinetics and pharmacodynamics and are more likely to be infected with more resistant pathogens. Beta-lactam antibiotics exhibit time-dependent pharmacodynamics; therefore, it is postulated that continuous infusion (CI) may optimize these parameters. Objective To perform a systematic review and meta- analysis of the available literature comparing CI versus intermittent bolus (IB) of beta-lactam antibiotics in critically ill adult patients with respiratory infections to determine if clinical benefits exist. Methods PubMed, EMBASE, and Web of Science were searched. Thirteen randomized controlled trials were included in the meta-analyses of clinical cure and/or mortality. Four retrospective studies reporting clinical cure and/or mortality, and 11 studies that reported pharma- cokinetic/pharmacodynamic parameters were included in the systematic review. Results The majority of patients in both groups maintained the percentage of time the free drug concentration excee- ded the minimum inhibitory concentration (%fT [ MIC) targets throughout the treatment, with differences favoring CI being more prevalent when the MIC of the offending pathogen increased. CI of beta-lactam antibiotics in criti- cally ill adult patients with respiratory infections signifi- cantly improved clinical cure rates when compared to IB (risk ratio [RR] 1.177; 95% CI 1.065–1.300). No signifi- cant differences in mortality rates were seen when patients were treated with either dosing modality (RR 0.845; 95% CI 0.644–1.108). Conclusions CI of beta-lactam antibiotics is associated with better cure rates and higher %fT [ MIC when administered to critically ill patients with respiratory infections, but may be most beneficial in severely ill patients with more resistant Gram-negative bacterial infections. Electronic supplementary material The online version of this article (http://doi.org/10.1007/s13318-017-0439-5) contains supple- mentary material, which is available to authorized users. & Young R. Lee young.lee@ttuhsc.edu Pamela D. Miller pamela.miller@ttuhsc.edu Saeed K. Alzghari s.alzghari@gmail.com Delilah D. Blanco dblanco@tgh.org Jackson D. Hager jackson.hager@ttuhsc.edu Kailey S. Kuntz kailey.kuntz@ttuhsc.edu 1 Department of Pharmacy Practice, Texas Tech University Health Sciences Center School of Pharmacy, 1718 Pine Street, Abilene, TX 79601, USA 2 Gulfstream Genomics, LLC, 9301 N Central Expressway STE 335, Dallas, TX 75231, USA 3 Tampa General Hospital, 1 Tampa General Circle, Tampa, FL 33606, USA Eur J Drug Metab Pharmacokinet DOI 10.1007/s13318-017-0439-5