Continuous Infusion Versus Intermittent Bolus of Beta-Lactams in Critically Ill Patients with Respiratory Infections: A Systematic Review and Meta-analysis

  • Young R. Lee
  • Pamela D. Miller
  • Saeed K. Alzghari
  • Delilah D. Blanco
  • Jackson D. Hager
  • Kailey S. Kuntz
Systematic Review



Critically ill patients display altered pharmacokinetics 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.


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.


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 pharmacokinetic/pharmacodynamic parameters were included in the systematic review.


The majority of patients in both groups maintained the percentage of time the free drug concentration exceeded 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 critically ill adult patients with respiratory infections significantly improved clinical cure rates when compared to IB (risk ratio [RR] 1.177; 95% CI 1.065–1.300). No significant differences in mortality rates were seen when patients were treated with either dosing modality (RR 0.845; 95% CI 0.644–1.108).


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.



Authors would like to thank Peggy Edwards, Reference Librarian and Unit Manager at the Preston Smith Library at the Texas Tech University Health Sciences Center for her assistance with the literature search and search strategy information. Authors would also like to thank Dr. Irene La-Beck, Associate Professor at the Texas Tech University Health Sciences Center School of Pharmacy for her advice on the meta-analysis.

Compliance with Ethical Standards

Conflict of interest

Author Young Lee, author Pamela Miller, author Saeed Alzghari, author Delilah Blanco, author Kailey Kuntz, and author Jackson Hager declare that they have no conflict of interest.


No funding was received for this review.

Supplementary material

13318_2017_439_MOESM1_ESM.pdf (79 kb)
Supplementary material 1 (PDF 79 kb)
13318_2017_439_MOESM2_ESM.docx (23 kb)
Supplementary material 2 (DOCX 22 kb)


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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Young R. Lee
    • 1
  • Pamela D. Miller
    • 1
  • Saeed K. Alzghari
    • 2
  • Delilah D. Blanco
    • 3
  • Jackson D. Hager
    • 1
  • Kailey S. Kuntz
    • 1
  1. 1.Department of Pharmacy PracticeTexas Tech University Health Sciences Center School of PharmacyAbileneUSA
  2. 2.Gulfstream Genomics, LLCDallasUSA
  3. 3.Tampa General HospitalTampaUSA

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