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October 24, 2017

EJRC Article Review

A Systematic Review and Network Meta-analysis

EJRC Article Review

Both the Healthcare Infection Control Practices Advisory Committee (2,3), the Centers for Disease Control & Prevention (6) and multiple other organisations (4,5) have published guidelines for the management of the increasing public health concern that is Multi-drug resistant Organisms. This is a meta-analysis into the effectiveness of these interventions, which have so far had inconclusive results.

This Systematic Review of Clinical Studies (1) compared at least two infection Prevention & Control interventions for the prevention of Multidrug Resistant Gram-Negative Bacteria in adults admitted to the Intensive Care Department including RCTs, Cohort Studies, Interrupted time-series studies and before-and-after studies only.

The Gram-Negative bacteria included in the search included MDR-AB (multidrug resistant acinetobacter), MDR-PA (multidrug resistant pseudomonas aeruginosa), ESBL (extended spectrum beta lactamase)-producing Enterobacteriacae & CRE (carbapenem resistant enterococci). Types of interventions included Standard Care (Hand-Hygiene & Contact Precautions), Antimicrobial stewardship (ASP), Environmental cleaning (ENV), Decolonisation (DCL) & Source Control (SCT).

Two reviewers independently screened each item, and data extracted including study characteristics, patient characteristics, interventions, outcomes and relevant findings were added to a standardised form.

3805 articles were identified which was narrowed down to 103 potential articles and finally triaged into 42 studies for the network meta-analysis. These included 62,068 patients, median age of 58.8 years of age and 60% were male. 22 studies out of the 42 were conducted in Europe and 28 of the 42 studies were conducted on ESBL-producing Enterobacteriaceae.

For the prevention of acquisition 4 component strategies (STD+ASP+ENV+SCT) was more effective than 3-component (STD+ASP+DCL, STD+ASP+ENV, STD+ASP+DCL) [RR 0.01 95% CI 0.01-0.04] which was more effective than 2 component strategies (STD+ENV, STD+DCL, STD+ASP) [RR 0.17-0.22 & 0.34-0.54 respectively].

For the prevention of infection STD+SCT was superior to STD alone (RR 0.25 [95%CI 0.10-0.61]).

There was no association between mortality in the Intensive Care Unit and number of IPC interventions used.

Subgroup analysis showed a significant reduction in MDR-GNB (Gram negative bacteria) acquisition for strategies using ASP as a core component. STD+DCL showed a significant reduction in MDR-GNB acquisition and infection in European countries only.

In the assessment of study quality, the Risk of Bias was high in the included Randomised Controlled Trials, Moderate in the observational studies, 2 studies as serious and 1 as critical. 20 studies out of the 42 were conducted during an outbreak of the organism, which limits its generalisability and brings concerns over whether these can be extrapolated to daily practice.

Much of the data was observational which limits our ability to assess causality as mentioned by the authors. The strength in this study is the large number of patients that were included.

The results showed a clear association between the number of interventions used and the prevention of both acquisition and infection with multidrug resistant Gram-Negative bacteria. This had a relative risk reduction for acquisition of MDR-GNB, which demonstrates how effective these interventions are and makes a strong case for implementing all of these interventions in the intensive care setting. The inability to demonstrate a mortality benefit is unfortunate given the magnitude of benefit but further studies are needed to further evaluate this in intensive care.

Article review was prepared and submitted by James Burton, Specialist registrar, University College London on behalf of the EJRC.



1) Teerawattanapong, Nattawat; Kengkla, Kirati; Dilokthornsakul, Piyameth; Saokaew, Surasak et al. Prevention and Control of Multidrug-Resistant Gram-Negative Bacteria in Adult Intensive Care Units: A systematic Review and Network Meta-analysis. Clinical Infectious Diseases 2017; 64(s2):S51-60

2) Siegel JD, Rhinehart E, Jackson M, Chiarello L. Management of multidrug-resistant organisms in health care settings, 2006. Am J Infect Control 2007; 35:S165–93.

3) Siegel JD, Rhinehart E, Jackson M, Chiarello L; Health Care Infection Control Practices Advisory Committee. 2007 guideline for isolation precautions: preventing transmission of infectious agents in health care settings. Am J Infect Control 2007; 35(10 suppl 2):S65–164.

4) Tacconelli E, Cataldo MA, Dancer SJ, et al; European Society of Clinical Microbiology. ESCMID guidelines for the management of the infection control measures to reduce transmission of multidrug-resistant gram-negative bacteria in hospitalised patients. Clin Microbiol Infect 2014; 20(suppl 1):1–55.

5) Yokoe DS, Anderson DJ, Berenholtz SM, et al; Society for Healthcare Epidemiology of America (SHEA). A compendium of strategies to prevent healthcare-associated infections in acute care hospitals: 2014 updates. Infect Control Hosp Epidemiol 2014; 35:967–77.

6) Centers for Disease Control and Prevention. Facility guidance for control of carbapenem-resistant Enterobacteriaceae (CRE) 2015. Available at: http://www.cdc. gov/hai/pdfs/cre/cre-guidance-508.pdf. Accessed 24 August 2016.

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