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      Risk factors for hospitalized patients with resistant or multidrug-resistant Pseudomonas aeruginosa infections: a systematic review and meta-analysis

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          Abstract

          Background

          Identifying risk factors predicting acquisition of resistant Pseudomonas aeruginosa will aid surveillance and diagnostic initiatives and can be crucial in early and appropriate antibiotic therapy. We conducted a systematic review examining risk factors of acquisition of resistant P. aeruginosa among hospitalized patients.

          Methods

          MEDLINE®, EMBASE®, and Cochrane Central were searched between 2000 and 2016 for studies examining independent risk factors associated with acquisition of resistant P. aeruginosa, among hospitalized patients. Random effects model meta-analysis was conducted when at least three or more studies were sufficiently similar.

          Results

          Of the 54 eligible articles, 28 publications (31studies) examined multi-drug resistant (MDR) or extensively drug resistant (XDR) P. aeruginosa and 26 publications (29 studies) examined resistant P. aeruginosa. The acquisition of MDR P. aeruginosa, as compared with non-MDR P. aeruginosa, was significantly associated with intensive care unit (ICU) admission (3 studies: summary adjusted odds ratio [OR] 2.2) or use of quinolones (4 studies: summary adjusted OR 3.59). Acquisition of MDR or XDR compared with susceptible P. aeruginosa was significantly associated with prior hospital stay (4 studies: summary adjusted OR 1.90), use of quinolones (3 studies: summary adjusted OR 4.34), or use of carbapenems (3 studies: summary adjusted OR 13.68). The acquisition of MDR P. aeruginosa compared with non- P. aeruginosa was significantly associated with prior use of cephalosporins (3 studies: summary adjusted OR 3.96), quinolones (4 studies: summary adjusted OR 2.96), carbapenems (6 studies: summary adjusted OR 2.61), and prior hospital stay (4 studies: summary adjusted OR 1.74). The acquisition of carbapenem-resistant P. aeruginosa compared with susceptible P. aeruginosa, was statistically significantly associated with prior use of piperacillin-tazobactam (3 studies: summary adjusted OR 2.64), vancomycin (3 studies: summary adjusted OR 1.76), and carbapenems (7 studies: summary adjusted OR 4.36).

          Conclusions

          Prior use of antibiotics and prior hospital or ICU stay was the most significant risk factors for acquisition of resistant P. aeruginosa. These findings provide guidance in identifying patients that may be at an elevated risk for a resistant infection and emphasize the importance of antimicrobial stewardship and infection control in hospitals.

          Electronic supplementary material

          The online version of this article (10.1186/s13756-018-0370-9) contains supplementary material, which is available to authorized users.

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          Most cited references57

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          The epidemiology, pathogenesis and treatment of Pseudomonas aeruginosa infections.

          Pseudomonas aeruginosa is an important bacterial pathogen, particularly as a cause of infections in hospitalised patients, immunocompromised hosts and patients with cystic fibrosis. Surveillance of nosocomial P. aeruginosa infections has revealed trends of increasing antimicrobial resistance, including carbapenem resistance and multidrug resistance. Mechanisms of antimicrobial resistance include multidrug efflux pumps, ss-lactamases and downregulation of outer membrane porins. Mechanisms of virulence include secreted toxins and the ability to form biofilms. The effective treatment of infections caused by P. aeruginosa includes prevention when possible, source control measures as necessary and prompt administration of appropriate antibacterial agents. Antibacterial de-escalation should be pursued in patients with an appropriate clinical response, especially when antibacterial susceptibilities are known. Multidrug-resistant P. aeruginosa may require treatment with less commonly used antibacterials (e.g. colistin), but newer anti-pseudomonal antibacterials are expected to be available in the near future.
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            Multidrug-resistant Pseudomonas aeruginosa: risk factors and clinical impact.

            Pseudomonas aeruginosa, a leading nosocomial pathogen, may become multidrug resistant (MDR). Its rate of occurrence, the individual risk factors among affected patients, and the clinical impact of infection are undetermined. We conducted an epidemiologic evaluation and molecular typing using pulsed-field gel electrophoresis (PFGE) of 36 isolates for 82 patients with MDR P. aeruginosa and 82 controls matched by ward, length of hospital stay, and calendar time. A matched case-control study identified individual risk factors for having MDR P. aeruginosa, and a retrospective matched-cohort study examined clinical outcomes of such infections. The 36 isolates belonged to 12 PFGE clones. Two clones dominated, with one originating in an intensive care unit (ICU). Cases and controls had similar demographic characteristics and numbers of comorbid conditions. A multivariate model identified ICU stay, being bedridden, having high invasive devices scores, and being treated with broad-spectrum cephalosporins and with aminoglycosides as significant risk factors for isolating MDR P. aeruginosa. Having a malignant disease was a protective factor (odds ratio [OR] = 0.2; P = 0.03). MDR P. aeruginosa was associated with severe outcomes compared to controls, including increased mortality (OR = 4.4; P = 0.04), hospital stay (hazard ratio, 2; P = 0.001), and requirement for procedures (OR = 5.4; P = 0.001). The survivors functioned more poorly at discharge than the controls, and more of the survivors were discharged to rehabilitation centers or chronic care facilities. The epidemiology of MDR P. aeruginosa is complex. Critically ill patients that require intensive care and are treated with multiple antibiotic agents are at high risk. MDR P. aeruginosa infections are associated with severe adverse clinical outcomes.
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              Clinical and economic consequences of hospital-acquired resistant and multidrug-resistant Pseudomonas aeruginosa infections: a systematic review and meta-analysis

              Background Increasing rates of resistant and multidrug-resistant (MDR) P. aeruginosa in hospitalized patients constitute a major public health threat. We present a systematic review of the clinical and economic impact of this resistant pathogen. Methods Studies indexed in MEDLINE and Cochrane databases between January 2000-February 2013, and reported all-cause mortality, length of stay, hospital costs, readmission, or recurrence in at least 20 hospitalized patients with laboratory confirmed resistant P. aeruginosa infection were included. We accepted individual study definitions of MDR, and assessed study methodological quality. Results The most common definition of MDR was resistance to more than one agent in three or more categories of antibiotics. Twenty-three studies (7,881 patients with susceptible P. aeruginosa, 1,653 with resistant P. aeruginosa, 559 with MDR P. aeruginosa, 387 non-infected patients without P. aeruginosa) were analyzed. A random effects model meta-analysis was feasible for the endpoint of all-cause in-hospital mortality. All-cause mortality was 34% (95% confidence interval (CI) 27% – 41%) in patients with any resistant P. aeruginosa compared to 22% (95% CI 14% – 29%) with susceptible P. aeruginosa. The meta-analysis demonstrated a > 2-fold increased risk of mortality with MDR P. aeruginosa (relative risk (RR) 2.34, 95% CI 1.53 – 3.57) and a 24% increased risk with resistant P. aeruginosa (RR 1.24, 95% CI 1.11 – 1.38), compared to susceptible P. aeruginosa. An adjusted meta-analysis of data from seven studies demonstrated a statistically non-significant increased risk of mortality in patients with any resistant P. aeruginosa (adjusted RR 1.24, 95% CI 0.98 – 1.57). All three studies that reported infection-related mortality found a statistically significantly increased risk in patients with MDR P. aeruginosa compared to those with susceptible P. aeruginosa. Across studies, hospital length of stay (LOS) was higher in patients with resistant and MDR P. aeruginosa infections, compared to susceptible P. aeruginosa and control patients. Limitations included heterogeneity in MDR definition, restriction to nosocomial infections, and potential confounding in analyses. Conclusions Hospitalized patients with resistant and MDR P. aeruginosa infections appear to have increased all-cause mortality and LOS. The negative clinical and economic impact of these pathogens warrants in-depth evaluation of optimal infection prevention and stewardship strategies. Electronic supplementary material The online version of this article (doi:10.1186/2047-2994-3-32) contains supplementary material, which is available to authorized users.
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                Author and article information

                Contributors
                617-636-5109 , graman@tuftsmedicalcenter.org
                eavendano@tuftsmedicalcenter.org
                Jeffrey.Chan@va.gov
                sanjay.merchant@merck.com
                laura.puzniak@merck.com
                Journal
                Antimicrob Resist Infect Control
                Antimicrob Resist Infect Control
                Antimicrobial Resistance and Infection Control
                BioMed Central (London )
                2047-2994
                4 July 2018
                4 July 2018
                2018
                : 7
                : 79
                Affiliations
                [1 ]ISNI 0000 0000 8934 4045, GRID grid.67033.31, Center for Clinical Evidence Synthesis, Tufts Medical Center, ; 800 Washington Street, Box 63, Boston, MA 02111 USA
                [2 ]ISNI 0000 0001 2260 0793, GRID grid.417993.1, Merck & Co., Inc., ; Kenilworth, NJ USA
                Author information
                http://orcid.org/0000-0003-4427-1083
                Article
                370
                10.1186/s13756-018-0370-9
                6032536
                29997889
                559f0ca6-b1ac-4aea-94ef-58ea05488fd9
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 23 March 2018
                : 14 June 2018
                Funding
                Funded by: Merck & Co., Inc.
                Categories
                Research
                Custom metadata
                © The Author(s) 2018

                Infectious disease & Microbiology
                resistant,multi-drug resistant,pseudomonas aeruginosa,risk factors,acquisition

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