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      An international multicenter retrospective study of Pseudomonas aeruginosa nosocomial pneumonia: impact of multidrug resistance

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          Abstract

          Introduction

          Pseudomonas aeruginosa nosocomial pneumonia ( Pa-NP) is associated with considerable morbidity, prolonged hospitalization, increased costs, and mortality.

          Methods

          We conducted a retrospective cohort study of adult patients with Pa-NP to determine 1) risk factors for multidrug-resistant (MDR) strains and 2) whether MDR increases the risk for hospital death. Twelve hospitals in 5 countries (United States, n = 3; France, n = 2; Germany, n = 2; Italy, n = 2; and Spain, n = 3) participated. We compared characteristics of patients who had MDR strains to those who did not and derived regression models to identify predictors of MDR and hospital mortality.

          Results

          Of 740 patients with Pa-NP, 226 patients (30.5%) were infected with MDR strains. In multivariable analyses, independent predictors of multidrug-resistance included decreasing age (adjusted odds ratio [AOR] 0.91, 95% confidence interval [CI] 0.96-0.98), diabetes mellitus (AOR 1.90, 95% CI 1.21-3.00) and ICU admission (AOR 1.73, 95% CI 1.06-2.81). Multidrug-resistance, heart failure, increasing age, mechanical ventilation, and bacteremia were independently associated with in-hospital mortality in the Cox Proportional Hazards Model analysis.

          Conclusions

          Among patients with Pa-NP the presence of infection with a MDR strain is associated with increased in-hospital mortality. Identification of patients at risk of MDR Pa-NP could facilitate appropriate empiric antibiotic decisions that in turn could lead to improved hospital survival.

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          Most cited references22

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          Antibiotic resistance--problems, progress, and prospects.

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            Risk factors for drug-resistant pathogens in community-acquired and healthcare-associated pneumonia.

            Identification of patients with drug-resistant pathogens at initial diagnosis is essential for treatment of pneumonia. To elucidate clinical features of community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP), and to clarify risk factors for drug-resistant pathogens in patients with CAP and HCAP. A prospective observational study was conducted in hospitalized patients with pneumonia at 10 institutions in Japan. Pathogens identified as not susceptible to ceftriaxone, ampicillin-sulbactam, macrolides, and respiratory fluoroquinolones were defined as CAP drug-resistant pathogens (CAP-DRPs). In total, 1,413 patients (887 CAP and 526 HCAP) were analyzed. CAP-DRPs were more frequently found in patients with HCAP (26.6%) than in patients with CAP (8.6%). Independent risk factors for CAP-DRPs were almost identical in patients with CAP and HCAP. These included prior hospitalization (adjusted odds ratio [AOR], 2.06; 95% confidence interval [CI], 1.23-3.43), immunosuppression (AOR, 2.31; 95% CI, 1.05-5.11), previous antibiotic use (AOR, 2.45; 95% CI, 1.51-3.98), use of gastric acid-suppressive agents (AOR, 2.22; 95% CI, 1.39-3.57), tube feeding (AOR, 2.43; 95% CI, 1.18-5.00), and nonambulatory status (AOR, 2.45; 95% CI, 1.40-4.30) in the combined patients with CAP and HCAP. The area under the receiver operating characteristic curve for counting the number of risk factors was 0.79 (95% CI, 0.74-0.84). The clinical profile of HCAP was different from that of CAP. However, physicians can predict drug resistance in patients with either CAP or HCAP by taking account of the cumulative number of the risk factors. Clinical trial registered with https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000004001&language=E ; number UMIN000003306.
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              Optimal management therapy for Pseudomonas aeruginosa ventilator-associated pneumonia: an observational, multicenter study comparing monotherapy with combination antibiotic therapy.

              To evaluate whether one antibiotic achieves equal outcomes compared with combination antibiotic therapy in patients with Pseudomonas aeruginosa ventilator-associated pneumonia. A retrospective, multicenter, observational, cohort study. Five intensive care units in Spanish university hospitals. Adult patients identified to have monomicrobial episodes of ventilator-associated pneumonia with significant quantitative respiratory cultures for P. aeruginosa. None. A total of 183 episodes of monomicrobial P. aeruginosa ventilator-associated pneumonia were analyzed. Monotherapy alone was used empirically in 67 episodes, being significantly associated with inappropriate therapy (56.7% vs. 90.5%, p < .001). Hospital mortality was significantly higher in the 40 patients with inappropriate therapy compared with those at least on antibiotic with activity in vitro (72.5% vs. 23.1%, p < .05). Excess mortality associated with monotherapy was estimated to be 13.6% (95% confidence interval -2.6 to 29.9). The use of monotherapy or combination therapy in the definitive regimen did not influence mortality, length of stay, development of resistance to the definitive treatment, or appearance of recurrences. Inappropriate empirical therapy was associated with increased mortality (adjusted hazard ratio 1.85; 95% confidence interval 1.07-3.10; p = .02) in a Cox proportional hazard regression analysis, after adjustment for disease severity, but not effective monotherapy (adjusted hazard ratio 0.90; 95% confidence interval 0.50-1.63; p = .73) compared with effective combination therapy (adjusted hazard ratio 1). The other two variables also independently associated with mortality were age (adjusted hazard ratio 1.02; 95% confidence interval 1.01-1.04; p = .005) and chronic cardiac insufficiency (adjusted hazard ratio 1.90; 95% confidence interval 1.04-3.47; p = .035). Initial use of combination therapy significantly reduces the likelihood of inappropriate therapy, which is associated with higher risk of death. However, administration of only one effective antimicrobial or combination therapy provides similar outcomes, suggesting that switching to monotherapy once the susceptibility is documented is feasible and safe.
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                Author and article information

                Contributors
                scott.micek@stlcop.edu
                r-wunderink@northwestern.edu
                mkollef@dom.wustl.edu
                cxchen@dom.wustl.edu
                jrello@crips.es
                jean.chastre@psl.aphp.fr
                m.antonelli@rm.unicatt.it
                welte.tobias@mh-hannover.de
                Bernard.clair@rpc.ap-hop-paris.fr
                helmut.ostermann@med.uni-muenchen.de
                ecalbo@mutuaterrassa.es
                ATORRES@clinic.ub.es
                menichettifrancesco@gmail.com
                schramm.garrett@mayo.edu
                Vandana.Menon@cubist.com
                Journal
                Crit Care
                Critical Care
                BioMed Central (London )
                1364-8535
                1466-609X
                6 May 2015
                6 May 2015
                2015
                : 19
                : 1
                : 219
                Affiliations
                [ ]St. Louis College of Pharmacy, 4588 Parkview Place, St. Louis, MO 63110-1088 USA
                [ ]Northwestern University Feinberg School of Medicine, McGaw Pavilion Suite M-300, 240 E Huron, Chicago, IL 60611 USA
                [ ]Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8052, St. Louis, MO 63110 USA
                [ ]Vall d’Hebron University Hospital, Passeig Vall d’Hebron, 119, Barcelona, 08035 Spain
                [ ]Service de Réanimation Médicale, Institut de Cardiologie, Groupe Hospitalier Pitié-Salpêtrière, 47-83 boulevard de l’Hôpital, 75651 Paris, Cedex 13 France
                [ ]Policlinico Universitario A Gemelli, Largo Agostino Gemelli 8, Rome, 00168 Italy
                [ ]Medizinische Hochschule, Carl-Neuberg-Str. 1, Hannover, 30625 Germany
                [ ]Hôpital Raymond Poincaré, 104 boulevard Raymond Poincaré, Garches, 92380 France
                [ ]Department of Hematology, University Hospital Grosshadern, Marchioninistr 15, Munich, D-81377 Germany
                [ ]Hospital Universitari MútuaTerrassa, Plaça Dr. Robert, 5, Terrassa, 08221 Spain
                [ ]Pneumology Department, Clinic Institute of Thorax, Villarroel 170, Barcelona, 08036 Spain
                [ ]Malattie Infettive, Az. Ospedaliera Universitaria Pisana, Via Paradisa 2 – Cisanello, Pisa, 56100 Italy
                [ ]Pharmacy Services, Mayo Clinic, 200 First St SW, Rochester, MN 55905 USA
                [ ]Cubist Pharmaceuticals, Inc., 65 Hayden Avenue, Lexington, MA 02421 USA
                Article
                926
                10.1186/s13054-015-0926-5
                4446947
                25944081
                11cbd84f-e243-4ac6-9241-45805b18be92
                © Micek et al.; licensee BioMed Central. 2015

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. 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
                : 26 January 2015
                : 15 April 2015
                Categories
                Research
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                © The Author(s) 2015

                Emergency medicine & Trauma
                Emergency medicine & Trauma

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