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      Outcomes of adult patients in the intensive care unit with Pseudomonas aeruginosa pneumonia who received an active anti‐pseudomonal β‐lactam: Does “S” equal success in the presence of resistance to other anti‐pseudomonal β‐lactams?

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          Abstract

          Study Objectives

          The most commonly prescribed antibiotics for patients with hospital‐acquired bacterial pneumonia (HABP) and ventilator‐associated bacterial pneumonia (VABP) due to Pseudomonas aeruginosa are the conventional anti‐pseudomonal β‐lactams (APBLs) (ie, ceftazidime, cefepime, meropenem, or piperacillin‐tazobactam). Similar resistance mechanisms in Paeruginosa affect the APBLs, and it is unclear if resistance to one APBL can affect the effectiveness of other APBLs. This exploratory, hypothesis‐generating analysis evaluates the impact of APBL resistance among patients in the intensive care unit (ICU) with Paeruginosa HABP/VABP who initially receive a microbiologically active APBL.

          Design

          A retrospective cohort [GJ1] [LT2] study.

          Setting

          Kaiser Permanente Southern California members (01/01/2011‐12/31/2017).

          Patients

          The study included adult patients admitted to the ICU with a monomicrobial P. aeruginosa HABP/VABP who received a microbiologically active APBL within 2 days of index P. aeruginosa respiratory culture.

          Intervention

          Patients were stratified by presence of resistance to APBL on index P. aeruginosa (0 vs. ≥1 resistant APBL).

          Measurements

          Primary outcomes were 30‐day mortality and discharge to home.

          Main Results

          Overall, 553 patients were included. Thirty‐day mortality was 28%, and 32% of patients were discharged home. Eighty‐eight patients (16%) had a Paeruginosa HABP/VABP that was resistant to ≥1 APBL (other than active empiric treatment). Relative to patients with no APBL resistance, patients with resistance to ≥1 APBL had a higher 30‐day mortality (adjusted odds ratio (aOR) [95% confidence interval (CI)]: 1.65 [1.02–2.66]) and were less likely to be discharged home (adjusted hazard ratio (aHR) [95% CI]: 0.50 [0.29–0.85]).

          Conclusion

          Further study is needed, but this exploratory analysis suggests that the full APBL susceptibility profile should be considered when selecting therapy for patients with Paeruginosa HABP/VABP.

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          Most cited references27

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          Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society.

          It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.These guidelines are intended for use by healthcare professionals who care for patients at risk for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), including specialists in infectious diseases, pulmonary diseases, critical care, and surgeons, anesthesiologists, hospitalists, and any clinicians and healthcare providers caring for hospitalized patients with nosocomial pneumonia. The panel's recommendations for the diagnosis and treatment of HAP and VAP are based upon evidence derived from topic-specific systematic literature reviews.
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            Pseudomonas aeruginosa Lifestyle: A Paradigm for Adaptation, Survival, and Persistence

            Pseudomonas aeruginosa is an opportunistic pathogen affecting immunocompromised patients. It is known as the leading cause of morbidity and mortality in cystic fibrosis (CF) patients and as one of the leading causes of nosocomial infections. Due to a range of mechanisms for adaptation, survival and resistance to multiple classes of antibiotics, infections by P. aeruginosa strains can be life-threatening and it is emerging worldwide as public health threat. This review highlights the diversity of mechanisms by which P. aeruginosa promotes its survival and persistence in various environments and particularly at different stages of pathogenesis. We will review the importance and complexity of regulatory networks and genotypic-phenotypic variations known as adaptive radiation by which P. aeruginosa adjusts physiological processes for adaptation and survival in response to environmental cues and stresses. Accordingly, we will review the central regulatory role of quorum sensing and signaling systems by nucleotide-based second messengers resulting in different lifestyles of P. aeruginosa. Furthermore, various regulatory proteins will be discussed which form a plethora of controlling systems acting at transcriptional level for timely expression of genes enabling rapid responses to external stimuli and unfavorable conditions. Antibiotic resistance is a natural trait for P. aeruginosa and multiple mechanisms underlying different forms of antibiotic resistance will be discussed here. The importance of each mechanism in conferring resistance to various antipseudomonal antibiotics and their prevalence in clinical strains will be described. The underlying principles for acquiring resistance leading pan-drug resistant strains will be summarized. A future outlook emphasizes the need for collaborative international multidisciplinary efforts to translate current knowledge into strategies to prevent and treat P. aeruginosa infections while reducing the rate of antibiotic resistance and avoiding the spreading of resistant strains.
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              Multiple mechanisms of antimicrobial resistance in Pseudomonas aeruginosa: our worst nightmare?

              Pseudomonas aeruginosa carries multiresistance plasmids less often than does Klebsiella pneumoniae, develops mutational resistance to cephalosporins less readily than Enterobacter species, and has less inherent resistance than Stenotrophomonas maltophilia. What nevertheless makes P. aeruginosa uniquely problematic is a combination of the following: the species' inherent resistance to many drug classes; its ability to acquire resistance, via mutations, to all relevant treatments; its high and increasing rates of resistance locally; and its frequent role in serious infections. A few isolates of P. aeruginosa are resistant to all reliable antibiotics, and this problem seems likely to grow with the emergence of integrins that carry gene cassettes encoding both carbapenemases and amikacin acetyltransferases.
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                Author and article information

                Contributors
                Thomas.Lodise@acphs.edu
                Sara.Y.Tartof@kp.org
                Journal
                Pharmacotherapy
                Pharmacotherapy
                10.1002/(ISSN)1875-9114
                PHAR
                Pharmacotherapy
                John Wiley and Sons Inc. (Hoboken )
                0277-0008
                1875-9114
                05 July 2021
                August 2021
                : 41
                : 8 ( doiID: 10.1002/phar.v41.8 )
                : 658-667
                Affiliations
                [ 1 ] Abany College of Pharmacy Health Sciences Albany New York USA
                [ 2 ] Merck & Co., Inc. Kenilworth New Jersey USA
                [ 3 ] Kaiser Permanente Southern California Department of Research & Evaluation Pasadena California USA
                Author notes
                [*] [* ] Correspondence

                Thomas P. Lodise, Department of Pharmacy Practice, Albany College of Pharmacy and Health Sciences, Albany, NY, USA.

                Email: Thomas.Lodise@ 123456acphs.edu

                Sara Y. Tartof, Southern California Permanente Medical Group, Department of Health Systems Science, Kaiser Permanente Bernard J. Tyson School of Medicine, Kaiser Permanente Research, Department of Research & Evaluation, Pasadena, CA 91101, USA.

                Email: Sara.Y.Tartof@ 123456kp.org

                Author information
                https://orcid.org/0000-0002-4730-0655
                Article
                PHAR2600
                10.1002/phar.2600
                8457199
                34097763
                6c262f43-266b-4f2a-9f76-492b69eb7293
                © 2021 The Authors. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy published by Wiley Periodicals LLC on behalf of Pharmacotherapy Publications, Inc.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 26 April 2021
                : 21 January 2021
                : 26 April 2021
                Page count
                Figures: 3, Tables: 2, Pages: 10, Words: 6758
                Funding
                Funded by: Merck , doi 10.13039/100004334;
                Categories
                Original Research Article
                Original Research Articles
                Custom metadata
                2.0
                August 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.0.7 mode:remove_FC converted:22.09.2021

                antibiotics,beta‐lactams,epidemiology,outcomes,pseudomonas,resistance,treatment

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