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      Management strategies for severe Pseudomonas aeruginosa infections

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          Abstract

          Purpose

          This review focuses on the management of severe Pseudomonas aeruginosa infections in critically ill patients.

          Recent findings

          Pseudomonas aeruginosa is the most common pathogen in intensive care; the main related infections are nosocomial pneumonias, then bloodstream infections. Antimicrobial resistance is common; despite new antibiotics, it is associated with increased mortality, and can lead to a therapeutic deadlock.

          Summary

          Carbapenem resistance in difficult-to-treat P. aeruginosa (DTR-PA) strains is primarily mediated by loss or reduction of the OprD porin, overexpression of the cephalosporinase AmpC, and/or overexpression of efflux pumps. However, the role of carbapenemases, particularly metallo-β-lactamases, has become more important. Ceftolozane-tazobactam, ceftazidime-avibactam and imipenem-relebactam are useful against DTR phenotypes (noncarbapenemase producers). Other new agents, such as aztreonam-ceftazidime-avibactam or cefiderocol, or colistin, might be effective for carbapenemase producers. Regarding nonantibiotic agents, only phages might be considered, pending further clinical trials. Combination therapy does not reduce mortality, but may be necessary for empirical treatment. Short-term treatment of severe P. aeruginosa infections should be preferred when it is expected that the clinical situation resolves rapidly.

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          Most cited references143

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          Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America

          Background: This document provides evidence-based clinical practice guidelines on the management of adult patients with community-acquired pneumonia. Methods: A multidisciplinary panel conducted pragmatic systematic reviews of the relevant research and applied Grading of Recommendations, Assessment, Development, and Evaluation methodology for clinical recommendations. Results: The panel addressed 16 specific areas for recommendations spanning questions of diagnostic testing, determination of site of care, selection of initial empiric antibiotic therapy, and subsequent management decisions. Although some recommendations remain unchanged from the 2007 guideline, the availability of results from new therapeutic trials and epidemiological investigations led to revised recommendations for empiric treatment strategies and additional management decisions. Conclusions: The panel formulated and provided the rationale for recommendations on selected diagnostic and treatment strategies for adult patients with community-acquired pneumonia.
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            A controlled clinical trial of a therapeutic bacteriophage preparation in chronic otitis due to antibiotic-resistant Pseudomonas aeruginosa; a preliminary report of efficacy.

            To evaluate the efficacy and safety of a therapeutic bacteriophage preparation (Biophage-PA) targeting antibiotic-resistant Pseudomonas aeruginosa in chronic otitis. Randomised, double-blind, placebo-controlled Phase I/II clinical trial approved by UK Medicines and Healthcare products Regulatory Agency (MHRA) and the Central Office for Research Ethics Committees (COREC) ethical review process. A single specialist university hospital. 24 patients with chronic otitis with a duration of several years (2-58). Each patient had, at the time of entry to the trial, an ear infection because of an antibiotic-resistant P. aeruginosa strain sensitive to one or more of the six phages present in Biophage-PA. Participants were randomised in two groups of 12 treated with either a single dose of Biophage-PA or placebo and followed up at 7, 21 and 42 days after treatment by the same otologist. Ears were thoroughly cleaned on each occasion and clinical and microbiological indicators measured. Physician assessed erythema/inflammation, ulceration/granulation/polyps, discharge quantity, discharge type and odour using a Visual Analogue Scale (VAS). Patients reported discomfort, itchiness, wetness and smell also using a VAS. Bacterial levels of P. aeruginosa and phage counts from swabs were measured initially and at follow-up. At each visit patients were asked about side effects using a structured form. Digital otoscopic images were obtained on days 0 and 42 for illustrative purposes only. Relative to day 0, pooled patient- and physician-reported clinical indicators improved for the phage treated group relative to the placebo group. Variation from baseline levels was statistically significant for combined data from all clinic days only for the phage treated group. Variation from baseline levels was statistically significant for the majority of the patient assessed clinical indicators only for the phage treated group. P. aeruginosa counts were significantly lower only in the phage treated group. No treatment related adverse event was reported. The first controlled clinical trial of a therapeutic bacteriophage preparation showed efficacy and safety in chronic otitis because of chemo-resistant P. aeruginosa.
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              International Consensus Guidelines for the Optimal Use of the Polymyxins

              The polymyxin antibiotics colistin (polymyxin E) and polymyxin B became available in the 1950s and thus did not undergo contemporary drug development procedures. Their clinical use has recently resurged, assuming an important role as salvage therapy for otherwise untreatable gram-negative infections. Since their reintroduction into the clinic, significant confusion remains due to the existence of several different conventions used to describe doses of the polymyxins, differences in their formulations, outdated product information, and uncertainties about susceptibility testing that has led to lack of clarity on how to optimally utilize and dose colistin and polymyxin B. We report consensus therapeutic guidelines for agent selection and dosing of the polymyxin antibiotics for optimal use in adult patients, as endorsed by the American College of Clinical Pharmacy (ACCP), Infectious Diseases Society of America (IDSA), International Society of Anti-Infective Pharmacology (ISAP), Society for Critical Care Medicine (SCCM), and Society of Infectious Diseases Pharmacists (SIDP). The European Society for Clinical Microbiology and Infectious Diseases (ESCMID) endorses this document as a consensus statement. The overall conclusions in the document are endorsed by the European Committee on Antimicrobial Susceptibility Testing (EUCAST). We established a diverse international expert panel to make therapeutic recommendations regarding the pharmacokinetic and pharmacodynamic properties of the drugs and pharmacokinetic targets, polymyxin agent selection, dosing, dosage adjustment and monitoring of colistin and polymyxin B, use of polymyxin-based combination therapy, intrathecal therapy, inhalation therapy, toxicity, and prevention of renal failure. The treatment guidelines provide the first ever consensus recommendations for colistin and polymyxin B therapy that are intended to guide optimal clinical use.
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                Author and article information

                Journal
                Current Opinion in Infectious Diseases
                Ovid Technologies (Wolters Kluwer Health)
                0951-7375
                1473-6527
                October 13 2023
                Affiliations
                [1 ]AP-HP, Bichat Hospital, Medical and infectious diseases intensive care unit
                [2 ]IAME Université Paris Cité, UMR 1137, Paris
                [3 ]Meta-network PROMISE, Inserm, Limoges Universit, Limoges University hospital (CHU), UMR1092, Limoges, France
                Article
                10.1097/QCO.0000000000000981
                22a6dca1-4730-4ddf-8f7b-7d2e9c73c38d
                © 2023
                History

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