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Antibiotics
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Antibiotic Treatment for Pseudomonas aeruginosa and Treatment Regimens
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Antibiotic Treatment for Pseudomonas aeruginosa and Treatment Regimens

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Antibiotic Therapy in Infectious Diseases".

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 6299

Special Issue Editor

Prof. Dr. Weihui Wu

E-Mail Website
Guest Editor
State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 30071, China
Interests: Regulation and function of pathogenic bacterial virulence factors; Mechanisms of antibiotics resistance in pathogenic bacteria; Host immune responses during infection

Special Issue Information

Dear Colleagues,

Pseudomonas aeruginosa is a prevalent opportunistic pathogen that causes various infections in human. It is intrinsically resistant to a variety of antibiotics. Biofilm formation drastically increases the resistance, and persister cells are phenotypic variants that are highly recalcitrant to lethal doses of antibiotics. Mutations and horizontal acquisition of resistant genes further broaden the resistance spectrum and increase the level of resistance. Therefore, it is critical to understand the mechanisms of antimicrobial resistance and the development of resistance. Novel antimicrobials and treatment strategies are urgently needed. This Special Issue welcomes manuscripts describing the study of resistance mechanisms, development of resistance, identification of novel treatment targets and antimicrobials as well as strategies to increase treatment efficacies and repress the evolution of resistance in P. aeruginosa.

Prof. Dr. Weihui Wu
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Pseudomonas aeruginosa
  • antibiotic resistance
  • novel antimicrobials
  • treatment strategies

Published Papers (3 papers)

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Research

19 pages, 3055 KiB  
Article
Carbapenem-Only Combination Therapy against Multi-Drug Resistant Pseudomonas aeruginosa: Assessment of In Vitro and In Vivo Efficacy and Mode of Action
by Brendan Mackay, Benjamin J. Parcell, Sally L. Shirran and Peter J. Coote
Antibiotics 2022, 11(11), 1467; https://doi.org/10.3390/antibiotics11111467 - 25 Oct 2022
Cited by 1 | Viewed by 1478
Abstract
The aim of the study was to determine the efficacy of carbapenem-only combination treatments derived from four approved drugs (meropenem, doripenem, ertapenem and imipenem) against a MDR strain of P. aeruginosa in a Galleria mellonella larvae infection model. G. mellonella larvae were infected [...] Read more.
The aim of the study was to determine the efficacy of carbapenem-only combination treatments derived from four approved drugs (meropenem, doripenem, ertapenem and imipenem) against a MDR strain of P. aeruginosa in a Galleria mellonella larvae infection model. G. mellonella larvae were infected with P. aeruginosa NCTC 13437 (carrying the VIM 10 carbapenamase) and the efficacy of the six possible dual, four triple, and one quadruple carbapenem combination(s) were compared to their constituent monotherapies. Four of these combinations showed significantly enhanced survival compared to monotherapies and reduced the bacterial burden inside infected larvae but without complete elimination. Bacteria that survived combination therapy were slower growing, less virulent but with unchanged carbapenem MICs—observations that are consistent with a persister phenotype. In vitro time-kill assays confirmed that the combinations were bactericidal and confirmed that a low number of bacteria survived exposure. Mass spectrometry was used to quantify changes in the concentration of carbapenems in the presence of carbapenemase-carrying P. aeruginosa. The rate of degradation of individual carbapenems was altered, and often significantly reduced, when the drugs were in combinations compared with the drugs alone. These differences may account for the enhanced inhibitory effects of the combinations against carbapenem-resistant P. aeruginosa and are consistent with a ‘shielding’ hypothesis. In conclusion, carbapenem combinations show promise in combating MDR P. aeruginosa and are worthy of additional study and development. Full article
(This article belongs to the Special Issue Antibiotic Treatment for Pseudomonas aeruginosa and Treatment Regimens)
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14 pages, 1186 KiB  
Article
Treatment Heterogeneity in Pseudomonas aeruginosa Pneumonia
by Aisling R. Caffrey, Haley J. Appaneal, J. Xin Liao, Emily C. Piehl, Vrishali Lopes and Laura A. Puzniak
Antibiotics 2022, 11(8), 1033; https://doi.org/10.3390/antibiotics11081033 - 30 Jul 2022
Cited by 2 | Viewed by 1758
Abstract
We have previously identified substantial antibiotic treatment heterogeneity, even among organism-specific and site-specific infections with treatment guidelines. Therefore, we sought to quantify the extent of treatment heterogeneity among patients hospitalized with P. aeruginosa pneumonia in the national Veterans Affairs Healthcare System from Jan-2015 [...] Read more.
We have previously identified substantial antibiotic treatment heterogeneity, even among organism-specific and site-specific infections with treatment guidelines. Therefore, we sought to quantify the extent of treatment heterogeneity among patients hospitalized with P. aeruginosa pneumonia in the national Veterans Affairs Healthcare System from Jan-2015 to Apr-2018. Daily antibiotic exposures were mapped from three days prior to culture collection until discharge. Heterogeneity was defined as unique patterns of antibiotic treatment (drug and duration) not shared by any other patient. Our study included 5300 patients, of whom 87.5% had unique patterns of antibiotic drug and duration. Among patients receiving any initial antibiotic/s with a change to at least one anti-pseudomonal antibiotic (n = 3530, 66.6%) heterogeneity was 97.2%, while heterogeneity was 91.5% in those changing from any initial antibiotic/s to only anti-pseudomonal antibiotics (n = 576, 10.9%). When assessing heterogeneity of anti-pseudomonal antibiotic classes, irrespective of other antibiotic/s received (n = 4542, 85.7%), 50.5% had unique patterns of antibiotic class and duration, with median time to first change of three days, and a median of two changes. Real-world evidence is needed to inform the development of treatment pathways and antibiotic stewardship initiatives based on clinical outcome data, which is currently lacking in the presence of such treatment heterogeneity. Full article
(This article belongs to the Special Issue Antibiotic Treatment for Pseudomonas aeruginosa and Treatment Regimens)
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11 pages, 372 KiB  
Article
The Comparative Effectiveness of Ceftolozane/Tazobactam versus Aminoglycoside- or Polymyxin-Based Regimens in Multi-Drug-Resistant Pseudomonas aeruginosa Infections
by Aisling R. Caffrey, Haley J. Appaneal, J. Xin Liao, Emily C. Piehl, Vrishali Lopes, Ryan J. Dillon, Laura A. Puzniak and Kerry L. LaPlante
Antibiotics 2022, 11(5), 626; https://doi.org/10.3390/antibiotics11050626 - 6 May 2022
Cited by 3 | Viewed by 2453
Abstract
Pseudomonas aeruginosa infections are challenging to treat due to multi-drug resistance (MDR) and the complexity of the patients affected by these serious infections. As new antibiotic therapies come on the market, limited data exist about the effectiveness of such treatments in clinical practice. [...] Read more.
Pseudomonas aeruginosa infections are challenging to treat due to multi-drug resistance (MDR) and the complexity of the patients affected by these serious infections. As new antibiotic therapies come on the market, limited data exist about the effectiveness of such treatments in clinical practice. In this comparative effectiveness study of ceftolozane/tazobactam versus aminoglycoside- or polymyxin-based therapies among hospitalized patients with positive MDR P. aeruginosa cultures, we identified 57 patients treated with ceftolozane/tazobactam compared with 155 patients treated with aminoglycoside- or polymyxin-based regimens. Patients treated with ceftolozane/tazobactam were younger (mean age 67.5 vs. 71.1, p = 0.03) and had a higher comorbidity burden prior to hospitalization (median Charlson 5 vs. 3, p = 0.01) as well as higher rates of spinal cord injury (38.6% vs. 21.9%, p = 0.02) and P. aeruginosa-positive bone/joint cultures (12.3% vs. 0.7%, p < 0.0001). Inpatient mortality was significantly lower in the ceftolozane/tazobactam group compared with aminoglycosides or polymyxins (15.8% vs. 27.7%, adjusted odds ratio 0.39, 95% confidence interval 0.16–0.93). There were no significant differences observed for the other outcomes assessed. In hospitalized patients with MDR P. aeruginosa, inpatient mortality was 61% lower among patients treated with ceftolozane/tazobactam compared to those treated with aminoglycoside- or polymyxin-based regimens. Full article
(This article belongs to the Special Issue Antibiotic Treatment for Pseudomonas aeruginosa and Treatment Regimens)
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