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Antibiotics
Special Issues
Epidemiology, Prognosis and Antimicrobial Treatment of Extensively Antibiotic-Resistant Bacterial Infections
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Epidemiology, Prognosis and Antimicrobial Treatment of Extensively Antibiotic-Resistant Bacterial Infections

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Mechanism and Evolution of Antibiotic Resistance".

Deadline for manuscript submissions: closed (30 March 2022) | Viewed by 34002

Special Issue Editors

Dr. Evangelos I. Kritsotakis

E-Mail Website1 Website2
Guest Editor
1. School of Medicine, University of Crete, Crete, Greece
2. School of Health and Related Research, University of Sheffield, Sheffield, UK
Interests: medical statistics; epidemiological methods; healthcare epidemiology; infection control; antimicrobial resistance; surveillance; public health
Special Issues, Collections and Topics in MDPI journals
Dr. Stamatis Karakonstantis

E-Mail Website
Guest Editor
Internal Medicine Department, Infectious Diseases Division, University Hospital of Heraklion, Heraklion, Greece
Interests: infectious diseases; infection control; antimicrobial resistance; antibiotic therapy; antibiotic stewardship; clinical epidemiology

Special Issue Information

Dear Colleagues,

Infections caused by extensively drug-resistant (XDR) bacteria, including pandrug-resistant (PDR) bacteria, are increasingly being reported in several countries worldwide. These organisms are typically isolated from patients in intensive care units, but intra- and inter-hospital dissemination, and even international spread, may be substantial. Timely research on the population burden (prevalence and incidence), time trends, geographical spread, and dissemination in long-term care facilities and community settings of XDR and PDR bacteria is of crucial importance. Prognostic studies, including diagnostic prediction models, for the emergence and spread of resistance to newer antibiotics (including cefiderocol, eravacycline, and plazomicin) and their impact on patient outcomes and on the effectiveness of antibiotic therapy (especially with newer antibiotics and synergistic combinations) related to infections caused by XDR and PDR bacteria are of special interest.

Antimicrobial resistance phenotypes for which timely research is much needed include (but are not limited to):

  • Acinetobacter spp susceptible only to one or more: polymyxins, tigecycline or minocycline or eravacycline, cefiderocol;
  • Metallo-beta-lactamase producing Pseudomonas aeruginosa (i.e., co-resistant to carbapenems, ceftazidime/avibactam, ceftolozane/tazobactam, and imipenem/relebactam);
  • Aztreonam/avibactam-resistant Enterobacterales;
  • XDR Stenotrophomonas maltophilia;
  • Cefiderocol-resistant XDR/PDR Gram-negative bacteria.

This Special Issue welcomes submissions of clinical and epidemiological original research, clinical prediction models, systematic reviews, meta-analyses, and narrative literature reviews on the current epidemiology, diagnosis, prognosis, and treatment options for pathogens exhibiting extensive resistance phenotypes.

Prof. Evangelos I. Kritsotakis
Dr. Stamatis Karakonstantis
Guest Editors

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

  • antibiotic resistance
  • extensive antimicrobial resistance
  • XDR
  • pan-resistance
  • PDR
  • infection
  • clinical epidemiology
  • burden
  • impact
  • prognosis
  • prediction
  • antibiotic therapy

Published Papers (6 papers)

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Editorial

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3 pages, 200 KiB  
Editorial
Editorial for the Special Issue: “Epidemiology, Prognosis and Antimicrobial Treatment of Extensively Antibiotic-Resistant Bacterial Infections”
by Stamatis Karakonstantis and Evangelos I. Kritsotakis
Antibiotics 2022, 11(6), 804; https://doi.org/10.3390/antibiotics11060804 - 15 Jun 2022
Cited by 1 | Viewed by 1622
Abstract
The increasing consumption of broad-spectrum antimicrobials is fuelling a vicious cycle leading to extensively drug-resistant (XDR) and pandrug-resistant (PDR) bacteria [...] Full article
(This article belongs to the Special Issue Epidemiology, Prognosis and Antimicrobial Treatment of Extensively Antibiotic-Resistant Bacterial Infections)

Research

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11 pages, 916 KiB  
Article
In Vitro Activity of Ceftolozane-Tazobactam and Other Antibiotics against Pseudomonas aeruginosa Infection-Isolates from an Academic Medical Center in Thailand
by Woraphot Tantisiriwat, Jirawat Buppanharun, Chatchai Ekpanyaskul, Kwanchai Onruang, Thitiya Yungyuen, Pattarachai Kiratisin and Somchai Santiwatanakul
Antibiotics 2022, 11(6), 732; https://doi.org/10.3390/antibiotics11060732 - 30 May 2022
Cited by 4 | Viewed by 1844
Abstract
(1) Background: Resistant Pseudomonas aeruginosa (PA) infections have limited treatment options. Data on the activity of ceftolozane-tazobactam (C-T) against PA in Thailand are limited. Objectives: The objective of this study was to identify the in vitro activity of C-T against general and resistant [...] Read more.
(1) Background: Resistant Pseudomonas aeruginosa (PA) infections have limited treatment options. Data on the activity of ceftolozane-tazobactam (C-T) against PA in Thailand are limited. Objectives: The objective of this study was to identify the in vitro activity of C-T against general and resistant PA isolates from patients with real clinical infections from the HRH Princess Maha Chakri Sirindhorn Medical Center (MSMC) compared to other antibiotics and to study the resistant molecular patterns of those PA strains which were resistant to C-T. (2) Materials and Methods: This was an in vitro susceptibility study of 100 PA isolates plus an additional seven resistant PA isolates collected from MSMC patients. All PA isolates were tested with susceptibility broth (Sensititre™) and C-T minimal inhibitory concentration (MIC) test strips (Liofilchem, Roseto degli, Abruzzi, Italy). The C-T-resistant PA isolates were analyzed for six β-lactamase genes (blaCTX-M, blaNDM, blaIMP, blaVIM, blaOXA-23 and blaOXA-48) and the mcr-1 gene. (3) Results: A total of 100 PA isolates were collected between January 2020 and January 2021 and between February 2021 and September 2021 for the additional 7 resistant isolates. There were 18 resistant PA isolates (6 MDR, 11 XDR and 1 pan-drug resistant isolate). The overall susceptibility of the initial 100 PA isolates and the 18 resistant PA isolates was 94% and 44.5%, respectively, for C-T. The C-T susceptibility rates for isolates non-susceptible to ceftazidime, piperacillin-tazobactam, carbapenems and antipseudomonal β-lactams were 65.5%, 69.7%, 50% and 44.5%, respectively. Among the 10 isolates which were resistant to C-T, there were only 3 isolates found to have the resistant gene, which included 1 for blaIMP, 1 for blaVIM and 1 for blaNDM. (4) Conclusions: Although C-T was the best susceptibility antibiotic overall for PA isolates and MDR PA isolates at the MSMC, most of the XDR PA isolates and the PDR PA isolate were not susceptible to C-T. The mechanisms for C-T resistance involved multiple factors including the presence of blaIMP, blaVIM and blaNDM. Full article
(This article belongs to the Special Issue Epidemiology, Prognosis and Antimicrobial Treatment of Extensively Antibiotic-Resistant Bacterial Infections)
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Review

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20 pages, 589 KiB  
Review
Cefiderocol: Systematic Review of Mechanisms of Resistance, Heteroresistance and In Vivo Emergence of Resistance
by Stamatis Karakonstantis, Maria Rousaki and Evangelos I. Kritsotakis
Antibiotics 2022, 11(6), 723; https://doi.org/10.3390/antibiotics11060723 - 27 May 2022
Cited by 75 | Viewed by 6937
Abstract
Cefiderocol appears promising, as it can overcome most β-lactam resistance mechanisms (including β-lactamases, porin mutations, and efflux pumps). Resistance is uncommon according to large multinational cohorts, including against isolates resistant to carbapenems, ceftazidime/avibactam, ceftolozane/tazobactam, and colistin. However, alarming proportions of resistance have been [...] Read more.
Cefiderocol appears promising, as it can overcome most β-lactam resistance mechanisms (including β-lactamases, porin mutations, and efflux pumps). Resistance is uncommon according to large multinational cohorts, including against isolates resistant to carbapenems, ceftazidime/avibactam, ceftolozane/tazobactam, and colistin. However, alarming proportions of resistance have been reported in some recent cohorts (up to 50%). A systematic review was conducted in PubMed and Scopus from inception to May 2022 to review mechanisms of resistance, prevalence of heteroresistance, and in vivo emergence of resistance to cefiderocol during treatment. A variety of mechanisms, typically acting in concert, have been reported to confer resistance to cefiderocol: β-lactamases (especially NDM, KPC and AmpC variants conferring resistance to ceftazidime/avibactam, OXA-427, and PER- and SHV-type ESBLs), porin mutations, and mutations affecting siderophore receptors, efflux pumps, and target (PBP-3) modifications. Coexpression of multiple β-lactamases, often in combination with permeability defects, appears to be the main mechanism of resistance. Heteroresistance is highly prevalent (especially in A. baumannii), but its clinical impact is unclear, considering that in vivo emergence of resistance appears to be low in clinical studies. Nevertheless, cases of in vivo emerging cefiderocol resistance are increasingly being reported. Continued surveillance of cefiderocol’s activity is important as this agent is introduced in clinical practice. Full article
(This article belongs to the Special Issue Epidemiology, Prognosis and Antimicrobial Treatment of Extensively Antibiotic-Resistant Bacterial Infections)
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25 pages, 1387 KiB  
Review
New Drugs for the Treatment of Pseudomonas aeruginosa Infections with Limited Treatment Options: A Narrative Review
by Angela Raffaella Losito, Francesca Raffaelli, Paola Del Giacomo and Mario Tumbarello
Antibiotics 2022, 11(5), 579; https://doi.org/10.3390/antibiotics11050579 - 26 Apr 2022
Cited by 31 | Viewed by 10245
Abstract
P. aeruginosa is still one of the most threatening pathogens responsible for serious hospital-acquired infections. It is intrinsically resistant to many antimicrobial agents and additional acquired resistance further complicates the management of such infections. High rates of combined antimicrobial resistance persist in many [...] Read more.
P. aeruginosa is still one of the most threatening pathogens responsible for serious hospital-acquired infections. It is intrinsically resistant to many antimicrobial agents and additional acquired resistance further complicates the management of such infections. High rates of combined antimicrobial resistance persist in many countries, especially in the eastern and south-eastern parts of Europe. The aim of this narrative review is to provide a comprehensive assessment of the epidemiology, latest data, and clinical evidence on the current and new available drugs active against P. aeruginosa isolates with limited treatment options. The latest evidence and recommendations supporting the use of ceftolozane-tazobactam and ceftazidime-avibactam, characterized by targeted clinical activity against a significant proportion of P. aeruginosa strains with limited treatment options, are described based on a review of the latest microbiological and clinical studies. Cefiderocol, with excellent in vitro activity against P. aeruginosa isolates, good stability to all β-lactamases and against porin and efflux pumps mutations, is also examined. New carbapenem combinations are explored, reviewing the latest experimental and initial clinical evidence. One section is devoted to a review of new anti-pseudomonal antibiotics in the pipeline, such as cefepime-taniborbactam and cefepime-zidebactam. Finally, other “old” antimicrobials, mainly fosfomycin, that can be used as combination strategies, are described. Full article
(This article belongs to the Special Issue Epidemiology, Prognosis and Antimicrobial Treatment of Extensively Antibiotic-Resistant Bacterial Infections)
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Other

6 pages, 231 KiB  
Case Report
Azithromycin: An Underappreciated Quinolone-Sparing Oral Treatment for Pseudomonas aeruginosa Infections
by Erlinda R. Ulloa and George Sakoulas
Antibiotics 2022, 11(4), 515; https://doi.org/10.3390/antibiotics11040515 - 13 Apr 2022
Cited by 6 | Viewed by 3346
Abstract
Outpatient treatment of Pseudomonas aeruginosa infections is challenged by increasing rates of resistance to fluoroquinolones, the only class of antibiotics which offers an established oral route of administration against this organism. Azithromycin does not demonstrate activity against P. aeruginosa when evaluated under standard [...] Read more.
Outpatient treatment of Pseudomonas aeruginosa infections is challenged by increasing rates of resistance to fluoroquinolones, the only class of antibiotics which offers an established oral route of administration against this organism. Azithromycin does not demonstrate activity against P. aeruginosa when evaluated under standard methods of susceptibility testing with bacteriologic media. However, growing evidence shows that azithromycin is very active against P. aeruginosa when using physiologic media that recapitulate the in vivo milieu and is supported by animal models of infection and various clinical settings, including cystic fibrosis. We present three cases of outpatient management of P. aeruginosa otolaryngological infections successfully treated with oral azithromycin, 500 mg daily ranging from 3–8 weeks, where use of fluoroquinolones was not possible due to either resistance or patient intolerance. We review the previous data supporting this clinical approach, in the hope that this will alert clinicians to this treatment option and to inspire a more thorough clinical trial evaluation of azithromycin in this environment of growing medical need. Full article
(This article belongs to the Special Issue Epidemiology, Prognosis and Antimicrobial Treatment of Extensively Antibiotic-Resistant Bacterial Infections)
14 pages, 329 KiB  
Systematic Review
Antimicrobial Treatment Strategies for Stenotrophomonas maltophilia: A Focus on Novel Therapies
by Jean Gibb and Darren W. Wong
Antibiotics 2021, 10(10), 1226; https://doi.org/10.3390/antibiotics10101226 - 09 Oct 2021
Cited by 29 | Viewed by 8469
Abstract
Stenotrophomonas maltophilia is an urgent global threat due to its increasing incidence and intrinsic antibiotic resistance. Antibiotic development has focused on carbapenem-resistant Enterobacteriaceae, Pseudomonas, and Acinetobacter, with approved antibiotics in recent years having limited activity for Stenotrophomonas. Accordingly, novel treatment strategies for Stenotrophomonas [...] Read more.
Stenotrophomonas maltophilia is an urgent global threat due to its increasing incidence and intrinsic antibiotic resistance. Antibiotic development has focused on carbapenem-resistant Enterobacteriaceae, Pseudomonas, and Acinetobacter, with approved antibiotics in recent years having limited activity for Stenotrophomonas. Accordingly, novel treatment strategies for Stenotrophomonas are desperately needed. We conducted a systemic literature review and offer recommendations based on current evidence for a treatment strategy of Stenotrophomonas infection. Full article
(This article belongs to the Special Issue Epidemiology, Prognosis and Antimicrobial Treatment of Extensively Antibiotic-Resistant Bacterial Infections)
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