Special Issue "Antimicrobial Resistance in Gram-negative Bacteria"

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: 31 August 2019

Special Issue Editor

Guest Editor
Prof. Dr. Yuji Morita

Department of Infection Control Science, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo, Japan
Website | E-Mail
Phone: +81-42-495-8591
Interests: antimicrobial resistance; antimicrobial action; development of antimicrobial agents or adjuvant; microbial transporter; microbial molecular genetics

Special Issue Information

Dear Colleagues,

Gram-negative bacteria possess an intrinsic resistance to many antimicrobials because of the bacterium's outer-membrane barrier, the presence of multidrug efflux transporters, and endogenous antimicrobial inactivation etc. Moreover, Gram-negative bacteria readily acquire resistance to antimicrobial agents via chromosomal mutations and lateral gene transfers. In order to overcome this problem, it is necessary to tackle the development of antibacterial agents, drug resistance inhibitors, anti-pathogenic factors and vaccines. Thus, this Special Issue features interdisciplinary studies that build our understanding of the underlying antimicrobial resistance in Gram-negative bacteria. It also covers studies on development of antibacterial agents and adjuvant against antimicrobial resistant Gram-negative bacteria.

Prof. Yuji Morita
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 papers will be 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.

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Keywords

  • antimicrobial resistance
  • antimicrobial response
  • development of antimicrobial agents or adjuvant

Published Papers (6 papers)

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Research

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Open AccessArticle Activity of Cefepime-Zidebactam against Multidrug-Resistant (MDR) Gram-Negative Pathogens
Antibiotics 2019, 8(1), 32; https://doi.org/10.3390/antibiotics8010032 (registering DOI)
Received: 18 February 2019 / Revised: 18 March 2019 / Accepted: 19 March 2019 / Published: 23 March 2019
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Abstract
This study compared the activity of cefepime + zidebactam (FEP-ZID) and selected currently available antibacterial agents against a panel of multidrug-resistant (MDR) clinical isolates chosen to provide an extreme challenge for antibacterial activity. FEP–ZID had a very broad and potent in vitro spectrum [...] Read more.
This study compared the activity of cefepime + zidebactam (FEP-ZID) and selected currently available antibacterial agents against a panel of multidrug-resistant (MDR) clinical isolates chosen to provide an extreme challenge for antibacterial activity. FEP–ZID had a very broad and potent in vitro spectrum of activity, and was highly active against many MDR isolates of Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii. Notably, it inhibited isolates producing carbapenemases of Ambler classes A, B, and D, and P. aeruginosa isolates with multiple resistance mechanisms including combinations of upregulated efflux, diminished or non-functional OprD porins, and AmpC overproduction. Its clinical role will be determined initially by the breakpoints assigned to it, comparison studies with other investigational β-lactamase inhibitor combinations, and ultimately by the developing body of therapeutic outcome data. Full article
(This article belongs to the Special Issue Antimicrobial Resistance in Gram-negative Bacteria)
Open AccessArticle Prevalence of Antibiotic Resistance Genes in Multidrug-Resistant Enterobacteriaceae on Portuguese Livestock Manure
Antibiotics 2019, 8(1), 23; https://doi.org/10.3390/antibiotics8010023
Received: 8 January 2019 / Revised: 22 February 2019 / Accepted: 23 February 2019 / Published: 13 March 2019
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Abstract
The exposure of both crop fields and humans to antibiotic-resistant bacteria in animal excreta is an emergent concern of the One Health initiative. This study assessed the contamination of livestock manure from poultry, pig, dairy farms and slaughterhouses in Portugal with resistance determinants. [...] Read more.
The exposure of both crop fields and humans to antibiotic-resistant bacteria in animal excreta is an emergent concern of the One Health initiative. This study assessed the contamination of livestock manure from poultry, pig, dairy farms and slaughterhouses in Portugal with resistance determinants. The resistance profiles of 331 Enterobacteriaceae isolates to eight β-lactam (amoxicillin, cefoxitin, cefotaxime, cefpirome, aztreonam, ceftazidime, imipenem and meropenem) and to five non-β-lactam antibiotics (tetracycline (TET), trimethoprim/sulfamethoxazole (SXT), ciprofloxacin (CIP), chloramphenicol (CHL) and gentamicin) was investigated. Forty-nine integron and non-β-lactam resistance genes were also screened for. Rates of resistance to the 13 antibiotics ranged from 80.8% to 0.6%. Multidrug resistance (MDR) rates were highest in pig farm samples (79%). Thirty different integron and resistance genes were identified. These were mainly associated with resistance to CHL (catI and catII), CIP (mainly, qnrS, qnrB and oqx), TET (mainly tet(A) and tet(M)) and SXT (mostly dfrIa group and sul3). In MDR isolates, integron presence and non-β-lactam resistance to TET, SXT and CHL were positively correlated. Overall, a high prevalence of MDR Enterobacteriaceae was found in livestock manure. The high gene diversity for antibiotic resistance identified in this study highlights the risk of MDR spread within the environment through manure use. Full article
(This article belongs to the Special Issue Antimicrobial Resistance in Gram-negative Bacteria)
Figures

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Open AccessArticle Utility of Combination Antimicrobial Therapy in Adults with Bloodstream Infections due to Enterobacteriaceae and Non-Fermenting Gram-Negative Bacilli Based on In Vitro Analysis at Two Community Hospitals
Antibiotics 2019, 8(1), 15; https://doi.org/10.3390/antibiotics8010015
Received: 20 December 2018 / Revised: 5 February 2019 / Accepted: 6 February 2019 / Published: 8 February 2019
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Abstract
This study examined the utility of combination therapy for bloodstream isolates of Enterobacteriaceae and non-fermenting Gram-negative bacilli (NFGN) from adults at two community hospitals from January 2010 through to June 2015. Changes to in vitro antimicrobial susceptibilities by adding ciprofloxacin or gentamicin to [...] Read more.
This study examined the utility of combination therapy for bloodstream isolates of Enterobacteriaceae and non-fermenting Gram-negative bacilli (NFGN) from adults at two community hospitals from January 2010 through to June 2015. Changes to in vitro antimicrobial susceptibilities by adding ciprofloxacin or gentamicin to third-generation cephalosporins (3GC) were examined overall and in patients with risk factors for 3GC resistance. Overall ceftriaxone susceptibility among Enterobacteriaceae was 996/1063 (94%) and 247/295 (84%) in patients with 3GC resistance risk factors. Susceptibilities increased marginally by adding ciprofloxacin or gentamicin (mean difference 2.4% (95% CI 1.5, 3.4) and 3.0% (95% CI 2.0, 4.0), respectively, overall and 5.4% (95% CI 2.8, 8.0) and 7.1% (95% CI 4.2, 10.1), respectively, in patients with risk factors). Eighty-three of 105 (79%) NFGN were susceptible to ceftazidime overall and 20/29 (69%) in patients with prior beta-lactam use. Overall mean increase in susceptibilities was 15.2% (95% CI: 8.3, 22.2) and 17.1% (95% CI: 9.8, 24.5) for ciprofloxacin and gentamicin combinations, respectively; and 27.6% (95% CI: 10.3, 44.9) for either one with recent beta-lactam use. In this setting, empirical combination therapy had limited utility for Enterobacteriaceae bloodstream isolates but provided significant additional antimicrobial coverage to ceftazidime for NFGN, particularly in patients with prior beta-lactam use. Full article
(This article belongs to the Special Issue Antimicrobial Resistance in Gram-negative Bacteria)

Review

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Open AccessReview Biocidal Agents Used for Disinfection Can Enhance Antibiotic Resistance in Gram-Negative Species
Antibiotics 2018, 7(4), 110; https://doi.org/10.3390/antibiotics7040110
Received: 20 November 2018 / Revised: 10 December 2018 / Accepted: 11 December 2018 / Published: 14 December 2018
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Abstract
Biocidal agents used for disinfection are usually not suspected to enhance cross-resistance to antibiotics. The aim of this review was therefore to evaluate the effect of 13 biocidal agents at sublethal concentrations on antibiotic resistance in Gram-negative species. A medline search was performed [...] Read more.
Biocidal agents used for disinfection are usually not suspected to enhance cross-resistance to antibiotics. The aim of this review was therefore to evaluate the effect of 13 biocidal agents at sublethal concentrations on antibiotic resistance in Gram-negative species. A medline search was performed for each biocidal agent on antibiotic tolerance, antibiotic resistance, horizontal gene transfer, and efflux pump. In cells adapted to benzalkonium chloride a new resistance was most frequently found to ampicillin (eight species), cefotaxime (six species), and sulfamethoxazole (three species), some of them with relevance for healthcare-associated infections such as Enterobacter cloacae or Escherichia coli. With chlorhexidine a new resistance was often found to ceftazidime, sulfamethoxazole and imipenem (eight species each) as well as cefotaxime and tetracycline (seven species each). Cross-resistance to antibiotics was also found with triclosan, octenidine, sodium hypochlorite, and didecyldimethylammonium chloride. No cross-resistance to antibiotics has been described after low level exposure to ethanol, propanol, peracetic acid, polyhexanide, povidone iodine, glutaraldehyde, and hydrogen peroxide. Taking into account that some biocidal agents used in disinfectants have no health benefit (e.g., in alcohol-based hand rubs) but may cause antibiotic resistance it is obvious to prefer products without them. Full article
(This article belongs to the Special Issue Antimicrobial Resistance in Gram-negative Bacteria)

Other

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Open AccessCase Report Emerging Chryseobacterium indologenes Infection in Indian Neonatal Intensive Care Units: A Case Report
Antibiotics 2018, 7(4), 109; https://doi.org/10.3390/antibiotics7040109
Received: 8 November 2018 / Revised: 5 December 2018 / Accepted: 12 December 2018 / Published: 14 December 2018
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Abstract
Antibiotic-resistant pathogens and nosocomial infections constitute common and serious problems for neonates admitted to neonatal intensive care units worldwide. Chryseobacterium indologenes is a non-lactose-fermenting, gram-negative, health care-associated pathogen (HCAP). It is ubiquitous and intrinsically resistant to several antibiotics. Despite its low virulence, C. [...] Read more.
Antibiotic-resistant pathogens and nosocomial infections constitute common and serious problems for neonates admitted to neonatal intensive care units worldwide. Chryseobacterium indologenes is a non-lactose-fermenting, gram-negative, health care-associated pathogen (HCAP). It is ubiquitous and intrinsically resistant to several antibiotics. Despite its low virulence, C. indologenes has been widely reported to cause life-threatening infections. Patients on chronic immunosuppressant drugs, harboring invasive devices and indwelling catheters become the nidus for C. indologenes. Typically, C. indologenes causes major health care-associated infections such as pneumonia, empyema, pyelonephritis, cystitis, peritonitis, meningitis, and bacteremia in patients harboring central venous catheters. Management of C. indologenes infection in neonates is not adequately documented owing to underreporting, particularly in India. Because of its multidrug resistance and the scant availability of data from the literature, the effective empirical treatment of C. indologenes is challenging. We present an uncommon case of bacteremia caused by C. indologenes in a preterm newborn baby with moderate respiratory distress syndrome who was successfully treated. We also provide a review of infections in the neonatal age group. Henceforth, in neonates receiving treatments involving invasive equipment use and long-term antibiotic therapy, multidrug resistant C. indologenes should be considered an HCAP. Full article
(This article belongs to the Special Issue Antimicrobial Resistance in Gram-negative Bacteria)
Open AccessCase Report First Description of Colistin and Tigecycline-Resistant Acinetobacter baumannii Producing KPC-3 Carbapenemase in Portugal
Antibiotics 2018, 7(4), 96; https://doi.org/10.3390/antibiotics7040096
Received: 7 September 2018 / Revised: 29 October 2018 / Accepted: 2 November 2018 / Published: 6 November 2018
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Abstract
Herein, we describe a case report of carbapenem-resistant Acinetobacter baumannii and Klebsiella pneumoniae isolates that were identified from the same patient at a Tertiary University Hospital Centre in Portugal. Antimicrobial susceptibility and the molecular characterization of resistance and virulence determinants were performed. PCR [...] Read more.
Herein, we describe a case report of carbapenem-resistant Acinetobacter baumannii and Klebsiella pneumoniae isolates that were identified from the same patient at a Tertiary University Hospital Centre in Portugal. Antimicrobial susceptibility and the molecular characterization of resistance and virulence determinants were performed. PCR screening identified the presence of the resistance genes blaKPC-3, blaTEM-1 and blaSHV-1 in both isolates. The KPC-3 K. pneumoniae isolate belonged to the ST-14 high risk clone and accumulated an uncommon resistance and virulence profile additional to a horizontal dissemination capacity. In conclusion, the molecular screening led to the first identification of the A. baumannii KPC-3 producer in Portugal with a full antimicrobial resistance profile including tigecycline and colistin. Full article
(This article belongs to the Special Issue Antimicrobial Resistance in Gram-negative Bacteria)
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