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Antibiotics
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Antibiotic Resistance in Acinetobacter and Associated Treatment Strategies
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Antibiotic Resistance in Acinetobacter and Associated Treatment Strategies

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 2024) | Viewed by 11122

Special Issue Editors

Dr. Steven E. Fiester

E-Mail Website
Guest Editor
1. Department of Chemistry, Furman University, Greenville, SC 29613, USA
2. Department of Pathology, Prisma Health, School of Health Science Research, Clemson University, Clemson, SC 29634, USA
3. Dorn Research Institute, Wm. Jennings Bryan Dorn VA Medical Center, Columbia, SC 29209, USA
Interests: Acinetobacter; Klebsiella; drug discovery; antimicrobial stewardship; virulence factors; infectious diseases; bacteriology
Special Issues, Collections and Topics in MDPI journals
Dr. William Penwell

E-Mail Website
Guest Editor
Department of Biology and Marine Science, Jacksonville University, Jacksonville, Fl, USA
Interests: Acinetobacter; Stenotrophomonas; drug discovery; virulence factors; infectious diseases; bacterial iron-acquisition
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We would like to invite you to submit your research pertaining to Acinetobacter resistance for publication in this Special Issue of Antibiotics. Acinetobacter infections cause a substantial burden on public health, with the Centers for Disease Control and Prevention specifically classifying carbapenem-resistant Acinetobacter as an urgent threat to public health with 8500 cases annually, 700 deaths, and USD 281 million in associated healthcare costs in the United States alone. These data coupled with the sparsity of information elucidating the pathophysiology of Acinetobacter, the lack of novel antibiotics in the developmental pipeline to treat Acinetobacter infections, the continued occurrence of multidrug-, extensively drug-, or even pandrug-resistant isolates from clinical settings and the association of Acinetobacter secondary infection in SARS-CoV-2 patients constitute a public health crisis warranting immediate attention. This Special Issue therefore particularly encourages submissions that describe resistance mechanisms of Acinetobacter that allow this human pathogen to resist destruction by the immune system, persist in the clinical environment due to resistance to disinfectants, and survive clinical treatment due to antibiotic resistance. The underlying mechanisms by which Acinetobacter resistance mechanisms allow it to survive these stressors all play a role in its pathogenicity and are valuable in understanding and treating this critical pathogen.

Dr. Steven E. Fiester
Dr. William Penwell
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

  • Acinetobacter
  • antibiotic resistance
  • resistance to disinfection
  • clinical management
  • secondary infections

Published Papers (6 papers)

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Research

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11 pages, 556 KiB  
Article
Co-Administration of High-Dose Nebulized Colistin for Acinetobacter baumannii Bacteremic Ventilator-Associated Pneumonia: Impact on Outcomes
by Ioannis Andrianopoulos, Nikolaos Kazakos, Nikolaos Lagos, Theodora Maniatopoulou, Athanasios Papathanasiou, Georgios Papathanakos, Despoina Koulenti, Eleni Toli, Konstantina Gartzonika and Vasilios Koulouras
Antibiotics 2024, 13(2), 169; https://doi.org/10.3390/antibiotics13020169 - 08 Feb 2024
Viewed by 1174
Abstract
Acinetobacter baumannii (A. baumannii) is a difficult-to-treat (DTR) pathogen that causes ventilator-associated pneumonia (VAP) associated with high mortality. To improve the outcome of DTR A. Baumannii VAP, nebulized colistin (NC) was introduced with promising but conflicting results on mortality in earlier [...] Read more.
Acinetobacter baumannii (A. baumannii) is a difficult-to-treat (DTR) pathogen that causes ventilator-associated pneumonia (VAP) associated with high mortality. To improve the outcome of DTR A. Baumannii VAP, nebulized colistin (NC) was introduced with promising but conflicting results on mortality in earlier studies. Currently, NC is used at a much higher daily dose compared to the past. Nevertheless, there is little evidence on the effect of high-dose NC on the outcomes of A. baumannii VAPs, especially in the current era where the percentage of colistin-resistant A. baumannii strains is rising. We conducted a retrospective study comparing bacteremic A. baumannii VAP patients who were treated with and without NC co-administration and were admitted in the Intensive Care Unit of University Hospital of Ioannina from March 2020 to August 2023. Overall, 59 patients (21 and 38 with and without NC coadministration, respectively) were included. Both 28-day and 7-day mortalities were significantly lower in the patient group treated with NC (52.4% vs. 78.9%, p 0.034 and 9.5% vs. 47.4%, p 0.003, respectively). Patients treated with NC had a higher percentage of sepsis resolution by day 7 (38.1% vs. 13.5%, p 0.023) and were more likely to be off vasopressors by day 7 (28.6% vs. 8.1%, p 0.039). The addition of NC in the treatment regime of A. baumannii VAP decreased mortality. Full article
(This article belongs to the Special Issue Antibiotic Resistance in Acinetobacter and Associated Treatment Strategies)
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22 pages, 5119 KiB  
Article
Genetic Determinants of Acinetobacter baumannii Serum-Associated Adaptive Efflux-Mediated Antibiotic Resistance
by Mikaeel Young, Michaelle Chojnacki, Catlyn Blanchard, Xufeng Cao, William L. Johnson, Daniel Flaherty and Paul M. Dunman
Antibiotics 2023, 12(7), 1173; https://doi.org/10.3390/antibiotics12071173 - 11 Jul 2023
Viewed by 1483
Abstract
Acinetobacter baumannii is a nosocomial pathogen of serious healthcare concern that is becoming increasingly difficult to treat due to antibiotic treatment failure. Recent studies have revealed that clinically defined antibiotic-susceptible strains upregulate the expression of a repertoire of putative drug efflux pumps during [...] Read more.
Acinetobacter baumannii is a nosocomial pathogen of serious healthcare concern that is becoming increasingly difficult to treat due to antibiotic treatment failure. Recent studies have revealed that clinically defined antibiotic-susceptible strains upregulate the expression of a repertoire of putative drug efflux pumps during their growth under biologically relevant conditions, e.g., in human serum, resulting in efflux-associated resistance to physiologically achievable antibiotic levels within a patient. This phenomenon, termed Adaptive Efflux Mediated Resistance (AEMR), has been hypothesized to account for one mechanism by which antibiotic-susceptible A. baumannii fails to respond to antibiotic treatment. In the current study, we sought to identify genetic determinants that contribute to A. baumannii serum-associated AEMR by screening a transposon mutant library for members that display a loss of the AEMR phenotype. Results revealed that mutation of a putative pirin-like protein, YhaK, results in a loss of AEMR, a phenotype that could be complemented by a wild-type copy of the yhaK gene and was verified in a second strain background. Ethidium bromide efflux assays confirmed that the loss of AEMR phenotype due to pirin-like protein mutation correlated with reduced overarching efflux capacity. Further, flow cytometry and confocal microscopy measures of a fluorophore 7-(dimethylamino)-coumarin-4-acetic acid (DMACA)-tagged levofloxacin isomer, ofloxacin, further verified that YhaK mutation reduces AEMR-mediated antibiotic efflux. RNA-sequencing studies revealed that YhaK may be required for the expression of multiple efflux-associated systems, including MATE and ABC families of efflux pumps. Collectively, the data indicate that the A. baumannii YhaK pirin-like protein plays a role in modulating the organism’s adaptive efflux-mediated resistance phenotype. Full article
(This article belongs to the Special Issue Antibiotic Resistance in Acinetobacter and Associated Treatment Strategies)
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22 pages, 3425 KiB  
Article
Acinetobacter baumannii Global Clone-Specific Resistomes Explored in Clinical Isolates Recovered from Egypt
by Samira M. Hamed, Walid F. Elkhatib, Hanka Brangsch, Ahmed S. Gesraha, Shawky Moustafa, Dalia F. Khater, Mathias W. Pletz, Lisa D. Sprague, Heinrich Neubauer and Gamal Wareth
Antibiotics 2023, 12(7), 1149; https://doi.org/10.3390/antibiotics12071149 - 04 Jul 2023
Cited by 1 | Viewed by 2146
Abstract
Acinetobacter baumannii (A. baumannii) is a highly problematic pathogen with an enormous capacity to acquire or upregulate antibiotic drug resistance determinants. The genomic epidemiology and resistome structure of 46 A. baumannii clinical isolates were studied using whole-genome sequencing. The isolates were [...] Read more.
Acinetobacter baumannii (A. baumannii) is a highly problematic pathogen with an enormous capacity to acquire or upregulate antibiotic drug resistance determinants. The genomic epidemiology and resistome structure of 46 A. baumannii clinical isolates were studied using whole-genome sequencing. The isolates were chosen based on reduced susceptibility to at least three classes of antimicrobial compounds and were initially identified using MALDI-TOF/MS, followed by polymerase chain reaction amplification of blaOXA-51-like genes. The susceptibility profiles were determined using a broth microdilution assay. Multi-, extensive-, and pan-drug resistance was shown by 34.8%, 63.0%, and 2.2% of the isolates, respectively. These were most susceptible to colistin (95.7%), amikacin, and trimethoprim/sulfamethoxazole (32.6% each), while only 26.1% of isolates were susceptible to tigecycline. In silico multi-locus sequence typing revealed 8 Pasteur and 22 Oxford sequence types (STs) including four novel STs (STOxf 2805, 2806, 2807, and 2808). The majority of the isolates belonged to Global Clone (GC) 2 (76.4%), GC5 (19.6%), GC4 (6.5%), GC9 (4.3%), and GC7 (2.2%) lineages. An extensive resistome potentially conferring resistance to the majority of the tested antimicrobials was identified in silico. Of all known carbapenem resistance genes, blaOXA-23 was carried by most of the isolates (69.6%), followed by ISAba1-amplified blaADC (56.5%), blaNDM-1 and blaGES-11 (21.7% each), and blaGES-35 (2.2%) genes. A significant correlation was found between carbapenem resistance and carO mutations, which were evident in 35 (76.0%) isolates. A lower proportion of carbapenem resistance was noted for strains possessing both blaOXA-23- and blaGES-11. Amikacin resistance was most probably mediated by armA, aac(6′)-Ib9, and aph(3′)-VI, most commonly coexisting in GC2 isolates. No mutations were found in pmrABC or lpxACD operons in the colistin-resistant isolates. Tigecycline resistance was associated with adeS (N268Y) and baeS (A436T) mutations. While the lineage-specific distribution of some genes (e.g., blaADC and blaOXA-51-like alleles) was evident, some resistance genes, such as blaOXA-23 and sul1, were found in all GCs. The data generated here highlight the contribution of five GCs in A. baumannii infections in Egypt and enable the comprehensive analysis of GC-specific resistomes, thus revealing the dissemination of the carbapenem resistance gene blaOXA-23 in isolates encompassing all GCs. Full article
(This article belongs to the Special Issue Antibiotic Resistance in Acinetobacter and Associated Treatment Strategies)
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13 pages, 808 KiB  
Article
The RND Efflux Pump Gene Expression in the Biofilm Formation of Acinetobacter baumannii
by Ola A. Abd El-Rahman, Fatma Rasslan, Safaa S. Hassan, Hossam M. Ashour and Reham Wasfi
Antibiotics 2023, 12(2), 419; https://doi.org/10.3390/antibiotics12020419 - 20 Feb 2023
Cited by 6 | Viewed by 2416
Abstract
Multidrug resistant (MDR) Acinetobacter baumannii is a critical opportunistic pathogen in healthcare-associated infections (HAI). This is attributed to several factors, including its ability to develop biofilms that can enhance antimicrobial resistance (AMR) in addition to creating an environment for horizontal transfer of antibiotic [...] Read more.
Multidrug resistant (MDR) Acinetobacter baumannii is a critical opportunistic pathogen in healthcare-associated infections (HAI). This is attributed to several factors, including its ability to develop biofilms that can enhance antimicrobial resistance (AMR) in addition to creating an environment for horizontal transfer of antibiotic resistance genes. The role of the efflux pump in biofilm formation is important for studies on alternative treatments for biofilms. One of the significant efflux pump families is the RND efflux pump family, which is common in Gram negative bacteria. The aim is to study the role of the RND efflux pump in biofilm formation by A. baumannii. The biofilm formation potential of thirty-four MDR A. baumannii isolates was evaluated by crystal violet assays. The effect of efflux pump inhibition and activation was studied using the efflux pump inhibitor carbonyl cyanide 3-chlorophenylhydrazone (CCCP) and the RND efflux pump substrate levofloxacin (at sub-MIC), respectively. The isolates were genotypically grouped by enterobacterial repetitive intergenic consensus (ERIC) typing and the expression of adeABC, adeFGH, and adeIJK efflux pump genes was measured by qPCR. Overall, 88.2% (30/34) of isolates were biofilm producers (the phenotype was variable including strong and weak producers). Efflux pump inhibition by CCCP reduced the biofilm formation significantly (p < 0.05) in 17.6% (6/34) of some isolates, whereas sub-MICs of the substrate levofloxacin increased biofilm formation in 20.5% (7/34) of other isolates. Overexpression of the three RND efflux pump genes was detected in five out of eleven selected isolates for qPCR with remarkable overexpression in the adeJ gene. No correlation was detected between the biofilm phenotype pattern and the RND efflux pump gene expression in biofilm cells relative to planktonic cells. In conclusion, the role of the RND efflux pumps AdeABC, AdeFGH, and AdeIJK in biofilm formation does not appear to be pivotal and the expression differs according to the genetic background of each strain. Thus, these pumps may not be a promising target for biofilm inhibition. Full article
(This article belongs to the Special Issue Antibiotic Resistance in Acinetobacter and Associated Treatment Strategies)
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11 pages, 1055 KiB  
Article
Evaluation of Fosfomycin-Sulbactam Combination Therapy against Carbapenem-Resistant Acinetobacter baumannii Isolates in a Hollow-Fibre Infection Model
by Sazlyna Mohd Sazlly Lim, Aaron Heffernan, Saiyuri Naicker, Steven Wallis, Jason A. Roberts and Fekade Bruck Sime
Antibiotics 2022, 11(11), 1578; https://doi.org/10.3390/antibiotics11111578 - 09 Nov 2022
Cited by 2 | Viewed by 1704
Abstract
Static concentration in vitro studies have demonstrated that fosfomycin- or sulbactam-based combinations may be efficacious against carbapenem-resistant Acinetobacter baumannii (CRAB). In the present study, we aimed to evaluate the bacterial killing and resistance suppression potential of fosfomycin-sulbactam combination therapies against CRAB isolates in [...] Read more.
Static concentration in vitro studies have demonstrated that fosfomycin- or sulbactam-based combinations may be efficacious against carbapenem-resistant Acinetobacter baumannii (CRAB). In the present study, we aimed to evaluate the bacterial killing and resistance suppression potential of fosfomycin-sulbactam combination therapies against CRAB isolates in a dynamic infection model. We simulated clinically relevant dosing regimens of fosfomycin (8 g every 8 h, 1 h infusion) and sulbactam (12 g continuous infusion or 4 g every 8 h, 4 h infusion) alone and in combination for 7 days in a hollow-fibre infection model (HFIM) against three clinical isolates of CRAB. The simulated pharmacokinetic profiles in the HFIM were based on fosfomycin and sulbactam data from critically ill patients. Fosfomycin monotherapy resulted in limited bacterial killing. Sulbactam monotherapies resulted in ~ 3 to 4 log10 kill within the first 8 to 32 h followed by regrowth of up to 8 to 10 log10 CFU/mL. A combination of fosfomycin and continuous infusion of sulbactam led to a ~2 to 4 log10 reduction in bacterial burden within the first 24 h, which was sustained throughout the duration of the experiments. A combination of fosfomycin and extended infusion of sulbactam produced a ~4 log10 reduction in colony count within 24 h. This study demonstrated that fosfomycin in combination with sulbactam is a promising option for the treatment of MDR A. baumannii. Further studies are needed to further assess the potential clinical utility of this combination. Full article
(This article belongs to the Special Issue Antibiotic Resistance in Acinetobacter and Associated Treatment Strategies)
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Review

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20 pages, 340 KiB  
Review
Current Therapeutic Approaches for Multidrug-Resistant and Extensively Drug-Resistant Acinetobacter baumannii Infections
by Petros Rafailidis, Periklis Panagopoulos, Christos Koutserimpas and George Samonis
Antibiotics 2024, 13(3), 261; https://doi.org/10.3390/antibiotics13030261 - 15 Mar 2024
Viewed by 1507
Abstract
The treatment of Acinetobacter baumannii infections remains a challenge for physicians worldwide in the 21st century. The bacterium possesses a multitude of mechanisms to escape the human immune system. The consequences of A. baumannii infections on morbidity and mortality, as well on financial [...] Read more.
The treatment of Acinetobacter baumannii infections remains a challenge for physicians worldwide in the 21st century. The bacterium possesses a multitude of mechanisms to escape the human immune system. The consequences of A. baumannii infections on morbidity and mortality, as well on financial resources, remain dire. Furthermore, A. baumannii superinfections have also occurred during the COVID-19 pandemic. While prevention is important, the antibiotic armamentarium remains the most essential factor for the treatment of these infections. The main problem is the notorious resistance profile (including resistance to carbapenems and colistin) that this bacterium exhibits. While newer beta lactam/beta-lactamase inhibitors have entered clinical practice, with excellent results against various infections due to Enterobacteriaceae, their contribution against A. baumannii infections is almost absent. Hence, we have to resort to at least one of the following, sulbactam, polymyxins E or B, tigecycline or aminoglycosides, against multidrug-resistant (MDR) and extensively drug-resistant (XDR) A. baumannii infections. Furthermore, the notable addition of cefiderocol in the fight against A. baumannii infections represents a useful addition. We present herein the existing information from the last decade regarding therapeutic advances against MDR/XDR A. baumannii infections. Full article
(This article belongs to the Special Issue Antibiotic Resistance in Acinetobacter and Associated Treatment Strategies)
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