Current Status of Acinetobacter Infections

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Bacterial Pathogens".

Deadline for manuscript submissions: closed (20 October 2022) | Viewed by 78293

Special Issue Editor


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Guest Editor
University of Naples Federico II – Department of Veterinary Medicine and Animal Production
Interests: bacteriology; antibiotic resistance; bacterial infections in domestic animals
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Acinetobacter baumannii has become a relevant threat for public health worldwide. This pathogen, belonging to the ESKAPE group, is one of the main causes of nosocomial infections with the highest mortality rates, such as pneumonia, blood infections, meningitis, UTIs, as well as skin and wound infections. Worryingly, A. baumannii infections are often difficult to treat because of the growing spread of multidrug-resistant strains globally. Even though few reports are described on A. baumannii infections in companion animals in veterinary medicine, the possible transmission from humans to animals or vice versa could represent a new issue for discussion.

This explains the great and recent interest in increasing studies about the pathogenesis, virulence factors, mechanisms of antibiotic resistance, diagnostic tools, therapeutic approaches, and prevention of Acinetobacter baumannii infections.

This Special Issue aims to collect papers on Acinetobacter baumannii infections in human and veterinary medicine, highlighting the importance of studies with a One Health approach to better define the real spread of this pathogen in hospital and extra-hospital reservoirs and environments.

For this Special Issue of Pathogens, I invite you to submit research articles, review articles, and short communications on the current status of Acinetobacter baumannii infections in human and veterinary medicine.

I look forward to your contributions.

Prof. Luisa De Martino
Guest Editor

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Keywords

  • Acinetobacter baumannii
  • Transmission
  • Pathogenesis of infections
  • Virulence factors
  • Antibiotic resistance
  • Therapy
  • One Health approach

Published Papers (12 papers)

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Editorial

Jump to: Research, Review

3 pages, 174 KiB  
Editorial
Editorial on the Research Topic of the Special Issue “Current Status of Acinetobacter Infections”
by Francesca Paola Nocera and Luisa De Martino
Pathogens 2023, 12(2), 219; https://doi.org/10.3390/pathogens12020219 - 31 Jan 2023
Cited by 1 | Viewed by 998
Abstract
Emerging bacterial infections will continue to be an important issue for public health, mostly because of the constant changes on our earth [...] Full article
(This article belongs to the Special Issue Current Status of Acinetobacter Infections)

Research

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14 pages, 1421 KiB  
Article
Genomic Investigation of Two Acinetobacter baumannii Outbreaks in a Veterinary Intensive Care Unit in The Netherlands
by Soe Yu Naing, Joost Hordijk, Birgitta Duim, Els M. Broens, Linda van der Graaf-van Bloois, John W. Rossen, Joris H. Robben, Masja Leendertse, Jaap A. Wagenaar and Aldert L. Zomer
Pathogens 2022, 11(2), 123; https://doi.org/10.3390/pathogens11020123 - 20 Jan 2022
Cited by 9 | Viewed by 3816
Abstract
Acinetobacter baumannii is a nosocomial pathogen that frequently causes healthcare-acquired infections. The global spread of multidrug-resistant (MDR) strains with its ability to survive in the environment for extended periods imposes a pressing public health threat. Two MDR A. baumannii outbreaks occurred in 2012 [...] Read more.
Acinetobacter baumannii is a nosocomial pathogen that frequently causes healthcare-acquired infections. The global spread of multidrug-resistant (MDR) strains with its ability to survive in the environment for extended periods imposes a pressing public health threat. Two MDR A. baumannii outbreaks occurred in 2012 and 2014 in a companion animal intensive care unit (caICU) in the Netherlands. Whole-genome sequencing (WGS) was performed on dog clinical isolates (n = 6), environmental isolates (n = 5), and human reference strains (n = 3) to investigate if the isolates of the two outbreaks were related. All clinical isolates shared identical resistance phenotypes displaying multidrug resistance. Multi-locus Sequence Typing (MLST) revealed that all clinical isolates belonged to sequence type ST2. The core genome MLST (cgMLST) results confirmed that the isolates of the two outbreaks were not related. Comparative genome analysis showed that the outbreak isolates contained different gene contents, including mobile genetic elements associated with antimicrobial resistance genes (ARGs). The time-measured phylogenetic reconstruction revealed that the outbreak isolates diverged approximately 30 years before 2014. Our study shows the importance of WGS analyses combined with molecular clock investigations to reduce transmission of MDR A. baumannii infections in companion animal clinics. Full article
(This article belongs to the Special Issue Current Status of Acinetobacter Infections)
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16 pages, 1256 KiB  
Article
Colistin Resistance Onset Strategies and Genomic Mosaicism in Clinical Acinetobacter baumannii Lineages
by Viviana Cafiso, Stefano Stracquadanio, Veronica Dovere, Flavia Lo Verde, Alessandra Zega, Giuseppe Pigola, Simona Barnini, Emilia Ghelardi and Stefania Stefani
Pathogens 2021, 10(11), 1516; https://doi.org/10.3390/pathogens10111516 - 20 Nov 2021
Cited by 3 | Viewed by 2517
Abstract
The treatment of multidrug-resistant Gram-negative infections is based on colistin. As result, COL-resistance (COL-R) can develop and spread. In Acinetobacter baumannii, a crucial step is to understand COL-R onset and stability, still far to be elucidated. COL-R phenotypic stability, onset modalities, and [...] Read more.
The treatment of multidrug-resistant Gram-negative infections is based on colistin. As result, COL-resistance (COL-R) can develop and spread. In Acinetobacter baumannii, a crucial step is to understand COL-R onset and stability, still far to be elucidated. COL-R phenotypic stability, onset modalities, and phylogenomics were investigated in a clinical A. baumannii sample showing a COL resistant (COLR) phenotype at first isolation. COL-R was confirmed by Minimum-Inhibitory-Concentrations as well as investigated by Resistance-Induction assays and Population-Analysis-Profiles (PAPs) to determine: (i) stability; (ii) inducibility; (iii) heteroresistance. Genomics was performed by Mi-Seq Whole-Genome-Sequencing, Phylogenesis, and Genomic Epidemiology by bioinformatics. COLRA. baumannii were subdivided as follows: (i) 3 A. baumannii with stable and high COL MICs defining the “homogeneous-resistant” onset phenotype; (ii) 6 A. baumannii with variable and lower COL MICs displaying a “COL-inducible” onset phenotype responsible for adaptive-resistance or a “subpopulation” onset phenotype responsible for COL-heteroresistance. COL-R stability and onset strategies were not uniquely linked to the amount of LPS and cell envelope charge. Phylogenomics categorized 3 lineages clustering stable and/or unstable COL-R phenotypes with increasing genomic complexity. Likewise, different nsSNP profiling in genes already associated with COL-R marked the stable and/or unstable COL-R phenotypes. Our investigation finds out that A. baumannii can range through unstable or stable COLR phenotypes emerging via different “onset strategies” within phylogenetic lineages displaying increasing genomic mosaicism. Full article
(This article belongs to the Special Issue Current Status of Acinetobacter Infections)
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12 pages, 1157 KiB  
Article
Correlation between Acinetobacter baumannii Resistance and Hospital Use of Meropenem, Cefepime, and Ciprofloxacin: Time Series Analysis and Dynamic Regression Models
by Rania Kousovista, Christos Athanasiou, Konstantinos Liaskonis, Olga Ivopoulou, George Ismailos and Vangelis Karalis
Pathogens 2021, 10(4), 480; https://doi.org/10.3390/pathogens10040480 - 15 Apr 2021
Cited by 9 | Viewed by 2455
Abstract
Acinetobacter baumannii is one of the most difficult-to-treat pathogens worldwide, due to developed resistance. The aim of this study was to evaluate the use of widely prescribed antimicrobials and the respective resistance rates of A. baumannii, and to explore the relationship between antimicrobial [...] Read more.
Acinetobacter baumannii is one of the most difficult-to-treat pathogens worldwide, due to developed resistance. The aim of this study was to evaluate the use of widely prescribed antimicrobials and the respective resistance rates of A. baumannii, and to explore the relationship between antimicrobial use and the emergence of A. baumannii resistance in a tertiary care hospital. Monthly data on A. baumannii susceptibility rates and antimicrobial use, between January 2014 and December 2017, were analyzed using time series analysis (Autoregressive Integrated Moving Average (ARIMA) models) and dynamic regression models. Temporal correlations between meropenem, cefepime, and ciprofloxacin use and the corresponding rates of A. baumannii resistance were documented. The results of ARIMA models showed statistically significant correlation between meropenem use and the detection rate of meropenem-resistant A. baumannii with a lag of two months (p = 0.024). A positive association, with one month lag, was identified between cefepime use and cefepime-resistant A. baumannii (p = 0.028), as well as between ciprofloxacin use and its resistance (p < 0.001). The dynamic regression models offered explanation of variance for the resistance rates (R2 > 0.60). The magnitude of the effect on resistance for each antimicrobial agent differed significantly. Full article
(This article belongs to the Special Issue Current Status of Acinetobacter Infections)
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13 pages, 1312 KiB  
Article
Human Pleural Fluid and Human Serum Albumin Modulate the Behavior of a Hypervirulent and Multidrug-Resistant (MDR) Acinetobacter baumannii Representative Strain
by Camila Pimentel, Casin Le, Marisel R. Tuttobene, Tomas Subils, Jasmine Martinez, Rodrigo Sieira, Krisztina M. Papp-Wallace, Niroshika Keppetipola, Robert A. Bonomo, Luis A. Actis, Marcelo E. Tolmasky and Maria Soledad Ramirez
Pathogens 2021, 10(4), 471; https://doi.org/10.3390/pathogens10040471 - 13 Apr 2021
Cited by 15 | Viewed by 3120
Abstract
Acinetobacter baumannii is a nosocomial pathogen capable of causing serious infections associated with high rates of morbidity and mortality. Due to its antimicrobial drug resistance profile, A. baumannii is categorized as an urgent priority pathogen by the Centers for Disease Control and Prevention [...] Read more.
Acinetobacter baumannii is a nosocomial pathogen capable of causing serious infections associated with high rates of morbidity and mortality. Due to its antimicrobial drug resistance profile, A. baumannii is categorized as an urgent priority pathogen by the Centers for Disease Control and Prevention in the United States and a priority group 1 critical microorganism by the World Health Organization. Understanding how A. baumannii adapts to different host environments may provide critical insights into strategically targeting this pathogen with novel antimicrobial and biological therapeutics. Exposure to human fluids was previously shown to alter the gene expression profile of a highly drug-susceptible A. baumannii strain A118 leading to persistence and survival of this pathogen. Herein, we explore the impact of human pleural fluid (HPF) and human serum albumin (HSA) on the gene expression profile of a highly multi-drug-resistant strain of A. baumannii AB5075. Differential expression was observed for ~30 genes, whose products are involved in quorum sensing, quorum quenching, iron acquisition, fatty acid metabolism, biofilm formation, secretion systems, and type IV pilus formation. Phenotypic and further transcriptomic analysis using quantitative RT-PCR confirmed RNA-seq data and demonstrated a distinctive role of HSA as the molecule involved in A. baumannii’s response. Full article
(This article belongs to the Special Issue Current Status of Acinetobacter Infections)
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10 pages, 1892 KiB  
Communication
OmpA Protein-Deficient Acinetobacter baumannii Outer Membrane Vesicles Trigger Reduced Inflammatory Response
by Jūratė Skerniškytė, Emilija Karazijaitė, Asta Lučiūnaitė and Edita Sužiedėlienė
Pathogens 2021, 10(4), 407; https://doi.org/10.3390/pathogens10040407 - 31 Mar 2021
Cited by 16 | Viewed by 3269
Abstract
Multidrug resistant Acinetobacter baumannii shows a growing number of nosocomial infections worldwide during the last decade. The outer membrane vesicles (OMVs) produced by this bacterium draw increasing attention as a possible treatment target. OMVs have been implicated in the reduction of antibiotic level [...] Read more.
Multidrug resistant Acinetobacter baumannii shows a growing number of nosocomial infections worldwide during the last decade. The outer membrane vesicles (OMVs) produced by this bacterium draw increasing attention as a possible treatment target. OMVs have been implicated in the reduction of antibiotic level in the surrounding environment, transfer of virulence factors into the host cells, and induction of inflammatory response. Although the evidence on the involvement of OMVs in A. baumannii pathogenesis is currently growing, their role during inflammation is insufficiently explored. It is likely that bacteria, by secreting OMVs, can expand the area of their exposure and prepare surrounding matrix for infection. Here, we investigated the impact of A. baumannii OMVs on activation of macrophages in vitro. We show that OmpA protein present in A. baumannii OMVs substantially contributes to the proinflammatory response in J774 murine macrophages and to the cell death in both lung epithelium cells and macrophages. The loss of OmpA protein in OMVs, obtained from A. baumanniiompA mutant, resulted in the altered expression of genes coding for IL-6, NLRP3 and IL-1β proinflammatory molecules in macrophages in vitro. These results imply that OmpA protein in bacterial OMVs could trigger a more intense proinflammatory response. Full article
(This article belongs to the Special Issue Current Status of Acinetobacter Infections)
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12 pages, 938 KiB  
Article
Acinetobacter baumannii LOS Regulate the Expression of Inflammatory Cytokine Genes and Proteins in Human Mast Cells
by Takane Kikuchi-Ueda, Tsuneyuki Ubagai, Go Kamoshida, Ryuichi Nakano, Akiyo Nakano and Yasuo Ono
Pathogens 2021, 10(3), 290; https://doi.org/10.3390/pathogens10030290 - 3 Mar 2021
Cited by 6 | Viewed by 1981
Abstract
Herein, we investigated the effect of bacterial lipooligosaccharides (LOS), from Acinetobacter baumannii, on the expression of pro-inflammatory genes that play an essential role in bacterial clearance. LAD2 human mast cells were stimulated with LOS derived from two strains of A. baumannii—ATCC [...] Read more.
Herein, we investigated the effect of bacterial lipooligosaccharides (LOS), from Acinetobacter baumannii, on the expression of pro-inflammatory genes that play an essential role in bacterial clearance. LAD2 human mast cells were stimulated with LOS derived from two strains of A. baumannii—ATCC 19606 and MDRA T14. LOS exposure induced the expression of genes for pro-inflammatory mediators, including TNF-α, IL-8, LTC4S, CCL4, and TLR4. The mRNA expression levels of a majority of the pro-inflammatory genes, except TLR4, in A. baumannii-LOS stimulated mast cells were increased. Moreover, co-culture of neutrophils with the supernatant obtained from LOS (ATCC 19606 and MDRA T14)-induced LAD2 cells increased the transmigration of neutrophils, which plays a critical role in the early protection against bacterial infections. The results of the present study suggest that LOS could be involved in the pathogenicity of A. baumannii by inducing inflammatory responses via mast cells and that IL-8 is involved in recruiting neutrophils in response to bacterial invasion. Full article
(This article belongs to the Special Issue Current Status of Acinetobacter Infections)
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16 pages, 5596 KiB  
Article
Genomic and Phenotypic Analysis of Multidrug-Resistant Acinetobacter baumannii Clinical Isolates Carrying Different Types of CRISPR/Cas Systems
by Marina Tyumentseva, Yulia Mikhaylova, Anna Prelovskaya, Aleksandr Tyumentsev, Lyudmila Petrova, Valeria Fomina, Mikhail Zamyatin, Andrey Shelenkov and Vasiliy Akimkin
Pathogens 2021, 10(2), 205; https://doi.org/10.3390/pathogens10020205 - 13 Feb 2021
Cited by 24 | Viewed by 3660
Abstract
Acinetobacter baumannii is an opportunistic pathogen being one of the most important causative agents of a wide range of nosocomial infections associated with multidrug resistance and high mortality rate. This study presents a multiparametric and correlation analyses of clinical multidrug-resistant A. baumannii isolates [...] Read more.
Acinetobacter baumannii is an opportunistic pathogen being one of the most important causative agents of a wide range of nosocomial infections associated with multidrug resistance and high mortality rate. This study presents a multiparametric and correlation analyses of clinical multidrug-resistant A. baumannii isolates using short- and long-read whole-genome sequencing, which allowed us to reveal specific characteristics of the isolates with different CRISPR/Cas systems. We also compared antibiotic resistance and virulence gene acquisition for the groups of the isolates having functional CRISPR/Cas systems, just CRISPR arrays without cas genes, and without detectable CRISPR spacers. The data include three schemes of molecular typing, phenotypic and genotypic antibiotic resistance determination, as well as phylogenetic analysis of full-length cas gene sequences, predicted prophage sequences and CRISPR array type determination. For the first time the differences between the isolates carrying Type I-F1 and Type I-F2 CRISPR/Cas systems were investigated. A. baumannii isolates with Type I-F1 system were shown to have smaller number of reliably detected CRISPR arrays, and thus they could more easily adapt to environmental conditions through acquisition of antibiotic resistance genes, while Type I-F2 A. baumannii might have stronger “immunity” and use CRISPR/Cas system to block the dissemination of these genes. In addition, virulence factors abaI, abaR, bap and bauA were overrepresented in A. baumannii isolates lacking CRISPR/Cas system. This indicates the role of CRISPR/Cas in fighting against phage infections and preventing horizontal gene transfer. We believe that the data presented will contribute to further investigations in the field of antimicrobial resistance and CRISPR/Cas studies. Full article
(This article belongs to the Special Issue Current Status of Acinetobacter Infections)
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Review

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13 pages, 590 KiB  
Review
Acinetobacter baumannii Infections in Times of COVID-19 Pandemic
by Karyne Rangel, Thiago Pavoni Gomes Chagas and Salvatore Giovanni De-Simone
Pathogens 2021, 10(8), 1006; https://doi.org/10.3390/pathogens10081006 - 10 Aug 2021
Cited by 89 | Viewed by 9567
Abstract
The COVID-19 pandemic has generated an overuse of antimicrobials in critically ill patients. Acinetobacter baumannii frequently causes nosocomial infections, particularly in intensive care units (ICUs), where the incidence has increased over time. Since the WHO declared the COVID-19 pandemic on 12 March 2020, [...] Read more.
The COVID-19 pandemic has generated an overuse of antimicrobials in critically ill patients. Acinetobacter baumannii frequently causes nosocomial infections, particularly in intensive care units (ICUs), where the incidence has increased over time. Since the WHO declared the COVID-19 pandemic on 12 March 2020, the disease has spread rapidly, and many of the patients infected with SARS-CoV-2 needed to be admitted to the ICU. Bacterial co-pathogens are commonly identified in viral respiratory infections and are important causes of morbidity and mortality. However, we cannot neglect the increased incidence of antimicrobial resistance, which may be attributed to the excess use of antimicrobial agents during the COVID-19 pandemic. Patients with COVID-19 could be vulnerable to other infections owing to multiple comorbidities with severe COVID-19, prolonged hospitalization, and SARS-CoV-2-associated immune dysfunction. These patients have acquired secondary bacterial infections or superinfections, mainly bacteremia and urinary tract infections. This review will summarize the prevalence of A. baumannii coinfection and secondary infection in patients with COVID-19. Full article
(This article belongs to the Special Issue Current Status of Acinetobacter Infections)
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25 pages, 2072 KiB  
Review
Acinetobacter baumannii: An Ancient Commensal with Weapons of a Pathogen
by Meysam Sarshar, Payam Behzadi, Daniela Scribano, Anna Teresa Palamara and Cecilia Ambrosi
Pathogens 2021, 10(4), 387; https://doi.org/10.3390/pathogens10040387 - 24 Mar 2021
Cited by 96 | Viewed by 11516
Abstract
Acinetobacter baumannii is regarded as a life-threatening pathogen associated with community-acquired and nosocomial infections, mainly pneumonia. The rise in the number of A. baumannii antibiotic-resistant strains reduces effective therapies and increases mortality. Bacterial comparative genomic studies have unraveled the innate and acquired virulence [...] Read more.
Acinetobacter baumannii is regarded as a life-threatening pathogen associated with community-acquired and nosocomial infections, mainly pneumonia. The rise in the number of A. baumannii antibiotic-resistant strains reduces effective therapies and increases mortality. Bacterial comparative genomic studies have unraveled the innate and acquired virulence factors of A. baumannii. These virulence factors are involved in antibiotic resistance, environmental persistence, host-pathogen interactions, and immune evasion. Studies on host–pathogen interactions revealed that A. baumannii evolved different mechanisms to adhere to in order to invade host respiratory cells as well as evade the host immune system. In this review, we discuss current data on A. baumannii genetic features and virulence factors. An emphasis is given to the players in host–pathogen interaction in the respiratory tract. In addition, we report recent investigations into host defense systems using in vitro and in vivo models, providing new insights into the innate immune response to A. baumannii infections. Increasing our knowledge of A. baumannii pathogenesis may help the development of novel therapeutic strategies based on anti-adhesive, anti-virulence, and anti-cell to cell signaling pathways drugs. Full article
(This article belongs to the Special Issue Current Status of Acinetobacter Infections)
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31 pages, 4564 KiB  
Review
Acinetobacter baumannii Antibiotic Resistance Mechanisms
by Ioannis Kyriakidis, Eleni Vasileiou, Zoi Dorothea Pana and Athanasios Tragiannidis
Pathogens 2021, 10(3), 373; https://doi.org/10.3390/pathogens10030373 - 19 Mar 2021
Cited by 216 | Viewed by 26938
Abstract
Acinetobacter baumannii is a Gram-negative ESKAPE microorganism that poses a threat to public health by causing severe and invasive (mostly nosocomial) infections linked with high mortality rates. During the last years, this pathogen displayed multidrug resistance (MDR), mainly due to extensive antibiotic abuse [...] Read more.
Acinetobacter baumannii is a Gram-negative ESKAPE microorganism that poses a threat to public health by causing severe and invasive (mostly nosocomial) infections linked with high mortality rates. During the last years, this pathogen displayed multidrug resistance (MDR), mainly due to extensive antibiotic abuse and poor stewardship. MDR isolates are associated with medical history of long hospitalization stays, presence of catheters, and mechanical ventilation, while immunocompromised and severely ill hosts predispose to invasive infections. Next-generation sequencing techniques have revolutionized diagnosis of severe A. baumannii infections, contributing to timely diagnosis and personalized therapeutic regimens according to the identification of the respective resistance genes. The aim of this review is to describe in detail all current knowledge on the genetic background of A. baumannii resistance mechanisms in humans as regards beta-lactams (penicillins, cephalosporins, carbapenems, monobactams, and beta-lactamase inhibitors), aminoglycosides, tetracyclines, fluoroquinolones, macrolides, lincosamides, streptogramin antibiotics, polymyxins, and others (amphenicols, oxazolidinones, rifamycins, fosfomycin, diaminopyrimidines, sulfonamides, glycopeptide, and lipopeptide antibiotics). Mechanisms of antimicrobial resistance refer mainly to regulation of antibiotic transportation through bacterial membranes, alteration of the antibiotic target site, and enzymatic modifications resulting in antibiotic neutralization. Virulence factors that may affect antibiotic susceptibility profiles and confer drug resistance are also being discussed. Reports from cases of A. baumannii coinfection with SARS-CoV-2 during the COVID-19 pandemic in terms of resistance profiles and MDR genes have been investigated. Full article
(This article belongs to the Special Issue Current Status of Acinetobacter Infections)
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13 pages, 327 KiB  
Review
Acinetobacter baumannii: Its Clinical Significance in Human and Veterinary Medicine
by Francesca Paola Nocera, Anna-Rita Attili and Luisa De Martino
Pathogens 2021, 10(2), 127; https://doi.org/10.3390/pathogens10020127 - 27 Jan 2021
Cited by 42 | Viewed by 6027
Abstract
Acinetobacter baumannii is a Gram-negative, opportunistic pathogen, causing severe infections difficult to treat. The A. baumannii infection rate has increased year by year in human medicine and it is also considered as a major cause of nosocomial infections worldwide. This bacterium, also well [...] Read more.
Acinetobacter baumannii is a Gram-negative, opportunistic pathogen, causing severe infections difficult to treat. The A. baumannii infection rate has increased year by year in human medicine and it is also considered as a major cause of nosocomial infections worldwide. This bacterium, also well known for its ability to form biofilms, has a strong environmental adaptability and the characteristics of multi-drug resistance. Indeed, strains showing fully resistant profiles represent a worrisome problem in clinical therapeutic treatment. Furthermore, A. baumannii-associated veterinary nosocomial infections has been reported in recent literature. Particularly, carbapenem-resistant A. baumannii can be considered an emerging opportunistic pathogen in human medicine as well as in veterinary medicine. Full article
(This article belongs to the Special Issue Current Status of Acinetobacter Infections)
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