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European Journal of Pharmaceutical... Mar 2022Antibiotic resistance is a major health concern globally and has been estimated to cause 10 million deaths worldwide by year 2050 if the current trend of inappropriate... (Review)
Review
Antibiotic resistance is a major health concern globally and has been estimated to cause 10 million deaths worldwide by year 2050 if the current trend of inappropriate and excessive use of antibiotics continues. Although, the discovery of antibiotics has saved countless of lives for the past 80 years, increasing levels of bacterial resistance to antibiotics would jeopardize the progress in clinical and agricultural sectors and may cause life-threatening situations even for previously treatable bacterial infections. Antibiotic resistance would increase the levels of poverty of low-middle income countries mostly due to extended hospital stays, higher cost of treatment and untimely deaths that directly affect the total productivity rate. Recent incidences of antibiotic resistance have been gradually increasing globally and this may potentiate horizontal transmission of the resistant gene and have been linked with cross-resistance to other antibiotic families as well. This review summarizes the global burden of antibiotic resistance from the economic viewpoint, highlights the recent incidences of antibiotic resistance mainly related to Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae, Salmonella spp. and Staphylococcus aureus, describes the common mechanistic actions of antibiotic resistance and potential strategies to overcome antibiotic resistance.
Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Drug Resistance, Bacterial; Financial Stress; Humans; Prevalence
PubMed: 34936936
DOI: 10.1016/j.ejps.2021.106103 -
Molecular Biology Reports Oct 2021Acinetobacter baumannii has become a major concern for scientific attention due to extensive antimicrobial resistance. This resistance causes an increase in mortality... (Review)
Review
Acinetobacter baumannii has become a major concern for scientific attention due to extensive antimicrobial resistance. This resistance causes an increase in mortality rate because strains resistant to antimicrobial agents are a major challenge for physicians and healthcare workers regarding the eradication of either hospital or community-based infections. These strains with emerging resistance are a serious issue for patients in the intensive care unit (ICU). Antibiotic resistance has increased because of the acquirement of mobile genetic elements such as transposons, plasmids, and integrons and causes the prevalence of multidrug resistance strains (MDR). In addition, an increase in carbapenem resistance, which is used as last line antibiotic treatment to eliminate infections with multidrug-resistant Gram-negative bacteria, is a major concern. Carbapenems resistant A. baumannii (CR-Ab) is a worldwide problem. Because these strains are often resistant to all other commonly used antibiotics. Therefore, pathogenic multi-drug resistance A. baumannii (MDR-Ab) associated infections become hard to eradicate. Plasmid-mediated resistance causes outbreaks of extensive drug-resistant. A. baumannii (XDR-Ab). In addition, recent outbreaks relating to livestock and community settings illustrate the existence of large MDR-Ab strain reservoirs within and outside hospital settings. The purpose of this review, proper monitoring, prevention, and treatment are required to control (XDR-Ab) infections. Attachment, the formation of biofilms and the secretion of toxins, and low activation of inflammatory responses are mechanisms used by pathogenic A. baumannii strain. This review will discuss some aspects associated with antibiotics resistance in A. baumannii as well as cover briefly phage therapy as an alternative therapeutic treatment.
Topics: Acinetobacter baumannii; Biofilms; Drug Resistance, Multiple, Bacterial; Hospitals; Host-Pathogen Interactions; Humans; Quorum Sensing; Virulence
PubMed: 34460060
DOI: 10.1007/s11033-021-06690-6 -
Viruses Mar 2023() is one of the most common clinical pathogens and a typical multi-drug resistant (MDR) bacterium. With the increase of drug-resistant infections, it is urgent to... (Review)
Review
() is one of the most common clinical pathogens and a typical multi-drug resistant (MDR) bacterium. With the increase of drug-resistant infections, it is urgent to find some new treatment strategies, such as phage therapy. In this paper, we described the different drug resistances of and some basic properties of phages, analyzed the interaction between phages and their hosts, and focused on phage therapies. Finally, we discussed the chance and challenge of phage therapy. This paper aims to provide a more comprehensive understanding of phages and theoretical support for the clinical application of phages.
Topics: Bacteriophages; Acinetobacter baumannii; Anti-Bacterial Agents
PubMed: 36992382
DOI: 10.3390/v15030673 -
Microbiological Research Jun 2021The Gram-negative opportunistic pathogen Acinetobacter baumannii has gain notoriety in recent decades, primarily due to its propensity to cause nosocomial infections in... (Review)
Review
The Gram-negative opportunistic pathogen Acinetobacter baumannii has gain notoriety in recent decades, primarily due to its propensity to cause nosocomial infections in critically ill patients. Its global spread, multi-drug resistance features and plethora of virulence factors make it a serious threat to public health worldwide. Though much effort has been expended in uncovering its successes, it continues to confound researchers due to its highly adaptive nature, mutating to meet the needs of a given environment. Its persistence in the clinical setting allows it to be in close proximity to a potential host, where contact can be made facilitating infection and colonization. In this article, we aim to provide a current overview of the bacterial virulence factors, specifically focusing on factors involved in the initial stages of infection, highlighting the role of adaptation facilitated by two-component systems and biofilm formation. Finally, the study of host-pathogen interactions using available animal models, their suitability, notable findings and some perspectives moving forward are also discussed.
Topics: Acinetobacter Infections; Acinetobacter baumannii; Animals; Biofilms; Cross Infection; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Host-Pathogen Interactions; Humans; Sepsis; Virulence Factors
PubMed: 33618061
DOI: 10.1016/j.micres.2021.126722 -
Biomolecules May 2020is a common cause of serious nosocomial infections. Although community-acquired infections are observed, the vast majority occur in people with preexisting... (Review)
Review
is a common cause of serious nosocomial infections. Although community-acquired infections are observed, the vast majority occur in people with preexisting comorbidities. emerged as a problematic pathogen in the 1980s when an increase in virulence, difficulty in treatment due to drug resistance, and opportunities for infection turned it into one of the most important threats to human health. Some of the clinical manifestations of nosocomial infection are pneumonia; bloodstream infections; lower respiratory tract, urinary tract, and wound infections; burn infections; skin and soft tissue infections (including necrotizing fasciitis); meningitis; osteomyelitis; and endocarditis. has an extraordinary genetic plasticity that results in a high capacity to acquire antimicrobial resistance traits. In particular, acquisition of resistance to carbapenems, which are among the antimicrobials of last resort for treatment of multidrug infections, is increasing among strains compounding the problem of nosocomial infections caused by this pathogen. It is not uncommon to find multidrug-resistant (MDR, resistance to at least three classes of antimicrobials), extensively drug-resistant (XDR, MDR plus resistance to carbapenems), and pan-drug-resistant (PDR, XDR plus resistance to polymyxins) nosocomial isolates that are hard to treat with the currently available drugs. In this article we review the acquired resistance to carbapenems by . We describe the enzymes within the OXA, NDM, VIM, IMP, and KPC groups of carbapenemases and the coding genes found in clinical isolates.
Topics: Acinetobacter baumannii; Bacterial Proteins; Carbapenems; Drug Resistance, Bacterial; Enzyme Inhibitors; beta-Lactamases
PubMed: 32384624
DOI: 10.3390/biom10050720 -
Microbiology Spectrum Oct 2021Tigecycline is regarded as a last-resort treatment for multidrug-resistant Acinetobacter baumannii. However, tigecycline resistance in A. baumannii has increased...
Tigecycline is regarded as a last-resort treatment for multidrug-resistant Acinetobacter baumannii. However, tigecycline resistance in A. baumannii has increased worldwide. In this study, we investigated tigecycline heteroresistance in A. baumannii isolates from South Korea. Antibiotic susceptibility testing was performed on 323 nonduplicated A. baumannii isolates. Among 260 and 37 tigecycline-susceptible and -intermediate-resistant A. baumannii isolates, 146 (56.2%) and 22 (59.5%) isolates were identified as heteroresistant to tigecycline through a disk diffusion assay and population analysis profiling. For selected isolates, an time-kill assay was performed, and survival rates were measured after preincubation with diverse concentrations of tigecycline. Heteroresistant isolates showed regrowth after 12 h of 2× MIC of tigecycline treatment, and resistant subpopulations were selected by preexposure to tigecycline. Furthermore, genetic alterations in , and were assessed, and the relative mRNA expression levels of and were compared. The tigecycline resistance in subpopulations might be due to the insertion of IS in , leading to the overexpression of the AdeABC efflux pump. However, the tigecycline resistance of subpopulations was not stable during serial passages in antibiotic-free medium. The reversion of tigecycline susceptibility by antibiotic-free passages might occur by additional insertions of IS in and nucleotide alterations in in some mutants. Tigecycline heteroresistance is prevalent in A. baumannii isolates, which results in treatment failure. Tigecycline resistance is mainly due to the overexpression of the AdeABC efflux pump, which is associated with genetic mutations, but this resistance could be reversed into susceptibility by additional mutations in antibiotic-free environments. The evidence that antibiotic heteroresistance is responsible for treatment failure in clinical settings is increasing. Thus, detection and characterization of heteroresistance would be important for appropriate therapeutic guidance to treat bacterial infections. However, data on tigecycline heteroresistance in Gram-negative bacteria is currently limited, although tigecycline is regarded as a last-line antibiotic against infections caused by antibiotic-resistant pathogens. In this study, we investigated the tigecycline heteroresistance in Acinetobacter baumannii, which has been listed by the WHO as a priority for research and development of new antibiotics. We found very high prevalence of tigecycline-heteroresistant A. baumannii clinical isolates, which may result in treatment failure due to the selection of resistant subpopulations. We also identified the main resistance mechanism in tigecycline-resistant subpopulations, that is, upregulation of AdeABC efflux pumps due to IS insertion in
Topics: Acinetobacter Infections; Acinetobacter baumannii; Anti-Bacterial Agents; Bacterial Proteins; Disk Diffusion Antimicrobial Tests; Drug Resistance, Multiple, Bacterial; Humans; Membrane Transport Proteins; RNA, Messenger; Ribosomal Proteins; Tigecycline
PubMed: 34523993
DOI: 10.1128/Spectrum.01010-21 -
Clinical Infectious Diseases : An... May 2023Acinetobacter baumannii-calcoaceticus complex is the most commonly identified species in the genus Acinetobacter and it accounts for a large percentage of nosocomial...
Acinetobacter baumannii-calcoaceticus complex is the most commonly identified species in the genus Acinetobacter and it accounts for a large percentage of nosocomial infections, including bacteremia, pneumonia, and infections of the skin and urinary tract. A few key clones of A. baumannii-calcoaceticus are currently responsible for the dissemination of these organisms worldwide. Unfortunately, multidrug resistance is a common trait among these clones due to their unrivalled adaptive nature. A. baumannii-calcoaceticus isolates can accumulate resistance traits by a plethora of mechanisms, including horizontal gene transfer, natural transformation, acquisition of mutations, and mobilization of genetic elements that modulate expression of intrinsic and acquired genes.
Topics: Humans; Acinetobacter baumannii; Anti-Bacterial Agents; Acinetobacter calcoaceticus; Acinetobacter Infections; Acinetobacter; Bacteremia; Drug Resistance, Multiple, Bacterial
PubMed: 37125466
DOI: 10.1093/cid/ciad109 -
Journal of Biomedical Science Jan 2020Acinetobacter baumannii (A. baumannii) is an important opportunistic pathogen causing serious nosocomial infections, which is considered as the most threatening... (Review)
Review
Acinetobacter baumannii (A. baumannii) is an important opportunistic pathogen causing serious nosocomial infections, which is considered as the most threatening Gram-negative bacteria (GNB). Outer membrane protein A (OmpA), a major component of outer membrane proteins (OMPs) in GNB, is a key virulence factor which mediates bacterial biofilm formation, eukaryotic cell infection, antibiotic resistance and immunomodulation. The characteristics of OmpA in Escherichia coli (E. coli) have been extensively studied since 1974, but only in recent years researchers started to clarify the functions of OmpA in A. baumannii. In this review, we summarized the structure and functions of OmpA in A. baumannii (AbOmpA), collected novel therapeutic strategies against it for treating A. baumannii infection, and emphasized the feasibility of using AbOmpA as a potential therapeutic target.
Topics: Acinetobacter Infections; Acinetobacter baumannii; Bacterial Outer Membrane Proteins; Humans
PubMed: 31954394
DOI: 10.1186/s12929-020-0617-7 -
International Journal of Antimicrobial... Aug 2022Management of patients with infections caused by multidrug-resistant organisms is challenging and requires a multidisciplinary approach to achieve successful clinical...
Diagnosis and management of infections caused by multidrug-resistant bacteria: guideline endorsed by the Italian Society of Infection and Tropical Diseases (SIMIT), the Italian Society of Anti-Infective Therapy (SITA), the Italian Group for Antimicrobial Stewardship (GISA), the Italian Association...
Management of patients with infections caused by multidrug-resistant organisms is challenging and requires a multidisciplinary approach to achieve successful clinical outcomes. The aim of this paper is to provide recommendations for the diagnosis and optimal management of these infections, with a focus on targeted antibiotic therapy. The document was produced by a panel of experts nominated by the five endorsing Italian societies, namely the Italian Association of Clinical Microbiologists (AMCLI), the Italian Group for Antimicrobial Stewardship (GISA), the Italian Society of Microbiology (SIM), the Italian Society of Infectious and Tropical Diseases (SIMIT) and the Italian Society of Anti-Infective Therapy (SITA). Population, Intervention, Comparison and Outcomes (PICO) questions about microbiological diagnosis, pharmacological strategies and targeted antibiotic therapy were addressed for the following pathogens: carbapenem-resistant Enterobacterales; carbapenem-resistant Pseudomonas aeruginosa; carbapenem-resistant Acinetobacter baumannii; and methicillin-resistant Staphylococcus aureus. A systematic review of the literature published from January 2011 to November 2020 was guided by the PICO strategy. As data from randomised controlled trials (RCTs) were expected to be limited, observational studies were also reviewed. The certainty of evidence was classified using the GRADE approach. Recommendations were classified as strong or conditional. Detailed recommendations were formulated for each pathogen. The majority of available RCTs have serious risk of bias, and many observational studies have several limitations, including small sample size, retrospective design and presence of confounders. Thus, some recommendations are based on low or very-low certainty of evidence. Importantly, these recommendations should be continually updated to reflect emerging evidence from clinical studies and real-world experience.
Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Antimicrobial Stewardship; Carbapenems; Drug Resistance, Multiple, Bacterial; Humans
PubMed: 35697179
DOI: 10.1016/j.ijantimicag.2022.106611 -
Journal of Global Antimicrobial... Sep 2020Multidrug-resistant (MDR) bacteria are a major public-health concern. Bacteriophage endolysins (lysins) can be used as novel antimicrobial agents against bacterial...
OBJECTIVES
Multidrug-resistant (MDR) bacteria are a major public-health concern. Bacteriophage endolysins (lysins) can be used as novel antimicrobial agents against bacterial infections. In this study, a novel endolysin (LysSS) containing a lysozyme-like domain was evaluated for its antibacterial activity against various species of bacteria.
METHODS
The LysSS-encoding gene was analyzed and cloned and the LysSS recombinant protein was expressed and purified. Purified LysSS was used to determine its antimicrobial activity against various bacterial species in vitro and to measure its protection rate against Acinetobacter baumannii systemic infection in an in vivo murine model.
RESULTS
Recombinant LysSS showed activity against MDR A. baumannii, MDR Escherichia coli, MDR Klebsiella pneumoniae, MDR Pseudomonas aeruginosa and Salmonella sp. without pre-treatment with an outer membrane permeabiliser. Moreover, LysSS inhibited the growth of methicillin-resistant Staphylococcus aureus (MRSA). The minimum inhibitory concentration (MIC) of LysSS against 16 MDR A. baumannii strains ranged from 0.063-0.25mg/mL. LysSS had no cytotoxic effect on A549 human lung cells below 250μg/mL. In an animal model, mice infected with A. baumannii were protected (40% survival rate with 125μg LysSS) by intraperitoneal injection of LysSS.
CONCLUSION
The current results demonstrate that LysSS may be a novel and promising antimicrobial agent against MRSA and MDR Gram-negative bacteria, including A. baumannii and P. aeruginosa.
Topics: Acinetobacter baumannii; Animals; Anti-Infective Agents; Bacteriophages; Endopeptidases; Methicillin-Resistant Staphylococcus aureus; Mice; Pseudomonas aeruginosa
PubMed: 32006750
DOI: 10.1016/j.jgar.2020.01.005