Baumannii Isolates Research Articles

"Characterization Of Acinetobacter Baumannii Resistance And Prevalence In Icu Settings: Insights From A Retrospective Study."

Purpose: This study aimed to determine the prevalence and antibiotic resistance patterns of Acinetobacter baumannii isolated from ICU patients at a tertiary care hospital. Understanding these patterns is crucial for informing infection control strategies and treatment protocols. Material and methods: A retrospective cross-sectional study was conducted at the Department of Microbiology, Government Medical College & New Civil Hospital, Surat. Clinical samples from ICUs were analyzed from January 2023 to December 2023. A total of 4,432 samples were processed for culture and sensitivity testing. Identification of A. baumannii was performed using Gram staining, motility tests, and biochemical tests. Antimicrobial susceptibility was assessed using the Kirby-Bauer disk diffusion method on Mueller-Hinton agar, with results interpreted according to CLSI guidelines. Results: Out of 4,432 samples, 650 showed significant bacterial growth. Acinetobacter baumannii was identified in 144 samples, accounting for 22% of all ICU culture-positive cases. The highest number of isolates was from the Medical ICU (MICU), representing 44% of total isolates. Over 95% of A. baumannii isolates were multidrugresistant (MDR). Resistance rates were highest for Ceftriaxone and Imipenem (92%), followed by Cefepime (90.2%). Colistin susceptibility was observed in all pan-drug-resistant isolates. Discussion: The high prevalence of A. baumannii in ICU-acquired infections and the observed multidrug resistance highlight a significant challenge in managing these infections. The resistance patterns are consistent with recent studies, confirming the persistent difficulty in treating A. baumannii infections with conventional antibiotics. The effectiveness of Colistin for pan-drug-resistant isolates underscores its continued relevance, despite concerns about potential side effects. Conclusion: The study reveals a high prevalence of multidrug-resistant A. baumannii in ICU settings, emphasizing the urgent need for effective infection control measures and antimicrobial stewardship. Continuous monitoring and stringent infection prevention practices are essential to combat the growing threat of A. baumannii in ICU environments

Examining the Frequency of Selected Genes Involved in Biofilm Formation in Clinical Isolates of Acinetobacter Baumannii

Introduction: Acinetobacter baumannii, a non-fermenting Gram-negative coccobacillus, exhibits high resistance to antimicrobial compounds. Biofilm formation is a crucial feature in many Acinetobacter species, contributing to their antibiotic resistance. The present study aimed to investigate the prevalence of ompA, csuA, bap and pgaB genes in clinical isolates of Acinetobacter baumannii with biofilm formation ability. Methods: In this cross-sectional study, 49 isolates of Acinetobacter baumannii were collected from patients hospitalized in the health centers of Borujerd City. Acinetobacter baumannii isolates were confirmed by biochemical tests. In these isolates, the biofilm production ability was investigated by microtitreplate method. Then, using PCR method and specific primers, ompA, csuA, bap and pgaB genes were identified.The collected data were analyzed descriptively and analytically using SPSS version 16 software. Data analysis was done with Chi-square test, Fisher's exact test, and P<0.05 was considered as the basis of significance. Results: The presence of ompA, csuA, bap, and pgaB genes was detected in 87%, 92%, 98%, and 100% of the isolates, respectively. Additionally, the microtitreplate method revealed that biofilm formation was strong in 3 isolates (6%), moderate in 17 isolates (35%), and weak in 29 isolates (59%). Conclusion: The prevalence of genes associated with biofilm formation in Acinetobacter baumannii isolates was high. This suggests that the studied isolates possess a significant ability to form biofilm structures.

Comparison of Beta-Lactamase Profiles and Epidemiology of Multi-Drug Resistant Acinetobacter baumannii Isolates in Southwest Turkey: 2011 vs. 2019 Study

Background: The most significant problem encountered with hospital infections caused by multi-drug resistant Acinetobacter baumannii isolates is the difficulty in treatment. Defining resistance mechanisms is important for the development of treatment strategies. Objectives: The aim of this study was to investigate the beta-lactamase genes and clonal relationship in multi-drug resistant A. baumannii isolates in Mugla, Turkey, as no data are currently available for this province. Methods: Total 96 multi-drug resistant A. baumannii isolates obtained from hospitalized patients, between 2011 - 2012 period (n = 61) and in year 2019 (n = 35) were investigated and compared for antibiotic susceptibilities, beta-lactamase enzyme encoding genes by polymerase chain reaction (PCR) method. Repetitive extragenic palindromic (REP) PCR was made for dendrogram analysis to illustrate hierarchical relationship between isolates. Results: Overall, 74.0% of the isolates were obtained from patients in intensive care units. All multi-drug resistant isolates were found resistant to ciprofloxacin, piperacillin, piperacillin-tazobactam, meropenem, and imipenem by the disk diffusion method. The minimum inhibitory concentration values indicated that all isolates were resistant to imipenem, while colistin resistance was determined as 21.9%. The ISAba-I insertion element was present in all isolates. BlaOXA-23-like was present in 96.9%, and blaOXA-24-like was detected in three (3.1%) isolates. blaNDM positivity was shown in 5.2% of isolates. The indistinguishable or closely related isolates ratio was detected as 29.5% for the 2011 - 2012 period and 80% for 2019. Conclusions: Our findings showed that antibiotic resistance rates were high in A. baumannii, particularly isolated from intensive care unit patients in Mugla province. The prevalence of beta-lactamase and metallo-beta-lactamase genes has been increasing year by year, with the blaOXA-23-like gene region being the most prevalent. Additionally, the co-existence of these genes among strains is also on the rise. These findings from two different periods may provide useful reference data for future studies.

Tracing Acinetobacter baumannii's Journey from Hospitals to Aquatic Ecosystems.

This study provides a comprehensive analysis of Acinetobacter baumannii in aquatic environments and fish microbiota by integrating culture-dependent methods, 16S metagenomics, and antibiotic resistance profiling. A total of 83 A. baumannii isolates were recovered using culture-dependent methods from intra-hospital infections (IHI) and wastewater (WW) and surface water (SW) samples from two southern Romanian cities in August 2022. The antibiotic susceptibility was screened using disc diffusion, microdilution, PCR, and Whole Genome Sequencing assays. The highest microbial load in the analyzed samples was found in Glina, Bucharest, for both WW and SW samples across all investigated phenotypes. For Bucharest isolates, the resistance levels corresponded to fluoroquinolones > aminoglycosides > β-lactam antibiotics. In contrast, A. baumannii from upstream SW samples in Târgoviște showed the highest resistance to aminoglycosides. The blaOXA-23 gene was frequently detected in IHI, WW, and SW isolates in Bucharest, but was absent in Târgoviște. Molecular phylogeny revealed the presence of ST10 in Târgoviște isolates and ST2 in Bucharest isolates, while other minor STs were not specifically correlated with a sampling point. Using 16S rRNA sequencing, significant differences in microbial populations between the two locations was identified. The low abundance of Alphaproteobacteria and Actinobacteria in both locations suggests environmental pressures or contamination events. These findings indicate significant fecal contamination and potential public health risks, emphasizing the need for improved water quality monitoring and management.

Characterisation of carbapenemase-producing Gram-negative bacilli among clinical isolates in a tertiary care centre in Kerala, South India

Background: Infections caused by carbapenem-resistant Gram-negative bacteria are a cause for concern due to the limited choice of antibiotics available for their treatment. Aims, Settings and Design: This study screened multidrug-resistant (MDR) Gram-negative bacilli isolated from clinical samples over a period of one year, for carbapenem resistance and characterised them using phenotypic methods such as combined disc diffusion test (CDDT), modified Hodge test (MHT), E-test for metallo-beta-lactamase (MBL) and molecular method, PCR. Materials and Methods: Two hundred and ten MDR Gram-negative bacilli were screened for carbapenem resistance using Imipenem and Meropenem disc diffusion. These were further checked for carbapenemase production by CDDT, MHT and E-test for MBL. Those positive by E-test were subjected to PCR. Uniplex PCR for New Delhi metallo-beta-lactamase-1 was used for Escherichia coli and Klebsiella pneumoniae , and multiplex PCR for Imipenemase and Verona imipenemase was used for Pseudomonas aeruginosa and Acinetobacter baumannii isolates. Results: Twenty-three (11%) isolates were found to be carbapenem-resistant and included E. coli (six) K. pneumoniae (three), P. aeruginosa (five) and A. baumannii (nine). Seventeen (74%) isolates were positive by phenotypic methods and were subjected to PCR. Out of eight Enterobacteriaceae isolates subjected to PCR, all were positive for bla NDM gene. All were negative for bla KPC gene. All five A. baumannii isolates subjected to PCR were found to contain bla VIM gene. Two out of four P. aeruginosa isolates were positive for bla IMP , one was positive for bla VIM gene. One P. aeruginosa isolate was positive for both bla IMP and bla VIM gene. Conclusions: In view of the increasing resistance of Gram-negative bacilli to carbapenems, rational use of antibiotics needs to be emphasised.

Identification of novel drug targets to counteract efflux pump mediated multidrug resistance in Acinetobacter baumannii

The emergence of multidrug-resistant (MDR) Acinetobacter baumannii poses an escalating threat to the healthcare system worldwide. A significant factor contributing to increasing resistance is the overexpression of chromosomally encoded efflux pumps, which expel antibiotics from bacterial cells, thereby rendering treatments less effective. The efflux pumps not only mediate resistance to antibiotics through drug efflux but also work synergistically with other resistance mechanisms, thereby doubling the resistance. Despite their crucial role in antibiotic resistance, understanding of the structure, function, mechanisms of action, and regulation of efflux pumps remains limited, which is necessary for devising effective strategies to restore drug susceptibility and to combat MDR isolates. In this context, the present study evaluated the prevalence of efflux pump overexpression in clinical A. baumannii isolates using phenotypic and genotypic methods and identified potential therapeutic targets employing a network-based approach. A total of 172 A. baumannii isolates were collected and subjected to antibiotic susceptibility tests using the Kirby-Bauer disk diffusion method. All the isolates were found to be MDR, with 94.76 % showing resistance to carbapenems. Efflux pump overexpression was detected in 54.65 % of isolates using the Ethidium-Bromide Agar Cartwheel method, and efflux pump inhibitory activity was observed in 68.71 % of isolates using cyanide m-chlorophenylhydrazone (CCCP). A total of thirteen efflux pump genes were detected in the tested isolates using diagnostic PCR, which were considered for interaction network analysis using STRING. Clustering analysis of the merged network identified two highly interconnected clusters, each comprising functional partners crucial for efflux pump function and regulation. Key hub genes, including AdeB, AdeJ, AdeK, AdeC, macB, tolC, AIL80285.1, AdeR, and AdeS, were identified as primary targets due to their significant influence on the network. Additionally, 24 clustered genes were pinpointed as potential drug targets for developing novel therapeutics to combat the formidable challenge of efflux pump-mediated MDR in A. baumannii.

Efficacy of aspergillomarasmine A/meropenem combinations with and without avibactam against bacterial strains producing multiple β-lactamases.

The effectiveness of β-lactam antibiotics is increasingly threatened by resistant bacteria that harbor hydrolytic β-lactamase enzymes. Depending on the class of β-lactamase present, β-lactam hydrolysis can occur through one of two general molecular mechanisms. Metallo-β-lactamases (MBLs) require active site Zn2+ ions, whereas serine-β-lactamases (SBLs) deploy a catalytic serine residue. The result in both cases is drug inactivation via the opening of the β-lactam warhead of the antibiotic. MBLs confer resistance to most β-lactams and are non-susceptible to SBL inhibitors, including recently approved diazabicyclooctanes, such as avibactam; consequently, these enzymes represent a growing threat to public health. Aspergillomarasmine A (AMA), a fungal natural product, can rescue the activity of the β-lactam antibiotic meropenem against MBL-expressing bacterial strains. However, the effectiveness of this β-lactam/β-lactamase inhibitor combination against bacteria producing multiple β-lactamases remains unknown. We systematically investigated the efficacy of AMA/meropenem combination therapy with and without avibactam against 10 Escherichia coli and 10 Klebsiella pneumoniae laboratory strains tandemly expressing single MBL and SBL enzymes. Cell-based assays demonstrated that laboratory strains producing NDM-1 and KPC-2 carbapenemases were resistant to the AMA/meropenem combination but became drug-susceptible upon adding avibactam. We also probed these combinations against 30 clinical isolates expressing multiple β-lactamases. E. coli, Enterobacter cloacae, and K. pneumoniae clinical isolates were more susceptible to AMA, avibactam, and meropenem than Pseudomonas aeruginosa and Acinetobacter baumannii isolates. Overall, the results demonstrate that a triple combination of AMA/avibactam/meropenem has potential for empirical treatment of infections caused by multiple β-lactamase-producing bacteria, especially Enterobacterales.

Alteration in the Morphological and Transcriptomic Profiles of Acinetobacter baumannii after Exposure to Colistin.

Acinetobacter baumannii is often highly resistant to multiple antimicrobials, posing a risk of treatment failure, and colistin is a "last resort" for treatment of the bacterial infection. However, colistin resistance is easily developed when the bacteria are exposed to the drug, and a comprehensive analysis of colistin-mediated changes in colistin-susceptible and -resistant A. baumannii is needed. In this study, using an isogenic pair of colistin-susceptible and -resistant A. baumannii isolates, alterations in morphologic and transcriptomic characteristics associated with colistin resistance were revealed. Whole-genome sequencing showed that the resistant isolate harbored a PmrBL208F mutation conferring colistin resistance, and all other single-nucleotide alterations were located in intergenic regions. Using scanning electron microscopy, it was determined that the colistin-resistant mutant had a shorter cell length than the parental isolate, and filamented cells were found when both isolates were exposed to the inhibitory concentration of colistin. When the isolates were treated with inhibitory concentrations of colistin, more than 80% of the genes were upregulated, including genes associated with antioxidative stress response pathways. The results elucidate the morphological difference between the colistin-susceptible and -resistant isolates and different colistin-mediated responses in A. baumannii isolates depending on their susceptibility to this drug.

MOLECULAR ANALYSIS OF THE MCR-1 GENE IN PSEUDOMONAS AERUGINOSA AND ACINETOBACTER BAUMANII STRAINS

Objective: The emergence of antibiotic resistance in Pseudomonas aeruginosa and Acinetobacter baumanii isolates poses serious risks to public health. Our study aimed to investigate the presence of colistin resistance and mcr-1 gene positivity in these isolates. Material and Method: Culture, biochemical tests, antibiotic susceptibility tests, and molecular tests were used to isolate and identify P. aeruginosa and A. baumanii strains. Result and Discussion: A sum of 156 clinical isolates of Pseudomonas aeruginosa (n = 89) and Acinetobacter baumannii (n = 67) were obtained using the 550 clinical samples collected in one year from the largest hospital in Van, Turkey. The results of antibiotic susceptibility tests showed that approximately 82.8% of P. aeruginosa and 94.6% of A. baumannii strains were multidrug-resistant (MDR). Colistin resistance was detected in 11.23% (10/89) of P. aeruginosa isolates and 11.94% (8/67) of A. baumannii isolates using agar dilution and microdilution methods. Out of the 18 colistin-resistant isolates, the mcr-1 gene was detected in three P. aeruginosa and two A. baumannii strains. The detection of plasmid-mediated colistin resistance in P. aeruginosa and A. baumannii is of great concern due to the high potential for colistin resistance to spread in clinical settings. Understanding the unique circumstances of worldwide colistin resistance can be facilitated by promoting the creation of quick processes for identifying colistin resistance profiles and putting them into practice in hospital laboratories. Colistin and carbapenem treatment are two effective ways to treat emerging resistant super-microbes and slow down the emergence of resistance.

Genotypic and phenotypic characteristics of Acinetobacter baumannii isolates from the people’s hospital of Qingyang City, Gansu province

BackgroundAcinetobacter baumannii (A. baumannii) is a common opportunistic pathogen in hospitals that causes nosocomial infection. In order to understand the phenotypic and genotypic characteristics of A. baumannii isolates, we sequenced and analyzed 62 A. baumannii isolates from a hospital in Gansu province.ResultsNon-repeated 62 A. baumannii isolates were collected from August 2015 to November 2021. Most isolates (56/62) were resistant to multiple drugs. All the 62 A. baumannii isolates were resistant to aztreonam and contained blaADC-25 gene which exists only on chromosome contigs. The 62 isolates in this study were not clustered in a single clade, but were dispersed among multiple clades in the common genome. Seven sequence types were identified by Multilocus sequence type (MLST) analysis and most isolates (52/62) belonged to ST2. The plasmids were grouped into 11 clusters by MOB-suite.ConclusionsThis study furthers the understanding of A. baumannii antimicrobial-resistant genotypes, and may aid in prevention and control nosocomial infection caused by drug-resistant A. baumannii.

Exploring the Sequence analysis of the Two-Component System Response Regulator OmpR in Multi-Drug Resistant (MDR) Acinetobacter baumannii

Background: The study focuses on the clinical profiles, antibiotic susceptibility, and genetic characteristics of 25 A. baumannii isolates from patients with urinary tract infections (UTIs). Patient Cohort: Ages range from 18 to 70 years, with a male to female ratio of 1.375. Notable Finding: Some multidrug-resistant (MDR) isolates had commonalities with extensively drug-resistant (XDR) variations, showing the evolution of drug resistance.Methods: Antibiotic Efficacy Analysis: Evaluation of antibiotic efficacy when the variable moved from lower (Bin 1) to higher (Bin 2) levels. Correlation Matrix: An analysis of antibiotic correlations to better identify potential cross-resistance and shared characteristics. Genetic Diversity Analysis: An examination of variants in the OmpR gene, including mutations and polymorphisms. Sequence analysis is used to identify point mutations in OmpR, with an emphasis on transitions such as adenine (A) to guanine (G).Results: Significant improvement in antibiotic efficacy from Bin 1 to Bin 2. Correlation Findings: Antibiotics have complex interactions, which may indicate cross-resistance. Genetic diversity: Variations in the OmpR gene have implications for virulence and adaptability. Sequence Analysis: The majority of point mutations in OmpR were transitions, with A typically changing to G.Conclusion: In Iraq, researchers have discovered the first evidence that clinical resistance in A. baumannii may be caused by structural alterations in the OmpR gene. A. baumannii isolates' genetic diversity at certain locations suggests possible implications on virulence and adaptation.Keywords: Acinetobacter baumannii; OmpR; Polymorphism; MDR

Ampicillin-sulbactam against Acinetobacter baumannii infections: pharmacokinetic/pharmacodynamic appraisal of current susceptibility breakpoints and dosing recommendations.

Sulbactam dosing for Acinetobacter baumannii infections has not been standardized due to limited available pharmacokinetics/pharmacodynamics (PK/PD) data. Herein, we report a comprehensive PK/PD analysis of ampicillin-sulbactam against A. baumannii pneumonia. Twenty-one A. baumannii clinical isolates were tested in the neutropenic murine pneumonia model. For dose-ranging studies, groups of mice were administered escalating doses of ampicillin-sulbactam. Changes in log10cfu/lungs relative to 0 h were assessed. Dose-fractionation studies were performed. Estimates of the percentage of of time during which the unbound plasma sulbactam concentrations exceeded the MIC (%fT > MIC) required for different efficacy endpoints were calculated. The probabilities of target attainment (PTA) for the 1-log kill plasma targets were estimated following clinically utilized sulbactam regimens. Dose-fractionation studies demonstrated time-dependent kill. Isolates resistant to both sulbactam and meropenem required three times the exposures to achieve 1-log kill; median [IQR] %fT > MIC of 60.37% [51.6-66.8] compared with other phenotypes (21.17 [16.0-32.9] %fT > MIC). Sulbactam standard dose (1 g q6h, 0.5 h infusion) provided >90% PTA up to MIC of 4 mg/L. Sulbactam 3 g q8h, 4 h inf provided greater PTA for isolates with sulbactam-intermediate susceptibility (8 mg/L, 100% versus 86% following the standard dose). Despite the higher exposure following 3 g q8h, 4 h inf, PTA was ≤57% among sulbactam-resistant/meropenem-resistant isolates. Sulbactam standard dose is a valuable regimen across sulbactam-susceptible isolates while the high-dose extended-infusion provides additional benefit against sulbactam-intermediate isolates. Given that most of the sulbactam-resistant A. baumannii isolates are meropenem-resistant, high-dose prolonged-infusion regimens are not expected to be effective as monotherapy against infections due to these isolates.

Carbapenem-resistant Acinetobacter baumannii infections among diabetic and non-diabetic patients and possible effective combination treatments

BackgroundCarbapenems are one of the most noteworthy choices for treating multidrug-resistant Acinetobacter baumannii (A. baumannii). Currently, carbapenem-resistant A. baumannii (CRAB) represents a healthcare problem worldwide, particularly among diabetic patients who are more susceptible to microbial infections. The aim of this study was to investigate the differences in antibiotic susceptibility profiles, the abundance of carbapenem resistance genes across A. baumannii-infected diabetic and non-diabetic patients, and the antimicrobial activity of different antibiotic combinations on highly resistant isolates.MethodsData of 99 A. baumannii-infected patients were collected during the period from 2018 to 2022 and categorized according to patients’ diabetes status into either diabetic or non-diabetic group. A total of 45 A. baumannii isolates were collected during 2021 and 2022 from the main hospital laboratory to be reidentified and genetically confirmed. Antibiotic susceptibility, including carbapenems, was determined using disc agar diffusion and broth microdilution methods. The isolates were screened for OXA-23, GES, VIM, and NDM carbapenem-resistant genes. Five antibiotic combinations were assessed using the double-disk synergy and checkerboard methods.ResultsThe findings of the current study revealed that multidrug resistance increased gradually, from 56% in 2018 to 95.6% in 2022. Moreover, CRAB increased among diabetics and non-diabetics. Resistance rates of imipenem, meropenem, and doripenem reached 68.8%, 61.8%, and 47.4% in diabetics and 97.9%, 83.3%, and 50% in non-diabetics, respectively. The VIM gene was the most prevalent gene with prevalence rates of 100% and 96.15% in diabetics and non-diabetics, respectively. Moreover, all A. baumannii isolates carried at least two of the selected carbapenem-resistant genes. Across the different used combinations, only the tigecycline-meropenem combination showed synergistic activity in 50% of diabetic and 66.7% of non-diabetic isolates.ConclusionsAn increased carbapenem resistance was observed among A. baumannii-infected individuals, both diabetic and non-diabetic. The MEM/TCG combination was the only one that showed synergistic or additive effects against highly resistant isolates making it a viable alternative treatment option.

Clinical and microbiological features of a cohort of patients with Acinetobacter baumannii bloodstream infections

PurposeAcinetobacter baumannii is emerging as a pathogen that is a focus of global concern due to the frequent occurrence of the strains those are extensively resistant to antibiotics. This study was aimed to analyze the clinical and microbiological characteristics of a cohort of patients with A. baumannii bloodstream infections (BSIs) in western China.MethodsA retrospective study of the patients at West China Hospital of Sichuan University with A. baumannii BSIs between Jan, 2018 and May, 2023 was conducted. Antimicrobial susceptibility of A. baumannii isolates was tested by microdilution broth method. Whole-genome sequencing and genetic analysis were also performed for these isolates.ResultsAmong the 117 patients included, longer intensive care unit stay, higher mortality, and more frequent invasive procedures and use of more than 3 classes of antibiotics were observed among the carbapenem-resistant A. baumannii (CRAB)-infected group (n = 76), compared to the carbapenem-susceptible A. baumannii (CSAB)-infected group (n = 41, all P ≤ 0.001). Twenty-four sequence types (STs) were determined for the 117 isolates, and 98.7% (75/76) of CRAB were identified as ST2. Compared to non-ST2 isolates, ST2 isolates exhibited higher antibiotic resistance, and carried more resistance and virulence genes (P < 0.05). In addition, 80 (68.4%) isolates were CRISPR-positive, showed higher antibiotic susceptibility, and harbored less resistance and virulence genes, in comparison to CRISPR-negative ones (P < 0.05). Phylogenetic clustering based on coregenome SNPs indicated a sporadic occurrence of clonal transmission.ConclusionOur findings demonstrate a high frequency of ST2 among A. baumannii causing BSIs, and high antibiotic susceptibility of non-ST2 and CRISPR-positive isolates. It is necessary to strengthen the surveillance of this pathogen.

Molecular epidemiology of Acinetobacter baumannii during COVID-19 at a hospital in northern China

BackgroundThe wide spread of carbapenem-resistance clones of Acinetobacter baumannii has made it a global public problem. Some studies have shown that the prevalence of Acinetobacter baumannii clones can change over time. However, few studies with respect to the change of epidemiological clones in Acinetobacter baumannii during Corona Virus Disease 2019 (COVID-19) were reported. This study aims to investigate the molecular epidemiology and resistance mechanisms of Acinetobacter baumannii during COVID-19.ResultsA total of 95 non-replicated Acinetobacter baumannii isolates were enrolled in this study, of which 60.0% (n = 57) were identified as carbapenem-resistant Acinetobacter baumannii (CRAB). The positive rate of the blaOXA−23 gene in CRAB isolates was 100%. A total of 28 Oxford sequence types (STs) were identified, of which the most prevalent STs were ST540 (n = 13, 13.7%), ST469 (n = 13, 13.7%), ST373 (n = 8, 8.4%), ST938 (n = 7, 7.4%) and ST208 (n = 6, 6.3%). Differently, the most widespread clone of Acinetobacter baumannii in China during COVID-19 was ST208 (22.1%). Further study of multidrug-resistant ST540 showed that all of them were carrying blaOXA−23, blaOXA−66, blaADC−25 and blaTEM−1D, simultaneously, and first detected Tn2009 in ST540. The blaOXA−23 gene was located on transposons Tn2006 or Tn2009. In addition, the ST540 strain also contains a drug-resistant plasmid with msr(E), armA, sul1 and mph(E) genes.ConclusionThe prevalent clones of Acinetobacter baumannii in our organization have changed during COVID-19, which was different from that of China. ST540 strains which carried multiple drug-resistant mobile elements was spreading, indicating that it is essential to strengthen the molecular epidemiology of Acinetobacter baumannii.

The Combinatory Effects of Essential Oil from Lippia macrophylla on Multidrug Resistant Acinetobacter baumannii Clinical Isolates.

To assess the antibacterial effectiveness of Lippia macrophylla essential oil (LMEO) against multidrug-resistant Acinetobacter baumannii isolates, both as a standalone treatment and in combination with conventional antibiotics. LMEO demonstrated a significant inhibitory effect on the growth of A. baumannii, with a minimum inhibitory concentration (MIC) below 500 μg/mL. Notably, LMEO was capable of reversing the antibiotic resistance of clinical isolates or reducing their MIC values when used in combination with antibiotics, showing synergistic (FICI≤0.5) or additive effects. The combination of LMEO and imipenem was particularly effective, displaying synergistic interactions for most isolates. Ultrastructural analyses supported these findings, revealing that the combination of LMEO+ceftazidime compromised the membrane integrity of the Acb35 isolate, leading to cytoplasmic leakage and increased formation of Outer Membrane Vesicles (OMVs). Taken together our results point for the use of LMEO alone or in combination as an antibacterial agent against A. baumannii. These findings offer promising avenues for utilizing LMEO as a novel antibacterial strategy against drug-resistant infections in healthcare settings, underscoring the potential of essential oils in enhancing antibiotic efficacy.

Defining optimal sulbactam regimens for treatment of Acinetobacter baumannii pneumonia and impact of blaOXA-23 on efficacy.

We evaluated the efficacies of human-simulated regimens (HSRs) of two clinically utilized sulbactam regimens: 1 g q6h 0.5 h infusion (maximum FDA-approved dosage) and 3 g q8h 4 h infusion (high-dose, prolonged-infusion regimen), against Acinetobacter baumannii in a translational murine model. Thirty-two clinical A. baumannii isolates were investigated, of which 16 were sulbactam resistant (MIC ≥ 16 mg/L), 6 were sulbactam intermediate (MIC = 8 mg/L) and 10 were sulbactam susceptible (MIC ≤ 4 mg/L). Efficacies of the two sulbactam HSRs were assessed in the neutropenic murine pneumonia model. Changes in log10 cfu/lungs at 24 h compared with 0 h controls were measured, and efficacy was defined as achieving 1 log kill relative to baseline. WGS of the isolates and bioinformatics analysis were performed to explore potential associations between the genomic backgrounds and the in vivo responses. Eleven isolates harboured blaOXA-23, of which 10 were sulbactam resistant, 1 was sulbactam intermediate while none was sulbactam susceptible. Both sulbactam HSRs achieved >1 log kill against sulbactam-susceptible isolates. Against sulbactam-intermediate and sulbactam-resistant isolates, lack of efficacy correlated with the presence of the blaOXA-23 gene; sulbactam 1 g HSR and 3 g HSR did not show efficacy against 11/11 and 9/11 blaOXA-23-positive isolates, respectively, while efficacy was observed against all 11 blaOXA-23-negative sulbactam-intermediate and sulbactam-resistant isolates (i.e. harbouring other resistance genes). A sulbactam high-dose prolonged-infusion regimen provides comparable activity to the standard dose against isolates currently considered sulbactam susceptible. However, the activity against isolates with intermediate and resistant susceptibility could be predicted by the detection of blaOXA-23. Enhancing detection capabilities of common diagnostic modalities to include OXA-23 can improve patient outcome.

Virulence Determinants of Acinetobacter baumannii Isolated from Different Infections in Baghdad Hospitals

Acinetobacter baumannii is an essential pathogenic bacteria cause nosocomial infections worldwide. The current work aimed to characterize several virulence factors in Acintobacter baumannii isolated from diverse clinical specimens in Baghdad. Clinical samples including sputum, blood, urine, CSF and wound swabs were collected from patients who were admitted to hospitals in Baghdad. Identification of Acinetobacter baumannii isolates was performed using Vitek 2 system. Phospholipase (plcN) and elastase (lasB) genes were identified using Polymerase chain reaction (PCR) technique. Other virulence factors such as motility, biofilm formation,hemolysin production were screened. Sixty-nine isolates were identified as Acinetobacter baumannii. The isolates were screened for Phospholipase (plcN) and elastase (lasB) production.The results of amplification revealed that out of the total isolates, 18 (26.6%) isolates included both (plcN) and (lasB) genes, 18(26.6%) isolates included only (plcN) and 23(33.3%) isolates have only (lasB). Sixty (86.9%) isolates were positive for biofilm formation, 8 (11.6%) isolates indicated intermediate biofilm producers and 52(75.4%) isolates were weak biofilm producers. Sixty six A.baumannii isolates were motile on Nutrient agar (0.3%). Sixteen isolates were intermediate motile and 50 were highly motile. Positive association was found between the biofilm formation capacity and surface associated motility. Fifty-seven isolates showed hemolysis on Blood agar on the second day of the incubation. Of these, 48 (69.56%) isolates show β –hemolysis and 9 (13.04%) isolates show α-hemolysis,

Evaluation of the in vitro activity of ampicillin-sulbactam and cefoperazone-sulbactam against A. Baumannii by the broth disk elution test.

To evaluate the in vitro activity of ampicillin-sulbactam and cefoperazone-sulbactam against A. baumannii using the broth disk elution testing, a total of 150 A. baumannii isolates were collected from across China between January 2019 and January 2021, including 51 carbapenem-susceptible and 99 carbapenem-resistant isolates. Broth disk elution (BDE) and the broth microdilution (BMD) method were performed for all strains. The concentration range of the BDE was 10/10 µg/mL, 20/20 µg/mL, and 30/30 µg/mL for ampicillin-sulbactam, and 37.5/15 µg/mL, 75/30 µg/mL, 112.5/45 µg/mL, and 150/60 µg/mL for cefoperazone-sulbactam, respectively. Compared with BMD, the BDE results of ampicillin-sulbactam and cefoperazone-sulbactam showed a categorical agreement of 83.3% (125/150) and 95.3% (143/150), with minor errors of 16.7% (25/150) and 4.7% (7/150), respectively. No major error or very major errors were detected. The sensitivity differences by BDE of carbapenem-resistant A. baumannii (CRAb)to different concentrations of ampicillin-sulbactam showed statistically significant (p < 0.017), while those to cefoperazone-sulbactam at 37.5/15 µg/mL, 75/30 µg/mL, and 112.5/45 µg/mL were significant (p < 0.008). However, no significant difference in sensitivity was observed between 112.5/45 µg/mL and 150/60 µg/mL (p > 0.008). In conclusion, the BDE is a reliable and convenient method to detect the in vitro activity of cefoperazone-sulbactam against A. baumannii, and the results could serve as a clinical reference value when deciding whether or not to use high-dose sulbactam for the treatment of A. baumannii infections.

Ampicillin-Sulbactam for Carbapenem-Susceptible Acinetobacter baumannii Pneumonia: A Case for High-Dose, Continuous Infusion Dosing Strategy in the Trauma ICU.

Background: The optimal ampicillin-sulbactam dosing regimen for carbapenem-susceptible Acinetobacter baumannii isolates in critically ill trauma patients has not been clearly defined. One strategy to provide the adequate sulbactam dose includes high-dose continuous infusion. Case(s) Description: We present three cases of critically ill trauma patients with augmented renal clearance treated with high-dose ampicillin-sulbactam through an intravenous continuous infusion for ventilator-associated pneumonia. All A. baumannii isolates were susceptible to sulbactam with low minimum inhibitory concentrations. All achieved clinical cure at the end of therapy and no recurrent pneumonia was noted. No clinically substantial adverse effect attributable to ampicillin-sulbactam therapy occurred. Discussion: There is limited evidence to endorse high-dose, continuous infusion ampicillin-sulbactam for treatment of infections caused by carbapenem-susceptible A. baumannii. This report presents three critically ill trauma patients with augmented renal clearance that achieved positive clinical outcomes with higher doses of ampicillin-sulbactam administered through a continuous infusion.