Carbapenem-resistant A. Baumannii Research Articles

Isolation and Pattern of Antimicrobial Susceptibility Testing of Acinetobacter baumannii Clinical Isolates at Taksin Hospital: A Retrospective Study from 2019 to 2021

Objective: To determine the number of isolates and drug susceptibility testing of Acinetobacter baumannii at Taksin Hospital. Materials and Methods: A 3-year retrospective descriptive study was conducted between January 2019 and December 2021. Drug susceptibility testing of isolates to 13 drugs, which included amikacin, gentamycin, piperacillin/tazobactam, cefotaxime, ceftazidime, cefepime, three carbapenem drugs that were imipenem, meropenem, and doripenem, ciprofloxacin, trimethoprim-sulfamethoxazole, colistin, and tigecycline, were evaluated by standard disk diffusion method and automated microdilution method. Results: One thousand six hundred sixty-five non-duplicate A. baumannii isolates from different patients were detected and included 535 in 2019, 500 in 2020, and 630 in 2021. The patients’ ages ranged from three days to 100 years. The median age of patients was 70 years with an interquartile range of 56 to 80 years. A. baumannii was mostly found in patients aged older than 50 years old at 83.6%. They were isolated from sputum in 72.3%, urine in 9%, pus in 6.3%, tissue in 6.3%, and blood in 5.2%. Overall, A. baumannii demonstrated 91.5% and 79.8% susceptibility to colistin and tigecycline, respectively, but less susceptible to other drugs tested, with a range of 0.4% to 32.6%. Drug susceptibility to carbapenem such as imipenem, meropenem, and doripenem were 19.5%, 20%, and 20.9%, respectively. The carbapenem-resistant A. baumannii (CRAB) was found at 77.6%, 80%, and 79.1% in 2019, 2020, and 2021, respectively. For total isolates tested, the mean of CRAB was 78.9±1.2%. Conclusion: The present study results suggested the importance of monitoring A. baumannii at a hospital in Bangkok. Colistin and tigecycline had the high percentages of drug susceptibility rates in vitro. The antibiogram of susceptibility helps provide guidelines for clinician to consider empirical treatment.

The context of blaOXA-23 gene in Iraqi carbapenem-resistant Acinetobacter baumannii isolates belonging to global clone 1 and global clone 2.

Of the genes conferring resistance to carbapenems in Acinetobacter baumannii, the blaOXA-23 gene is the most widely found across the world. The gene carrying blaOXA-23 transposons in A. baumannii isolates of global clones GC1 and GC2 is found worldwide. Here, we examined whether transposons play a role in the dissemination of the blaOXA-23 in globally distributed clones, GC1 and GC2 A. baumannii isolates from Iraq. The 119 non-repetitive A. baumannii isolates including 94 recovered from clinical specimens and 25 isolates from hospital environment between September 2021 and April 2022 from different medical centers located at various regions in Baghdad, Iraq. The global clones (GC) and the genes encoding carbapenem resistance, including blaOXA-23, blaOXA-24, and blaOXA-58 were identified using multiplex PCR assays. Antibiotic susceptibility testing was performed by the Kirby-Bauer disk diffusion susceptibility method. The transposons carrying blaOXA-23 were examined using PCR mapping. In cases when carbapenem susceptible A. baumannii isolates were found, they were subjected to E test, full length sequencing of blaOXA-Ab (blaOXA-51-like) and Institut Pasteur multi-locus sequence typing scheme. All but two isolates (92 clinical and 25 environmental) were identified carbapenem-resistant A. baumannii (CRAB). Of 117 CRAB isolates, 20 belong to GC1, 19 contained blaOXA-23; of them, 17 isolates harbored the blaOXA-23 located on Tn2006. Among the 46 CRAB belonging to GC2, 39 contained blaOXA-23; of them, 34 carried the blaOXA-23 located on Tn2006. The remaining GC1 and GC2 isolates, one GC1 as well as one GC2 isolate, were susceptible to imipenem, doripenem, and meropenem and considered carbapenem-susceptible A. baumannii (CSAB). Full-length sequencing of the blaOXA-Ab and MLST for the two CSAB isolates belonging to GC1 and GC2 confirmed that the GC1 isolate belongs to ST 623 and contained an allele that encodes an blaOXA-69 variant of the blaOXA-Ab while the GC2 belong to ST2 and carried an blaOXA-66 variant. This study provides evidence for the dissemination of blaOXA-23 on the Tn2006 in CRAB isolates in Baghdad, Iraq. It appears that this transposon is widespread in GC1 and 2 isolates as in the other parts of the world. Interestingly, one GC1 and one GC2 isolate from Iraq were found to be susceptible to carbapenem while the isolates belonging to GC1 and GC2 have so far rarely been found to be susceptible to carbapenem globally.

Nosocomial, Healthcare-Associated, and Community-Acquired Acinetobacter baumannii in China: Clinical Characteristics, Antimicrobial Resistance Patterns and Risk Factors Associated with Carbapenem Resistance.

Acinetobacter baumannii (A. baumannii) is an widespread pathogen and carbapenem-resistant strains are great threat to hospitalized patients. This study is aimed to investigate the clinical characteristics, antimicrobial resistance patterns, and risk factors associated with carbapenem resistance in nosocomial, healthcare-associated (HCA), and community-acquired (CA) A. baumannii infections. This study retrospectively reviewed cases in a tertiary hospital in southern China between January 1, 2019, and December 31, 2021. Univariate and multivariate logistic regression analyses were performed to identified the risk factors of carbapenem resistance in nosocomial, HCA and CA A. baumannii infections. A total of 391 patients with A. baumannii infection were included. Of these patients, 96 (24.6%) had nosocomial infections, 215 (55.0%) had HCA infections, and 80 (20.5%) had CA infections. The overall 30-day mortality rates of nosocomial and HCA infection patients was significantly higher than that of CA infection (P<0.05). The incidence of antimicrobial resistance was also higher in nosocomial and HCA bacteremia than that in CA bacteremia (P<0.05). Logistic regression analysis identified age ≥60 years, urethral catheterization, and exposure to two or more antibiotics as the independent risk factors for carbapenem-resistant A. baumannii (CRAB) infection in the nosocomial infection group and exposure to two or more antibiotics and endotracheal intubation in the HCA infection group. However, malignant tumors and hematological diseases were identified as protective factors against CRAB infection in the HCA group. These data suggest that HCA A. baumannii infection is quite different from CA infection, with antimicrobial resistance and 30-day mortality rates similar to those of nosocomial infections. Additionally, the risk factors for CRAB development in the CA, HCA, and nosocomial groups were not the same, which may provides the help for controlling practices and instruction empirical clinical medication.

Antibacterial activity evaluation of a novel K3-specific phage against Acinetobacter baumannii and evidence for receptor-binding domain transfer across morphologies

Acinetobacter baumannii (A. baumannii) poses a serious public health challenge due to its notorious antimicrobial resistance, particularly carbapenem-resistant A. baumannii (CRAB). In this study, we isolated a virulent phage, named P1068, from medical wastewater capable of lysing CRAB, primarily targeting the K3 capsule type. Basic characterization showed that P1068 infected the A. baumannii ZWAb014 with an optimal MOI of 1, experienced a latent period of 10 ​min and maintained stability over a temperature range of 4–37 ​°C and pH range of 3–10. Phylogenetic and average nucleotide identity analyses indicate that P1068 can be classified as a novel species within the genus Obolenskvirus of the Caudoviricetes class as per the most recent virus classification released by the International Committee on Taxonomy of Viruses (ICTV). Additionally, according to classical morphological classification, P1068 is identified as a T4-like phage (Myoviridae). Interestingly, we found that the tail fiber protein (TFP) of P1068 shares 74% coverage and 88.99% identity with the TFP of a T7-like phage (Podoviridae), AbKT21phiIII (NC_048142.1). This finding suggests that the TFP gene of phages may undergo horizontal transfer across different genera and morphologies. In vitro antimicrobial assays showed that P1068 exhibited antimicrobial activity against A. baumannii in both biofilm and planktonic states. In mouse models of intraperitoneal infection, P1068 phage protected mice from A. baumannii infection and significantly reduced bacterial loads in various tissues such as the brain, blood, lung, spleen, and liver compared to controls. In conclusion, this study demonstrates that phage P1068 might be a potential candidate for the treatment of carbapenem-resistant and biofilm-forming A. baumannii infections, and expands the understanding of horizontal transfer of phage TFP genes.

Predictive modeling of mortality in carbapenem-resistant Acinetobacter baumannii bloodstream infections using machine learning.

Acinetobacter baumannii, a notable drug-resistant bacterium, often induces severe infections in healthcare settings, prompting a deeper exploration of treatment alternatives due to escalating carbapenem resistance. This study meticulously examined clinical, microbiological, and molecular aspects related to in-hospital mortality in patients with carbapenem-resistant A. baumannii (CRAB) bloodstream infections (BSIs). From 292 isolates, 153 cases were scrutinized, reidentified through matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS), and evaluated for antimicrobial susceptibility and carbapenemase genes via multiplex polymerase chain reaction (PCR). Utilizing supervised machine learning, the study constructed models to predict 14- and 30-day mortality rates, revealing the Naïve Bayes model's superior specificity (0.75) and area under the curve (0.822) for 14-day mortality, and the Random Forest model's impressive recall (0.85) for 30-day mortality. These models delineated eight and nine significant features for 14- and 30-day mortality predictions, respectively, with "septic shock" as a pivotal variable. Additional variables such as neutropenia with neutropenic days prior to sepsis, mechanical ventilator support, chronic kidney disease, and heart failure were also identified as ranking features. However, empirical antibiotic therapy appropriateness and specific microbiological data had minimal predictive efficacy. This research offers foundational data for assessing mortality risks associated with CRAB BSI and underscores the importance of stringent infection control practices in the wake of the scarcity of new effective antibiotics against resistant strains. The advanced models and insights generated in this study serve as significant resources for managing the repercussions of A. baumannii infections, contributing substantially to the clinical understanding and management of such infections in healthcare environments.

Antibiofilm effect of biogenic silver nanoparticle alone and combined with polymyxin B against carbapenem-resistant Acinetobacter baumannii.

Acinetobacter baumannii is a bacteria associated with nosocomial infections and outbreaks, difficult to control due to its antibiotic resistance, ability to survive in adverse conditions, and biofilm formation adhering to biotic and abiotic surfaces. Therefore, this study aimed to evaluate the antibiofilm activity of biogenic silver nanoparticle (Bio-AgNP) and polymyxin B alone and combined in biofilms formed by isolates of carbapenem-resistant A. baumannii (CR-Ab). In the biofilm formation inhibition assay, CR-Ab strains were exposed to different concentrations of the treatments before inducing biofilm formation, to determine the ability to inhibit/prevent bacterial biofilm formation. While in the biofilm rupture assay, the bacterial biofilm formation step was previously carried out and the adhered cells were exposed to different concentrations of the treatments to evaluate their ability to destroy the bacterial biofilm formed. All CR-Ab isolates and ATCC® 19606™ used in this study are strong biofilm formers. The antibiofilm activity of Bio-AgNP and polymyxin B against CR-Ab and ATCC® 19606™ demonstrated inhibitory and biofilm-disrupting activity. When used in combination, Bio-AgNP and polymyxin B inhibited 4.9-100% of biofilm formation in the CR-Ab isolates and ATCC® 19606™. Meanwhile, when Bio-AgNP and polymyxin B were combined, disruption of 6.8-77.8% of biofilm formed was observed. Thus, antibiofilm activity against CR-Ab was demonstrated when Bio-AgNP was used alone or in combination with polymyxin B, emerging as an alternative in the control of CR-Ab strains.

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.

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.

Genomic Insights into and In Vitro Evaluation of Antimicrobial Combination Therapies for Carbapenem-Resistant Acinetobacter baumannii.

Background and Objectives: Acinetobacter baumannii (A. baumannii), particularly carbapenem-resistant A. baumannii (CRAB), represents a grave concern in healthcare settings and is associated with high mortality. This study aimed to conduct molecular, mutational, and phylogenetic analyses of specific genes in CRAB and evaluate the synergistic effects of selected antimicrobial combinations. Materials and Methods: Phenotypic characterization was performed on six CRAB strains by using the Modified Hodge Test (MHT) and IMP-EDTA Double-Disc Synergy Test (IMP-EDTA DDST). Carbapenemase- and metallo-beta-lactamase-encoding genes were amplified by using Polymerase Chain Reaction. Phylogenetic analysis using the MEGA 11 tool was used to determine the evolutionary relatedness of these genes. Mutational analysis was performed by using I-Mutant, MUPro, and PHD-SNP bioinformatics tools to predict mutations in the carbapenemase-encoding genes. Microdilution checkerboard titration assessed the synergistic effects of antimicrobial combinations (azithromycin-meropenem, rifampicin-meropenem, meropenem-colistin, and azithromycin-colistin) on these CRAB isolates. Results: The phenotypic characterization of six CRAB isolates revealed positive results for MHT and IMP-EDTA DDST. The molecular characterization revealed that carbapenemase- and MBL-encoding genes were present in all isolates with varying frequencies, including blaOXA-51 (100%) and blaIMP (0%). The sequence analysis revealed high evolutionary relatedness to sequences in the NCBI database. The mutational analysis identified 16 mutations, of which 1 mutation (P116L) in the blaOXA-58 gene predicted a change in the protein product, potentially contributing to carbapenem resistance. The checkerboard titration method did not reveal any synergism among the tested antimicrobial combinations against CRAB. Conclusion: This study's findings underscore the significant challenges posed by CRAB isolates harboring multiple resistant genes in treatment. This highlights the urgent need for novel antimicrobial agents, a crucial step towards reducing mortality rates not only in Pakistan but also globally.

Anti-biofilm Activity of Phage ΦKAB and Colistin Against Carbapenem Resistance &lt;i&gt;Acinetobacter baumannii&lt;/i&gt;

Background: Carbapenem-resistant A. baumannii (CRAB) bacterium is difficult to treat with available antimicrobial agents leading to use a few antibiotics such as colistin as an option for treatment. However, the use of the colistin has serious side effects and leads to developing bacterial resistance. Objective: This study aimed to determine effectiveness of phage/colistin combination to inhibit biofilm formation of CRAB. Methods: Sixty clinical A. baummanii isolates were identified with the VITEKII system and 16S rRNA gene. The antibiotic susceptibility and detection of Oxacillinases genes were tested for all isolates. Results: The antibiotic sensitivity of A. baumannii isolates showed a high resistance percentage to Ceftriaxone (CRO) with 92% (55 isolates), and Cefotiam (CTF) with 87% (52 isolates), while the lowest percent related to Colistin (CO) with 17% (10 isolates). The results of antibiotic resistance and Oxacillinases genes reported that only 14 isolates from the current study were CRAB. Phage and host A. baumannii of phage were isolated and characterized previously. Biofilm production assay of CRAB isolates were showed that among 14 isolates including the phage host: 57% (8) was weak and 43% (6) was moderate biofilm producer. Therefore, the synergistic effect of a combination ΦKAB phage in MOI (10) and Colistin with MIC=8 µg/ml against CRAB isolates was evaluated and showed complete transfer of isolates by 100 % to weak biofilm producer compared with CRAB isolates. Conclusions: Among 60 isolates of A. baumannii, most isolates were MDR 44 (73.3%) and only 14 (23.3%) isolates were CRAB that were 57% weak and 43% moderate biofilm producers. The mixture of Colistin/ΦKAB phage could inhibit and reduce biofilm forming in CRAB isolates. Overall, the present study may provide evidence on the capability of the isolated phage to serve as a novel strategy to treat infections caused by MDR A. baumannii.

Analysis of the Class 1 Integrons, Carbapenemase Genes and Biofilm Formation Genes Occurrence in Acinetobacter baumannii Clinical Isolates.

Acinetobacter baumannii is a non-fermentative Gram-negative bacterium that can cause nosocomial infections in critically ill patients. Carbapenem-resistant A. baumannii (CRAB) has spread rapidly in clinical settings and has become a key concern. The main objective of this study was to identify the distribution of integrons and biofilm-formation-related virulence genes in CRAB isolates. A total of 269 A. baumannii isolates (219 isolates of CRAB and 50 isolates of carbapenem-sensitive A. baumannii (CSAB)) were collected. Carbapenemase genes (bla KPC, bla VIM, bla IMP, bla NDM, and bla OXA-23-like) and biofilm-formation-related virulence genes (abal, bfms, bap, and cusE) were screened with PCR. Class 1 integron was screened with PCR, and common promoters and gene cassette arrays were determined with restriction pattern analysis combined with primer walking sequencing. Whole-genome sequencing was conducted, and data were analyzed for a bla OXA-23-like-negative isolate. All 219 CRAB isolates were negative for bla KPC, bla VIM, bla IMP, and bla NDM, while bla OXA-23-like was detected in 218 isolates. The detection rates for abal, bfms, bap, and cusE in 219 CRAB were 93.15%, 63.93%, 88.13%, and 77.63%, respectively. Class 1 integron was detected in 75 CRAB (34.25%) and in 3 CSAB. The single gene cassette array aacA4-catB8-aadA1 with relatively strong PcH2 promoter was detected in class 1 integrons. The bla OXA-23-like-negative CRAB isolate was revealed to be a new sequence type (Oxford 3272, Pasteur 2520) carrying bla OXA-72, bla OXA-259, and bla ADC-26. In conclusion, bla OXA-23-like was the main reason for CRAB's resistance to carbapenems. A new (Oxford 3272, Pasteur 2520) CRAB sequence type carrying the bla OXA-72, bla OXA-259, and bla ADC-26 was reported.

Risk factors for bacteremic pneumonia and mortality (28-day mortality) in patients with Acinetobacter baumannii bacteremia

BackgroundPatients infected with Acinetobacter baumannii (AB) bacteremia in hospital have high morbidity and mortality. We analyzed the clinical characteristics of pneumonia and nonpneumonia-related AB bloodstream infections (AB BSIs) and explored the possible independent risk factors for the incidence and prognosis of pneumonia-related AB BSIs.MethodsA retrospective monocentric observational study was performed. All 117 episodes of hospital-acquired AB bacteremia sorted into groups of pneumonia-related AB BSIs (n = 45) and nonpneumonia-related AB BSIs (n = 72) were eligible. Univariate/multivariate logistic regression analysis was used to explore the independent risk factors. The primary outcome was the antibiotic susceptibility in vitro of pneumonia-related AB BSIs group. The secondary outcome was the independent risk factor for the pneumonia-related AB BSIs group.ResultsAmong 117 patients with AB BSIs, the pneumonia-related group had a greater risk of multidrug resistant A. baumannii (MDRAB) infection (84.44%) and carbapenem-resistant A. baumannii (CRAB) infection (80%). Polymyxin, minocycline and amikacin had relatively high susceptibility rates (> 80%) in the nonpneumonia-related group. However, in the pneumonia-related group, only polymyxin had a drug susceptibility rate of over 80%. Univariate analysis showed that survival time (day), CRAB, MDRAB, length of hospital stay prior to culture, length of ICU stay prior to culture, immunocompromised status, antibiotics used prior to culture (n > = 3 types), endotracheal tube, fiberoptic bronchoscopy, PITT, SOFA and invasive interventions (n > = 3 types) were associated with pneumonia-related AB bacteremia. The multivariate logistic regression analysis revealed that recent surgery (within 1 mo) [P = 0.043; 0.306 (0.098–0.962)] and invasive interventions (n > = 3 types) [P = 0.021; 0.072 (0.008–0.671)] were independent risk factors related to pneumonia-related AB bacteremia. Multivariate logistic regression analysis revealed that length of ICU stay prior to culture [P = 0.009; 0.959 (0.930–0.990)] and recent surgery (within 1 mo) [P = 0.004; 0.260 (0.105–0.646)] were independent risk factors for mortality in patients with pneumonia-related AB bacteremia. The Kaplan‒Meier curve and the timing test showed that patients with pneumonia-related AB bacteremia had shorter survival time compared to those with nonpneumonia-related AB bacteremia.ConclusionsOur study found that A. baumannii had a high rate of antibiotic resistance in vitro in the pneumonia-related bacteremia group, and was only sensitive to polymyxin. Recent surgery was a significantly independent predictor in patients with pneumonia-related AB bacteremia.

Molecular epidemiology and clinical significance of carbapenemase genes in carbapenem-resistant Acinetobacter baumannii isolates in southern Poland.

A complex interplay between Acinetobacter spp., patients, and the environment has made it increasingly difficult to optimally treat patients infected with Acinetobacter spp., mainly due to rising antimicrobial resistance and challenges with surveillance. This study evaluated carbapenem‑resistant A. baumannii (CRAB) isolates to determine their resistance profiles and the presence of specific β‑lactamases to inform CRAB surveillance upon hospital admission and regional empiric antibiotic therapies. The study was conducted at 4 hospitals in southern Poland between June and December 2022. Only health care-associated infections caused by A. baumannii were considered. A total of 82 CRAB isolates were included in the analysis. Species identification was performed by matrix‑assisted laser desorption / ionization time‑of‑flight mass spectrometry, antimicrobial susceptibility was determined phenotypically, and polymerase chain reactions were carried out to identify the resistance genes. Depending on the hospital, the incidence of CRAB infections varied from 428.6 to 759.5 per 10 000 admissions in intensive care units (ICUs), and from 0.3 to 21 per 10 000 admissions in non‑ICUs. CRAB antibiotic susceptibility was the highest for cefiderocol (100%), colistin (96%), tigecycline (77%), gentamicin (51%), and ampicillin / sulbactam (36%). The most prevalent blaOXA genes were blaOXA‑66‑1 (95%) and blaOXA‑40 (71%), and additionally the extended‑spectrum β‑lactamase gene blaTEM‑1 (41%). An unexpectedly high incidence of CRAB infections occurred in Polish hospitals. There is a need for effective CRAB prevention and control that includes effective hospital screening, national surveillance, and improved treatment options.

Based on molecular docking and real-time PCR technology, the two-component system Bae SR was investigated on the mechanism of drug resistance in CRAB.

This study aimed to explore the role of the two-component system Bae SR in the mechanism of drug resistance in carbapenem-resistant A. baumannii (CRAB) using molecular docking and real-time polymerase chain reaction (PCR). The two-component system Bae SR of Acinetobacter baumannii was subjected to molecular docking with imipenem, meropenem, and levofloxacin. Antibacterial assays and fluorescence quantitative PCR were used to explore protein-ligand interactions and molecular biological resistance mechanisms related to CRAB. The analysis of the two-component system in A. baumannii revealed that imipenem exhibited the highest docking energy in Bae S at - 5.81kcal/mol, while the docking energy for meropenem was - 4.92kcal/mol. For Bae R, imipenem had a maximum docking energy of - 4.28kcal/mol, compared with - 4.60kcal/mol for meropenem. The highest binding energies for Bae S-levofloxacin and Bae R-levofloxacin were - 3.60 and - 3.65kcal/mol, respectively. All imipenem-resistant strains had minimum inhibitory concentration (MIC) values of 16µg/mL, whereas levofloxacin-resistant strains had MIC values of 8µg/mL. The time-sterilization curve showed a significant decrease in bacterial colony numbers at 2h under the action of 8µg/mL imipenem, indicating antibacterial effects. In contrast, levofloxacin did not exhibit any antibacterial activity. Fluorescence quantitative PCR results revealed significantly increased relative expression levels of bae S and bae R genes in the CRAB group, which were 2 and 1.5 times higher than those in the CSAB group, respectively, with statistically significant differences. Molecular docking in this study found that the combination of Bae SR and carbapenem antibiotics (imipenem, meropenem) exhibited stronger affinity and stability compared with levofloxacin. Moreover, the overexpression of the two-component system genes in carbapenem-resistant A. baumannii enhanced its resistance to carbapenem, providing theoretical and practical insights into carbapenem resistance in respiratory tract infections caused by A. baumannii.

Epidemiology, resistance genomics and susceptibility of Acinetobacter species: results from the 2020 Spanish nationwide surveillance study.

BackgroundAs increasing antibiotic resistance in Acinetobacter baumannii poses a global healthcare challenge, understanding its evolution is crucial for effective control strategies.AimWe aimed to evaluate the epidemiology, antimicrobial susceptibility and main resistance mechanisms of Acinetobacter spp. in Spain in 2020, and to explore temporal trends of A. baumannii.MethodsWe collected 199 single-patient Acinetobacter spp. clinical isolates in 2020 from 18 Spanish tertiary hospitals. Minimum inhibitory concentrations (MICs) for nine antimicrobials were determined. Short-read sequencing was performed for all isolates, and targeted long-read sequencing for A. baumannii. Resistance mechanisms, phylogenetics and clonality were assessed. Findings on resistance rates and infection types were compared with data from 2000 and 2010.ResultsCefiderocol and colistin exhibited the highest activity against A. baumannii, although colistin susceptibility has significantly declined over 2 decades. A. non-baumannii strains were highly susceptible to most tested antibiotics. Of the A. baumannii isolates, 47.5% (56/118) were multidrug-resistant (MDR). Phylogeny and clonal relationship analysis of A. baumannii revealed five prevalent international clones, notably IC2 (ST2, n = 52; ST745, n = 4) and IC1 (ST1, n = 14), and some episodes of clonal dissemination. Genes bla OXA-23, bla OXA-58 and bla OXA-24/40 were identified in 49 (41.5%), eight (6.8%) and one (0.8%) A. baumannii isolates, respectively. ISAba1 was found upstream of the gene (a bla OXA-51-like) in 10 isolates.ConclusionsThe emergence of OXA-23-producing ST1 and ST2, the predominant MDR lineages, shows a pivotal shift in carbapenem-resistant A. baumannii (CRAB) epidemiology in Spain. Coupled with increased colistin resistance, these changes underscore notable alterations in regional antimicrobial resistance dynamics.

The Distribution of Carbapenem-Resistant Acinetobacter Species and High Prevalence of CC92 OXA-23-Producing Acinetobacter Baumannii in Community Hospitals in South Korea.

Clinical isolates of Acinetobacter species in South Korea are continuously exhibiting high rates of antimicrobial resistance to carbapenems, indicating that there are public health concerns among both healthcare-associated infections and community-associated infections. The aim of this study was to describe the prevalence and characteristics of carbapenem-resistant Acinetobacter isolates originating from community hospitals. A total of 817 non-duplicated Acinetobacter species were isolated from December 2022 to July 2023 at long-term care facilities and general hospitals in 16 regions geographically distributed throughout South Korea. Bacterial identification and antimicrobial susceptibility testing were performed using the VITEK-2 system. The bacteria were identified as Acinetobacter baumannii by blaOXA-51 PCR and as non-baumannii Acinetobacter species by rpoB sequence analysis. The carbapenem resistance genes (OXA-23, OXA-48, OXA-58, IMP, VIM, NDM, GES, and KPC) were identified via PCR and sequencing. The genetic relatedness of carbapenem-resistant A. baumannii (CRAB) isolates was assessed by multilocus sequence typing. A total of 659 A. baumannii and 158 non-baumannii Acinetobacter isolates, comprising 19 different species, were identified in all 16 regions. The carbapenem resistance rate was 87.4% (n=576) for the A. baumannii isolates, and all the strains produced blaOXA-23. For non-baumannii Acinetobacter, the rate of carbapenem resistance was 8.9% (n=14); this resistance was primarily caused by blaOXA-23 (n=9), followed by blaNDM-1 (n=3) and blaVIM-2 (n=2). Of the 576 CRAB isolates, clonal complex 92 (CC92) was the predominant genotypes, followed by sequence type 229 (ST229), ST373, ST397, ST447, and ST620. Our results showed the distribution of Acinetobacter species and showed that CC92 CRAB clinical isolates with widespread production of blaOXA-23 were predominant in community hospitals. Our findings suggest that there is a need for urgent and effective methods to reduce carbapenem resistance in A. baumannii in South Korea.

Ineffectiveness of colistin monotherapy in treating carbapenem-resistant Acinetobacter baumannii Pneumonia: A retrospective single-center cohort study

BackgroundAcinetobacter baumannii, a common carbapenem-resistant gram-negative bacillus, usually causes nosocomial infections. Colistin has been used for carbapenem-resistant A. baumannii (CRAB) infections; however, only a few studies have evaluated colistin as a treatment option compared to appropriate controls. We investigated the effectiveness of colistin monotherapy in treating CRAB pneumonia compared to those treated without an active drug. MethodsAdult patients (≥ 18 years) with CRAB isolated from respiratory specimens were screened from September 2017 to August 2022. Only patients with pneumonia treated with colistin monotherapy (colistin group) were included and compared to those without any active antibiotics (no active antibiotics [NAA] group). The primary and secondary outcomes were 30-day all-cause mortality and acute kidney injury within 30 days. The inverse probability of the treatment-weighted Cox proportional hazard model was used to compare mortality between groups. ResultsAmong the 826 adult patients with CRAB in their respiratory specimens, 45 and 123 patients were included in the colistin and NAA groups, respectively. Most of the CRAB pneumonia (91.1%) cases were hospital-acquired pneumonia. The 30-day all-cause mortality rates in the colistin and NAA groups were 58.3% and 56.1%, respectively, and no difference was observed after adjustments (adjusted hazard ratio, 0.74; 95% CI, 0.47–1.17). The incidence of acute kidney injury was higher in the colistin group (65.3%) compared to the NAA group (39.0%) (P = 0.143). ConclusionsColistin monotherapy did not significantly improve treatment outcomes for CRAB pneumonia. The development and evaluation of new antimicrobials for CRAB pneumonia should be advocated in clinical practice.

A multicentre evaluation of the NG-test DetecTool OXA-23 for the rapid detection of OXA-23 carbapenemase directly from blood cultures.

A multicentre study evaluating NG-Test DetecTool OXA-23 for the detection of OXA-23 carbapenemase directly from positive blood cultures (PBCs). The NG-Test DetecTool OXA-23 is an immunoassay that integrates a sample preparation device. We evaluated NG-Test DetecTool OXA-23 on 189 spiked and 126 clinical PBCs. The clinical samples' standard-of-care procedure consisted of bacterial identification from the first day of positivity by MALDI-TOF MS, conventional culture and antimicrobial susceptibility testing. The immunoassay results were verified molecularly. The strains used for the spiked samples consisted of well-characterized Acinetobacter baumannii and Proteus mirabilis strains. The NG-Test DetecTool OXA-23 was evaluated on 315 PBCs and revealed sensitivity of 100% (95% CI: 98.21%-100.00%) and specificity of 100% (95% CI: 96.73%-100.00%). It provided 204 true-positive results for OXA-23 in 196 bottles with carbapenem-resistant A. baumannii (CRAB) and 8 bottles with carbapenem-resistant P. mirabilis and also provided 111 true-negative results. There were no false-positive and no false-negative results. Among the 315 PBCs studied, 83 clinical blood cultures collected in the ICU of a Greek university hospital, which were tested prospectively, all yielded CRAB, and OXA-23 was correctly detected in all samples from the first day of positivity using the NG-Test DetecTool OXA-23. The NG-Test DetecTool OXA-23 has exhibited excellent sensitivity and specificity for OXA-23 detection in PBCs and can provide valuable information for appropriate selection of antibiotic therapy and early implementation of infection control measures.

A retrospective analysis of carbapenem-resistant Acinetobacter baumannii infections in critically ill patients: Experience at a tertiary-care teaching hospital ICU

BackgroundAcinetobacter baumannii is a clinically significant pathogen with a high incidence of multidrug resistance that is associated with life-threatening nosocomial infections. Here, we aimed to provide an insight into the clinical characteristics and outcomes of a unique group of A. baumannii infections in which the isolates were resistant to carbapenems and most other antibiotic groups in a tertiary-care intensive care unit (ICU). MethodsWe performed a retrospective observational study in which records of patients hospitalized in the ICU between June 1, 2021 and June 1, 2023 were reviewed. We checked the clinical, laboratory, and microbiological records of all adult patients who had carbapenem-resistant A. baumannii (CRAB) infections. Prior antibiotic treatments and definitive antibiotic treatments after culture positivity and susceptibility test results were recorded. C-reactive protein (CRP) and procalcitonin levels and leukocyte counts were noted. Length of ICU stay and 30-day mortality were defined as the outcome parameters. ResultsDuring the study period, 57 patients were diagnosed with CRAB infections. The respiratory tract was the leading infection site (80.7%). In non-survivors, bloodstream infections (21.9% vs. 4.0% P=0.05) and colistin-resistant (col-R) CRAB infections (43.8% vs. 24.0%, P=0.12) were more common than in survivors, but these parameters were not statistically significant. The length of ICU stay was not different between survivors and non-survivors. Overall, the rate of col-R among CRAB clinical isolates was 35.1%. The 30-day mortality in all patients with CRAB infection was 56.1%. Mortality in col-R CRAB and colistin-susceptible (col-S) CRAB infections was 70.0% and 48.6%, respectively (P=0.12). Prior carbapenem use was 56.1%. Prior colistin use before col-R and col-S CRAB infections was not significant (35.0% vs. 27.0%, P=0.53). ConclusionsOur study provides real-world data on highly resistant A. baumannii infections and shares the characteristics of infections with such resistant strains. Unfortunately, carbapenem resistance in A. baumannii is a challenge for intensive care specialists who are faced with few treatment options, and colistin resistance further complicates the problem.