Multidrug-resistant Acinetobacter Research Articles

Antimicrobial susceptibility and genetic characteristics of multi-drug resistant Acinetobacter baumannii isolates in Northwest China

IntroductionIn recent decades, widespread multi-drug resistant (MDR) bacteria have become a serious problem in healthcare facilities.MethodsTo systematically summarize and investigate the prevalence and genomic features of clinical MDR Acinetobacter baumannii (A. baumannii) clinical isolates recovered from the first hospital of Lanzhou University, we collected 50 MDR A. baumannii isolates isolated in the first quarter of 2022 and using whole-genome sequencing investigate the genotypic characteristics.ResultsAll of these isolates were generally resistant to the common β-lactamase antibiotics. Resistance to cefoperazone-sulbactam varies greatly between different clones. The proportion of CC208 isolates resistant and mediated to cefoperazone-sulbactam is as high as 84.6%. There were no isolates resistant to tigecycline and colistin. The presence of blaOXA − 23 (94.0%) and blaOXA − 66 (98.0%) were the most frequent determinants for carbapenem resistance. Two main endemic clones were identified, one (ST469oxf) was predominantly circulating in ICUs and carried the same resistance genes, virulence genes and transposons, and the other clone (CC208) carried more resistance genes and had more widely disseminated.DiscussionOur study showed that clinical MDR A. baumannii isolates circulating in our hospital exhibited highly similar genetic features. We should take timely and effective measures to control the further epidemic of these isolates.

Enhancing effect of natural adjuvant, panduratin A, on antibacterial activity of colistin against multidrug-resistant Acinetobacter baumannii

Colistin- and carbapenem-resistant Acinetobacter baumannii is a serious multidrug resistant (MDR) bacterium in clinical settings. Discovery of new antibacterial drugs against MDR is facing multiple challenges in drug development. Combination of known antibiotics with a robust adjuvant might be an alternative effective strategy for MDR treatment. In the study herein, we report an antibiotic adjuvant activity of a natural compound panduratin A from fingerroot (Boesenbergia rotunda) as a potent adjuvant to colistin. The present study investigated the antibiotic adjuvant effect of panduratin A against 10 colistin- and carbapenem-resistant A. baumannii. Antibacterial activities were tested by broth microdilution method. Biofilm assay was used to determine the efficacy of panduratin A in biofilm formation inhibition on two representative strains Aci46 and Aci44. Genomic and transcriptomic analyses of colistin- and carbapenem-resistant A. baumannii strains were used to identify potential resistance and tolerance mechanism in the bacteria. Panduratin A-colistin combination showed an increased effect on antibacterial in the A. baumannii. However, panduratin A did not improve the antibacterial activity of imipenem. In addition, panduratin A improves anti-biofilm activity of colistin against Aci44 and Aci46, the colistin- and carbapenem-resistant A. baumannii. Panduratin A markedly enhances bactericidal and anti-biofilm activity of colistin against colistin- resistant A. baumannii. Based on genome comparisons, single nucleotide polymorphism (SNP) patterns in six genes encoding biofilm and lipid A biosynthesis were shared in Aci44 and Aci46. In Aci44, we identified a partial sequence of pmrB encoding a polymyxin resistant component PmrB, whereas a full length of pmrB was observed in Aci46. RNA-seq analyses of Aci44 revealed that panduratin A-colistin combination induced expression of ribosomal proteins and oxidative stress response proteins, whereas iron transporter and MFS-type transporter systems were suppressed. Panduratin A-colistin combination could promote intracellular reactive oxygen species (ROS) accumulation could lead to the cidal effect on colistin-resistant A. baumannii. Combination of panduratin A and colistin showed a significant increase in colistin efficacy against colistin- resistant A. baumannii in comparison of colistin alone. Genomic comparison between Aci44 and Aci46 showed mutations and SNPs that might affect different phenotypes. Additionally, based on RNA-Seq, panduratin A-colistin combination could lead to ROS production and accumulation. These findings confirmed the potency of panduratin as colistin adjuvant against multidrug resistant A. baumannii.

Dihydrophenazine: a multifunctional new weapon that kills multidrug-resistant Acinetobacter baumannii and restores carbapenem and oxidative stress susceptibilities.

The current work aims to fully characterize a new antimicrobial agent against Acinetobacter baumannii, which continues to represent a growing threat to healthcare settings worldwide. With minimal treatment options due to the extensive spread of resistance to almost all the available antimicrobials, the hunt for new antimicrobial agents is a high priority. An Egyptian soil-derived bacterium strain NHM-077B proved to be a promising source for a new antimicrobial agent. Bio-guided fractionation of the culture supernatants of NHM-077B followed by chemical structure elucidation identified the active antimicrobial agent as 1-hydroxy phenazine. Chemical synthesis yielded more derivatives, including dihydrophenazine (DHP), which proved to be the most potent against A. baumannii, yet it exhibited a marginally safe cytotoxicity profile against human skin fibroblasts. Proteomics analysis of the cells treated with DHP revealed multiple proteins with altered expression that could be correlated to the observed phenotypes and potential mechanism of the antimicrobial action of DHP. DHP is a multipronged agent that affects membrane integrity, increases susceptibility to oxidative stress, interferes with amino acids/protein synthesis, and modulates virulence-related proteins. Interestingly, DHP in subinhibitory concentrations re-sensitizes the highly virulent carbapenem-resistant A. baumannii strain AB5075 to carbapenems providing great hope in regaining some of the benefits of this important class of antibiotics. This work underscores the potential of DHP as a promising new agent with multifunctional roles as both a classical and nonconventional antimicrobial agent that is urgently needed.

Epidemiology of antibiotic consumption and resistance in Mauritius

IntroductionThis study aims at determining the pattern of antibiotic consumption and resistance in Mauritius, a tropical island in the Indian Ocean.MethodologyAntibiotic consumption was measured in kilograms of purchased antibiotics and also in defined daily dose (DDD) in different health institutions from 2015 to 2017. Data on antibiotic resistance was collected at the Central Health Laboratory (CHL) at Victoria Hospital and at Jeetoo Hospital Laboratory, where antibiotic sensitivity testing is done for all public health institutions. For this study, Escherichia coli, Klebsiella species, Acinetobacter species, and Pseudomonas aeruginosa isolates from blood samples of patients from 2015 to 2023 were included. The resistance rate and prevalence of multi-drug-resistant (MDR) organisms were calculated.ResultsThe amount of antibiotics (in kilograms) distributed to the human sector was between 11,000 to 13,000 kg, compared to only 700 to 1,500 kg in the animal sector. The DDD per 1,000 inhabitants per day was 20.9, 22.1, and 21.7 in 2015, 2016, and 2017, respectively, with a greater consumption of WATCH and RESERVE group antibiotics in the private sector. In public health institutions, health centers in the northern region had the highest DDD per 1,000 outpatients per day for beta-lactams penicillins and quinolones. Concerning antibiotic resistance, the proportion of MDR Acinetobacter baumannii and Pseudomonas aeruginosa has increased from 58% to 74% and from 33% to 45%, respectively, from 2015 to 2023. During the same period, the proportion of E. coli and K. pneumoniae isolates sensitive to ceftriaxone decreased from 55% to 39% and from 37% to 22%, respectively, while the proportion of E. coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa isolates sensitive to meropenem decreased from 98% to 94%, 83% to 53%, 45% to 28%, and 63% to 47%, respectively.ConclusionThis study provides valuable insights on antibiotic consumption and resistance in the country and emphasizes the significance of adopting a One Health approach to combat antimicrobial resistance (AMR) effectively. These findings will aid policymakers in formulating targeted strategies to address the challenge of AMR and should be integrated into the National Action Plan on AMR in Mauritius.

Characterization of Aminoglycoside-Resistant Acinetobacter baumannii in Respiratory Specimens: Phenotypic and Molecular Insights

Background: The global rise of antibiotic-resistant bacteria presents a formidable challenge to healthcare systems, with Acinetobacter baumannii standing out as a particularly resilient pathogen in hospital settings. The propensity of this organism to exhibit multidrug resistance complicates treatment protocols and underscores the need for in-depth research into its resistance mechanisms. Objective: The objective of this study was to characterize the allelotypic and molecular features of aminoglycoside-resistant Acinetobacter baumannii isolates from respiratory specimens and to determine their antibiotic susceptibility profiles to inform better clinical decision-making and treatment approaches. Methods: This cross-sectional study was conducted at the different labs of various institute of Lahore. A total of 50 respiratory specimens were cultured on selective media. The isolates underwent phenotypic characterization through colony morphology and biochemical tests. Antimicrobial susceptibility was assessed using the disc diffusion method, and molecular analysis was performed using polymerase chain reaction (PCR) to identify the armA gene associated with aminoglycoside resistance. Statistical analysis was executed using SPSS Version 25. Results: Of the 50 isolates, 54% were from male patients and 46% from female patients. Antibiotic resistance was alarmingly high, with resistance rates of 92% for TZP, 90% for FEP, CAZ, IPM, MEM, 86% for AK, 74% for CN, 54% for TOB, and 48% for DO. The presence of the armA gene was detected in 86% of the isolates, suggesting a link to the high levels of aminoglycoside resistance observed. Conclusion: The study revealed a high prevalence of multidrug-resistant Acinetobacter baumannii in respiratory specimens, with significant resistance to commonly used antibiotics. These findings highlight the necessity for continuous surveillance of antibiotic resistance patterns and call for innovative approaches to antimicrobial therapy.

Dual-targeting tigecycline nanoparticles for treating intracranial infections caused by multidrug-resistant Acinetobacter baumannii

Multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) is a formidable pathogen responsible for severe intracranial infections post-craniotomy, exhibiting a mortality rate as high as 71%. Tigecycline (TGC), a broad-spectrum antibiotic, emerged as a potential therapeutic agent for MDR A. baumannii infections. Nonetheless, its clinical application was hindered by a short in vivo half-life and limited permeability through the blood–brain barrier (BBB). In this study, we prepared a novel core–shell nanoparticle encapsulating water-soluble tigecycline using a blend of mPEG-PLGA and PLGA materials. This nanoparticle, modified with a dual-targeting peptide Aβ11 and Tween 80 (Aβ11/T80@CSs), was specifically designed to enhance the delivery of tigecycline to the brain for treating A. baumannii-induced intracranial infections. Our findings demonstrated that Aβ11/T80@CSs nanocarriers successfully traversed the BBB and effectively delivered TGC into the cerebrospinal fluid (CSF), leading to a significant therapeutic response in a model of MDR A. baumannii intracranial infection. This study offers initial evidence and a platform for the application of brain-targeted nanocarrier delivery systems, showcasing their potential in administering water-soluble anti-infection drugs for intracranial infection treatments, and suggesting promising avenues for clinical translation.Graphical abstract

Development and Evaluation of an Immunoinformatics-Based Multi-Peptide Vaccine against Acinetobacter baumannii Infection.

Multi-drug-resistant (MDR) Acinetobacter baumannii is an opportunistic pathogen associated with hospital-acquired infections. Due to its environmental persistence, virulence, and limited treatment options, this organism causes both increased patient mortality and incurred healthcare costs. Thus, prophylactic vaccination could be ideal for intervention against MDR Acinetobacter infection in susceptible populations. In this study, we employed immunoinformatics to identify peptides containing both putative B- and T-cell epitopes from proteins associated with A. baumannii pathogenesis. A novel Acinetobacter Multi-Epitope Vaccine (AMEV2) was constructed using an A. baumannii thioredoxin A (TrxA) leading protein sequence followed by five identified peptide antigens. Antisera from A. baumannii infected mice demonstrated reactivity to rAMEV2, and subcutaneous immunization of mice with rAMEV2 produced high antibody titer against the construct as well as peptide components. Immunization results in increased frequency of IL-4-secreting splenocytes indicative of a Th2 response. AMEV2-immunized mice were protected against intranasal challenge with a hypervirulent strain of A. baumannii and demonstrated reduced bacterial burden at 48 h. In contrast, all mock vaccinated mice succumbed to infection within 3 days. Results presented here provide insight into the effectiveness of immunoinformatic-based vaccine design and its potential as an effective strategy to combat the rise of MDR pathogens.

Characterization of the diversity of type IV secretion system-encoding plasmids in Acinetobacter

ABSTRACT The multi-drug resistant pathogen Acinetobacter baumannii has gained global attention as an important clinical challenge. Owing to its ability to survive on surfaces, its capacity for horizontal gene transfer, and its resistance to front-line antibiotics, A. baumannii has established itself as a successful pathogen. Bacterial conjugation is a central mechanism for pathogen evolution. The epidemic multidrug-resistant A. baumannii ACICU harbours a plasmid encoding a Type IV Secretion System (T4SS) with homology to the E. coli F-plasmid, and plasmids with homologous gene clusters have been identified in several A. baumannii sequence types. However the genetic and host strain diversity, global distribution, and functional ability of this group of plasmids is not fully understood. Using systematic analysis, we show that pACICU2 belongs to a group of almost 120 T4SS-encoding plasmids within four different species of Acinetobacter and one strain of Klebsiella pneumoniae from human and environmental origin, and globally distributed across 20 countries spanning 4 continents. Genetic diversity was observed both outside and within the T4SS-encoding cluster, and 47% of plasmids harboured resistance determinants, with two plasmids harbouring eleven. Conjugation studies with an extensively drug-resistant (XDR) strain showed that the XDR plasmid could be successfully transferred to a more divergent A. baumanii, and transconjugants exhibited the resistance phenotype of the plasmid. Collectively, this demonstrates that these T4SS-encoding plasmids are globally distributed and more widespread among Acinetobacter than previously thought, and that they represent an important potential reservoir for future clinical concern.

In vitro activity of human defensins HNP-1 and hBD-3 against multidrug-resistant ESKAPE Gram-negatives of clinical origin and selected peptidoglycan recycling-defective mutants.

In the current scenario of critical need for new antimicrobials against multidrug-resistant bacteria, all options must be considered, including classic ideas such as the use of purified immune compounds. However, information regarding the activity of certain human defensins against ESKAPE Gram-negatives was incomplete. This is the first study comparatively assessing the in vitro activity of two membrane-permeabilizing/peptidoglycan construction-blocking defensins (HNP-1 and hBD-3) against relevant clinical collections of ESKAPE Gram-negatives, alone or in combination with permeabilizers, additional peptidoglycan-targeting attacks, or the blockade of its recycling. Our data suggest that hBD-3 has a notable bactericidal activity against multidrug-resistant Acinetobacter baumannii and Enterobacter cloacae strains that should be considered as potential adjuvant option. Our results suggest for the first time an increased resistance of Pseudomonas aeruginosa strains from chronic infection compared to acute origin ones, and provide new clues about the predominant mode of action of hBD-3 against Gram-negatives (permeabilization rather than peptidoglycan-targeting).

Prevalence of Extended-spectrum Beta-lactamase (ESBL), Metallo Beta-lactamase (MBL) and Carbapenemase Producing Acinetobacter Species Isolated from Various Clinical Samples in Tertiary Care Hospital

Acinetobacter is an important nosocomial pathogen causing health care associated infections. It is highly antibiotic resistant gram-negative bacilli. The study was done to determine the prevalence of Acinetobacter species isolated from various clinical samples with their antibiotic susceptibility pattern. To determine the antimicrobial susceptibility pattern of the isolated Acinetobacter species and also the multidrug resistant mechanisms by phenotypic characterization. The retrospective study was carried out in patients diagnosed with Acinetobacter infection in the Microbiology Department, Krishna Institute of Medical Sciences, Krishna Vishwa Vidyapeeth, Deemed To Be University, Karad, a tertiary care hospital, including the clinical departments, during the period of two years from November 2020 till November 2022. Organism identification, biochemical test, antibiotic resistance pattern and phenotypic tests such as ESBL, MBL and Carbapenemase production were performed as per the Clinical and Laboratory Standards Institute (CLSI). The Modified Hodge test (MHT) was performed for Carbapenemase production detection in Acinetobacter species. A total of 150 Acinetobacter species were isolated from clinical samples. Acinetobacter baumannii was the most prevalent species 138 (92%), followed by Acinetobacter lwoffii 10 (7%) and Acinetobacter hemolyticus 2 (1%). The isolates showed highest resistance to Ampicillin 130 (87%) and sensitive to Colistin 113 (75.3%). Most of the isolates of of Acinetobacter baumannii showed maximum ESBL 21(14%) and MBL 75 (93%) production. Modified Hodge test showed positive results in Acinetobacter baumannii, only 11 (7%). The study showed that Acinetobacter baumannii was the most prevalent species showing drug resistance by phenotypic detection methods. At present Acinetobacter is a frequent pathogen in hospital acquired infections in critically ill patients admitted to ICU. The isolates of Acinetobacter species in our study showed resistant to most commonly used antibiotics. The study showed that ESBL production in Acinetobacter was 22 (15%) and MBL 80 (53%). Most Acinetobacter isolates were Multi Drug Resistant (MDR). MDR Acinetobacter is widely increasing due to inappropriate use of antibiotics in healthcare hospital. In our study, detection of carbapenemase by Modified Hodge test was positive in 11 (7%) isolates.

Analysis of Blood Cultures from Major Burns Patients in a Tertiary Care Burn Unit in Oman.

This study aimed to review the blood stream infections of major burn patients in a tertiary care burn unit to determine the most prevalent infecting organisms in order to have a better empirical therapy protocol. This retrospective study analysed the blood stream infection of 155 major burn (>20% Total Body Surface Area [TBSA]) patients in Khoula Hospital, Muscat, Oman between January 2014 to December 2019. The median age was 33 years and 57.42% of patients were male. The median TBSA was 38%, mortality was 25.16% and 50.9% of patients had positive blood cultures. The expired patients had higher TBSAs, Abbreviated Burns Severity Index scores and earlier first positive blood cultures. Candida was commonly grown in all the blood cultures, but the most prevalent organisms were Acinetobacter, Staphylococci, Klebsiella, Enterococcus and Pseudomonas. All Acinetobacter species are multidrug resistant. Of the 17 patients who had Kelbsiella grown in the blood culture, 8 grew multidrug-resistant Klebsiella. Only 4 patients' blood cultures grew methicillin-resistant Staphylococcus aureus. The number of blood culture samples taken ranged between 1-28 (median = 6). The first positive blood culture showed that Staphylococcus epidermidis and Acinetobacter were the most common infecting organisms. Multidrug-resistant Acinetobacter was the most predominant microorganism grown from the blood cultures of major burn patients in a tertiary care burn unit. Empirical therapy should include antibiotics that are effective against this organism to reduce the mortality.

Deciphering the structure of a multi-drug resistant Acinetobacter baumannii short-chain dehydrogenase reductase.

The rapidly increasing threat of multi-drug-resistant Acinetobacter baumannii infections globally, encompassing a range of clinical manifestations from skin and soft tissue infections to life-threatening conditions like meningitis and pneumonia, underscores an urgent need for novel therapeutic strategies. These infections, prevalent in both hospital and community settings, present a formidable challenge to the healthcare system due to the bacterium's widespread nature and dwindling effective treatment options. Against this backdrop, the exploration of bacterial short-chain dehydrogenase reductases (SDRs) emerges as a promising avenue. These enzymes play pivotal roles in various critical bacterial processes, including fatty acid synthesis, homeostasis, metabolism, and contributing to drug resistance mechanisms. In this study, we present the first examination of the X-ray crystallographic structure of an uncharacterized SDR enzyme from A. baumannii. The tertiary structure of this SDR is distinguished by a central parallel β-sheet, consisting of seven strands, which is flanked by eight α-helices. This configuration exhibits structural parallels with other enzymes in the SDR family, underscoring a conserved architectural theme within this enzyme class. Despite the current ambiguity regarding the enzyme's natural substrate, the importance of many SDR enzymes as targets in anti-bacterial agent design is well-established. Therefore, the detailed structural insights provided in this study open new pathways for the in-silico design of therapeutic agents. By offering a structural blueprint, our findings may provide a platform for future research aimed at developing targeted treatments against this and other multi-drug-resistant infections.

Host range expansion of Acinetobacter phage vB_Ab4_Hep4 driven by a spontaneous tail tubular mutation.

Bacteriophages (phages) represent promising alternative treatments against multidrug-resistant Acinetobacter baumannii (MDRAB) infections. The application of phages as antibacterial agents is limited by their generally narrow host ranges, so changing or expanding the host ranges of phages is beneficial for phage therapy. Multiple studies have identified that phage tail fiber protein mediates the recognition and binding to the host as receptor binding protein in phage infection. However, the tail tubular-dependent host specificity of phages has not been studied well. In this study, we isolated and characterized a novel lytic phage, vB_Ab4_Hep4, specifically infecting MDRAB strains. Meanwhile, we identified a spontaneous mutant of the phage, vB_Ab4_Hep4-M, which revealed an expanded host range compared to the wild-type phage. A single mutation of G to C was detected in the gene encoding the phage tail tubular protein B and thus resulted in an aspartate to histidine change. We further demonstrated that the host range expansion of the phage mutant is driven by the spontaneous mutation of guanine to cytosine using expressed tail tubular protein B. Moreover, we established that the bacterial capsule is the receptor for phage Abp4 and Abp4-M by identifying mutant genes in phage-resistant strains. In conclusion, our study provided a detailed description of phage vB_Ab4_Hep4 and revealed the tail tubular-dependent host specificity in A. baumannii phages, which may provide new insights into extending the host ranges of phages by gene-modifying tail tubular proteins.

The Effect of Citric and Ascorbic Acids as Anti-Biofilm and Anti-Capsular Agents on Multidrug Resistant Acinetobacter baumannii.

Acinetobacter baumannii (A. baumannii) is an opportunistic bacterium with multiple virulence factors, including capsule and biofilm, and is known for its high drug resistance. Anti-virulence natural substances have been suggested as novel alternatives to conventional antibiotics. We aimed to evaluate the effect of citric acid and ascorbic acid as anti-biofilm and anti-capsular agents against multidrug resistant (MDR) A. baumannii clinical isolates. Twenty-eight A. baumannii MDR isolates were collected from different clinical sources. The minimum inhibitory concentration (MIC) of each agent was estimated. Biofilm formation and capsule were investigated phenotypically in the absence and presence both agents at ½ and ¼ MICs. The presence of 14 adhesive and non-adhesive virulence genes was investigated. Phenotypically, all the isolates were biofilm producers and were capsulated. The MIC of citric acid ranged from 1.25 to 2.5 mg/ml while that of ascorbic acid was 3 mg/ml for all isolates. Both agents showed significant reduction in biofilm and capsular thinning. Ascorbic acid showed a dose-dependent effect in both biofilm reduction and capsule thinning unlike citric acid. Four genes, papG23, sfa1, fyuA and cvaC, were absent among all isolates, while iutA was present in 100% of isolates. Other genes showed different distributions among the isolates. These virulence genes were not correlated to the antibiofilm effect of both agents. Ascorbic acid was observed to have a better effect than citric acid. This can provide a clue for a better treatment regimen including ascorbic acid against MDR A. baumannii infections. .

Antibacterial Potential of Tetrahydrocarbazoles (THCZ): A Review

Abstract: Antibiotic resistance has become a major public threat across the globe associated with human health. Some bacterial and fungal infections produce bacterial resistance, such as methicillin- resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium (VRE) and multidrug-resistant (MDR) species Acinetobacter baumannii etc. Tetrahydrocarbazoles (THCz) are a sub-class of indole alkaloids profoundly present in natural products and biologically active compounds and have displayed potential biological activities in literature. THCz exhibit potential antibacterial activities through major bacterial pathways like cell wall synthesis inhibition and DNA gyrase enzyme inhibition with DNA sliding clamp inhibitors and MreB inhibitors. These THCZ also showed significant in vitro antibacterial activities against bacterial-resistant species, such as MRSA, VRE and Acinetobacter baumannii (MDR) in literature. MTDL (Multi Target Direct ligand) approach has been significantly used for the design of THC motif-based antibacterial agents. In this review article, we collected literature on THCz as a potential antibacterial agent from 2014 to date. The review study of THC core-based derivatives found excellent in vitro antibacterial profiles and revealed that they can play a significant role in drug discovery and the development of new antibiotics against various infectious diseases.

Comparison of in vitro synergy between polymyxin B or colistin in combination with 16 antimicrobial agents against multidrug-resistant Acinetobacter baumannii isolates

PurposesThis study determined the synergy of polymyxin B (POLB) and colistin (COL) with 16 other tested antimicrobial agents in the inhibition of multidrug-resistant Acinetobacter baumannii (MDR-AB). MethodsWe used chequerboard assays to determine synergy between the drugs against 50 clinical MDR-AB from a tertiary hospital in the Zhejiang province in 2019, classifying combinations as either antagonistic, independent, additive, or synergistic. The efficacy of hit combinations which showed highest synergistic rate were confirmed using time-kill assays. ResultsBoth POLB and COL displayed similar bactericidal effects when used in combination with these 16 tested drugs. Antagonism was only observed for a few strains (2%) exposed to a combination of POLB and cefoperazone/sulbactam (CSL). A higher percentage of synergistic combinations with POLB and COL were observed with rifabutin (RFB; 90%/96%), rifampicin (RIF; 60%/78%) and rifapentine (RFP; 56%/76%). Time-kill assays also confirmed the synergistic effect of POLB and rifamycin class combinations. 1/2 MIC rifamycin exposure can achieve bacterial clearance when combined with 1/2 MIC POLB or COL. ConclusionNearly no antagonism was observed when combining polymyxins with other drugs by both chequerboard and time-kill assays, suggesting that polymyxins may be effective in combination therapy. The combinations of POLB/COL with RFB, RIF, and RFP displayed neat synergy, with RFB showing the greatest effect.

Genomic Characterization of Mobile Genetic Elements Associated with Multidrug-Resistant Acinetobacter Non-baumannii Species from Southern Thailand.

This study investigated the genetic diversity, antimicrobial resistance profiles, and virulence characteristics of Acinetobacter non-baumannii isolates obtained from four hospitals in southern Thailand. Clinical data, genome information, and average nucleotide identity (ANI) were analyzed for eight isolates, revealing diverse genetic profiles and novel sequence types (STs). Minimum spanning tree analysis indicated potential clonal spread of certain STs across different geographic regions. Antimicrobial resistance genes (ARGs) were detected in all isolates, with a high prevalence of genes conferring resistance to carbapenems, highlighting the challenge of antimicrobial resistance in Acinetobacter spp. infections. Mobile genetic elements (MGEs) carrying ARGs were also identified, emphasizing the role of horizontal gene transfer in spreading resistance. Evaluation of virulence-associated genes revealed a diverse range of virulence factors, including those related to biofilm formation and antibiotic resistance. However, no direct correlation was found between virulence-associated genes in Acinetobacter spp. and specific clinical outcomes, such as infection severity or patient mortality. This complexity suggests that factors beyond gene presence may influence disease progression and outcomes. This study emphasizes the importance of continued surveillance and molecular epidemiological studies to combat the spread of multidrug-resistant (MDR) Acinetobacter non-baumannii strains. The findings provide valuable insights into the epidemiology and genetic characteristics of this bacteria in southern Thailand, with implications for infection control and antimicrobial management efforts.

Multi-drug Resistant Acinetobacter baumannii: Phenotypic and Genotypic Resistance Profiles and the Associated Risk Factors in Teaching Hospital in Jordan

BackgroundThis study aimed to determine the prevalence of Antimicrobial Resistance Genes (ARGs), with a focus on colistin resistance in clinical A. baumannii, as well as the risk factors associated with A. baumannii infection in Jordanian patients. MethodsIn total, 150 A. baumannii isolates were obtained from patients at a teaching hospital. The isolates were tested for antimicrobial susceptibility using disc diffusion and microdilution methods. PCR amplification was used to detect ARGs, and statistical analysis was conducted to evaluate the influence of identified risk factors on the ARGs acquisition. ResultsMore than 90% of A. baumannii isolates were resistant to monobactam, carbapenem, cephalosporins, Fluoroquinolones, penicillin, and β-lactam agents. Moreover, 20.6% of the isolates (n = 31) were colistin-resistant. Several ARGs were also detected in A. baumannii isolates. Univariate analysis indicated that risk factors and the carriage of ARGs were significantly associated P ≤ (0.05) with gender, invasive devices, immunodeficiency, systemic diseases, tumors, and covid-19. Logistic regression analysis indicated seven risk factors, and three protective factors were associated with the ARGs (armA, strA, and strB) P ≤ (0.05). In contrast, tetB and TEM were associated with 2 risk factors each P ≤ (0.05). ConclusionOur study indicates a high prevalence of MDR A. baumannii infections in ICU patients, as well as describing the case of colistin-resistant A. baumannii for the first time in Jordan. Additionally, the risk factors associated with ARGs-producing A. baumannii infections among ICU patients suggest a rapid emergence and spread of MDR A. baumannii without adequate surveillance and control measures.

Clinical Efficacy of Sitafloxacin-Colistin-Meropenem and Colistin-Meropenem in Patients with Carbapenem-Resistant and Multidrug-Resistant Acinetobacter baumannii Hospital-Acquired Pneumonia (HAP)/Ventilator-Associated Pneumonia (VAP) in One Super-Tertiary Hospital in Bangkok, Thailand: A Randomized Controlled Trial.

Carbapenem-resistant A. baumannii (CRAB) hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) is now a therapeutic problem worldwide. An open-label, randomized, superiority, single-blind trial was conducted in Rajavithi Hospital, a super-tertiary care facility in Bangkok, Thailand. CRAB HAP/VAP patients were randomly assigned to receive either sitafloxacin-colistin-meropenem or colistin-meropenem. Outcomes in the two groups were then assessed with respect to mortality, clinical response, and adverse effects. Between April 2021 and April 2022, 77 patients were treated with combinations of either sitafloxacin plus colistin plus meropenem (n = 40) or colistin plus meropenem (n = 37). There were no significant differences between the two groups with respect to all-cause mortality rates at 7 days and 14 days (respectively, 7.5% vs. 2.7%; p = 0.616, and 10% vs. 10%; p = 1). Patients who received sitafloxacin-colistin-meropenem showed improved clinical response compared with patients who received colistin-meropenem in terms of both intention-to-treat (87.5% vs. 62.2%; p = 0.016) and per-protocol analysis (87.2% vs. 67.7%; p = 0.049). There were no significant differences between the two groups with respect to adverse effects. Adding sitafloxacin as a third agent to meropenem plus colistin could improve clinical outcomes in CRAB HAP/VAP with little or no impact on adverse effects. In short, sitafloxacin-meropenem-colistin could be another therapeutic option for combatting CRAB HAP/VAP.

Risk factors for bacteremia and mortality due to multidrug-resistant Acinetobacter baumannii: a retrospective study.

This research aimed to determine the relationships between the risk factors for nosocomial multidrug-resistant Acinetobacter baumannii (MDRAB) bacteremia and associated mortality. We analyzed 144 patients treated for A. baumannii bacteremia, including 120 patients with MDRAB bacteremia, from March 2015 to March 2020, in this retrospective study. The overall bacteremia-related mortality rate was 48.6%. The mortality rates were 25.0% and 53.3% for non-MDRAB and MDRAB bacteremia, respectively. Risk factors for the development of MDRAB bacteremia were prior use of cephalosporins [odds ratio (OR): 8.62; P<.001], carbapenems (OR: 15.04; P<.001), or quinolones (OR: 5.02; P=.040); indwelling urinary catheters (OR: 21.38; P<.001); and respiratory tract as the source of bacteremia (OR: 75.33; P<.001). Patients with elective surgeries were inclined to develop non-MDRAB bacteremia (OR: 0.45; P=.029). High scores in the Acute Physiology and Chronic Health Evaluation II (OR: 1.321; P<.001) and Sequential Organ Failure Assessment (OR: 1.326; P<.001) were risk factors for mortality from MDRAB infection. In summary, higher mortality rates occur in patients with MDRAB bacteremia, and risk factors include prior use of cephalosporins, carbapenems, or quinolones. Urinary catheters and the respiratory tract as sources of the infection increase the risk of MDRAB bacteremia.