Resistant Acinetobacter Baumannii 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.

Seasonal meropenem resistance in Acinetobacter baumannii and influence of temperature-driven adaptation

BackgroundRecognition of seasonal trends in bacterial infection and drug resistance rates may enhance diagnosis, direct therapeutic strategies, and inform preventive measures. Limited data exist on the seasonal variability of Acinetobacter baumannii. We investigated the seasonality of A. baumannii, the correlation between temperature and meropenem resistance, and the impact of temperature on this bacterium.ResultsMeropenem resistance rates increased with lower temperatures, peaking in winter/colder months. Nonresistant strain detection exhibited temperature-dependent seasonality, rising in summer/warmer months and declining in winter/colder months. In contrast, resistant strains showed no seasonality. Variations in meropenem-resistant and nonresistant bacterial resilience to temperature changes were observed. Nonresistant strains displayed growth advantages at temperatures ≥ 25 °C, whereas meropenem-resistant A. baumannii with β-lactamase OXA-23 exhibited greater resistance to low-temperature (4 °C) stress. Furthermore, at 4 °C, A. baumannii upregulated carbapenem resistance-related genes (adeJ, oxa-51, and oxa-23) and increased meropenem stress tolerance.ConclusionsMeropenem resistance rates in A. baumannii display seasonality and are negatively correlated with local temperature, with rates peaking in winter, possibly linked to the differential adaptation of resistant and nonresistant isolates to temperature fluctuations. Furthermore, due to significant resistance rate variations between quarters, compiling monthly or quarterly reports might enhance comprehension of antibiotic resistance trends. Consequently, this could assist in formulating strategies to control and prevent resistance within healthcare facilities.

[Characteristics of drug resistance and biofilm formation in carbapenem-resistant Acinetobacter baumannii in hospitalized children].

To study the distribution, drug resistance, and biofilm characteristics of carbapenem-resistant Acinetobacter baumannii (CRAB) isolated from hospitalized children, providing a reference for the prevention and treatment of CRAB infections in hospitalized children. Forty-eight CRAB strains isolated from January 2019 to December 2022 were classified into epidemic and sporadic strains using repetitive extragenic palindromic sequence-based polymerase chain reaction. The drug resistance, biofilm phenotypes, and gene carriage of these two types of strains were compared. Both the 22 epidemic strains and the 26 sporadic strains were producers of Class D carbapenemases or extended-spectrum β-lactamases with downregulated outer membrane porins, harboring the VIM, OXA-23, and OXA-51 genes. The biofilm formation capability of the sporadic strains was stronger than that of the epidemic strains (P<0.05). Genes related to biofilm formation, including Bap, bfs, OmpA, CsuE, and intI1, were detected in both epidemic and sporadic strains, with a higher detection rate of the intI1 gene in epidemic strains (P<0.05). CRAB strains are colonized in the hospital, with sporadic strains having a stronger ability to form biofilms, suggesting the potential for forming new clonal transmissions in the hospital. Continuous monitoring of the epidemic trends of CRAB and early warning of the distribution of epidemic strains are necessary to reduce the risk of CRAB infections in hospitalized children.

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.

Outcome of Acinetobacter baumannii Ventilator Associated Pneumonia in Upper Egypt: does the resistance profile play a role?

Abstract Background Ventilator-associated pneumonia (VAP) due to drug resistant Acinetobacter baumannii (A. baumannii) is a challenging nosocomial problem associated with increased morbidity and risk of mortality. Objective This study aimed to investigate plasmid mediated quinolone resistance genes (PMQR) as a mechanism of resistance transmission, risk factors and outcome of A. baumannii VAP. Methods This prospective cohort study included 100 VAP patients between October 2020 and December 2022. Microbiological confirmation of A. baumannii. was done and PMQR genes were exposed by polymerase chain reaction (PCR). Pneumonia severity index (PSI), risk factors for developing drug resistant A. baumannii VAP, and the outcome were studied. Results The proportions of drug sensitive (DS), multidrug (MDR), extensive drug (XDR), and pan drug (PDR) resistant A. baumannii were 14%, 35%, 50%, and 1%, respectively. Majority of PSI classes IV and V showed XDR (66%) and PDR (100%) isolates. Detection of qnrA, qepA and aac(6′)-Ib-cr genes was predominant in PSI classes IV and V. The in-hospital mortality for MDR, XDR, and PDR was 22.7%, 70.5%, and 2.3%, respectively. ICU duration, prior use of carbapenems and use more than 2 antibiotics prior to VAP were risk factors for developing MDR A. baumannii while septic shock, multilobar chest radiography (CXR) infiltration and PSI class were predictors of in-hospital mortality. Conclusions VAP caused by MDR, XDR and PDR isolates of A. baumannii which harbors qnrA, qepA and aac(6’)-Ib-cr PMQR genes showed higher PSI classes and increased in-hospital mortality. The number of PMQR genes in A. baumannii isolates, ICU days, use of more than 2 antibiotics, and use of carbapenem prior to VAP, were independent risk factors for the development of drug resistant A. baumannii VAP.

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.

Genotypic Detection of Carbapenems Resistance Genes in Acinetobacter baumannii Isolated from Urinary Tract Infection Patients

Acinetobacter baumannii is a Gram-negative bacterium characterized by its short, round, rod-shaped morphology. It is an opportunistic pathogen that poses a significant threat, particularly to immunocompromised patients, often those with hospital stays lasting less than 90 days. Between June 2022 and July 2023, 214 urine samples were collected from individuals suspected of having urinary tract infections (UTIs). These samples were subjected to antibiotic resistance testing, focusing on detecting specific genes related to carbapenem resistance, namely blaNDM, blaKPC, and blaVIM.The study's results revealed a notable trend in antibiotic resistance among the bacterial isolates. Ceftazidime, cefotaxime, and ceftriaxone, commonly used antibiotics for UTIs, showed a high resistance rate among the tested isolates. This resistance highlights the challenges healthcare professionals face when treating UTIs caused by Acinetobacter baumannii. On the other hand, the isolates displayed a comparatively lower resistance rate to imipenem and meropenem, two necessary carbapenem antibiotics. This lower resistance to carbapenems is encouraging as these drugs are often considered the last line of defense against multidrug-resistant bacterial infections. The presence of carbapenem resistance genes, such as blaNDM, blaKPC, and blaVIM, in the Acinetobacter baumannii isolates is of particular concern. These genes confer resistance to carbapenem antibiotics, crucial for treating severe infections caused by multidrug-resistant bacteria. In conclusion, the study aims to study the growth of antibiotic resistance in Acinetobacter baumannii, especially in urinary tract infections in immunocompromised patients with more extended hospital stays. It also highlights the need for Surveys and periodic examinations to detect the spread of bacteria and their resistance. Keywords: Carbapenems, UTI, genes, blaNDM, blaKPC, and blaVIM.

Genotypic Detection of Carbapenems Resistance Genes in Acinetobacter baumannii Isolated from Urinary Tract Infection Patients

Acinetobacter baumannii is a Gram-negative bacterium characterized by its short, round, rod-shaped morphology. It is an opportunistic pathogen that poses a significant threat, particularly to immunocompromised patients, often those with hospital stays lasting less than 90 days. Between June 2022 and July 2023, 214 urine samples were collected from individuals suspected of having urinary tract infections (UTIs). These samples were subjected to antibiotic resistance testing, focusing on detecting specific genes related to carbapenem resistance, namely blaNDM, blaKPC, and blaVIM.The study's results revealed a notable trend in antibiotic resistance among the bacterial isolates. Ceftazidime, cefotaxime, and ceftriaxone, commonly used antibiotics for UTIs, showed a high resistance rate among the tested isolates. This resistance highlights the challenges healthcare professionals face when treating UTIs caused by Acinetobacter baumannii. On the other hand, the isolates displayed a comparatively lower resistance rate to imipenem and meropenem, two necessary carbapenem antibiotics. This lower resistance to carbapenems is encouraging as these drugs are often considered the last line of defense against multidrug-resistant bacterial infections. The presence of carbapenem resistance genes, such as blaNDM, blaKPC, and blaVIM, in the Acinetobacter baumannii isolates is of particular concern. These genes confer resistance to carbapenem antibiotics, crucial for treating severe infections caused by multidrug-resistant bacteria. In conclusion, the study aims to study the growth of antibiotic resistance in Acinetobacter baumannii, especially in urinary tract infections in immunocompromised patients with more extended hospital stays. It also highlights the need for Surveys and periodic examinations to detect the spread of bacteria and their resistance. Keywords: Carbapenems, UTI, genes, blaNDM, blaKPC, and blaVIM.

Phylogenomic and phenotypic analyses highlight the diversity of antibiotic resistance and virulence in both human and non-human Acinetobacter baumannii.

Acinetobacter baumannii is a Gram-negative, opportunistic pathogen that causes infections in the immunocompromised. With a high incidence of muti-drug resistance, carbapenem-resistant A. baumannii is designated as a priority 1 pathogen by the WHO. The current literature has expertly characterized clinical isolates of A. baumannii. As the challenge of these infections has recently been classified as a One Health issue, we set out to explore the diversity of isolates from human and non-clinical sources, such as agricultural surface water, urban streams, various effluents from wastewater treatment plants, and food (tank milk); and, importantly, these isolates came from a wide geographic distribution. Phylogenomic analysis considering almost 200 isolates showed that our diverse set is well-differentiated from the main international clones of A. baumannii. We discovered novel sequence types in both hospital and non-clinical settings and five strains that overexpress the resistance-nodulation-division efflux pump adeIJK without changes in susceptibility reflected by this overexpression. Furthermore, we detected a bla ADC-79 in a non-human isolate despite its sensitivity to all antibiotics. There was no significant differentiation between the virulence profiles of clinical and non-clinical isolates in the Galleria mellonella insect model of virulence, suggesting that virulence is neither dependent on geographic origin nor isolation source. The detection of antibiotic resistance and virulence genes in non-human strains suggests that these isolates may act as a genetic reservoir for clinical strains. This endorses the notion that in order to combat multi-drug-resistant infection caused by A. baumannii, a One Health approach is required, and a deeper understanding of non-clinical strains must be achieved.IMPORTANCEThe global crisis of antibiotic resistance is a silent one. More and more bacteria are becoming resistant to all antibiotics available for treatment, leaving no options remaining. This includes Acinetobacter baumannii. This Gram-negative, opportunistic pathogen shows a high frequency of multi-drug resistance, and many strains are resistant to the last-resort drugs carbapenem and colistin. Research has focused on strains of clinical origin, but there is a knowledge gap regarding virulence traits, particularly how A. baumannii became the notorious pathogen of today. Antibiotic resistance and virulence genes have been detected in strains from animals and environmental locations such as grass and soil. As such, A. baumannii is a One Health concern, which includes the health of humans, animals, and the environment. Thus, in order to truly combat the antibiotic resistance crisis, we need to understand the antibiotic resistance and virulence gene reservoirs of this pathogen under the One Health continuum.

Molecular Identification of Carbapenem Resistance Acinetobacter baumannii causing Ventilator-Associated Pneumonia Isolated from Intensive Care Unit of Tertiary Care Hospital

Ventilator-associated pneumonia (VAP) is a serious complication in critically ill patients, significantly increasing morbidity and mortality. One concerning organism behind VAP is Acinetobacter baumannii, a multidrug-resistant bacterium has ability to evade treatment, particularly with carbapenems, the last-line antibiotics. This is especially worrisome within the confines of Intensive Care Units (ICUs) of tertiary care hospitals, hubs for high-risk patients and potential reservoirs of antimicrobial resistance. This study focused on identifying carbapenem-resistant Acinetobacter baumannii using both phenotypic and genotypic methods. In 132 isolates of Acinetobacter baumannii, we observed 96% resistance to the cephalosporins while least resistance found to colistin and tigecycline. However, a concerning 51.5% of isolates exhibited carbapenem resistance. Phenotypically confirmation of carbapenem resistance detected in 47% isolates by Combined Disc Test and 51.5% isolates by Modified Hodge Test and E-test. Genotypic analysis with RT-PCR revealed a diverse array of resistance genes: blaIMP (33.82%), blaVIM (25%), blaOXA-Group (20.58%), and blaNDM (8.82%). These findings highlight the alarming prevalence of carbapenem-resistant Acinetobacter baumannii in healthcare settings.

Exploring the resistome and virulome in major sequence types of Acinetobacter baumannii genomes: Correlations with genome divergence and sequence types

The increasing global prevalence of antimicrobial resistance in Acinetobacter baumannii has led to concerns regarding the effectiveness of infection treatment. Moreover, the critical role of virulence factor genes in A. baumannii's pathogenesis and its propensity to cause severe disease is of particular importance. Comparative genomics, including multi-locus sequence typing (MLST), enhances our understanding of A. baumannii epidemiology. While there is substantial documentation on A. baumannii, a comprehensive study of the antibiotic-resistant mechanisms and the virulence factors contributing to pathogenesis, and their correlation with Sequence Types (STs) remains incompletely elucidated. In this study, we aim to explore the relationship between antimicrobial resistance genes, virulence factor genes, and STs using genomic data from 223 publicly available A. baumannii strains. The core phylogeny analysis revealed five predominant STs in A. baumannii genomes, linked to their geographical sources of isolation. Furthermore, the resistome and virulome of A. baumannii followed an evolutionary pattern consistent with their pan-genome evolution. Among the major STs, we observed significant variations in resistant genes against “aminoglycoside” and “sulphonamide” antibiotics, highlighting the role of genotypic variations in determining resistance profiles. Furthermore, the presence of virulence factor genes, particularly exotoxin and nutritional / metabolic factor genes, played a crucial role in distinguishing the major STs, suggesting a potential link between genetic makeup and pathogenicity. Understanding these associations can provide valuable insights into A. baumannii's virulence potential and clinical outcomes, enabling the development of effective strategies to combat infections caused by this opportunistic pathogen.

Novel mechanisms of diversity generation in Acinetobacter baumannii resistance islands driven by Tn7-like elements.

Mobile genetic elements play an important role in the acquisition of antibiotic and biocide resistance, especially through the formation of resistance islands in bacterial chromosomes. We analyzed the contribution of Tn7-like transposons to island formation and diversification in the nosocomial pathogen Acinetobacter baumannii and identified four separate families that recognize different integration sites. One integration site is within the comM gene and coincides with the previously described Tn6022 elements suggested to account for the AbaR resistance island. We established Tn6022 in a heterologous E. coli host and confirmed basic features of transposition into the comM attachment site and the use of a novel transposition protein. By analyzing population features within Tn6022 elements we identified two potential novel transposon-encoded diversification mechanisms with this dynamic genetic island. The activities of these diversification features were confirmed in E. coli. One was a novel natural gain-of-activity allele that could function to broaden transposition targeting. The second was a transposon-encoded hybrid dif-like site that parasitizes the host dimer chromosome resolution system to function with its own tyrosine recombinase. This work establishes a highly active Tn7-like transposon that harnesses novel features allowing the spread and diversification of genetic islands in pathogenic bacteria.

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.

PREVALENCE AND ANTIBIOTIC SUSCEPTIBILITY PATTERN OF GRAM NEGATIVE BACILLI ISOLATED FROM URINARY TRACT INFECTIONS

The aim of the study was to find out the prevalence and antibiotic susceptibility pattern of Gram negative bacilli isolated from urinary tract infections. This cross-sectional study was conducted at the department of urology Lady reading hospital Peshawar from February 2021 to August 2023. Mid-stream urine samples were collected from individual having the symptoms of urinary tract infection and were processed and identified through various biochemical tests. Following CLSI recommendations, the isolated bacteria were screened for sensitivity to antibiotics. Kirby-Bauer disc diffusion method was used in the current study. Through MS Excel, data were analyzed. The Chi-square test was applied for calculating the p value (significant i.e. &lt;0.05) and antibiotic resistant profiles of GNB isolated from urine samples. A total of 60000 urine samples were collected in which 65% (n=3900) patients were outdoor and 35% (n=2100) were hospitalized patients. Among them 20 % (n=1200) were culture positive. Among which 58% urine samples were from outdoor patients and 42% samples were from hospitalized patients. E.coli, Klebsiella pneumonia, P. aeruginosa and Acinetobacter   baumannii were the Gram negative bacilli (GNB) isolated in our study. The most prevalent (72%) GNB was E. coli. Pseudomonas aeruginosa isolated from indoor patients’ urine samples showed high resistance. The antibiotic sensitivity pattern of K. Pneumonia was same as E.coli both in out and indoor patients. The .Acinetobacter baumannii resistance pattern was quite lower observed as 85% in Nitrofurantoin (F), 80% in Ampicillin (AMP) and 11% in Fosfomycin (FOS) respectively   in   urine samples of   indoor as compare to outdoor patient. The most prevalent GNB observed in our study were E. coli, Klebsiella pneumonia, P. aeruginosa and Acinetobacter baumannii involved in UTIS. The choice of antibiotic for its treatment were Fosfomycin, Piperacillintazobactam, Cefoperazone-sulbactam, Amikacin   and Nitrofurantoin.

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. .

Molecular Characteristics of Colistin Resistance in Acinetobacter baumannii and the Activity of Antimicrobial Combination Therapy in a Tertiary Care Medical Center in Lebanon.

(1) Background: Infections with pan-drug-resistant (PDR) bacteria, such as A. baumannii, are becoming increasingly common, especially in healthcare facilities. In this study, we selected 15 colistin-resistant clinical A. baumannii isolates from a hospital in Beirut, Lebanon, to test combination therapies and determine their sequence types (STs) and the mechanism of colistin resistance using whole-genome sequencing (WGS). (2) Methods: Antimicrobial susceptibility testing via broth microdilution against 12 antimicrobials from different classes and growth rate assays were performed. A checkerboard assay was conducted on PDR isolates using six different antimicrobials, each in combination with colistin. Genomic DNA was extracted from all isolates and subjected to WGS. (3) Results: All isolates were resistant to all tested antimicrobials with the one exception that was susceptible to gentamicin. Combining colistin with either meropenem, ceftolozane-tazobactam, or teicoplanin showed synergistic activity. Sequencing data revealed that 67% of the isolates belonged to Pasteur ST2 and 33% to ST187. Furthermore, these isolates harbored a number of resistance genes, including blaOXA-23. Mutations in the pmrC gene were behind colistin resistance. (4) Conclusions: With the rise in antimicrobial resistance and the absence of novel antimicrobial production, alternative treatments must be found. The combination therapy results from this study suggest treatment options for PDR ST2 A. baumannii-infected patients.

Ciprofloxacin- and levofloxacin-loaded nanoparticles efficiently suppressed fluoroquinolone resistance and biofilm formation in Acinetobacter baumannii

The spread of fluoroquinolone (FQ) resistance in Acinetobacter baumannii represents a critical health threat. This study aims to overcome FQ resistance in A. baumannii via the formulation of polymeric nanoFQs. Herein, 80 A. baumannii isolates were obtained from diverse clinical sources. All A. baumannii isolates showed high resistance to most of the investigated antimicrobials, including ciprofloxacin (CIP) and levofloxacin (LEV) (97.5%). FQ resistance-determining regions of the gyrA and parC genes were the most predominant resistant mechanism, harbored by 69 (86.3%) and 75 (93.8%) of the isolates, respectively. Additionally, plasmid-mediated quinolone resistance genes aac(6′)-Ib and qnrS were detected in 61 (76.3%) and 2 (2.5%) of the 80 isolates, respectively. The CIP- and LEV-loaded poly ε-caprolactone (PCL) nanoparticles, FCIP and FLEV, respectively, showed a 1.5–6- and 6–12-fold decrease in the MIC, respectively, against the tested isolates. Interestingly, the time kill assay demonstrated that MICs of FCIP and FLEV completely killed A. baumannii isolates after 5–6 h of treatment. Furthermore, FCIP and FLEV were found to be efficient in overcoming the FQ resistance mediated by the efflux pumps in A. baumannii isolates as revealed by decreasing the MIC four-fold lower than that of free CIP and LEV, respectively. Moreover, FCIP and FLEV at 1/2 and 1/4 MIC significantly decreased biofilm formation by 47–93% and 69–91%, respectively. These findings suggest that polymeric nanoparticles can restore the effectiveness of FQs and represent a paradigm shift in the fight against A. baumannii isolates.

The Mechanism of Tigecycline Resistance in Acinetobacter baumannii under Sub-Minimal Inhibitory Concentrations of Tigecycline.

The presence of sub-minimal inhibitory concentration (sub-MIC) antibiotics in our environment is widespread, and their ability to induce antibiotic resistance is inevitable. Acinetobacter baumannii, a pathogen known for its strong ability to acquire antibiotic resistance, has recently shown clinical resistance to the last-line antibiotic tigecycline. To unravel the complex mechanism of A. baumannii drug resistance, we subjected tigecycline-susceptible, -intermediate, and -mildly-resistant strains to successive increases in sub-MIC tigecycline and ultimately obtained tigecycline-resistant strains. The proteome of both key intermediate and final strains during the selection process was analyzed using nanoLC-MS/MS. Among the more than 2600 proteins detected in all strains, we found that RND efflux pump AdeABC was associated with the adaptability of A. baumannii to tigecycline under sub-MIC pressure. qRT-PCR analysis also revealed higher expression of AdeAB in strains that can quickly acquire tigecycline resistance compared with strains that displayed lower adaptability. To validate our findings, we added an efflux pump inhibitor, carbonyl cyanide m-chlorophenyl hydrazine (CCCP), to the medium and observed its ability to inhibit tigecycline resistance in A. baumannii strains with quick adaptability. This study contributes to a better understanding of the mechanisms underlying tigecycline resistance in A. baumannii under sub-MIC pressure.

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.

In vivo development of cefiderocol resistance in carbapenem-resistant Acinetobacter baumannii associated with the downregulation of a TonB-dependent siderophore receptor, PiuA.

In vivo development of cefiderocol resistance in carbapenem-resistant Acinetobacter baumannii associated with the downregulation of a TonB-dependent siderophore receptor, PiuA.