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The increasing prevalence of multidrug-resistant (MDR) Acinetobacter baumannii limits effective therapeutic options, and tigecycline has been considered one of the last resort therapies for MDR A. baumannii infections. Nevertheless, A. baumannii isolates resistant to tigecycline are becoming increasingly reported, mostly due to overexpression of efflux pumps. The three major RND efflux systems conferring tigecycline resistance in A. baumannii are AdeABC, AdeFGH, and AdeIJK, and their expression is regulated by the two-component system AdeRS, the LysR-type regulator AdeL, and the TetR-type regulator AdeN, respectively. Following the above, we aimed to determine the role of efflux pumps in tigecycline resistance of thirty-seven A. baumannii isolates collected from Western Balkan healthcare settings (Serbia, Bosnia and Herzegovina and Montenegro) in 2016 and 2022. The majority of isolates belonged to the most prevalent international clonal lineage IC2 (n = 32), four isolates are members of IC1, while only one isolate is identified as IC3. All tested isolates demonstrated a significant decrease in tigecycline MIC in presence of efflux pump inhibitor CCCP (≥16-fold reduction) indicating that mechanism responsible for tigecycline resistance is antibiotic efflux. The comparison of target efflux pump regulatory proteins, translated from nucleotide sequences, to reference strains ATCC19606 and ATCC17978 revealed that most of the isolates have G186V and N268H alternations in AdeS (n = 32), while most common changes in AdeR were V120I and A136V (n = 29) as described in previous studies. Substitution Q262R was detected exclusively in AdeL proteins of IC1 isolates, while no mutations were observed within AdeN regulators. Expression of the adeB, adeG, and adeJ genes in six selected isolates was upregulated in four (1,4- to 3-fold), six (1,6- to 2,6-fold), and three isolates (1,7- to 4-fold), respectively. This study confirmed that overexpression of efflux pump encoding genes enab

Acinetobacter baumannii is considered one of the greatest threats to public health on a global scale. This Gram-negative pathogen causes severe infections, mostly of nosocomial origin, with a high mortality rate. In recent years, the rapid increase in the emergence and spread of antibiotic resistance in A. baumannii has significantly limited the effective therapeutic options against infections caused by this bacterium. The last-line antibiotics used in the treatment of multidrug-resistant (MDR) A. baumannii are carbapenems, tigecycline and polymyxins. However, resistance to these antibiotics is steadily increasing, especially to carbapenems, leading to an extensively drug-resistant (XDR) and even pandrug-resistant (PDR) phenotype of A. baumannii. In 2021, the European Centre for Disease Prevention and Control (ECDC) reported that resistance of Acinetobacter spp. to carbapenems reached 50% or more, mostly in Southern and Eastern European countries. Although the Western Balkans is a part of this region, detailed studies on the epidemiology and antibiotic resistance of A. baumannii are mainly limited to Serbia and Croatia. In most cases, carbapenem resistance in A. baumannii is due to the production of carbapenemases, in particular b-lactamases belonging to the class D known as oxacillinases. The studies from the Western Balkan countries revealed that besides the intrinsic blaOXA-51-like gene, the most prevalent acquired oxacillinase gene was the blaOXA- 24-like followed by the blaOXA-23-like, while the blaOXA-58-like and metallo- b-lactamase blaNDM-1 genes were less common. Although significantly lower compared to carbapenem-resistant, the number of A. baumannii isolates resistant to tigecycline and colistin is on a continual rise in the Western Balkans. As worldwide, the main mechanism conferring tigecycline resistance to A. baumannii from the Western Balkans was overexpression of efflux pumps. Also, the majority of reported alternations leading to colistin resistanc

Introduction: Acinetobacter baumannii , renowned for its exceptional multidrug resistance and its role as a prevalent nosocomial pathogen, poses a formidable challenge to conventional antibiotic therapies. The primary objective of this investigation was to evaluate the efficacy of Secapin, an antimicrobial peptide, against multidrug-resistant (MDR) baumannii . Furthermore, the mechanisms underlying Secapin's antibacterial and antibiofilm activities were elucidated.Methods: The antimicrobial and antibiofilm effectiveness of Secapin against MDR A. baumannii was assessed through a series of experiments. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of Secapin were determined using established protocols. Time-kill kinetic analysis was performed to assess the concentration-dependent bactericidal effect of Secapin. Additionally, the capacity of Secapin to impede biofilm formation and eradicate A. b aumannii biofilms was investigated. Hemolytic potential was evaluated using human red blood cells, while mammalian cell viability was examined at varying Secapin concentrations.Results: Secapin exhibited robust bactericidal activity at minimal concentrations, with an MIC of 5 µg/mL and an MBC of 10 µg/mL against MDR A. baumannii . The time-kill kinetic analysis confirmed the concentration-dependent efficacy of Secapin in diminishing bacterial viability. Moreover, Secapin demonstrated the ability to prevent biofilm formation and eliminate established A. baumannii biofilms. Notably, Secapin exhibited no hemolytic activity and preserved mammalian cell viability up to a concentration of 100 µg/mL.Conclusion: These findings underscore the substantial potential of Secapin as a potent agent against multidrug-resistant A. baumannii , showcasing its efficacy in both antibacterial and antibiofilm capacities. The favorable attributes of Secapin, characterized by its minimal hemolytic effects and high mammalian cell viability, position it as a prom, Hintergrund: Acinetobacter baumannii , bekannt für seine außergewöhnliche Multiresistenz und seine Rolle als häufiger nosokomialer Erreger, stellt eine Herausforderung für herkömmliche Antibiotikabehandlungen dar. Das Hauptziel dieser Studie war es, die Wirksamkeit von Secapin, einem antimikrobiellen Peptid, gegen multiresistente A. baumannii zu bewerten. Darüber hinaus wurden die Mechanismen, durch die Secapin seine antibakterielle und antibiofilmbildende Aktivitäten entfaltet, aufgeklärt.Methoden: Die antimikrobielle und antibiofilmbildende Wirksamkeit von Secapin gegen MDR A. baumannii wurde in einer Reihe von Experimenten untersucht. Die minimale Hemmkonzentration (MIC) und die minimale bakterizide Konzentration (MBC) von Secapin wurden unter Verwendung etablierter Protokolle bestimmt. Es wurde eine zeitabhängige Abtötungskinetik ermittelt, um die konzentrationsabhängige bakterizide Wirkung von Secapin zu bewerten. Darüber hinaus wurde die Fähigkeit von Secapin, die Bildung von Biofilmen zu hemmen und etablierte A. baumannii -Biofilme zu beseitigen, untersucht. Das hämolytische Potenzial wurde unter Verwendung von menschlichen roten Blutkörperchen bewertet, während die Lebensfähigkeit von Säugetierzellen bei verschiedenen Secapin-Konzentrationen untersucht wurde.Ergebnisse: Secapin zeigte eine starke bakterizide Aktivität bei geringen Konzentrationen mit einer MIC von 5 µg/mL und einer MBC von 10 µg/mL gegen MDR A. baumannii . Die zeitabhängige Abtötungskinetik bestätigte die konzentrationsabhängige Wirksamkeit von Secapin. Darüber hinaus zeigte Secapin die Fähigkeit, die Bildung von Biofilmen zu verhindern und etablierte A. baumannii -Biofilme zu eliminieren. Bemerkenswert ist, dass Secapin keine hämolytische Aktivität aufwies und die Lebensfähigkeit von Säugetierzellen bis zu einer Konzentration von 100 µg/mL aufrechterhielt.Fazit: Die Ergebnisse unterstreichen das erhebliche Potenzial von Secapin als wirksames Mittel gegen multiresistente A. baumannii sowohl

Acinetobacter baumannii is a Gram-negative opportunistic pathogen that has a high incidence of infection among individuals with compromised immune systems. Currently, 80% of all hospital-acquired A. baumannii infections are multidrug-resistant to at least three different families of antibiotics, including last-line treatments. Therefore, there is an urgent need for effective therapeutic strategies which requires a thorough understanding of bacterial mechanisms of resistance. Infections caused by A. baumannii are difficult to eradicate, not only due to its extensive antibiotic resistance, but also due to its ability to adapt and persist against harsh environmental and host stressors; a prominent one being oxidative stress via the generation of reactive oxygen species (e.g., H2O2). A. baumannii is known to employ protective enzymes such as catalases to degrade hydrogen peroxide to water and oxygen. Mutants with single- and double-deletions of the catalase genes katG and katE, and their respective complements, were subjected to phenotypic assays and omics analysis to help us elucidate the overall contribution of this oxidative stress response in A. baumannii. The catalase mutants exhibited reduced fitness in rich medium, which was exacerbated when supplemented with H2O2. They also displayed differential antibiotic susceptibilities that were presumed to be mediated by the resistance-nodulation-division (RND) efflux pumps. Further assessment of overall efflux activity and expression profile of the RND efflux pump-encoding genes inferred alternative antibiotic resistance mechanism(s), most likely secondary to oxidative stress. Moreover, as H2O2 is generated by the innate immune cells as a pathogen containment and clearing strategy, we were prompted to examine bacterial virulence with a macrophage survivability assay. While the absence of catalases KatG and KatE sensitized A. baumannii to oxidative stress, their involvement in the virulence of this bacterium proved to be c

The Fabaceae genus Trifolium comprises around 250 species widely distributed worldwide, with the temperate Northern Hemisphere exhibiting the highest variety. The plants in this genus are widely used as livestock fodder crops and are particularly significant economically.This study's objective included isolating bacteria from the root nodules of the Trifolium repens plant and diagnosing it at the molecular and microbiological levels. T. repens root nodules were used as the source of an endophytic bacteria isolated on Yeast Extract Mannitol (YEM) media that had solidified and diagnosed at the molecular level by DNA Sequencing technique for analysis of the sequence of the nitrogenous bases of 16S rRNA gene with the global database. The isolated bacteria were characteristic of greyish-white color after 48 hours of growth and appeared as a circular shape, slightly convex and gram-negative. The bacteria were resistant to the antibiotics 20µg/ml Aztreonam.The DNA sequencing technique for analysis of the sequence of the nitrogenous bases of 16S rRNA gene with the global database of the National Center for Biotechnology Information (NCBI) showed that the isolated bacteria was at least 96.22% similar to the species Acinetobacter baumannii As a result, it was recorded for the first time as Acinetobacter sp. AZS1 strain in NCBI.

[Abstract]: Background: As increasing antibiotic resistance in Acinetobacter baumannii poses a global healthcare challenge, understanding its evolution is crucial for effective control strategies. Aim: We 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. Methods: We 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. Results: Cefiderocol 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 blaOXA-23, blaOXA-58 and blaOXA-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 blaOXA-51-like) in 10 isolates. Conclusions: The 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.

Integrons are one genetic factor that can contribute to the high prevalence of antibiotic resistance among Acinetobacter baumannii isolates and their spread. This research aimed to study the prevalence of class 1,2 and 3 integron in A. baumannii isolates and their relatedness to virulence factors of antibiotics resistance. Seventy clinical isolates of A.baumannii were isolated from several sources such as blood, urinary tract infection (UTI), sputum, urine, and cerebrospinal fluid (CSF). First, the isolates were identified and characterized according to certain morphology, cultural and biochemical tests. Second genotypic ally Identification of the isolates was confirmed by Polymerase chain reaction (PCR), which was performed by housekeeping gene 16sRNA and by (blaOxa 51gene) for A. baumannii species. The antimicrobial susceptibility technique was evaluated through disk diffusion methods. These isolates resistant to various antibiotics were analyzed for integron class I, II and III content and sequences of the amplification products by PCR. The findings showed that the predominant A. baumannii isolates were multidrug resistant and they were most resistant to 15 antibiotics. The higher resistance of A. baumannii to Gatifloxacin and lower resistance to polymyxin. Sixty clinical Multidrug resistance (MDR) isolates of A. baumannii had class I integron and five class III integron, but class II integron was not detected in the isolates. This revealed that the dissemination of MDR among A. baumannii may be associated with the presence of integrons class I and class III. These data indicate that integrons are gene cassettes containing antibiotic-resistance genes that play a major role in the virulence characteristics of MDR and Extensively-drug resistance (XDR) in Acinetobacter baumannii.

Acinetobacter baumannii is highly invasive, resistant to multiple drugs bacteria that are primary source of nosocomial illness in the modern hospital systems. It has been linked to a significant death rate or has been identified as a causative of meningitis, pneumonia; a condition called urine tract illnesses, or wound diseases. Many virulence variables, such as as porins, capsules, including cell wall a substance called lip digestive enzymes, biofilm formation, movement, or iron-acquisition structures, amongst other people, contribute to severity in A. baumannii illnesses. These virulence factors aid in the organism's ability to withstand harsh ecological circumstances also permit the growth of serious diseases. For tandem to the rise for A. baumannii diseases, difficult varied resistant pathways for this pathogen are effectively known, leading to the low efficacy of main antibiotics groups. A. baumannii has a distinct capacity to sustain a resistant to multiple drugs phenotype via a diverse range of antibiotic-hydrolyzing digestive enzymes, modifications to the efflux pumps, impermeability, or alterations in pharmaceutical targets, making therapy even more intricate. Understanding of A. baumannii's transmissible diseases revolves on a comprehension of the processes underlying illness, pathogenicity, or resistant development. This review's objectives are to emphasize A. baumannii illnesses major disease-causing variables while also touching on the processes behind resistant to different antibiotics groups.

Introduction: Bacteria are unicellular organisms that inhabit ecological niches, often hospital places. Objective: Describe the ecological niches of bacteria in physical spaces of a hospital in Machala through direct observation and documentary analysis for the prevention of cases with bacterial resistance in areas with the highest reported cases. Methodology: A descriptive, quantitative cross-sectional research was carried out. The sample was 25 patients with bacteria resistant to carbapenems, related to the IASS of the year 2022. Results: P. Aeruginosa (40%) was the most found bacteria, Adult ICU (68%) was the area with the most reported cases. P. Aeruginosa (28%) K. Pneumoniae (16%) A. Baumannii (8%) was found in the ventilation devices. Conclusion: Nursing staff are responsible for preventing and caring for the spread of resistant bacteria through safe practices, and even more so in the ICU where their environment has a high viral load., Introducción: Las bacterias son organismos unicelulares que habitan en nichos ecológico frecuentemente lugares hospitalarios. Objetivo: Describir los nichos ecológicos de bacterias en espacios físicos de un hospital de Machala mediante la observación directa y análisis documental para la prevención de casos con resistencia bacteriana en áreas con mayores casos reportados. Metodología: Se realizó una investigación descriptiva, cuantitativa de corte transversal. La muestra fueron 25 pacientes con bacterias resistentes a carbapenémicos, relacionadas con las IASS del año 2022. Resultados: Acinetobacter Baumannii se encuentra en dispositivos de ventilación, Klebsiella Pneumoniae se presenta en dispositivos de ventilación y Conjuntivitis, y las Pseudomonas Aeruginosa se presenta en dispositivos de ventilación, dispositivos del tracto urinario y conjuntivitis. Conclusión: El personal de enfermería se encarga de la prevención y el cuidado del contagio de las bacterias resistentes por medio de prácticas seguras, y más en UCI donde su ambiente tiene una elevada carga viral.

Infections caused by carbapenem-resistant Acinetobacter baumannii are a global threat causing a high number of fatal infections. This microorganism can also easily acquire antibiotic resistance determinants, making the treatment of infections a big challenge, and has the ability to persist in the hospital environment under a wide range of conditions. The objective of this work was to study the molecular epidemiology and genetic characteristics of two blaOXA24/40 Acinetobacter baumannii outbreaks (2009 and 2020-21) at a tertiary hospital in Northern Spain. Thirty-six isolates were investigated and genotypically screened by Whole Genome Sequencing to analyse the resistome and virulome. Isolates were resistant to carbapenems, aminoglycosides and fluoroquinolones. Multi-Locus Sequence Typing analysis identified that Outbreak 1 was mainly produced by isolates belonging to ST3Pas/ST106Oxf (IC3) containing blaOXA24/40, blaOXA71 and blaADC119. Outbreak 2 isolates were exclusively ST2Pas/ST801Oxf (IC2) blaOXA24/40, blaOXA66 and blaADC30, the same genotype seen in two isolates from 2009. Virulome analysis showed that IC2 isolates contained genes for capsular polysaccharide KL32 and lipooligosacharide OCL5. A 8.9 Kb plasmid encoding the blaOXA24/40 gene was common in all isolates. The persistance over time of a virulent IC2 clone highlights the need of active surveillance to control its spread.

Acinetobacter baumannii has been described as a cause of serious community-acquired infections in tropical countries. Currently, its implications when simultaneously identified with other pathogens are not yet adequately understood. A descriptive study was conducted on hospitalized patients with a diagnosis of moderate/severe SARS-CoV-2-induced pneumonia confirmed via real-time RT-PCR. Patients aged > 18 years who were admitted to a specialized COVID-19 treatment center in Peru were selected for enrollment. A. baumannii was detected via the PCR amplification of the blaOXA-51 gene obtained from nasopharyngeal swabs within 48 h of hospitalization. A total of 295 patients with COVID-19 who met the study inclusion criteria were enrolled. A. baumannii was simultaneously identified in 40/295 (13.5%) of COVID-19-hospitalized patients. Demographic data and comorbidities were comparable in both Acinetobacter-positive and -negative subgroups. However, patients identified as being infected with Acinetobacter were more likely to have received outpatient antibiotics prior to hospitalization, had a higher requirement for high-flow nasal cannula and a higher subjective incidence of fatigue, and were more likely to develop Acinetobacter-induced pneumonia during hospitalization. Conclusions: The group in which SARS-CoV-2 and A. baumannii were simultaneously identified had a higher proportion of fatigue, a higher frequency of requiring a high-flow cannula, and a higher proportion of superinfection with the same microorganism during hospitalization., Postprint (published version)

Colistin heteroresistance (HR) refers to a bacterial population comprised of several subpopulations with different levels of resistance to colistin. In this study, we discuss the classic form of HR, in which a resistant subpopulation exists within a predominantly susceptible population. We investigated the prevalence of colistin HR and its evolution into full resistance among 173 clinical carbapenem-resistant Acinetobacter baumannii isolates and examined the effect of HR on clinical outcomes. To determine HR, we performed population analysis profiling. Our results showed a high prevalence of HR (67.1%). To examine evolution of HR strains into full resistance, the HR strains were grown in colistin-containing broth, transferred onto colistin-containing plates, and colonies on these plates were transferred into colistin-free broth. Many of the HR strains (80.2%) evolved into full resistance, 17.2% reverted to HR, and 2.6% were borderline. We used logistic regression to compare 14-day clinical failure and 14-day mortality between patients infected by HR versus susceptible non-HR carbapenem-resistant A. baumannii. In the subgroup of patients with bacteremia, HR was significantly associated with 14-day mortality.IMPORTANCE To our knowledge, this is the first large-scale study to report on HR in Gram-negative bacteria. We described the prevalence of colistin HR in a large sample of carbapenem-resistant A. baumannii isolates, the evolution of many colistin HR isolates to a resistant phenotype following colistin exposure and withdrawal, and the clinical consequences of colistin HR. We found a high prevalence of HR among clinical carbapenem-resistant A. baumannii isolates; most evolved into a resistant phenotype following colistin exposure and withdrawal. In patients treated with colistin, evolution of HR A. baumannii into full resistance could lead to higher rates of treatment failure and contribute to the reservoir of colistin-resistant pathogens in health care settings. To

Although the combination of polymyxin and tigecycline is widely used in treating carbapenem-resistant bacterial infections, the benefit of this combination is still uncertain. To assess whether adding polymyxin B to the high-dose tigecycline regimen would result in better clinical outcomes than the high-dose tigecycline therapy in patients with pneumonia caused by carbapenem-resistant Klebsiella pneumoniae and Acinetobacter baumannii, we conducted a propensity score-matched cohort study in a single center between July 2019 and December 2021. Of the 162 eligible patients, 102 were included in the 1:1 matched cohort. The overall 14-day mortality in the matched cohort was 24.5%. Compared with high-dose tigecycline, the combination therapy was not associated with better clinical outcomes, and showed similar 14-day mortality (OR, 0.72, 95% CI 0.27–1.83, p = 0.486), clinical cure (OR, 1.09, 95% CI 0.48–2.54, p = 0.823), microbiological cure (OR, 0.96, 95% CI 0.39–2.53, p = 0.928) and rate of nephrotoxicity (OR 0.85, 95% CI 0.36–1.99, p = 0.712). Subgroup analyses also did not demonstrate any statistical differences. Based on these results, it is reasonable to recommend against adding polymyxin B to the high-dose tigecycline regimen in treating pneumonia caused by carbapenem-resistant K. pneumoniae and A. baumannii.

Acinetobacter baumannii is a major multi-drug resistant nosocomial pathogen and the cause of a significant number of hospital-acquired infections worldwide for which new treatment options are urgently needed. Due to the multi-drug resistance and prevalence of A. baumannii it is considered a critical top priority pathogen for research and development of new therapies and treatments by the World Health Organisation (WHO) and Centres for Disease Control and Prevention (CDC). A. baumannii encodes several major outer membrane proteins, called adhesins, that have all previously been determined to be involved in host adherence, and more broadly in pathobiology. However, the specific host receptors that these outer-membrane proteins interact with remains undefined. Our lab has demonstrated, for the first time, that a major A. baumannii surface adhesin, Ata, interacts with host glycans with high affinity. Ata bound to terminal and core galactose and Nacetylglucosamine structures with high affinity. The interaction of Ata with the host extracellular matrix (ECM) protein fibronectin, which is heavily glycosylated, was absolutely dependent of the presence of these glycan structures, as no interaction between Ata and deglycosylated fibronectin occurred. This Masters research project, demonstrates that the major outer-membrane protein from A. baumannii, OmpA, interacts with host glycans. Using a parallel approach of heterologousover-expression of OmpA at the E.coli cell surface, characterisation of purified protein, and study of knock-out mutants in A. baumannii, demonstrated that this major A. baumannii virulence factor interacts directly with host glycan moieties such as; Lewis antigens, Blood group H antigen, fucosyllatose structures, O-glycans like Tn and sTn. This knowledge will enable further investigation of precisely how A. baumannii interacts with the human host and pave the way for new ways to treat infections caused by a major human pathogen for which traditional antib, Thesis (Masters), Master of Medical Research (MMedRes), School of Pharmacy & Med Sci, Griffith Health, Full Text

Facultative intracellular bacteria of the Brucella genus cause brucellosis, a zoonotic infectionwith a significant socioeconomic impact in southern countries. The recommended liveattenuated vaccines (LAVs) against brucellosis, Rev.1 and S19, provide satisfactory protectionfor livestock but can induce abortions and are virulent for humans. This situation causes seriouseconomic losses and human infections. These first-generation LAVs were generated byempirical methods such as random attenuation by successive passages. The transposonsequencing (Tn-seq) approach offers a new avenue for the rational development of safer LAVs.Indeed, the Tn-seq approach makes it possible to predict the genes required by the bacteria togrow in different conditions such as culture medium, cell infection (in vitro) and mice infection(in vivo). These genes can then be deleted to weaken the strain and try to select new LAVcandidates. Our results demonstrate that Brucella melitensis faces different selection pressuresdepending on the infected organ. Based on our Tn-seq data, we selected genes whose deletiongenerates strains capable of multiplying temporarily in the lungs and the spleen and inducingprotective immunity but without establishing themselves permanently in the spleen, the mainreservoir organ. We tested the persistence and the induced immune protective memory of a plsCgene deletion mutant, involved in the biosynthesis of membrane phospholipids. We observedthat this mutant induces similar protection but persists less in the spleen than the referenceRev.1 vaccine, which suggests that it could be safer.Acinetobacter baumannii is a bacterium responsible for serious nosocomial infections,including pneumonia, mainly affecting immunocompromised individuals. The outbreak of drugmulti-resistant A. baumannii strains to antibiotics makes the development of a vaccine againstthis pathogen essential. In an intranasal infection model in mice, vaccination with theinactivated LAC-4 or AB5075 strain in, Doctorat en Sciences, info:eu-repo/semantics/nonPublished

Acinetobacter baumannii is considered one of the important pathogenic bacteria and responsible for several nosocomial and community infections in humans, such as the lungs (pneumonia), the bloodstream of ICU patients, burns, surgical wounds and meningitis. During the period from September to the end of December 2022, a total of 210 blood specimens were collected inDiyala governorate Baqubah Teaching Hospital, Iraq.To investigate the prevalence of bacterial isolates among ICU patients by identifying bacteria depending on suitable media under suitable environmental conditions for growth, morphological characteristics, biochemical tests, and confirmation of identification isolates by molecular detection of blaOXA- 51gene, antibiotic resistance, phenotypic and molecular detection of efflux pumps adeF gene, and activity of ciprofloxacin andresveratrol on gene expression. The percentage positive growth of A. baumannii isolates from blood specimens among ICU patients was 12 %, and the highest resistance of 25 isolates against fourteen types of antibiotics was equal to cefotaxime (100 % ), ticarcillin-clavulanate, and ceftriaxone ( 96 %), and ( 92 % )for each of Cefepime and Tobramycin, the lowest percentage was for doxycycline (64 % ).MIC value for ciprofloxacin and doxycycline between (8- 512 mg/ml) and ( 4 - 128 mg/ml) respectively. Molecular studies indicate the presence of blaOXA- 51gene and adeF in all isolates under study ( 100 % ). The treatment of resistance isolates with ciprofloxacin, resveratrol and their combination resulted in reduction of adeF gene. The resveratrol effect on efflux pumps gene adeF gene expression occurred for the first time in Iraq and even at the level of the Arab world.

[EN] Infections caused by multidrug resistant Gram-negative bacteria are becoming a worldwide problem due to their increasing incidence and associated high mortality. Carbapenem-resistant bacteria such as Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii are the most important in clinical practice. The objective of these guidelines is to update the recommendations for the diagnosis and treatment of infections caused by these multidrug resistant bacteria. Although ‘old’ antibiotics such as aminoglycosides, colistin, or tigecycline are frequently used for therapy of these bacteria, the ‘new’ beta-lactams such as ceftazidime–avibactam, ceftolozane–tazobactam, meropenem–vaborbactam, imipenem–cilastatin–relebactam or cefiderocol are progressively becoming the first-line therapy for most of these microorganisms. The Spanish Society of Infectious Diseases and Clinical Microbiology (Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica) designated a panel of experts in the field to provide evidence-based recommendations in response to common clinical questions. This document is primarily focused on microbiological diagnosis, clinical management, and targeted antimicrobial therapy of these infections, with special attention to defining the role of the new antimicrobials in the treatment of these bacteria., [ES] Las infecciones causadas por bacterias gramnegativas multirresistentes se han convertido en un problema mundial debido a su creciente incidencia y alta mortalidad asociada. Las bacterias resistentes a carbapenémicos como Klebsiella pneumoniae, Pseudomonas aeruginosa y Acinetobacter baumannii son las más importantes en la práctica clínica. El objetivo de este documento de consenso es actualizar las recomendaciones sobre diagnóstico y tratamiento de las infecciones causadas por estas bacterias multirresistentes. Aunque los antibióticos ‘antiguos’ como aminoglucósidos, colistina o tigeciclina se utilizan con frecuencia en el tratamiento de estas bacterias, los ‘nuevos’ betalactámicos como ceftazidima-avibactam, ceftolozano-tazobactam, meropenem-vaborbactam, imipenem-cilastatina-relebactam o cefiderocol se están convirtiendo de forma progresiva en el tratamiento de primera elección para la mayoría de estos microorganismos. La Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica ha designado un grupo de expertos en la materia para elaborar una guía de recomendaciones basadas en la evidencia sobre las cuestiones clínicas más habituales. Este documento está principalmente centrado en el diagnóstico microbiológico, el manejo clínico y el tratamiento dirigido de estas infecciones, con especial referencia a definir el papel de los nuevos antimicrobianos en el tratamiento de estas bacterias.

Introduction: Multidrug-resistant (MDR) Acinetobacter baumannii has been recognized as one of the most serious healthcare challenges worldwide. Although tigecycline represents one of the last resort therapies for MDR A. baumannii, resistance to this antibiotic has been reported and mostly is mediated by AdeABC efflux pump. The aim of our study was to investigate the molecular mechanism responsible for tigecycline resistance of thirty-seven A. baumannii isolates from Balkan medical settings (Serbia, Bosnia and Herzegovina and Montenegro) gathered in 2016 and 2022. Methods: Minimal inhibitory concentration (MIC) values for tigecycline were determined using microdilution method according to EUCAST guidelines. Inhibition of the efflux of tigecycline wastested by the same method using a combination of antibiotic and efflux pump inhibitor (CCCP). Amino acid alternations within AdeS and AdeR proteins were detected by comparing to sequences of referent isolates ATCC19606 and ATCC17978. Expression of the adeB gene ofselected isolates was monitored by RT-qPCR. Results: All tested isolates were resistant to tigecycline and showed significant decrease in tigecycline MIC values in presence of CCCP (≥16-fold reduction) indicating that antibiotic efflux is responsible for tigecycline resistance. The analysis of two-component system AdeRS, regulatory system of RND efflux pump AdeABC, revealed that most of the isolates have G186V and N268H alternations in AdeS (n=32), while most common changes in AdeR were V120I and A136V (n=29). In addition, RT-qPCR showed that selected isolates upregulate expression of the adeB gene (from 1,13- to 3-fold). Conclusion: This study revealed that AdeABC overexpression is the main mechanism of tigecycline resistance in A. baumannii isolated in Balkan hospitals.

Acinetobacter baumannii is responsible for causing difficult-to-treat healthcare-associated infections globally, owing to its resistance to antibiotics. The intensive care unit (ICU) settings mediate spread of multidrug resistance (MDR) strains. This research aimed to evaluate non-susceptible colistin and fosfomycin A. baumannii, harboring extended-spectrum beta-lactamases (ESBLs) and carbapenemases in ICU setting. During the period of 2019-2021, this study obtained 200 A. baumanni isolates out of 1410 burns samples from an ICU setting. The antibiotic sensitivity, ESBLs and carbapenemase production were determined using clinical and laboratory standards institute (CLSI) 2020. The colistin (mcr-1 and mcr-2) and fosfomycin (fosA3) resistance genes was amplified. The highest resistance was to ceftazidime (98%), cefepime (86%), tetracycline (84%), levofloxacin (78%) and piperacillin-tazobactam (76%), while the highest sensitivity was to meropenem (63%) and tigecycline (62%). ESBL production was determined in 94% and carbapenemases were observed in 54% of A. baumannii. Four isolates (2%) were found to carry the mcr-1 gene, and three isolates (1.5%) were found to carry the mcr-2 gene. Moreover, the fosA3 was not detected in the isolates. This study showed that MDR A. baumannii was high in ICU settings. The spread of antibiotics considered the last line of defense against infections is a concern that necessitates surveillance and control measures.

Biofilm production facilitates microbial colonization of wounds and catheters. Acinetobacter baumannii produces high levels of biofilm and causes difficult-to-treat nosocomial infections. Candida albicans is another strong biofilm producer which may facilitate A. baumannii adhesion by providing hyphae-mediated OmpA-binding sites. Here we tested the potential of 2′-hydroxychalcones to inhibit dual-species biofilm production of A. baumannii and Candida spp., and further predicted the mechanism of structure-related difference in activity. The results suggest that 2′-hydroxychalcones exhibit potent activity against Candida spp./A. baumannii dual-species biofilm production. Particularly active was trifluoromethyl-substituted derivative (p-CF3), which decreased C. albicans/A. baumannii biomass produced on vein-indwelling parts of the central venous catheterization set by up to 99%. Further, higher OmpA-binding affinity was also calculated for p-CF3, which together with demonstrated significant ompA-downregulating activity, suggests that superior antibiofilm activity of this chalcone against the tested dual-species community of A. baumannii is mediated through the OmpA.

The Search included 300 different clinical specimens from patients at Al-Diwaniyah General Teaching Hospital were collected for the study From September to December 2022. These specimens comprised blood, urine, burns, and wounds. 40(13.3%) A.baumannii  out of 300 isolates. The focus of the study is to characterize the CarO protein, Int-2 and blaoxa-51 resistance mechanisms in Acinetobacter baumannii isolates recovered from different specimens. The samples were taken from various clinical specimens, which were then dispersed as follows: 40 isolates were tested for antibiotic susceptibility using the (Antibiotic Susceptibility Test-AST) on 15 (37.5%) swabs from burns, 10 (25%) swabs from wounds, 10 (25%) from urine, and 5 (12.5%) from blood samples. All isolates were found to be antibiotic-resistant, with the exception of polymyxin B, which had a 30% sensitivity rate and a 70% resistance rateThe gene Caro was found in 10 (25%) of the 40 isolates genetically analyzed using the PCR method, the gene Int-2 was found in 8 (20%) of the 40 specimens, and the gene blaOXA-51 was found in 19 (47.5%) of the 40 isolates. These results show that the gene Caro is present in proteins that encode the enzyme Carbapenemase. The findings of this investigation confirmed previous findings that bacteria have substantial polymyxin B resistance and are resistant to the majority of antibiotics. For the diagnosis of this bacteria, the blaOXA-51 gene was regarded as a diagnostic marker (A baumannii). In Conclusion Polymerase chain reaction technique was found to be simple and useful tool for detection of outer membrane protiens carO. Class 2-Integron was found to be carried by A. baumannii isolates and antibiotic resistance genes were distributed on this integron.                                       &

An opportunistic bacterium called Acinetobacter baumannii has significantly increased the frequency of infections in recent years. With only a limited number of “traditional” virulence factors, It is infections have spread rapidly through hospitals across the globe. The present study aimed to work out the relationship between the multi-drug resistance (MDR) of A. Baumannii and biofilm formation. A total of 150 samples were collected from various clinical sources from different age groups and gender patients in Ghazi AL Hariri Hospital and Baghdad Teaching laboratories in Medical City in Baghdad, Iraq from December 2021 to March 2022. Microscopical inspection and cultural features on various culture media, including culturing on selective medium CHROMagar, were used to identify bacterial isolates. The characteristics of the isolates were then established by some biochemical tests. Identification was confirmed using the Vitek-2 system with an accuracy of 99%, which revealed that only (50) isolates were given identical morphological characteristics and biochemical tests belonging to Acinetobacter baumannii isolates. 28 (56%) isolates were collected from burns. 10 isolates (20%) and 9 isolates (18% were collected from wound and sputum cultures of A. baumannii , respectively, while only 3 isolates (6%) were from urine culture. The susceptibility test for all the fifty clinical isolates of A. baumannii was performed against 10 different antibiotics. The results showed that A. baumannii isolates were Multidrug-resistant (MDR) (98%), while the other (2%) of the isolates were extensively drug-resistance (XDR) to themajority of antibiotics tested. All 50 isolates in the present study were subjected to the micro-titer plate (MTP) assay method (96 walls). The results indicated that strong biofilm was detected in 40 (80.0%) of the tested isolates. Thirty bacterial isolates were were found to be MDR and had strong biofilm production.

(1) Background: Colistin-only susceptible (COS) Acinetobacter baumannii (AB) ventilator-associated pneumonia (VAP) represents a clinical challenge in the Intensive Care Unit (ICU) due to the negligible lung diffusion of this molecule and the low-grade evidence on efficacy of its nebulization. (2) Methods: We conducted a prospective observational study on 134 ICU patients with COS-AB VAP to describe the 'real life' clinical use of high-dose (5 MIU q8) aerosolized colistin, using a vibrating mesh nebulizer. Lung pharmacokinetics and microbiome features were investigated. (3) Results: Patients were enrolled during the COVID-19 pandemic with the ICU presenting a SAPS II of 42 [32-57]. At VAP diagnosis, the median PaO2/FiO(2) was 120 [100-164], 40.3% were in septic shock, and 24.6% had secondary bacteremia. The twenty-eight day mortality was 50.7% with 60.4% and 40.3% rates of clinical cure and microbiological eradication, respectively. We did not observe any drug-related adverse events. Epithelial lining fluid colistin concentrations were far above the CRAB minimal-inhibitory concentration and the duration of nebulized therapy was an independent predictor of microbiological eradication (12 [9.75-14] vs. 7 [4-13] days, OR (95% CI): 1.069 (1.003-1.138), p = 0.039). (4) Conclusions: High-dose and prolonged colistin nebulization, using a vibrating mesh, was a safe adjunctive therapeutic strategy for COS-AB VAP. Its right place and efficacy in this setting warrant investigation in interventional studies.

Acinetobacter baumannii is recognized as a clinically significant pathogen causing a wide spectrum of nosocomial infections. Colistin was considered a last-resort antibiotic for the treatment of infections caused by multidrug-resistant A. baumannii. Since the reintroduction of colistin, a number of mechanisms of colistin resistance in A. baumannii have been reported, including complete loss of LPS by inactivation of the biosynthetic pathway, modifications of target LPS driven by the addition of phosphoethanolamine (PEtN) moieties to lipid A mediated by the chromosomal pmrCAB operon and eptA gene-encoded enzymes or plasmid-encoded mcr genes and efflux of colistin from the cell. In addition to resistance to colistin, widespread heteroresistance is another feature of A. baumannii that leads to colistin treatment failure. This review aims to present a critical assessment of relevant published (>50 experimental papers) up-to-date knowledge on the molecular mechanisms of colistin resistance in A. baumannii with a detailed review of implicated mutations and the global distribution of colistin-resistant strains.

Engineered lysins are considered as highly promising alternatives for antibiotics. Our previous screening study using VersaTile technology identified 1D10 as a possible lead compound with activity against Acinetobacter baumannii strains under elevated human serum concentrations. In this manuscript, we reveal an unexpected mode of action and exceptional thermoresistance for lysin 1D10. Our findings shed new light on the development of engineered lysins, providing valuable insights for future research in this field.

Acinetobacter baumannii is a nosocomial pathogen that frequently causes healthcare-acquired infections. The global spread of multidrug-resistant (MDR) strains with its ability to survive in the environment for extended periods imposes a pressing public health threat. Two MDR A. baumannii outbreaks occurred in 2012 and 2014 in a companion animal intensive care unit (caICU) in the Netherlands. Whole-genome sequencing (WGS) was performed on dog clinical isolates (n = 6), environmental isolates (n = 5), and human reference strains (n = 3) to investigate if the isolates of the two outbreaks were related. All clinical isolates shared identical resistance phenotypes displaying multidrug resistance. Multi-locus Sequence Typing (MLST) revealed that all clinical isolates belonged to sequence type ST2. The core genome MLST (cgMLST) results confirmed that the isolates of the two outbreaks were not related. Comparative genome analysis showed that the outbreak isolates contained different gene contents, including mobile genetic elements associated with antimicrobial resistance genes (ARGs). The time-measured phylogenetic reconstruction revealed that the outbreak isolates diverged approximately 30 years before 2014. Our study shows the importance of WGS analyses combined with molecular clock investigations to reduce transmission of MDR A. baumannii infections in companion animal clinics.

Antimicrobial-resistance (AMR) has become the greatest concern and highly challenging issue when treating nosocomial infections. The exigency to develop new potent compounds continues to increase worldwide, whereby derivatives of natural products are becoming more attractive. In the present paper, the microbiological assessment of a series of 12 cinnamide hydrazides, four of them completely novel, against clinically relevant pathogens has discovered several derivatives with promising in vitro activities against Acinetobacter baumannii, one of the most dreaded opportunistic pathogens in hospitals. The compounds were synthesized by combining one of three different natural acids (cinnamic, 4-chloro or 4-methoxy) with four monothiocarbohydrazones (MTCHs) - an important class of synthetic organic molecules. Their structure was confirmed by elemental microanalysis, as well as ATR-FTIR, 1H and 13C NMR spectra, with the addition of 2D NMR spectra for novel compounds. The hybrids of cinnamic acids and pyridine derivatives are particularly active compounds with the lowest MIC50 value of 10.4 µM for p-chloro cinnamic acid and acetyl pyridine derivatives. An alignment-independent 3D QSAR model identified pharmacophoric hotspots and suggested several structural modifications that might improve the potency of this class of compounds against A. baumannii. The compounds are strong iron-chelating agents forming complexes with a stability constant between 107 and 109. The synthesized derivatives represent a promising class of antibacterial compounds with activities comparable to the commonly used antibiotics.

Acinetobacter baumannii is an emerging gram-negative pathogen that is listed by the center of disease control as an urgent threat and is part of a select group of pathogens known as the ESKAPE pathogens due to its ability to continuously escape the lethal action of antibiotics. A. baumannii infection is most common in the healthcare setting putting immunocompromised patients at increased risk of infection through disease such as ventilator associated pneumonia. For pathogens such as A. baumannii, the mechanisms of antimicrobial resistance are well understood but the understanding of the determinants of virulence have yet to catch up. A virulence factor of particular interest in the scientific community is the capsular polysaccharide and how it can play a role in pathogenicity. Bacterial capsules, comprised of tightly packed polysaccharide units, have been shown to provide various strains of bacteria protection from environmental pressures such as host immune response and antimicrobial agents. However, capsule loci in A. baumannii are highly variable providing the question if capsular virulence is specific to certain capsule types or universal. This study generated an unmarked knockout mutant of LAC-4 in which the capsule locus has been deleted. The resulting mutant was evaluated with in vitro cell based assays and against an established mouse model of bacterial systemic infection. Capsule deficient mutants of LAC-4 were found to be significantly less virulent than the wildtype LAC-4 strain showing that the capsule gene cluster appears to contribute to LAC-4’s hypervirulence.

Objectives The resistome, virulome, mobilome and phylogenetic relationship of the Acinetobacter baumannii isolate FG121 depicting the multilocus sequence type (ST) 231 isolated from hospital effluent water in South Africa was determined using whole-genome sequence analysis. Method A. baumannii FG121 was isolated on Leed Acinetobacter Medium (LAM) agar and the bacterial isolate was identified using the VITEK®2 platform. Antibiotic susceptibility testing was performed using Kirby–Bauer Disk diffusion method. A whole genome sequencing library was constructed from DNA extracted from the isolate using the Illumina Nextera XT library preparation kit and was sequenced using the Illumina NextSeq500 platform. Generated reads were de novo assembled using SpAdes v.3.9. The assembled contigs were annotated, and multilocus sequence type, antimicrobial resistance, and virulence genes were identified. Results The resistome was consistent with the resistance phenotype of the isolate with resistance determinants for beta-lactams, aminoglycosides, and tetracycline (blaADC-25, blaOXA-23, blaOXA-51, blaNDM-1, aph[3’]-VIa and tet[B]). Global phylogenomic analysis using BacWGSTdb revealed that the isolate belonged to the multilocus sequence type ST-231, similar to previously reported isolates from South Africa, the United States, and related to the invasive KR3831 isolate identified from Oman in 2012, suggesting the isolate might be imported from abroad. Virulome analysis predicted both virulence and biofilm-determinants of A. baumannii, which may help to establish infections in adverse conditions. Conclusion This is the first report on a carbapenemase-encoding A. baumannii ST-231 isolated from hospital effluent water. Our data will offer insight into the global phylogenetic, pathogenicity and distribution of A. baumannii in South Africa.

Scope: These ESCMID guidelines address the targeted antibiotic treatment of third-generation cepha losporin-resistant Enterobacterales (3GCephRE) and carbapenem-resistant Gram-negative bacteria, focusing on the effectiveness of individual antibiotics and on combination versus monotherapy. Methods: An expert panel was convened by ESCMID. A systematic review was performed including randomized controlled trials and observational studies, examining different antibiotic treatment regi mens for the targeted treatment of infections caused by the 3GCephRE, carbapenem-resistant Enter obacterales, carbapenem-resistant Pseudomonas aeruginosa and carbapenem-resistant Acinetobacter baumannii. Treatments were classified as head-to-head comparisons between individual antibiotics and between monotherapy and combination therapy regimens, including defined monotherapy and com bination regimens only. The primary outcome was all-cause mortality, preferably at 30 days and sec ondary outcomes included clinical failure, microbiological failure, development of resistance, relapse/ recurrence, adverse events and length of hospital stay. The last search of all databases was conducted in December 2019, followed by a focused search for relevant studies up until ECCMID 2021. Data were summarized narratively. The certainty of the evidence for each comparison between antibiotics and between monotherapy and combination therapy regimens was classified by the GRADE recommenda tions. The strength of the recommendations for or against treatments was classified as strong or con ditional (weak). Recommendations: The guideline panel reviewed the evidence per pathogen, preferably per site of infection, critically appraising the existing studies. Many of the comparisons were addressed in small observational studies at high risk of bias only. Notably, there was very little evidence on the effects of the new, recently approved, b-lactam/b-lactamase inhibitors on infections caused by carbapenem-resistant Gram

OBJECTIVE: To describe the course of the outbreak and infection control measures to stop the spread of sequence type 15 OXA-23-producing Acinetobacter baumannii in the Burn Center of Uppsala University Hospital, between November 2014 and the end of April 2015. METHODS: Compliance with hand hygiene, dress code, and cleaning routines were reviewed, the ward's environment was systematically investigated to identify potential environmental sources. Sampling routines for A. baumannii, from patients and environment, were established, and the epidemiological relationship was analysed for all carbapenem-resistant A. baumannii isolates using arbitrarily primed polymerase chain reaction (AP-PCR) and pulsed-field gel electrophoresis (PFGE). RESULTS: A total of 54 patients were treated at the burn intensive care unit during the studied, approximately five months period, and an OXA-23-producing A. baumannii was isolated from nine patients (9/54, 17%), whereof two died (2/9, 22.2%). All isolates shared identical PFGE-genotype patterns and belonged to sequence type 15; AP-PCR was eligible for prompt epidemiological investigations. CONCLUSIONS: Higher awareness and increased compliance with hand hygiene and dress code as well as intensified cleaning protocols of the environment and equipment were successfully established and likely to have led to stop the spread of sequence type 15 OXA-23-producing Acinetobacter baumannii.

Objectives: Acinetobacter baumannii is a significant opportunistic pathogen causing nosocomial infections. Infections caused by A. baumannii are often difficult to treat because this bacterium is often multidrug-resistant and shows high environmental adaptability. Here, we report on the analysis of three A. bauman-nii strains isolated from hospital effluents in South Africa.Methods: Strains were isolated on Leeds Acinetobacter agar and were identified using VITEK (R) 2 platform. Antibiotic susceptibility testing was performed using the Kirby-Bauer Disk diffusion method. Whole-genome sequencing was performed. The assembled contigs were annotated. Multilocus sequence type, antimicrobial resistance, and virulence genes were identified.Results: The strains showed two multilocus sequence types, ST231 (FA34) and ST1552 (PL448, FG116). Based on their antibiotic susceptibility profiles, PL448 and FG116 were classified as extensively drug -resistant and FA34 as pandrug-resistant. FA34 harbored mutations in LpxA, LpxC, and PmrB, conferring resistance to colistin, but not mcr genes. All three strains encoded virulence genes for immune evasion (capsule, lipopolysaccharide [LPS]), iron uptake, and biofilm formation. FA34 was related to human strains from South Africa; PL448 and FG116 were related to a strain isolated in the United States from a human wound.Conclusions: The detection of extensively drug-and pandrug-resistant A. baumannii strains in hospital effluents is of particular concern. It indicates that wastewater might play a role in the spread of these bacteria. Our data provide insight into the molecular epidemiology, resistance, pathogenicity, and distri-bution of A. baumannii in South Africa.

Carbapenem resistant Acinetobacter baumannii has emerged as one of the most difficult to treat nosocomial bacterial infections in recent years. It was one of the major causes of secondary infections in Covid-19 patients in developing countries. The polycationic polypeptide antibiotic colistin is used as a last resort drug to treat carbapenem resistant A. baumannii infections. Therefore, resistance to colistin is considered as a serious medical threat. The purpose of this study was to assess the current status of colistin resistance in Pakistan, a country where carbapenem resistant A. bumannii infections are endemic, to understand the impact of colistin resistance on virulence in mice and to assess alternative strategies to treat such infections. Out of 150 isolates collected from five hospitals in Pakistan during 2019–20, 84% were carbapenem resistant and 7.3% were additionally resistant to colistin. There were two isolates resistant to all tested antibiotics and 83% of colistin resistant isolates were susceptible to only tetracycline family drugs doxycycline and minocycline. Doxycycline exhibited a synergetic bactericidal effect with colistin even in colistin resistant isolates. Exposure of A. baumannii 17978 to sub inhibitory concentrations of colistin identified novel point mutations associated with colistin resistance. Colistin tolerance acquired independent of mutations in lpxA, lpxB, lpxC, lpxD, and pmrAB supressed the proinflammatory immune response in epithelial cells and the virulence in a mouse infection model. Moreover, the oral administration of water extract of Saussuria lappa, although not showing antimicrobial activity against A. baumannii in vitro, lowered the number of colonizing bacteria in liver, spleen and lung of the mouse model and also lowered the levels of neutrophils and interleukin 8 in mice. Our findings suggest that the S. lappa extract exhibits an immunomodulatory effect with potential to reduce and cure systemic infections by both opaqu

Acinetobacter baumannii is a leading cause of antibiotic-resistant nosocomial infections with high mortality rates, yet there is currently no clinically approved vaccine formulation. During the onset of A. baumannii infection, neutrophils are the primary responders and play a major role in resisting the pathogen. Here, we design a biomimetic nanotoxoid for antivirulence vaccination by using neutrophil membrane-coated nanoparticles to safely capture secreted A. baumannii factors. Vaccination with the nanotoxoid formulation rapidly mobilizes innate immune cells and promotes pathogen-specific adaptive immunity. In murine models of pneumonia, septicemia, and superficial wound infection, immunization with the nanovaccine offers significant protection, improving survival and reducing signs of acute inflammation. Lower bacterial burdens are observed in vaccinated animals regardless of the infection route. Altogether, neutrophil nanotoxoids represent an effective platform for eliciting multivalent immunity to protect against multidrug-resistant A. baumannii in a wide range of disease conditions.

The objective of this research was to determine the in vitro inhibitory effect of the aqueous extract of Allium sativum L. “garlic” at concentrations of 100, 200. 300, 400, 500 mg / ml against Pseudomonas aeruginosa and Acinetobacter baumannii isolated from the Regional Hospital of Lambayeque, minimum inhibitory concentration and minimum bactericidal concentration. Using as methods: diffusion of modified Kirby Bauer, tube macrodilution technique and minimum bactericidal concentration according to Abadie et al. The aqueous extract of Allium sativum L. “garlic” showed significant in vitro inhibitory effect on Acinetobacter baumannii multidrug with an average halo of inhibition of 22.02 mm and mild in Pseudomonas aeruginosa multugistant with a mean halo of inhibition of 7.28 mm. The minimum inhibitory concentration (MIC) of the aqueous extract of Allium sativum L. “garlic” on multi-resistant strains of Acinetobacter baumannii was determined to be 1.56 mg / ml, while in Pseudomonas aeruginosa 12.25 mg / ml (strains 2, 3) and 25 mg / ml (strain 1). It was determined that the aqueous extract of Allium sativum L. had lower minimum bactericidal concentration (CMB) on Acinetobacter baumannii multi-resistant strain 3 equals to 1.56 mg / ml and higher in Pseudomonas aeruginosa multi-resistant strain 3 equal to 50 mg / ml., La presente investigación tuvo como objetivos determinar el efecto inhibitorio in vitro del extracto acuoso de Allium sativum L. “ajo” a concentraciones de 100, 200. 300, 400, 500 mg/ml frente a Pseudomonas aeruginosa y Acinetobacter baumannii multirresistentes aisladas del Hospital Regional de Lambayeque, concentración mínima inhibitoria y concentración mínima bactericida. Utilizando como métodos: la difusión de Kirby Bauer modificada, técnica de macrodilución en tubo y concentración mínima bactericida según Abadie et al. El extracto acuoso de Allium sativum L. “ajo” presentó efecto inhibitorio in vitro significativo sobre Acinetobacter baumannii multirresistente con un promedio de halo de inhibición de 22.02 mm y leve en Pseudomonas aeruginosa multirresistente con un promedio de halo de inhibicion de 7.28 mm. Se determinó que la concentración mínima inhibitoria (CMI) del extracto acuoso de Allium sativum L. “ajo” sobre cepas multirresitentes de Acinetobacter baumannii es de 1.56 mg/ml, mientras que en Pseudomonas aeruginosa es de 12.25 mg/ml (cepas 2, 3) y 25 mg/ml (cepa 1). Se determinó que el extracto acuoso de Allium sativum L. tuvo menor concentración mínima bactericida (CMB) sobre Acinetobacter baumannii multirresistente (cepa 3) igual a 1.56 mg/ml y mayor en Pseudomonas aeruginosa multirresistente (cepa 3) igual a 50 mg/ml.

Acinetobacter baumannii is a pathogenic bacterium responsible for various hospital-acquired infections in immunocompromised patients. It is highly resilient and can survive in harsh environmental conditions. A. baumannii is infamous for its ability to develop resistance against various antimicrobials. Two Component Systems (TCS) are signal transduction systems which enable bacteria to sense and adapt to changes in environmental conditions. Various studies have indicated their involvement in regulation of antibiotic susceptibility and virulence mechanisms in bacteria. In this project, we investigated the functional characteristics of novel and putative TCSs in A. baumannii and their role in regulation of antibiotic susceptibility and virulence phenotypes. The first part of this study involved the functional characterization of AvnR, a conserved response regulator, in the clinical isolate - A. baumannii AB030. AvnR has previously been linked with regulation of various virulence-associated phenotypes including biofilm formation, motility, and nitrogen metabolism. The avnR gene in A. baumannii AB030 has been found to be naturally disrupted by an insertion sequence, rendering it non-functional. We investigated the impact of this disruption on biofilm formation, motility, and nitrogen metabolism in AB030. Complementation of avnR in AB030 had no effect on biofilm formation and motility phenotypes; however, changes in its nitrogen metabolism profile was observed. Complement strain, AB030:mini-Tn7:avnR, exhibited enhanced growth in L-serine and L-arginine compared to the wild type, whereas a decrease in growth was observed in Alanine-Histidine, Alanine-Leucine, and L-Valine. In the second part of this study, the functional characteristics of a putative TCS, A1S_1977-78, was investigated in A. baumannii ATCC 17978. Previous studies have indicated a potential link between this TCS and regulation of AdeN, a Tet-R type regulator protein. AdeN is associated with expression of Ade

Acinetobacter baumannii je nozokomijalni, multirezistentni patogen, koga karakteriše sposobnost perzistencije na neživim površinama i mogućnost veoma brzog sticanja rezistencije na antibiotike. Danas su u svetu rasprostranjeni izrazito rezistentni sojevi protiv kojih u mnogim zdravstvenim ustanovama ne postoji efikasna terapija, a pronalazak alternativnih terapijskih pristupa je od izuzetne važnosti. Halkoni su jedinjenja sa potvrđenim antimikrobnim svojstvima i pokazanim različitim antivirulentnim aktivnostima. Ciljevi istraživanja ovog rada bili su određivanje profila rezistencije, ispitivanje mogućnosti kontaminacije antiseptika i ispitivanje produkcije biofilma identifikovanih kliničkih izolata A. baumannii, kao i sinteza derivata hidroksihalkona i ispitivanje njihovih antimikrobnih i antivirulentnih aktivnosti protiv ovih izolata. Osetljivost izolata na antibiotike ispitana je kombinacijom difuzionih, dilucionih i automatizovanih metoda, a identifikovani kolistin-rezistentni izolati dodatno su podvrgnuti sekvenciranju celog genoma (WGS) i genetički su okarakterisani. Takođe, mehanizmi rezistencije na kolistin ispitani su primenom komparativne analize genoma i Real-Time kvantitativne lančane reakcije polimeraze (RT-qPCR). Time-kill test je primenjen za ispitivanje perzistencije u antisepticima, a nivo produkcije biofilma ispitan je pod različitim uslovima kultivacije in vitro statičkom metodom uz bojenje safraninom. Derivati hidroksihalkona sintetisani su pomoću Claisen- Schmidt kondenzacije i njihove antimikrobne aktivnosti, samih i u kombinaciji sa antibioticima, ispitane su bujon-mikrodilucionom, Time-kill i Checkerboard analizom. Antivirulentne aktivnosti odabranih halkona procenjene su posredstvom uticaja na produkciju biofilma (monomikrobnog i polimikrobnog), vijabilnost biofilmskih ćelija, ekspresiju motiliteta, gensku ekspresiju faktora virulencije (OmpA, Bap i AbaI), adheziju A. baumannii na komponente ekstracelularnog matriksa (ECM), kao što su fibrone, Acinetobacter baumannii is a nosocomial, multiresistant pathogen, able to persist on abiotic surfaces and to rapidly acquire antibiotic resistance. Nowadays, highly resistant strains are widely disseminated throughout the world, and the discovery of alternative therapeutic strategies is of utter importance. Chalcones are compounds whose antimicrobial properties are well-known and for which different antivirulence activities have been demonstrated. The aims of this research were to determine resistance profiles, to evaluate the possibility of antiseptic contamination, and to analyze the biofilm production of identified A. baumannii clinical isolates, as well as to synthesize hydroxychalcone derivatives and to investigate their antimicrobial and antivirulence activities against these isolates. Antibiotic susceptibility of the isolates was tested by combination of diffusion, dilution, and automated methods, and additionally, identified colistin-resistant isolates were subjected to whole genome sequencing (WGS) and were genetically characterized. Also, colistin resistance mechanisms were explored by using comparative genome analysis and Real-Time quantitative polymerase chain reaction (RT-qPCR). Time-kill test was used for the measurement of bacterial survival in antiseptics, whereas the level of biofilm production under different cultivation conditions was quantified by in vitro static method using safranin stain. Hydroxychalcone derivatives were synthesized by Claisen-Schmidt condensation, and their antimicrobial activities, alone and in combination with antibiotics, were investigated using broth-microdilution, Time-kill, and Checkerboard analyses. Antivirulence activities of selected chalcones were evaluated based on the impact on biofilm production (monomicrobial and polymicrobial), biofilm cell viability, motility, virulence factors (OmpA, Bap, and AbaI) gene expression, fibronectin- and collagen- mediated adhesion, and quorum-sensing (QS) activity. A. baumannii cl

[Abstract] To optimize phage therapy, we need to understand how bacteria evolve against phage attacks. One of the main problems of phage therapy is the appearance of bacterial resistance variants. The use of genomics to track antimicrobial resistance is increasingly developed and used in clinical laboratories. For that reason, it is important to consider, in an emerging future with phage therapy, to detect and avoid phage-resistant strains that can be overcome by the analysis of metadata provided by whole-genome sequencing. Here, we identified genes associated with phage resistance in 18 Acinetobacter baumannii clinical strains belonging to the ST-2 clonal complex during a decade (Ab2000 vs. 2010): 9 from 2000 to 9 from 2010. The presence of genes putatively associated with phage resistance was detected. Genes detected were associated with an abortive infection system, restriction–modification system, genes predicted to be associated with defense systems but with unknown function, and CRISPR-Cas system. Between 118 and 171 genes were found in the 18 clinical strains. On average, 26% of these genes were detected inside genomic islands in the 2000 strains and 32% in the 2010 strains. Furthermore, 38 potential CRISPR arrays in 17 of 18 of the strains were found, as well as 705 proteins associated with CRISPR-Cas systems. A moderately higher presence of these genes in the strains of 2010 in comparison with those of 2000 was found, especially those related to the restriction–modification system and CRISPR-Cas system. The presence of these genes in genomic islands at a higher rate in the strains of 2010 compared with those of 2000 was also detected. Whole-genome sequencing and bioinformatics could be powerful tools to avoid drawbacks when a personalized therapy is applied. In this study, it allows us to take care of the phage resistance in A. baumannii clinical strains to prevent a failure in possible phage therapy.

Background: Acinetobacter baumannii are of major human health importance because they cause life-threatening nosocomial infections and often are highly resistant to antimicrobials. Specific multidrug-resistant A. baumannii lineages are implicated in hospital outbreaks globally. We retrospectively investigated a suspected outbreak of carbapenem-resistant A. baumannii (CRAB) colonizing patients in an intensive care unit (ICU) of a tertiary hospital in Southwest Nigeria where genomic surveillance of Acinetobacter has hitherto not been conducted. Methods: A prospective observational study was conducted among all patients admitted to the ICU between August 2017 and June 2018. Acinetobacter species were isolated from rectal swabs and verified phenotypically with the Biomerieux Vitek 2 system. Whole genome sequencing (WGS) was performed on the Illumina platform to characterize isolates from a suspected outbreak during the study period. Phylogenetic analysis, multilocus sequence typing, and antimicrobial resistance gene prediction were carried out in silico. Results: Acinetobacter isolates belonging to the A. baumannii complex were recovered from 20 (18.5%) ICU patients. Single nucleotide polymorphism (SNP) analysis and epidemiological information revealed a putative outbreak clone comprising seven CRAB strains belonging to the globally disseminated international clone (IC) 2. These isolates had ≤2 SNP differences, identical antimicrobial resistance and virulence genes, and were all ST1114/1841. Conclusion: We report a carbapenem-resistant IC2 A. baumannii clone causing an outbreak in an ICU in Nigeria. The study findings underscore the need to strengthen the capacity to detect A. baumannii in human clinical samples in Nigeria and assess which interventions can effectively mitigate CRAB transmission in Nigerian hospital settings.

Acinetobacter baumannii is an emerging nosocomial pathogen resistant to a wide spectrum of antibiotics, with great potential to form a biofilm, which further aggravates treatment of infections caused by it. Therefore, searching for new potent agents that are efficient against A. baumannii seems to be a necessity. One of them, which has already been proven to possess a wide spectrum of biological activities, including antimicrobial effect, is cinnamon essential oil. Still, further increase of antibacterial efficacy and improvement of bioavailability of cinnamon oil is possible by emulsification process. The aim of this study was comparative analysis of cinnamon essential oil and its emulsion against biofilm forming A. baumannii clinical isolates. Furthermore, the investigation of toxicological aspects of possible applications of essential oil and emulsion was done as well. Gas chromatography–mass spectrometry of essential oil indicated trans-cinnamaldehyde as the most abundant component. The cinnamon emulsion was synthesized from cinnamon essential oil by combining modified low- and high- energy methods. Synthesized emulsion was characterized with Fourier-transform infrared spectroscopy and photon correlation spectroscopy. Both substances exhibited significant antibacterial (minimal inhibitory concentrations in the range 0.125–0.5 mg/ml) and antibiofilm effects (inhibitions of formation and reduction of pre-formed biofilm were 47–81 and 30–62%, respectively). Compared to essential oil, the efficacy of emulsion was even stronger considering the small share of pure oil (20%) in the emulsion. The result of biofilm eradication assay was confirmed by scanning electron microscopy. Even though the cytotoxicity was high especially for the emulsion, genotoxicity was not determined. In conclusion, strong antibacterial/antibiofilm effect against A. baumannii of the cinnamon essential oil and the fact that emulsification even potentiated the activity, seems to be of great signif

Objective: Acinetobacter baumannii is a pathogenic species which presents a danger to healthcare facilities due to the rapid spread of antibiotic resistance. Plants are currently being explored as a potential source of bioactive compounds that could be used to combat infectious diseases. Cinnamon is used as a food spice, but essential oil has been proven for antimicrobial activity. Due to reduced stability and solubility of essential oil, nanoemulsion (NE) synthesis could provide stronger antimicrobial effects. Investigation and comparison of antimicrobial activity of cinnamon (Cinnamomum zeylanicum L.) bark essential oil (EO) and NE on the A. baumannii ATCC19606 and clinical isolates. Effect of EO and NE on biofilm formation and biofilm eradication. Methods: GC/MS was performed in order to determine chemical composition of commercially purchased EO (P0125285, Frey + Lau, GmbH, Henstedt-Ulzburg, Germany). Droplet/particle size and polydispersity index of NE was determined by photon correlation spectroscopy (PCS). Minimal inhibitory concentration of EO and NE were defined using MIC assay. Effects of EO and NE were also examined on biofilm formation and eradication. Crystal violet staining was used for biofilm biomass quantification. Results: GC/MS analysis determined that the most common compound was trans-Cinnamaldehyde (61.9%). NE droplet/particles had multimodal distribution, shown by PCS. MIC values for EO were in range 0.25mg/mL — 0.5mg/mL, and for NE 0.125mg/mL — 0.25mg/mL. Both tested substances showed good effect on biofilm eradication, and destroyed biofilm biomass up to 64%, whilst the inhibition of biofilm formation was up to 70%. Conclusion: Taking all the results into account, it is a good start for further investigations of both EO and NE as a potential antimicrobial agent. Deeper knowledge about the mechanisms of actions of both of these tested substances could help us to understand the best and the most effective way to use them, in order to combat ag

Antibiotic resistance is today an important threat to global health. The misuse and overuse of antibiotics has led to the emergence and spread of antibiotic-resistant pathogens worldwide. There is therefore an urgent need for the discovery and development of new antibiotics. As a result, natural products are re-emerging as a source for new drugs engineered by evolution. In this context, marine sponge-associated bacteria are an important and underused source of bioactive compounds. Indeed, these bacteria produce a large array of secondary metabolites, including antibiotics, as defence mechanisms against the threats to which they are exposed due to the filtration activity of the sponge host.We contributed to this line of investigation by exploring the antibacterial potential of cultivable bacteria associated to the marine sponges Hymeniacidon perlevis and Halichondria panicea. Specimens of these intertidal sponges were sampled in the North Atlantic coast of France. A hundred and fourteen bacterial isolates were recovered from the sponge tissue using commercial and dilute media. Numerous isolates demonstrated antibacterial action against methicillin-resistant Staphylococcus aureus and carbapenem-resistant Acinetobacter baumannii clinical strains. These are two of the antibiotic-resistant pathogens prioritized by the World Health Organization for the development of new antibiotics. In particular, sponge-isolated strains of the genera Lactococcus, Pseudomonas and Vagococcus exhibited antibacterial activity against both pathogens. This activity was characterised as bactericidal through co-cultivation of the sponge bacteria with the target strains.We further focused on the sponge-isolated Vagococcus fluvialis strains, as they exhibited potent bactericidal activity against all clinical strains tested. Moreover, this genus has not been previously reported to produce antibiotic compounds. Traditional and gene-based approaches were applied to characterise the antibacterial fac, La résistance aux antibiotiques constitue une menace importante pour la santé mondiale. Le mauvais usage d'antibiotiques a conduit à l'émergence et à la propagation d'agents pathogènes résistants aux antibiotiques. Il existe donc un besoin urgent de nouveaux antibiotiques. Les produits naturels resurgissent comme une source de nouveaux médicaments issus de l'évolution. Dans ce contexte, les bactéries associées aux éponges constituent une source importante et sous-utilisée de composés bioactifs, qu’elles produisent comme défense contre les menaces auxquelles elles sont exposées par l'activité de filtration de l'éponge.Nous avons exploré le potentiel antibactérien des bactéries cultivables associées aux éponges marines Hymeniacidon perlevis et Halichondria panicea, prélevées sur la côte Atlantique Nord de la France. Cent quatorze souches bactériennes ont été isolées du tissu des éponges en utilisant des milieux commerciaux et dilués. Nombreux isolats ont inhibé la croissance de souches cliniques de Staphylococcus aureus résistantes à la méticilline et d'Acinetobacter baumannii résistantes aux carbapénèmes. Ces deux agents sont considérés par l'Organisation Mondiale de la Santé comme prioritaires pour le développement de nouveaux antibiotiques. Les souches des genres Lactococcus, Pseudomonas et Vagococcus ont présenté une activité antibactérienne contre les deux pathogènes. Cette activité a été caractérisée comme bactéricide par des co-cultures entre les bactéries d’éponges et les souches cibles.Nous nous sommes concentrés sur les souches de Vagococcus fluvialis, qui ont démontré une puissante activité bactéricide contre toutes les souches cliniques résistantes aux antibiotiques testées. Ce genre n'avait pas été signalé auparavant pour produire des composés antibiotiques. Des approches traditionnelles et génétiques ont été appliquées pour caractériser le(s) facteur(s) antibactérien(s) responsable(s) de l'activité observée, mais l'indisponibilité d'outils et de protocol, Doctorat en Sciences agronomiques et ingénierie biologique, info:eu-repo/semantics/nonPublished

Objectives: The spread of antibiotic resistant bacteria is an important threat for human health. Acinetobacter baumannii bacteria impose such a major issue, as multidrug- to pandrug-resistant strains have been isolated, rendering some infections untreatable. In this context, carbapenem-resistant A. baumannii bacteria were ranked as top priority by both WHO and CDC. In addition, A. baumannii bacteria survive in harsh environments, being capable of resisting to disinfectants and to persist prolonged periods of desiccation. Due to the high degree of variability found in A. baumannii isolates, the search for new antibacterials is very challenging because of the requirement of drug target conservation amongst the different strains. Here, we screened a chemical library to identify compounds active against several reference strains and carbapenem-resistant A. baumannii bacteria. Methods: A repurposing drug screen was undertaken to identify A. baumannii growth inhibitors. One hit was further characterized by determining the IC50 and testing the activity on 43 modern clinical A. baumannii isolates, amongst which 40 are carbapenem-resistant. Results: The repurposing screen led to the identification of a harmine-derived compound, called HDC1, which proves to have bactericidal activity on the multidrug-resistant AB5075-VUB reference strain with an IC50 of 48.23 µM. In addition, HDC1 impairs growth of 43 clinical A. baumannii isolates. Conclusions: We identified a compound with inhibitory activity on all tested strains, including carbapenem-resistant clinical A. baumannii isolates., SCOPUS: ar.j, info:eu-repo/semantics/published

Purpose: The study aimed to determine the clinical conditions and risk factors associated with MBL produced by A.bumannii among hospitalized patients. Subjects and Methods: The clinical samples were collected from inpatients and subcultured on routine culture media for growth. Identification of bacteria along with antimicrobial sensitivity testing was done by VITEK®2 compact (bioMerieux). Isolates that were resistant to Meropenem and/or Imipenem were followed to detection of MBL by using metallo-β-lactamases by imipenem EDTA combined disc test (IMP-EDTA CDT) method. Demographic and clinical data of each patient were collected in terms of the type of infection, hospital-stay, associated factors, and outcome till discharge. Results: A number of 73(86.9%) isolates of A.baumannii were resistant to carbapenem. out of 73 carbapenem-resistant isolates, 64(87.7%) were found to be MBL positive. The patients with age more than 60 years i.e. 35.9% (23/64) were found to be more common in MBL positive isolates of A. baumannii. The difference in the distribution of MBL positive and MBL negative cases with endotracheal intubation and in Surgery during the last 30 days of incubation was found to be statistically significant. The mortality rate of patients infected by MBL positive isolates of A.baumannii was 12.5%. Conclusion: The MBL positive strains among carbapenem-resistant isolates of A.baumannii were high. endotracheal intubation and Surgery during the last 30 days were independently associated with MBL positive cases.

[ES] Uno de los retos emergentes más complejos en el mundo de la salud es la resistencia a los tratamientos con antibióticos (AMR). El uso a nivel mundial de los fármacos antibióticos ha sido un factor clave en la lucha contra las enfermedades infecciosas, pero a su vez ha provocado que cada vez más microorganismos desarrollen, mediante adaptaciones genéticas, resistencia o incluso inmunidad frente a los fármacos. Según las previsiones del informe elaborado por la comisión Review of Antimicrobial Resistance a petición del gobierno británico de David Cameron y presentado en el Foro de Davos 2016, se estimó que unas 700.000 personas fallecieron en 2016 a causa de microorganismos infecciosos resistentes - cifra que el propio informe considera infraestimada -, y que en 2050 las previsiones apuntan a 10 millones de muertes al año con un coste económico asociado de 100 billones de dólares si no se actúa adecuadamente. Ante esta amenaza de salud pública, los modelos matemáticos van a resultar fundamentales en la predicción de la evolución de la AMR y en la toma de decisiones objetivas en materia de salud pública. En este trabajo proponemos un modelo basado en agentes que describe la evolución de una bacteria resistente a antibiótico en una población sintética. En este caso, se ha escogido la bacteria Acinetobacter baumannii, caracterizada por su adaptación y resistencia a los antibióticos, y el antibiótico colistina, uno de los pocos antibióticos eficaces contra el microorganismo a día de hoy. El modelo basado en agentes propuesto describe la evolución de los casos de A. baumannii sensibles y resistentes a la colistina a lo largo del tiempo, en una población sintética con las características demográficas de la ciudad de Valencia, y con unas reglas de comportamiento de los individuos que imitan al proceso natural de contagio por A. baumannii, y que se producen en base a una serie de probabilidades. Para hallar los parámetros desconocidos del modelo, se ha llevado a cabo un, [EN] One of the most complex emerging challenges in the world of healthcare is antibiotic resistance (AMR). The global use of antibiotic drugs has been a key factor in the fight against infectious diseases, but it has also led to an increasing number of microorganisms developing resistance or even immunity to the drugs through genetic adaptations. According to the forecasts of the report prepared by the Review of Antimicrobial Resistance commission at the request of David Cameron's British government and presented at the Davos Forum 2016, it was estimated that some 700,000 people died in 2016 as a result of resistant infectious microorganisms - a value that the report itself considers to be an underestimate - and that by 2050 the forecasts point to 10 million deaths per year with an associated economic cost of 100 trillion dollars if appropriate action is not taken. In the face of this public health threat, mathematical models will be fundamental in predicting the evolution of AMR and in making objective public health decisions. In this study we propose an agent-based model that describes the evolution of antibiotic-resistant bacteria in a synthetic population. In this case, we have chosen the bacterium Acinetobacter baumannii, characterised by its adaptation and resistance to antibiotics, and the antibiotic colistin, one of the few antibiotics currently effective against the microorganism. The proposed agent-based model describes the evolution of colistin-sensitive and colistin-resistant cases of A. baumannii over time, in a synthetic population with the demographic characteristics of the city of Valencia, and with rules for the behaviour of individuals that mimic the natural process of infection by A. baumannii, and which are produced on the basis of a series of probabilities. To find the unknown parameters of the model, a calibration process was carried out using the Particle Swarm Optimization (PSO) algorithm and a fitness function that measures the error betwee