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Nosocomial infections caused by Acinetobacter baumannii currently represent a serious challenge for clinicians because treatment options are limited and frequently associated with significant toxicity. Cefiderocol is a first-in-class siderophore cephalosporin that has a proven efficacy for the treatment of multidrug-resistant Gram-negative infections, including carbapenem-resistant A. baumannii. The aim of this review is to evaluate the current evidence for the role of cefiderocol in the management of A. baumannii infections.In this review, we briefly summarize the available data on the efficacy (from randomized controlled trials) and on effectiveness and cure rates (from observational studies), pertaining to the use of cefiderocol for treatment of serious A. baumannii infections.Cefiderocol represents a promising and safe antibiotic option for treating patients with carbapenem-resistant A. baumannii infections. Due to conflicting mortality data from available experience, well-designed future randomized controlled trials and real-life studies are needed.

The main objective of this study was to identify carbapenem resistance mechanisms among clinical, commensal and environmental carbapenem-resistant Acinetobacter baumannii (CRAB) strains isolated in 5 Tunisian intensive care units (ICUs).CRAB isolates were recovered from different sources: clinical specimens, rectal and environmental swabs. Bacterial identification was carried out using conventional methods and susceptibility testing according to EUCAST recommendations. Evaluation of phenotypic carbapenemase production of was performed using seven different methods, and molecular detection of carbapenemase-coding genes (blaAll in all, 46 CRAB isolates were identified in clinical specimens (n = 26/26), rectal swabs (n = 17/36) and environmental swabs (n = 3/63). Most of them (n = 41/46) were clonally related and found in the different ICUs. All of the CARB isolates harbored blaThe emergence and diffusion of clonal CRAB strains inducing high mortality rates in ICUs is a major public health concern. Enhanced infection control practices and mandatory staff education are needed to control the spread of these multidrug-resistant bacteria.

BACKGROUND: Viet Nam has high rates of antimicrobial resistance (AMR) but little capacity for genomic surveillance. This study used whole genome sequencing to examine the prevalence and transmission of three key AMR pathogens in two intensive care units (ICUs) in Hanoi, Viet Nam. METHODS: A prospective surveillance study of all adults admitted to ICUs at the National Hospital for Tropical Diseases and Bach Mai Hospital was done between June 19, 2017, and Jan 16, 2018. Clinical and environmental samples were cultured on selective media, characterised with MALDI TOF mass spectrometry, and sequenced with Illumina. Phylogenies based on the de-novo assemblies (SPAdes) were constructed with MAFFT (PARsnp), Gubbins, and RAxML. Resistance genes were detected with Abricate against the US National Center for Biotechnology Information database. FINDINGS: 3153 Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii isolates from 369 patients were analysed. Phylogenetic analysis revealed predominant lineages within A baumannii (global clone 2, sequence types ST2 and ST571) and K pneumoniae (ST15, ST16, ST656, ST11, and ST147) isolates. Isolation from stool was most common with E coli (87·0%) followed by K pneumoniae (62·5%). Of the E coli, 85·0% carried a blaCTX-M variant, while 81·8% of K pneumoniae isolates carried blaNDM (54·4%), or blaKPC (45·1%), or both. Transmission analysis with single nucleotide polymorphisms identified 167 clusters involving 251 (68%) of 369 patients, in some cases involving patients from both ICUs. There were no clear differences between the lineages or AMR genes recovered between the two ICUs. INTERPRETATION: This study represents the largest prospective surveillance study of key AMR pathogens in Vietnamese ICUs. Clusters of closely related isolates in patients across both ICUs suggests recent transmission before ICU admission in other health-care settings or in the community. FUNDING: UK Medical Research Council Newton Fund, Viet Nam Ministry of Science and Technology, Wellcome Trust, Academy of Medical Sciences, Health Foundation, and UK National Institute for Health and Care Research Cambridge Biomedical Research Centre.

In clinical practice, polymyxins are suggested to be used in combination with other antibiotics for improving their antibacterial efficacy and preventing the emergency of antibiotic-resistant strains. However, even though synergistic combination of polymyxin B with many antibiotics have been confirmed in various studies with different bacterial species and analyzing methods, which antibiotic is the best option for combination therapy of polymyxin B against MDR A. baumannii remains uncertain. In this study, we systematically analyzed the synergistic combination of polymyxin B with 12 other antibiotics against MDR A. baumannii isolated from a Chinese tertiary hospital using the checkerboard assay. The results suggest that, for polymyxin B-based combination therapy against MDR A. baumannii as characterized in this hospital, cefperazone-sulbactam may be the best partner, since it has the highest synergistic rate and the best synergistic effect with polymyxin B. Minocycline, imipenem, meropenem, ceftazidime, cefepime, amikacin and sulfamethoxazole also have some synergistic effects with polymyxin B, but piperacillin-tazobactam, ciprofloxacin, levofloxacin and tobramycin show no synergism. None of these 12 antibiotics has an antagonistic effect when combined with polymyxin B.

The goal of this work was to systematically characterize and detect class 1, 2, and 3 integrons with many antibiotic resistance A. baumannii strains collected from a clinical environment in Iraq's Al-Muthanna hospitals. In this investigation, 24 non-replicated clinical strains of A. baumannii were evaluated using Chrome agar as a selective medium and PCR of the rplB gene. The clonal relatedness of the isolates to class 1 integron was evaluated using a PCR technique. The prevalence of class 1 integron was detected by PCR in only 12 clones of A. baumannii followed by HinfI digestion analysis showing three identical bands at 160 bp, 1350 bp, and 870 bp. In addition, PCR sequencing confirmed the presence of gene cassette arrays consisting of aacA4-catB8-aadA1 (100%) in class 1 integron. The sequence analysis of the integron shows 97.87 identity with A. baumannii isolates from Australia (GenBank accession number CP054302) among A. baumannii isolates. The blast analysis of this class I integron showed that the presence of the intI1, aacA4-catB8-aadA1 genes can considerably boost the acquisition of MDR phenotypes in A. baumannii isolates. We concluded that antibiotics of many types are widely used. The presence of integrons in A. baumannii is concerning for public health. In the clinical setting, it appears that the class 1 integron can be used as a predictive biomarker for the presence of MDR phenotypes. In these bacteria, however, the integron does not possess carbapenemases genes.

Introduction: Mortality of healthcare-associated Acinetobacter baumannii bacteremia can be 50-60% in intensive care units (ICUs). We aimed to determine the risk factors for 28-day mortality in patients with sepsis due to A. baumannii bacteremia during their ICU follow-up. Methodology: Demographic characteristics, disease severity scores on admission and bacteremia day (BD), resistance status, invasive interventions, and laboratory values showing the infection and severity of the BD, were compared between groups with and without mortality as a retrospective cohort study in the ICU of a tertiary hospital. Results: Of a total of 2411 patients, there were 192 cases of bacteremia. After applying the exclusion criteria, 39 patients were recruited for the study, 25 of whom died (mortality rate 64.1%). Higher age, Simplified Acute Physiology Score II (SAPS II) on admission and high Sequential Organ Failure Assessment Score (SOFA), Red Blood Cell Distribution Width (RDW) (p < 0.001), and C-Reactive Protein (CRP) (p = 0.002) on the BD and invasive intervention in follow-up were associated with mortality. When CRP and RDW were both positive, sensitivity was 72%, specificity was 100%, negative predictive value was 33%, and positive predictive value was 100% for the 28-day mortality after BD. Based on multivariate analysis, CRP and RDW values on the BD were independent risk factors for mortality. Conclusions: It is critical to monitor SOFA, RDW, and CRP values in older ICU patients with SAPS II scores and who undergo invasive intervention in follow-up. Increases in these parameters may indicate bacteremia with high mortality due to A. baumannii.

The incidence of liquefied petroleum gas (LPG)-related accidents in China has increased over the recent years. In addition, infection remains a big challenge in cases of severe burns. Therefore, the present study aimed to provide valuable information for a better control of infections in the event of such disasters. In this study, a total of 16 patients who suffered extremely severe burns after an LPG tanker explosion were included. Thereafter, bacteriological culture results were collected within a week. Of 16 patients, 13 (81.25%) were male and the average age of all patients was 60.63 years. In addition, the mean burned area was 83.03% TBSA. Additionally, a total of 553 organism cultures were conducted out of which 287 isolates (51.90%) showed positive results. Notably, 38.52% were Gram-negative bacteria, 7.59% were Gram-positive bacteria and 5.79% were fungi. Moreover, the most prevalent Gram-negative bacteria were Stenotrophomonas maltophilia (28.97%) followed by Acinetobacter baumannii (28.53%), and Klebsiella pneumoniae (14.02%). On the other hand, the three most predominant Gram-positive bacteria were Enterococcus faecalis (33.33%), Staphylococcus aureus (28.89%) and Staphylococcus sciuri (17.78%). Furthermore, the most common fungi included Candida (38.24%), Fusarium (20.59%) and Aspergillus fumigatus (14.71%). With regard to the bacterial resistance patterns, carbapenem-resistant organisms included Acinetobacter baumannii (97.80%), Pseudomonas aeruginosa (67.57%), and Klebsiella pneumoniae (75.56%). In addition, Staphylococcus sciuri, Staphylococcus epidermidis, and Staphylococcus haemolyticus were identified to be methicillin-resistant. This study revealed that there was a high incidence of infection in victims of severe burns as a result of mass burn accidents, accompanied by early fungal infection.

Carbapenem-resistant Acinetobacter baumannii (CRAB) sepsis is becoming an extreme threat caused by high-case fatality rates and poor prevention and control in ICUs worldwide. However, the risk of mortality among neonatal CRAB sepsis is still unclear.A retrospective medical records review study, which aimed to identify the risk factors of mortality in neonates with CRAB sepsis (including both bacteremia and/or meningitis) in Thailand from 1996 to 2019. All cases featuring positive blood and cerebrospinal fluid cultures for CRAB were reviewed. A multivariable logistic regression model was analyzed for nonsurvivors and survivors of neonatal CRAB sepsis.In a 24-year period, 47 of these were identified with CRAB sepsis. The median (interquartile range) gestational age and birth weight were 30 (28-35) weeks and 1500 (933-2482) g, respectively. The 30-day case fatality rate was 55% (26/47). In multivariable analysis, nonsurvivors of neonatal CRAB sepsis were associated with congenital heart disease (adjusted odds ratio [OR] = 1.33; 95% CI 1.06-1.66, P = 0.02), CRIB II score ≥9 (adjusted OR = 1.65; 95% CI: 1.20-2.27, P = 0.004), severe thrombocytopenia (adjusted OR = 1.45; 95% CI: 1.09-1.94, P = 0.02), and septic shock (adjusted OR = 1.62; 95% CI: 1.33-1.99, P0.001).The risk factors of mortality in neonates with CRAB sepsis are associated with congenital heart disease, CRIB II score ≥9, shock, and severe thrombocytopenia.

Carbapenem-resistant Acinetobacter baumannii (CRAB) is a prevalent pathogen contributing to hospital infections. Pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST) and core-genome MLST (cgMLST) are frequently used methods to illuminate the nosocomial transmission of CRAB. In this study, we compared the discriminatory power of the three typing methods.Antimicrobial susceptibility tests were performed by the broth microdilution and Vitek2 methods. PFGE, MLST and cgMLST were conducted to determine the clonality and phylogenetic relationship of the strains. Whole-genome sequence data were acquired by an Illumina HiSeq 2000, and cgMLST was analysed by the Ridom SeqSphere+ v.7.2.3 software.A total of 149 carbapenem-resistant A. baumannii isolates had 15 different PFGE profiles (A-O type), and 73 of the isolates had related subtypes (A1 and A2), accounting for the majority of type A isolates. The maximum-likelihood phylogenetic analysis based on the cgMLST genes grouped the same PFGE clonal pattern A into nine different clusters. ST_Pasteur grouped all the strains into ST2, whereas ST_Oxford grouped the PFGE clonal pattern A isolates into six STs. In addition, the gdhB allele in the ST_Oxford scheme had two copies in five strains, which complicated the ST_Oxford typing.cgMLST was more discriminant than PFGE and MLST. CgMLST is the most suitable and comprehensive method for genotyping A. baumannii in surveillance and epidemiological research.

Multidrug-resistant Acinetobacter baumannii (MDR-Ab), particularly strains producing oxacillinase (OXA)-type carbapenemases, have rapidly emerged in health care settings as a frequent cause of serious infections with limited treatment options. This study evaluated the in vitro activity of sulbactam (SUL) combined with durlobactam (DUR) against a collection of carbapenemase-producing A. baumannii, and investigated the mechanisms of resistance.Susceptibility testing was performed on 100 isolates by either broth microdilution or by the Epsilometer test. Isolates were screened for the insertion sequence ISAba1 upstream of the intrinsic chromosomal blaADC by polymerase chain reaction (PCR). Whole genome sequencing was performed on 25 SUL-DUR resistant isolates, and analyses were performed using the Center for Genomic Epidemiology platform. Target gene sequences were compared to A. baumannii American Type Culture Collection (ATCC) 17978.SUL-DUR exhibited excellent activity against A. baumannii isolates with susceptibility levels as follows: amikacin, 18%; colistin, 91%; cefepime, 5%; imipenem, 0%; minocycline, 46%; SUL, 3%; sulbactam-cefoperazone, 8%; SUL-DUR, 71% (based on a breakpoint at 4 mg/L). Twenty-five non-New Delhi metallo-ß-lactamase (NDM)-producing isolates had SUL-DUR MIC values4 mg/L, amongst which 14 isolates showed substitutions in penicillin-binding protein (PBP)3, previously shown to be associated with SUL-DUR resistance. Substitutions that have not previously been described were detected in SUL-DUR targets, namely PBP1a, PBP1b, PBP2, and PBP3. By contrast, there was no evidence of the involvement of permeability or efflux.SUL-DUR exhibited excellent in vitro antibacterial activity against carbapenemase-producing A. baumannii isolates. Amongst the 25 resistant isolates, we identified a number of mechanisms which may be contributing factors, in particular PBP substitutions and the production of specific beta-lactamases.

Guidelines for treatment of resistant Acinetobacter baumannii (AB) are limited, leaving a knowledge gap in best practices for treatment. This study described treatments and outcomes of extensively-drug resistant (XDR) AB.Retrospective cohort study including patients with XDRAB (non-susceptible to at least 1 agent in all but 2 or fewer classes) and antibiotic treatment between 2012 and 2018 at Veterans Affairs Medical Centers. Descriptive statistics summarized antibiotics; propensity score adjusted regression models were fit to compare outcomes.Two hundred and seventy-six patients with 439 XDRAB cultures and Gram-negative targeted antibiotic treatment were included. One hundred and eighteen (43%) patients received monotherapy while 158 (57%) received combination therapy, most commonly including a carbapenem (n = 106, 67%) and polymyxin (n = 66, 42%). One hundred and eighty-four (67%) patients received inadequate treatment. In adjusted models, combination therapy did not decrease the odds of in-hospital (aOR 1.24, 95%CI 0.60-2.59) or 30-day (aOR 1.43, 95%CI 0.86-2.38) mortality, or median postculture length of stay (aIRR 1.11, 95%CI 0.86-1.43). Likewise, receipt of inadequate treatment was not associated with poorer outcomes.In this national cohort of patients with XDRAB, neither combination therapy nor receipt of adequate treatment improved outcomes. Further research is needed on optimal management of this difficult-to-treat pathogen with few effective antibiotic options.

Introduction: We sought to evaluate secondary infections (SIs) in patients admitted to the intensive care unit (ICU) for COVID-19 with respect to incidence, causative pathogens, and clinical outcomes. Methodology: In this two-centre retrospective study, we analysed 146 patients (96 males, 50 females; median age, 64 years) admitted to the ICU with COVID-19 between March 26 and December 31, 2020. Inclusion criteria were an ICU admission for at least 48 hours and age beyond 18 years. Patients with and without SIs were compared and the impacts of SIs and carbapenem resistance on mortality were analysed. Results: During ICU admission, 84 episodes of SIs developed in 58 patients (39.7%). A total of 104 isolates were recovered, with Gram-negative bacteria most frequent accounting for 74%. At least one carbapenem-resistant pathogen (n = 61) was recovered in 41 patients (70.1%). In multivariate analysis, the use of ECMO and an elevated procalcitonin level were significantly associated with the development of SIs. The mortality rate and the incidence of carbapenem resistance did not differ significantly in COVID-19 patients with and without SIs (p = 0.059 and p = 0.083, respectively). Conclusions: The incidences of SIs and carbapenem resistance among COVID-19 patients were alarming, emphasizing stricter infection control measures in the ICU setting. © 2022 Journal of Infection in Developing Countries. All rights reserved.

Bacterial resistance is a problem that is giving serious cause for concern because bacterial strains such as Acinetobacter baumannii and Pseudomonas aeruginosa are difficult to treat and highly opportunistic. These bacteria easily acquire resistance genes even from other species, which confers greater persistence and tolerance towards conventional antibiotics. These bacteria have the highest death rate in hospitalized intensive care patients, so strong measures must be taken. In this review, we focus on the use of antimicrobial peptides (AMPs) as an alternative to traditional drugs, due to their rapid action and lower risk of generating resistance by microorganisms. We also present an overview of beta-lactams and explicitly explain the activity of AMPs against carbapenemase-producing bacteria as potential alternative agents for infection control.

Aim: To control the spread of Acinetobacter baumannii in hospitals, it is necessary to identify the reservoir of organisms and the way they are transmitted. This study analyzed samples by BOX-PCR and enterobacterial repetitive intergenic consensus PCR techniques. Methods: Isolated strains were identified using the Microgen kit and blaOXA-51 gene. The genetic diversity of strains that were sensitive or resistant to colistin was evaluated by BOX-PCR and enterobacterial repetitive intergenic consensus PCR methods. Results: A total of 13% of the isolates were resistant to colistin, whereas 87% of the strains were sensitive to this medication. A. baumannii strains that were resistant or sensitive to colistin were divided into five groups using the BOX-PCR method and six groups using the enterobacterial repetitive intergenic consensus PCR method. Conclusion: Rapid identification and the use of appropriate tools to control colistin-resistant clones are essential to prevent the further spread of A. baumannii.

Introduction: Secondary Bacterial Infections (SBIs) of the respiratory system are one of the biggest medical concerns in patients undergoing hospitalization with a diagnosis of COVID-19. This study aims to provide relevant data for the initiation of appropriate empirical treatment after examining the etiology and antimicrobial resistance of SBIs in COVID-19 patients under care in the Intensive Care Units (ICUs) in the largest pandemic hospital of our country. Methodology: Between March 16, 2020 and December 31, 2021, 56,993 COVID patients were hospitalized, of which 7684 were admitted to ICUs. A total of 1513 patients diagnosed with SBIs have been included in this study. During the course of the study, demographic data, clinical course, etiology and antimicrobial resistance data of all patients were collected. Results: The most common causative agents of SBIs were inferred as Acinetobacter baumanii (35.1%), Staphylococcus aureus (15.2%), Klebsiella pneumoniae (12.3%) and Pseudomonas aeruginosa (10.4%). The isolation rates of carbapenem-resistant and colistin-resistant A. baumannii, K. pneumoniae and P. aeruginosa were 83.7%; 42.7%, 79.2%, and 5.6%, 42.7%, 1.7%, respectively. Acinetobacter pittii clustering was seen in one of the ICUs in the hospital. Multidrug resistant 92 (5.4%) Corynebacterium striatum isolates were also found as a causative agent with increasing frequency during the study period. Conclusions: SBI of the respiratory system is one of the major complications in patients hospitalized with COVID-19. The antimicrobial resistance rates of the isolated bacteria are generally high, which indicates that more accurate use of antibacterial agents is necessary for SBIs in patients hospitalized with COVID-19 diagnosis.

Background To date, no real-world data are available to describe cefiderocol use in carbapenem-resistant Acinetobacter baumannii (CRAB) meningitis. Furthermore, cefiderocol pharmacokinetic (PK) data to support CNS penetration in human subjects are limited. These gaps pose a significant concern for clinicians who are faced with treating such infections when considering cefiderocol use. Objectives To describe cefiderocol CSF and plasma PK and pharmacodynamic (PD) data from two different dosing regimens [2 g IV q6h (regimen 1) and 2 g IV q8h (regimen 2)] during treatment of CRAB meningitis. Patients and methods A 61-year-old woman with CRAB meningitis was treated with cefiderocol and intraventricular gentamicin. Steady-state plasma and CSF cefiderocol concentrations were evaluated on Day 19 (regimen 1) and Day 24 (regimen 2) during the cefiderocol treatment course. Results CSF AUC was 146.49 and 118.28 mg·h/L, as determined by the linear-log trapezoidal method for regimens 1 and 2, respectively. Penetration into CSF estimated as the AUCCSF/AUCfree plasma ratio was 68% and 60% for regimens 1 and 2, respectively. Estimated free plasma and CSF concentrations exceeded the MIC of the isolate for 100% of the dosing interval. Microbiological and clinical cure were achieved, and no cefiderocol-associated adverse effects were observed. Conclusions Cefiderocol, when given as 2 g q8h and 2 g q6h, attained CSF concentrations that exceeded the organism-specific MIC and the CLSI susceptible breakpoint (≤4 mg/L) for 100% of the dosing interval.

Introduction : Clinical use of mobile phones have increased exponentially. Whilst evidence of contamination is documented, a key factor when determining potential risks of contamination, is establishing the duration the organism remains viable on the device. If pathogens are found to persist for extended duration, healthcare mobile phones may become fomites for cross departmental transmission. Aim : Determine the duration pathogenic bacteria, Acinetobacter baumannii, Escherichia coli, two Pseudomonas sp. Bacillus cereus, Enterococcus faecalis susceptible and resistant to vancomycin (VSE and VRE) Staphylococcus aureus susceptible and resistant to methicillin (MSSA and MRSA), and a coagulase negative Staphylococcus (CoNs) can remain viable on a mobile phone under controlled conditions. Method : Phones were inoculated with 106 – 107 of each bacterium. The duration of viability was measured from the point the inoculum had dried and CFUs retrieved at timed intervals over 28 days. Results : The mean percentage of bacteria viable at each time point was significantly different (20mins, p=0.004, 1hour p=0.014, 6hours p = 0.006, 24hours p=0.004, 7 days p = 0.007, 14 days p = 0.003, 21 days p = 0.002- and 28-days p =0.004). Gram-positive bacteria remained viable longer than gram-negative bacteria (p=0.010). MSSA declined faster than MRSA within the first 6 hours (p=0.036). Conclusion : The extended duration of bacterial viability indicates the ability for pathogens to persist on a device and remain viable long enough to be transmitted to new areas both within the hospital and out to the community. Mobile phone decontamination should occur in combination of hand hygiene.

Multidrug-resistant Acinetobacter baumannii (A. baumannii) infections are becoming more prevalent all over the world. As a cost-effective and preventative method, vaccination seems to be required against this bacterium. In the present study, subtractive proteomics along with reverse vaccinology approaches was used to predict suitable therapeutics against A. baumannii. Using the Vaxign online tool, we studied over 35 genomes of A. baumannii strains and chose outer membrane and secreted proteins of A. baumannii 1656-2 as possible vaccine candidates. Then, investigations were performed on the immunogenicity, antigenic characteristics, physicochemical properties, B-cell and MHC class I, and MHC class II molecules epitope densities of proteins. After optimizing the codon of the proteins, the pcDNA3.1( +) expression construct was designed and the immunogenicity, allergenicity, and physicochemical properties of the vaccine construct were predicted. Hcp and OmpC proteins were predicted as extracellular and outer membrane proteins, respectively. These proteins interact with 10 other proteins to form a network of protein interactions with virulence properties. Immunoassays of Hcp and OmpC proteins showed antigenicity of 0.88 and 0.79, respectively. These proteins have 5 structural cell epitope points and 5 linear B epitope points. They are also able to bind to different HLA alleles of MCH class I/class II as selected immunogenic proteins and designed non-allergenic structures with solubility of 0.650 and immunogenicity score of 0.91. The results of this "in silico" study indicate high specificity and the development of a significant humoral and cellular immune response. It can be concluded that the Hcp and OmpC dual vaccine construct is one of the promising candidates against A. baumannii. The findings of this "in silico" study show excellent specificity and the emergence of a substantial humoral and cellular immune response. This is a computer-based study that needs to be tested in vitro and in vivo to corroborate the conclusions of the vaccine design procedures.

The opportunistic human pathogen Acinetobacter baumannii can grow with carnitine but its metabolism, regulation and role in virulence remained elusive. Recently, we identified a carnitine transporter encoded by a gene closely associated with potential carnitine degradation genes. Among those is a gene coding for a putative d-malate dehydrogenase (Mdh). Deletion of the mdh gene led to a loss of growth with carnitine but not l-malate; growth with d-malate was strongly reduced. Therefore, it is hypothesized that d-malate is formed during carnitine oxidation and further oxidized to CO

Antimicrobial drug resistance is one of the major threats to global health. It has made common infections increasingly difficult or impossible to treat, and leads to higher medical costs, prolonged hospital stays and increased mortality. Infection rates due to multidrug-resistant organisms (MDRO) are increasing globally. Active agents against MDRO are limited despite an increased in the availability of novel antibiotics in recent years. This guideline aims to assist clinicians in the management of infections due to MDRO. The 2019 Guidelines Recommendations for Evidence-based Antimicrobial agents use in Taiwan (GREAT) working group, comprising of infectious disease specialists from 14 medical centers in Taiwan, reviewed current evidences and drafted recommendations for the treatment of infections due to MDRO. A nationwide expert panel reviewed the recommendations during a consensus meeting in Aug 2020, and the guideline was endorsed by the Infectious Diseases Society of Taiwan (IDST). This guideline includes recommendations for selecting antimicrobial therapy for infections caused by carbapenem-resistant Acinetobacter baumannii, carbapenem-resistant Pseudomonas aeruginosa, carbapenem-resistant Enterobacterales, and vancomycin-resistant Enterococcus. The guideline takes into consideration the local epidemiology, and includes antimicrobial agents that may not yet be available in Taiwan. It is intended to serve as a clinical guide and not to supersede the clinical judgment of physicians in the management of individual patients.

Objectives To explore the in vitro antimicrobial susceptibility among clinically important Gram-negative bacteria (GNB) in Taiwan. Methods From 2016 through 2018, a total of 5458 GNB isolates, including Escherichia coli (n = 1545), Klebsiella pneumoniae (n = 1255), Enterobacter species (n = 259), Pseudomonas aeruginosa (n = 1127), Acinetobacter baumannii complex (n = 368), and Stenotrophomonas maltophilia (n = 179), were collected. The susceptibility results were summarized by the breakpoints of minimum inhibitory concentration (MIC) of CLSI 2020, EUCAST 2020 (for colistin), or published articles (for ceftolozane/tazobactam). The resistance genes among multidrug-resistant (MDR) or extensively drug-resistant (XDR)-GNB were investigated by multiplex PCR. Results Significantly higher rates of non-susceptibility (NS) to ertapenem and carbapenemase production, predominantly KPC and OXA-48-like beta-lactamase, were observed in Enterobacterales isolates causing respiratory tract infection than those causing complicated urinary tract or intra-abdominal infection (12.7%/3.44% vs. 5.7%/0.76% or 7.7%/0.97%, respectively). Isolates of Enterobacter species showed higher rates of phenotypic extended-spectrum β-lactamase and NS to ertapenem than E. coli or K. pneumoniae isolates. Although moderate activity (54–83%) was observed against most potential AmpC-producing Enterobacterales isolates, ceftolozane/tazobactam exhibited poor in vitro (44.7–47.4%) activity against phenotypic AmpC Enterobacter cloacae isolates. Additionally, 251 (22.3%) P. aeruginosa isolates exhibited the carbapenem-NS phenotype, and their MDR and XDR rate was 63.3% and 33.5%, respectively. Fifteen (75%) of twenty Burkholderia cenocepacia complex isolates were inhibited by ceftolozane/tazobactam at MICs of ≤4 μg/mL. Conclusions With the increase in antibiotic resistance in Taiwan, it is imperative to periodically monitor the susceptibility profiles of clinically important GNB.

We identify a new mechanism mediating capsule production and virulence in the WHO and CDC priority ESKAPE pathogen Acinetobacter baumannii. Non-capsulated and avirulent bacteria can revert into a capsulated and virulent state upon scarless excision of an ISAba13 insertion sequence under stress conditions. Reversion events fully restore capsule production and in vivo virulence. This increases our knowledge about A. baumannii genome dynamics, and the regulation of capsule production, virulence and resistance.

A carbapenem-resistant Acinetobacter baumannii outbreak in the COVID intensive care unit of a community hospital was contained using multidrug resistant organism guidelines. The purpose of this study is to report on an outbreak investigation and containment strategy that was used, and to discuss prevention strategy.A multidisciplinary approach contained the spread of infection. Strategies implemented included consultation with experts, screening, and reversal of personal protective equipment conservation. Ensuring infection control best practices are maintained remain important efforts to reduce the spread of multidrug resistant organisms.Five patients with carbapenem-resistant Acinetobacter baumannii were identified from routine clinical cultures within one week and one patient was identified from active surveillance cultures.Personal protective equipment conservation, strategies to prevent health care personnel exposure, and patient surge staffing protocols may have increased the likelihood of multidrug resistant organism transmission. Environmental and behavioral infection control regulations with effective administrative guidance, active surveillance cultures, and antimicrobial stewardship are critical to prevent future outbreaks.After outbreak containment strategies were implemented, no additional patients were identified with carbapenem-resistant Acinetobacter baumannii. Conventional infection prevention and control strategies were re-instituted. A multidisciplinary approach with continued focus on hand hygiene, environmental cleaning, and correct use of personal protective equipment needs to be put in place to successfully contain and prevent the spread of carbapenem resistant infections.

Acinetobacter baumannii is known to be an opportunistic pathogen frequently responsible for outbreaks in health-care facilities, particularly in Intensive Care Units (ICU). It can easily survive in the hospital setting for long periods and can be transmitted throughout the hospital in a variety of ways, explored in this review. It can also easily acquire antibiotic resistance determinants rendering several antibiotic drugs useless. In 2019, the US Centre for Disease Control (CDC) considered the organism as an urgent threat. The aim of this review was to raise the awareness of the medical community about the relevance of this pathogen and discuss how it may impact seriously the healthcare institutions particularly in the aftermath of the recent COVID-19 pandemic. PubMed was searched, and articles that met inclusion criteria were reviewed. We conclude by the need to raise awareness to this pathogen's relevance and to encourage the implementation of preventive measures in order to mitigate its consequences namely the triage of specific high-risk patients.

Objectives To examine the causes of antibiotic resistance in the extensively resistant global clone 1 (GC1) Acinetobacter baumannii isolate MRSN 56 recovered at a US military treatment facility. Methods MRSN 56 was sequenced using MinION (Oxford Nanopore) and the reads combined with available Illumina MiSeq data using Unicycler. Acquired resistance genes were identified using ABRicate and their environment examined. ISAba1 and ISAba125 copies were located. Results MRSN 56 is ST1IP:ST231Ox:KL1:OCL1 and the complete genome includes four small plasmids, none of which carry resistance genes. The acquired resistance genes were found at four locations in the chromosome in addition to AbaR28 (aphA1, aacC1, aadA1, sul1) in comM. Tn2006 (oxa23, carbapenem resistance) was both in AbaR4 and alone elsewhere. Two copies of Tn7 (dfrA1, sat, aadA1) were identified. One was associated with a 22 852 bp adjacent segment [tetA(B), sul2] derived from the AbGRI1 island, and this novel configuration was designated Tn7+. Tn7+ was incorporated in the position preferred by Tn7, downstream of glmS, by transposition using a sequence in AbGRI1 resembling the Tn7 terminal inverted repeats. Tn7 was found at a secondary site. Fluoroquinolone resistance appears to involve a mutation in gyrA combined with inactivation by ISAba1 of the marR gene in the mar operon and constitutive expression of marA from the promoter internal to ISAba1. Conclusions MRSN 56 represents a new sublineage of GC1 lineage 1 with novel features that had not been detected previously. The involvement of the mar operon in fluoroquinolone resistance has not been noted previously.

Acinetobacter baumannii is a Gram-negative bacterium commonly found in soil and water that can cause human infections of the blood, lungs, and urinary tract. Of particular concern is its prevalence in health-care settings where it can survive on surfaces and shared equipment for extended periods of time. The capsular polysaccharide surrounding the organism is known to be the major contributor to virulence. The structure of the K57 capsular polysaccharide produced by A. baumannii isolate BAL_212 from Vietnam was recently shown to contain the rare sugar 4-acetamido-4,6-dideoxy-d-glucose. Three enzymes are required for its biosynthesis, one of which is encoded by the gene H6W49_RS17300 and referred to as VioB, a putative N-acetyltransferase. Here, we describe a combined structural and functional analysis of VioB. Kinetic analyses show that the enzyme does, indeed, function on dTDP-4-amino-4,6-dideoxy-d-glucose with a catalytic efficiency of 3.9 x 10

Background During the COVID-19 pandemic, the burden of nosocomial infections caused by MDR pathogens has caused a shortage of polymyxins. Thus, we evaluated the in vitro synergism and antibiofilm activity of antimicrobial combinations and propose a test kit for synergism against carbapenem-resistant Acinetobacter baumannii (CRAB). Methods Fifty-six CRAB isolates were tested for synergy between meropenem, gentamicin and ampicillin/sulbactam. MICs were determined by broth microdilution. Synergism was tested using chequerboard analysis, followed by a time–kill curve. Additionally, minimum biofilm eradication concentration was determined and the antibiofilm activity of the combinations was evaluated by MTT assay and biomass reduction. A test kit was developed for routine laboratory testing to detect synergism. Results All CRAB isolates were resistant to gentamicin and ampicillin/sulbactam. Chequerboard synergism occurred against 75% of the isolates. Meropenem + ampicillin/sulbactam was the most frequent combination with synergism (69%), followed by ampicillin/sulbactam + gentamicin (64%) and meropenem + gentamicin (51%). All combinations presented only bacteriostatic activity and no bactericidal or antibiofilm effects. The routine laboratory test showed 100% accuracy compared with other in vitro assays. Conclusions Our study demonstrates the potential role of antibiotic combinations against planktonic bacteria. In vitro synergism is possible and can be an alternative treatment for patients with CRAB infection during a polymyxin shortage.

This study evaluated the spread and possible changes in resistance patterns of ESKAPE bacteria to first-choice antibiotics from 2015 to 2019 at a third-level university hospital after persuasive stewardship measures were implemented. Isolates were divided into three groups (group 1, low drug-resistant; group 2, multidrug/extremely drug-resistant; and group 3, pan-resistant bacteria) and a

BACKGROUND: Methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci and Acinetobacter baumannii cause serious antibiotic-resistant infections. Finding new antibiotics to treat these infections is imperative for combating this worldwide menace. METHODS & RESULTS: In this study, the authors designed and synthesized potent antimicrobial agents using 4-trifluoromethylphenyl-substituted pyrazole derivatives. In addition to their potency against planktonic bacteria, potent compounds effectively eradicated S. aureus and Enterococcus faecalis biofilms. Human cells tolerated these compounds with good selectivity factors. Furthermore, the authors provide evidence for the mode of action of compounds based on time-kill kinetics, flow cytometry analysis of propidium iodide-treated bacteria and oxygen uptake studies. CONCLUSION: This study demonstrated 20 novel compounds with potent antibacterial activity that are tolerated by human cell lines.

Antibiotics and disinfectants resistance is acquired by activating RecA-mediated DNA repair, which maintains ROS-dependent DNA damage caused by the antimicrobial molecules. To increase the efficacy of different antimicrobials, an inhibitor can be developed against RecA protein. The present study aims to design a denovo inhibitor against RecA protein of Acinetobacter baumannii. Pharmacophore-based screening, molecular mechanics, molecular dynamics simulation (MDS), retrosynthetic analysis, and combinatorial synthesis were used to design lead VTRA1.1 against RecA of A. baumannii. Pharmacophore models (structure-based and ligand-based) were created, and a phase library of FDA-approved drugs was prepared. Screening of the phase library against these pharmacophore models selected thirteen lead molecules. These filtered leads were used for the denovo fragment-based design, which produced 253 combinations. These designed molecules were further analyzed for its interaction with active site of RecA that selected a hybrid VTRA1. Further, retrosynthetic analysis and combinatorial synthesis produced 1000 analogs of VTRA1 by more than 100 modifications. These analogs were used for XP docking, binding free energy calculation, and MDS analysis which finally select lead VTRA1.1 against RecA protein. Further, mutations at the interacting residues of RecA with VTRA1.1, alter the unfolding rate of RecA, which suggests the binding of VTRA1.1 to these residues may alter the stability of RecA. It is also found that VTRA1.1 had reduced interaction of RecA with LexA and ssDNA polydT, showing the lead's efficacy in controlling the SOS response. Further, it was also observed that VTRA1.1 does not contain any predicted human off-targets and no cytotoxicity to cell lines. As functional RecA is involved in antimicrobial resistance, denovo designed lead VTRA1.1 against RecA may be further developed as a significant combination for therapeutic uses against A. baumannii.

Available antibiotics to treat Acinetobacter baumannii infection is limited due to increasing resistance and the emergence of multiple drug-resistant strains. Hence, discovering effective agents against A. baumannii to reduce the number of infection-related deaths is imperative. In search of novel and alternative antibiotics, the antibacterial function of lipocalin2 (Lcn2) was investigated to treat systemic infections of A. baumannii using a mouse neutropenia model. We observed a significant increase in serum Lcn2 levels upon bacterial injection into the mouse, and the administration of recombinant Lcn2 (rmLcn2) extended their survival. Such protective effects were also observed in rmLcn2-pretreated macrophages, where rmLcn2 reduced the survival of the pathogen inside the macrophages. The underlying molecular mechanism of Lcn2 protection was also investigated. We observed that pretreatment of the Raw-264.7 macrophages with rmLcn2 markedly altered the expression of tonB3, which encodes a component of the transporter for ferrisiderophores in A. baumannii. However, the expression of katG, the gene encoding catalase, remained unaffected. These indicate that Lcn2-mediated defense against the pathogen is related to nutritional immunity rather than reactive oxygen species (ROS) production. Furthermore, the addition of rmLcn2 in infected mice diminished bacterial burden in multiple organs and enhanced the expression of tonB3 in the liver, spleen, and lungs of the infected mice. Increased survival rate due to rmLcn2 treatment declined when the infection model was established using lcn2-defective (lcn2

Objectives: Cefiderocol (CFDC), a siderophore cephalosporin, is active against Gram-negative bacteria including carbapenem-resistant Acinetobacter baumannii (CRAB). In this study, 100 CRAB isolates from patients with bacteraemia in Taiwan were characterised, among which 21 CFDC-non-susceptible isolates were identified with a minimum inhibitory concentration (MIC) of ≥8 mg/L. Methods: The effect of avibactam on CFDC activity was evaluated using broth microdilution methods according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Whole-genome sequencing (WGS) was performed on all CFDC-non-susceptible isolates (MIC ≥ 8 mg/L) for multilocus sequence typing (MLST) analysis, possession of β-lactamase genes and identification of possible variations in the PiuA iron transporter. Results: Addition of avibactam, a diazabicyclooctane inhibitor for serine-type β-lactamases, resulted in a ≥8-fold decrease in the CFDC MIC for 15 of 21 CFDC-non-susceptible isolates compared with only 1 of 79 CFDC-susceptible isolates (MIC ≤ 4 mg/L). WGS analysis confirmed that all CFDC-non-susceptible isolates harboured multiple β-lactamases including ADC-30 homologues, OXA-23 and OXA-66. One isolate with a high MIC (>32 mg/L) had a PER-type extended-spectrum β-lactamase (ESBL) gene. Twenty other isolates belonged to ST455, ST473 and ST787. Among these, thirteen ST455 isolates were deficient in PiuA, a siderophore uptake receptor that may be required for optimal penetration of CFDC. Conclusion: MICs of CFDC-non-susceptible CRAB isolates from Taiwan could be significantly decreased to susceptible levels by the addition of avibactam, suggesting the involvement of β-lactamases in resistance. Among the 21 CFDC-non-susceptible isolates, 1 isolate had a PER-type ESBL gene and 13 isolates lacked a PiuA iron siderophore transporter.

Carbapenem-resistant Acinetobacter baumannii (CRAB) infections present great challenges in clinical practices with high mortality. The aim of this study is to identify the impact of CRAB infections on acute pancreatitis (AP).A case-control study was performed via collecting data from March 1st, 2016 to August 1st, 2020 in two comprehensive teaching hospital. Clinical data of the CRAB-positive AP patients were analyzed and compared to a matched control group (case-control ratio of 1:1). Comparisons were preformed between with/without CRAB infections and multiple organ failure (MOF), respectively. Independent risk factors of overall mortality were determined via univariate and multivariate analyses.CRAB infections were associated with higher mortality (49.2% vs. 23.0%, P 0.01). CRAB combined with MOF increased a mortality up to 90% (P 0.01). MOF (Odds ratio (OR) = 21.49, 95% confidence interval (CI) = 5.26-87.80, P 0.01), CRAB infections (OR = 3.58, 95%CI = 1.24-10.37, P = 0.02) and hemorrhage (OR = 3.70, 95%CI = 1.21-11.28, P = 0.02) were independent risk factors of overall mortality. Lung was the most common site of strains (37 of 82). CRAB strains were highly resistant (60%) to ten of eleven common antibiotics, except for tigecycline (28%).High mortality rate in AP patients was associated with CRAB infections and further increased when CRAB infections combined with MOF.

Bacteria within the genus Acinetobacter (principally A. baumannii–calcoaceticus complex [ABC]) are gram-negative coccobacilli that most often cause infections in nosocomial settings. Community-acquired infections are rare, but may occur in patients with comorbidities, advanced age, diabetes mellitus, chronic lung or renal disease, malignancy, or impaired immunity. Most common sites of infections include blood stream, skin/soft-tissue/surgical wounds, ventilator-associated pneumonia, orthopaedic or neurosurgical procedures, and urinary tract. Acinetobacter species are intrinsically resistant to multiple antimicrobials, and have a remarkable ability to acquire new resistance determinants via plasmids, transposons, integrons, and resistance islands. Since the 1990s, antimicrobial resistance (AMR) has escalated dramatically among ABC. Global spread of multidrug-resistant (MDR)-ABC strains reflects dissemination of a few clones between hospitals, geographic regions, and continents; excessive antibiotic use amplifies this spread. Many isolates are resistant to all antimicrobials except colistimethate sodium and tetracyclines (minocycline or tigecycline); some infections are untreatable with existing antimicrobial agents. AMR poses a serious threat to effectively treat or prevent ABC infections. Strategies to curtail environmental colonization with MDR-ABC require aggressive infection-control efforts and cohorting of infected patients. Thoughtful antibiotic strategies are essential to limit the spread of MDR-ABC. Optimal therapy will likely require combination antimicrobial therapy with existing antibiotics as well as development of novel antibiotic classes.

Introduction : There is no consensual definition of risk factors for drug resistant pathogens (DRP) in community-onset pneumonia (COP). Healthcare-associated pneumonia criteria have been abandoned because they were found to have weak discriminative power. Our aim was to identify risk factors for DRP in COP. Methods : Prospective cohort study, conducted over a two years’ period, in a community-based hospital, including all adult patients with COP criteria. Univariate and multivariate logistic regression modeling were performed to understand the association of risk factors (demographic, clinical and epidemiological) with COP by a DRP (PES: Pseudomonas aeruginosa, extended-spectrum s-lactamase producing Enterobacteriaceae, Methicillin-resistant Staphylococcus aureus; and other non-fermenting gram-negative bacteria, namely Acinetobacter baumannii). Results : A total of 660 cases of COP were included, with a mean (±SD) age of 74±15 years and 58.9% of males. Microbiological documentation was possible in 32.6% of the cases. There were 197 cases selected for further analysis, of which 37 were cases of PES. The multivariate logistic regression model retained antibiotic use in the previous 90 days (adjusted OR=4.411, 95%CI [1.745-11.148]) and being bed-ridden (adjusted OR=5.492, 95%CI [2.121-14.222]), adjusted for Charlson's Index, CURB 65 and provenience from a long-term care facility. The area under the ROC curve for this model was 0.832, 95%CI [0.756-0.908], higher than the application of the HCAP criteria (AUROC = 0.676, 95%CI [0.582-0.770]). Conclusion : In this study, antibiotic use in the previous 90 days and being bed-ridden were independently associated with COP caused by DRP, after adjustment for Charlson's Index, CURB 65 and provenience from a long-term care facility.

Antimicrobial resistance (AMR) and hospital-acquired infections (HAIs) are global health challenges. The burden of antibiotic resistance in HAIs is still unclear in low- and lower-middle-income countries (L-LMICs). This study summarizes recent data on antibiotic resistance in priority HAIs (ESKAPE-E) in L-LMICs and compares them with data from high-income countries (HICs). EMBASE, Web of Science, and Global Index Medicus were searched for studies on AMR patterns in HAIs published from 01/2010 to 10/2020. Random-effects meta-analyses were performed to obtain pooled estimates. In total, 163 eligible studies were included in the review and meta-analysis. The pooled methicillin resistance proportion in Staphylococcus aureus was 48.4% (95% confidence interval [95%CI] 41·7-55·2, n = 80). Pooled carbapenem resistance proportions were high in Gram-negative pathogens: Escherichia coli: 16·6% (95%CI 10·7-23·4, n = 60); Klebsiella pneumoniae: 34·9% (95%CI 24·6-45·9, n = 50); Pseudomonas aeruginosa: 37.1% (95%CI 24·6-45·9, n = 56); Enterobacter spp.: 51·2% (95%CI 27·5-74·7, n = 7); and Acinetobacter baumannii (complex): 72·4% (95%CI 62·1-81·7%, n = 36). A higher resistance proportions were observed for third-generation cephalosporins: Klebsiella pneumoniae: 78·7% (95%CI 71·5-85·2, n = 46); Escherichia coli: 78·5% (95%CI 72·1-84·2%, n = 58); and Enterobacter spp.: 83·5% (95%CI 71·9-92·8, n = 8). We observed a high between-study heterogeneity (I2 > 80%), which could not be explained by our set of moderators. Pooled resistance proportions for Gram-negative pathogens were higher in L-LMICs than regional and national estimates from HICs. Patients in resource-constrained regions are particularly affected by AMR. To combat the high resistance to critical antibiotics in L-LMICs, and bridge disparities in health, it is crucial to strengthen local surveillance and the health systems in general.

Purpose: This study aims to characterize antimicrobial resistance (AMR), with particular reference to carbapenems and aminoglycosides, in MDR A. baumannii isolates recovered from an intensive care unit in a tertiary hospital. Methods: A. baumannii (n = 95 strains) isolated from patients were subjected to antimicrobial susceptibility test (AST) by Vitek 2 Compact system to determine minimum inhibitory concentrations, followed by genotyping by enterobacterial repetitive intergenic consensus-PCR (ERIC-PCR). Resistance genes of interest were PCR-amplified and sequenced. Results: All isolates were qualified as MDR, with a resistance rate of >80% to 8 antimicrobials tested. In terms of beta-lactamase detection, the blaOXA23 and blaTEM-1 genes were detected frequently at 92.63% and 91.58%, respectively. The metallo-β-lactamase genes blaIMP, blaVIM, and blaNDM were undetected. Aph (3’)-I was detected in 82 isolates (86.32%), making it the most prevalent aminoglycoside-modifying enzyme (AMEs) encoding gene. In addition, ant (3”)-I was detected at 30.53%, while 26.32% of the strains harboured an aac (6')-Ib gene. ERIC-PCR typing suggested moderate genetic diversity among the isolates, which might be organized into 10 distinct clusters, with Cluster A (n = 86 isolates or 90.53%) being a dominant cluster of epidemic clones.Conclusions: Substantial fractions of the A. baumannii strains prevailing in the ICU were MDR clones exhibiting extremely high resistance to carbapenems and aminoglycosides as monitored throughout the study period. They principally belonged to a single cluster of isolates carrying blaOXA23 and armA co-producing different AMEs genes.

Drug combinations may have a crucial role in treating infections due to multidrug resistant Acinetobacter spp. One suggested combination is colistin with teicoplanin. The effect of colistin on Acinetobacter spp. outer membrane can permit teicoplanin to its target in the cell wall. The aim of this study was to evaluate the synergistic activity of colistin and teicoplanin combination against 29 multidrug resistant isolates of Acinetobacter spp. The antimicrobial activity of colistin alone and in combination with teicoplanin was assessed using MIC and time–kill assays. The combination of 1 mg/l colistin and 10 mg/l teicoplanin showed in vitro synergism against all tested Acinetobacter isolates except one (Acinetobacter lowffii). The combination of 1 mg/l colistin and 10 mg/l teicoplanin was bactericidal at 6 h against 100% of Acinetobacter baumannii isolates with no bacterial regrowth at 24 h. The same combination was bactericidal against three out of seven non-baumannii Acinetobacter isolates. The increased concentration of teicoplanin (20 mg/l) was synergistic but still not bactericidal against the four remaining isolates. The combination of colistin and teicoplanin was synergistic against all tested Acinetobacter spp It is therefore recommended that clinical trials are conducted to clarify the therapeutic potential of the combination.

We observed high rates of bloodstream infections (BSIs) following fecal microbiota transplantation (FMT) for graft-versus-host-disease (33 events in 22 patients). To trace the BSIs' origin, we applied a metagenomic bioinformatic pipeline screening donor and recipient stool samples for bacteremia-causing strains in 13 cases. Offending strains were not detected in FMT donations. Enterococcus faecium, Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii could be detected in stool samples before emerging in the blood. In this largest report of BSIs post-FMT, we present an approach that may be applicable for evaluating BSI origin following microbiota-based interventions. Our findings support FMT safety in immunocompromised patients but do not rule out FMT as an inducer of bacterial translocation.

Objectives Mortality among patients with carbapenem-resistant Acinetobacter baumannii (CRAB) infections varies between studies. We examined whether in vivo fitness of CRAB strains is associated with clinical outcomes in patients with CRAB infections. Methods Isolates were collected from patients enrolled in the AIDA trial with hospital-acquired pneumonia, bloodstream infections and/or urinary tract infections caused by CRAB. The primary outcome was 14-day clinical failure, defined as failure to meet all criteria: alive; haemodynamically stable; improved or stable Sequential Organ Failure Assessment (SOFA) score; improved or stable oxygenation; and microbiological cure of bacteraemia. The secondary outcome was 14-day mortality. We tested in vivo growth using a neutropenic murine thigh infection model. Fitness was defined based on the CFU count 24 hours after injection of an inoculum of 105 CFU. We used mixed-effects logistic regression to test the association between fitness and the two outcomes. Results The sample included 266 patients; 215 (80.8%) experienced clinical failure. CRAB fitness ranged from 5.23 to 10.08 log CFU/g. The odds of clinical failure increased by 62% for every 1-log CFU/g increase in fitness (OR 1.62, 95% CI 1.04–2.52). After adjusting for age, Charlson score, SOFA score and acquisition in the intensive care unit, fitness remained significant (adjusted OR 1.63, 95% CI 1.03–2.59). CRAB fitness had a similar effect on 14-day mortailty, although the association was not statistically significant (OR 1.56, 95% CI 0.95–2.57). It became significant after adjusting for age, Charlson score, SOFA score and recent surgery (adjusted OR 1.88, 95% CI 1.09–3.25). Conclusions In vivo CRAB fitness was associated with clinical failure in patients with CRAB infection.