Last-resort Antibiotics Research Articles

Evaluating the effects of intravenous magnesium sulfate for prevention of colistin induced acute kidney injury: an open-label, placebo-controlled, block randomized clinical trial.

Colistin, has reinstated as a last-resort antibiotic despite its known nephrotoxicity. The aim of this study was to determine the potential nephroprotective effects of Magnesium (Mg) Sulfate during colistin therapy. This study was an open-label, placebo-controlled, block-randomized clinical trial conducted from January 2023 to February 2024 involving 87 patients eligible for colistin therapy. Patients were randomly assigned to receive either Mg sulfate (16 mEq in 100 mL of normal saline) or 100 mL of normal saline as placebo before each dose of colistin. The primary outcome of the study was the incidence of Acute Kidney Injury (AKI) during the first week of colistin therapy, while the secondary outcomes included colistin dose adjustments, length of stay in the ICU and hospital, and overall mortality. This study was registered in The Iranian Registry of Clinical Trials (IRCT20130917014693N15; 2023-01-12). A total of 87 patients (46 in Mg and 41 in control group) completed the study. Fourteen patients (30.43%) in the Mg group and twenty-one patients (51.21%) in the control group developed AKI during the first week of colistin therapy (p = 0.048). Although AKI incidence was not statistically different between the groups in unadjusted Cox regression model (HR =0.51, 95% CI =0.26-1.01, P =0.057), it became significant after adjusting for confounding factors (HR =0.40,95% CI =0.18-0.86, P =0.021). The length of hospital stay was 48.62 ± 18.82 and 44.82 ± 20.23 days for Mg and control groups respectively (p=0.373). In the Mg group, 25 out of 46 patients (54.34 %) and in the control group, 24 out of 41 patients (58.53%) eventually expired (p=0.694). This study indicates that Mg sulfate significantly reduces AKI rates and prevents hypomagnesemia, optimizing dosing and enhancing patient safety during colistin therapy.

Role and mechanism of the outer membrane porin LamB in T-2 mycotoxin-mediated extensive drug resistance in Escherichia coli

The influence of mycotoxins in ecological niches shared with antibiotic-resistant bacteria (ARB) remains underexplored. This study examined the impact of T-2 mycotoxin on the evolution of antibiotic resistance in Escherichia coli, highlighting the role of specific porins. Our findings revealed that exposure to 10ng/mL of T-2 toxin induced multi-drug resistant (MDR) phenotypes in three E. coli. At 10-5ng/mL, T-2 toxin caused E. coli ATCC 25922 to develop stable resistance to 13 critical antibiotics, with minimum inhibitory concentrations (MICs) increasing 16- to several thousand-fold. This resistance was linked to the downregulation of the mal gene cluster. Notably, T-2 toxin reduced membrane permeability by downregulating lamB, facilitating its own entry and reducing the intracellular accumulation of both the toxin and antibiotics, thereby enhancing resistance development. LamB mediated the XDR phenotypes in E. coli, particularly by blocking last-resort antibiotics such as cephalosporins, carbapenems, tigecycline, and colistin, complicating treatment strategies. LamB demonstrated high binding affinities for T-2 toxin and various antibiotics, with specific binding sites identified for meropenem (Arg134), imipenem (Ser148, Arg170, Lys129), ceftazidime (Phe106, Lys129), and cefepime (Tyr66, Gln267, Lys269), exhibiting binding energies of -2.93, -2.58, -2.53, and -4.3, respectively. These findings suggest that even low levels of T-2 mycotoxin pose a substantial public health risk. They underscore the urgent need to address these contaminants and open new avenues for antibiotic resistance research.

Development of a Providencia stuartii multilocus sequence typing scheme.

The Providencia genus is assuming greater clinical relevance among infections caused by Enterobacterales also because of its intrinsic and acquired resistance to last-resort antibiotics. However, despite having been known and studied for over 50 years, genomics and taxonomy of the Providencia genus are currently undergoing a deep rearrangement. In this study we aim to outline and characterized the P. stuartii species. We retrieved from the GenBank database all genomes labelled as Providencia and performed a comprehensive genome-based species definition founded on average nucleotide identity (ANI) and on alignment-free approaches. After defining the genomes assuredly identifiable as P. stuartii, we devised a MultiLocus Sequence Typing (MLST) and a core-genome MLST (cgMLST) schemes, based on 7 and 2,296 loci respectively. This work hence provides a framework for understanding the role of P. stuartii and of other members of this genus, which should be considered as emerging multidrug-resistant pathogens.

Observation of two novel mcr-10.1–carrying plasmids in clinical Escherichia coli strains

Abstract Polymyxins are a class of last-resort antibiotics used to treat infections caused by multidrug-resistant bacteria. Mobile resistance determinants for polymyxins, including mcr-1 to mcr-10 genes, have previously been reported. Among them, mcr-10 has commonly been observed in Enterobacter and Klebsiella species. However, the presence of mcr-10 in Escherichia coli, an important opportunistic pathogen, has rarely been reported. This work describes the observation of mcr-10.1 in two clinical E. coli strains, with mcr-10.1 hosted on two novel plasmids, one of which carrying transconjugation genes. These strains were isolated from anal fistula–suffering patients, suggesting their close relation to human bacterial infection. The genetic context of mcr-10.1 was also found to differ from those previously identified in E. coli strains. This work is the first observation of mcr-10.1–carrying E. coli in clinical settings, expanding our knowledge of this important antibiotic resistance gene.

Rifaximin prophylaxis causes resistance to the last-resort antibiotic daptomycin.

Multidrug-resistant bacterial pathogens like vancomycin-resistant Enterococcus faecium (VREfm) are a critical threat to human health1. Daptomycin is a last-resort antibiotic for VREfm infections with a novel mode of action2, but for which resistance has been widely reported but is unexplained. Here we show that rifaximin, an unrelated antibiotic used prophylactically to prevent hepatic encephalopathy in patients with liver disease3, causes cross-resistance to daptomycin in VREfm. Amino acid changes arising within the bacterial RNA polymerase in response to rifaximin exposure cause upregulation of a previously uncharacterized operon (prdRAB) that leads to cell membrane remodelling and cross-resistance to daptomycin through reduced binding of the antibiotic. VREfm with these mutations are spread globally, making this a major mechanism of resistance. Rifaximin has been considered 'low risk' for the development of antibiotic resistance. Our study shows that this assumption is flawed and that widespread rifaximin use, particularly in patients with liver cirrhosis, may be compromising the clinical use of daptomycin, a major last-resort intervention for multidrug-resistant pathogens. These findings demonstrate how unanticipated antibiotic cross-resistance can undermine global strategies designed to preserve the clinical use of critical antibiotics.

Resistance to carbapenems in the urban soil isolate Cupriavidus taiwanensis S2-1-W is associated with OXA-1206, a newly discovered carbapenemase.

Cupriavidus isolates are found in environmental and clinical samples and are often resistant to carbapenems, which are last-resort antibiotics. However, their carbapenem-resistance molecular mechanisms remain unknown. This study aimed to: 1) characterize and sequence the carbapenem-resistant soil isolate Cupriavidus taiwanensis S2-1-W to uncover its antibiotic resistance determinants; and 2) clone and characterize a putative novel carbapenemase gene identified in this isolate. Antibiotic susceptibility testing of C. taiwanensis S2-1-W revealed that it was resistant to most carbapenems, other β-lactams, and aminoglycosides tested. Genome sequencing of this isolate revealed a complex chromosomal resistome that included multidrug efflux pump genes, one aminoglycoside transferase gene, and three β-lactamase genes. Among them, we identified a novel putative class D β-lactamase gene (blaOXA-1206) that is highly conserved among other sequenced C. taiwanensis isolates. Cloning and characterization of blaOXA-1206 confirmed that it encodes for a newly discovered carbapenemase (OXA-1206) that confers resistance to carbapenems and other β-lactams. Carbapenem-resistance in C. taiwanensis S2-1-W is associated with a newly discovered carbapenemase, OXA-1206.

Cost-effectiveness analysis of polymyxin B versus colistin for treating patients with carbapenem-resistant gram-negative bacterial infections

The prevalence of carbapenem-resistant gram-negative bacterial (CRGNB) infection is continuously increasing, and polymyxin B and colistin are considered last-resort drugs. This study compared the cost-effectiveness of polymyxin B with that of colistin for the treatment of intensive care unit patients with CRGNB infection from the Chinese healthcare perspective. A decision-analytic Markov model was constructed to assess the cost-effectiveness of polymyxin B compared with colistin over a period of 5 years using evidence from phase trials and other publicly available studies. The model was developed in Treeage Pro 2022 and comprises a decision tree depicting initial hospitalization and a Markov model with four states projecting long-term health and economic impacts following discharge. Uncertainty was tested with one-way sensitivity analyses and probabilistic sensitivity analyses. The quality-adjusted life years (QALYs), direct medical costs, and incremental cost-effectiveness ratio (ICER) were estimated at willingness-to-pay (WTP) thresholds of $12,674 to $38,024 per QALY. According to the base analyses, the cost incurred by patients receiving colistin treatment was $12,244.77, leading to a gain of 1.35 QALYs. In contrast, patients treated with polymyxin B had a lower cost of $7,306.71 but yielded 1.07 QALYs. The ICRE of colistin was $18032.25/QALY. At a $12,674/QALY threshold, the results were sensitive to several variables, including the probability of cure with polymyxin B, the cost of drugs, the utility of discharge to home, the utility of discharge to long-term care, and the cost of nephrotoxicity with renal replacement therapy. After all model inputs varied across a wide range of reasonable values, only the probability of being cured with polymyxin B resulted in an ICER above the $38,024/QALY threshold. According to the probabilistic sensitivity analyses, colistin was the optimal strategy in 38.2% and 62.8% of the simulations, at $12,674/QALY and $38,024/QALY, respectively. Our study findings suggest that, when considering the Chinese healthcare perspective, colistin is likely to be more cost-effective than polymyxin B for patients with CRGNB infection, especially when the WTP threshold is set at one-time the per capita GDP. However, as the WTP threshold increases from one to three times the per capita GDP, the cost-effectiveness acceptability of colistin improves, increasing from 38.2 to 62.8%.

Pangenomes of human gut microbiota uncover links between genetic diversity and stress response

The genetic diversity of the gut microbiota has a central role in host health. Here, we created pangenomes for 728 human gut prokaryotic species, quadrupling the genes of strain-specific genomes. Each of these species has a core set of a thousand genes, differing even between closely related species, and an accessory set of genes unique to the different strains. Functional analysis shows high strain variability associates with sporulation, whereas low variability is linked with antibiotic resistance. We further map the antibiotic resistome across the human gut population and find 237 cases of extreme resistance even to last-resort antibiotics, with a predominance among Enterobacteriaceae. Lastly, the presence of specific genes in the microbiota relates to host age and sex. Our study underscores the genetic complexity of the human gut microbiota, emphasizing its significant implications for host health. The pangenomes and antibiotic resistance map constitute a valuable resource for further research.

Epidemiology, antimicrobial resistance profile and management of carbapenem-resistant Klebsiella pneumoniae among mothers with suspected sepsis in Ethiopia

BackgroundEarly detection and proper management of maternal sepsis caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) can significantly reduce severe complications and maternal mortality. This study aimed to describe the epidemiology, antimicrobial resistance profile, and management of carbapenem-resistant K. pneumoniae among sepsis-suspected maternal cases in Ethiopia.MethodsA prospective cross-sectional study was conducted in five tertiary hospitals from June 2021 to December 2023. Isolation, identification, and antimicrobial susceptibility testing of the isolates were carried out following standard microbiological procedures as stated in the CLSI guidelines. Data on socio-demographics, risk factors, and management strategies were collected with structured questionnaires. Associations between variables were determined using logistic regression analysis in STATA-21. A p-value of less than 0.05 was statistically significant.ResultsOf the 5613 total women suspected of having maternal sepsis, 609 (10.8%) of them were infected with K. pneumoniae. The prevalence rates of MDR, XDR, and PDR K. pneumoniae strains were 93.9%, 24.3%, and 10.9%, respectively. The resistance rates for the last-resort antibiotics; amikacin, tigecycline, carbapenem, and third-generation cephalosporin were 16.4%, 29.1%, 31.9%, and 93.0%, respectively. The combination of carbapenem with tigecycline or amikacin therapy was used to manage maternal sepsis caused by cephalosporin-and carbapenem-resistant strains. Sepsis associated risk factors, including septic abortion [AOR = 5.3; 95%CI:2.2–14.4]; extended hospitalization [AOR = 3.7; 95%CI: 1.6–19.4]; dilatation and curettage [AOR = 2.2; 95%CI:1.3–13.4]; cesarean wound infection [AOR = 4.1; 95%CI:2.0–9.2]; indwelling catheterization [AOR = 2.1;95%CI: 1.4–6.2]; ICU admission [AOR = 4.3; 95%CI:2.4–11.2]; post abortion [AOR = 9.8; 95%CI:5.7–16.3], and recurrent UTI [AOR = 3.3; 95%CI: 1.6–13.2] were significantly associated with maternal sepsis caused by K. pneumoniae.ConclusionsThe prevalence of maternal sepsis caused by carbapenem- resistant K. pneumoniae is high and serious attention needs to be given to combat transmission. Therefore, improving awareness, early diagnosis, IPC, integrated maternal surveillance, improved sanitation and efficient antimicrobial stewardship are crucial to combating bacterial maternal sepsis.

Valnemulin restores colistin sensitivity against multidrug-resistant gram-negative pathogens

Colistin is one of the last-resort antibiotics in treating infections caused by multidrug-resistant (MDR) pathogens. Unfortunately, the emergence of colistin-resistant gram-negative strains limit its clinical application. Here, we identify an FDA-approved drug, valnemulin (Val), exhibit a synergistic effect with colistin in eradicating both colistin-resistant and colistin-susceptible gram-negative pathogens both in vitro and in the mouse infection model. Furthermore, Val acts synergistically with colistin in eliminating intracellular bacteria in vitro. Functional studies and transcriptional analysis confirm that the combinational use of Val and colistin could cause membrane permeabilization, proton motive force dissipation, reduction in intracellular ATP level, and suppression in bacterial motility, which result in bacterial membrane disruption and finally cell death. Our findings reveal the potential of Val as a colistin adjuvant to combat MDR bacterial pathogens and treat recalcitrant infections.

Detection of extended-spectrum β-lactamase producing Escherichia coli in table eggs from Istanbul.

ESBL-producing Escherichia coli strains threaten public health and obligate the use of last-resort antibiotics. This study identified 15 E. coli isolates through 16S rRNA and gyrB genes, specific to E. coli, in 120 egg samples (12.5%). Antibiotic resistance was detected according to the EUCAST and CLSI in E. coli isolates. 2 isolates were susceptible to all antibiotics, one isolate was resistant to one antibiotic, one isolate was resistant to 2 antibiotics, and 11 E. coli isolates (73.3%) had multidrug resistance. Most frequent antibiotic resistances were detected against ampicillin (80%), tetracycline (66.6%), and chloramphenicol (66.6%). A double-disc confirmation test was used to detect ESBL production, and blaTEM, blaSHV, blaCTX-M and blaOXA genes were searched by PCR. The blaTEM (100%) gene was found in all resistant E. coli isolates, and the blaCTX-M gene was detected in only 3 (20%) E. coli isolates. None of the E. coli isolates contained the genes responsible for carbapenem and colistin resistance. Our results show that multi-drug antibiotic resistance and the blaTEM gene are frequent in E. coli from table eggs in Istanbul. This is the first preliminary study on ESBL-producing E. coli isolates in table eggs in Türkiye.

Occurrence and Antimicrobial Susceptibility Profile of Vancomycin Resistance among Clinical Isolates of Staphylococcus aureus in Enugu Metropolis, Nigeria

Introduction: Staphylococcus aureus is a significant cause of community-acquired and healthcare-acquired infections worldwide. Methicillin-resistant Staphylococcus aureus infections have been treated with vancomycin, a last-resort antibiotic. This study aimed to investigate the occurrence of vancomycin resistance among Staphylococcus aureus isolates obtained from different clinical samples. Materials and Methods: The study was conducted from February to August 2022 in the Microbiology Laboratory of the University of Nigeria Teaching Hospital Ituku-Ozalla, Enugu. A total of 150 Staphylococcus aureus isolates from different clinical samples were used for the study. The antimicrobial susceptibility profile was done using the Kirby-Bauer disc diffusion procedure. Methicillin resistance was detected using the cefoxitin disc diffusion technique. VRSA was confirmed using the broth dilution method. Results: Isolates showed high resistance to cephalosporins; 100% resistance to cefixime, to cefotaxime 98.7%, to cefuroxime 93.3%, and to ceftriaxone 80%. There was also high resistance of isolates to imipenem 98.7%, Augmentin 92.2%, erythromycin, and azithromycin 81.3% and 80.0% respectively. Of the 150 isolates, 51(34.0%) were methicillin-sensitive Staphylococcus aureus (MSSA) and 99(66.0%) were MRSA. Of the 99 MRSA strains, 9 (9.1%) were vancomycin-resistant (VRSA), 24 (24.2%) were vancomycin intermediate (VISA) and 66 (66.7%) were vancomycin-sensitive (VSSA). The overall prevalence of VRSA was 6%. Conclusion: The isolates had a high resistance to the antibiotics used in our study. The proportion of MRSA was high. A high percentage of VRSA/VISA was also detected. To prevent the further spread of VRSA, rigorous monitoring of vancomycin treatment, response, and the development of appropriate control guidelines are strongly recommended and required.

Tigecycline Resistant Pattern among Carbapenem Resistant Gram-negative Bacilli: Prospective Cross-sectional Study

Introduction: Tigecycline is a unique tetracycline class of semi-synthetic, last-line broad spectrum antibiotic against multi-drug-resistant bacteria. However, recently, resistance to this antibiotic is on the rise. Aims: This study was conducted to determine the prevalence of tigecycline resistance amongst carbapenem-resistant Gram-negative bacilli (GNB) isolated from clinical samples (pus and sputum) as well as to evaluate their antimicrobial susceptibility pattern. Study design: Prospective cross sectional Place and Duration of Study: Department of Microbiology at Sanjay Gandhi Post Graduate Institute of Medical Sciences Lucknow, between January 2023 and December 2023. Methodology: Identification of GNB grown on culture was done by conventional biochemical tests and later validated by MALDI-TOF MS. The antimicrobial sensitivity testing of isolates was done using the E-test, and disk diffusion method. Minimum inhibitory concentration determination was done by Broth micro-dilution (BMD) method. Results: Amongst 8326 pus and respiratory samples, GNBs were recovered from 63.15% (5258/8326). Of 5258 GNB isolates, 50.74% (2668) were carbapenem-resistant, while 7.85% (413) demonstrated resistance to both tigecycline and carbapenem. Common isolates in this group were Klebsiella pneumoniae (37.04%), Acinetobacter spp. (25.18%), Enterobacter spp. (14.28%) and Escherichia coli (12.59%). BMD results demonstrated highest activity of tigecycline against carbapenem-resistant E. coli, followed by Citrobacter and Enterobacter. It works against resistant strains of Acinetobacter baumannii and K. pneumoniae as well, but in higher concentrations. Conclusion: High tigecycline resistance (one of the last-resort drugs) among carbapenem resistant GNB isolates is a matter of clinical concern, leaving physicians with limited options for treatment of such infections. Proper adherence to the policies of antimicrobial stewardship programs can reduce the emergence of resistance.

Molecular characterization of NDM and OXA-48-like-producing Klebsiella pneumoniae ST16 and hypervirulent ST337 clone among two patients; a case report

Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections are a major public health problem, requiring the use of last-resort antibiotics such as colistin. However, there is concern regarding the emergence of isolates resistant to this agent. The report describes two patients with urinary tract infection (UTI) and ventilator-associated pneumonia (VAP) infection caused by CRKP strains. The first case was a 23-year-old male with UTI caused by a strain of ST16 co-harboring blaCTX-M, blaTEM, blaSHV, blaNDM, blaOXA-48-like genes. The second case was a 39-year-old woman with VAP due to hypervirulent ST337-K2 co-harboring blaSHV, blaNDM, blaOXA-48-like,iucA, rmpA2 and rmpA. The patients’ general condition improved after combination therapy with colistin (plus meropenem and rifampin, respectively) and both of them recovered and were discharged from the hospital. This study highlights the necessary prevention and control steps to prevent the further spread of CRKP strains should be a priority in our hospital.

The Occurrence of Colistin Resistance in Potential Lactic Acid Bacteria of Food-Producing Animals in India.

The overuse of colistin, the last-resort antibiotic, has led to the emergence of colistin-resistant bacteria, which is a major concern. Lactic acid bacteria which are generally regarded as safe are known to be reservoirs of antibiotic resistance that possibly pose a threat to human and animal health. Therefore, this study assessed the prevalence of colistin antimicrobial resistance in livestock in India, that is lactic acid bacteria in healthy chickens, sheep, beef, and swine of Mysore. Diverse phenotypic and genotypic colistin resistance were examined among the lactic acid bacterial species (n = 84) isolated from chicken (n = 44), sheep (n = 16), beef (n = 14), and swine (n = 10). Hi-comb, double-disk diffusion tests, Minimum Inhibitory Concentration (MIC), and biofilm formation were assessed for phenotypic colistin resistance. Specific primers for colistin-resistant genes were used for the determination of genotypic colistin resistance. Around 20%, 18%, and 1% were colistin-resistant Lactobacillus, Enterococcus, and Pediococcus species, respectively. Among these, 66.67% exhibited MDR phenotypes, including colistin antibiotic. The identified resistant isolates are Levilactobacillus brevis LBA and LBB (2), Limosilactobacillus fermentum LBF (1), and Pediococcus acidilactici CHBI (1). The mcr-1 and mcr-3 genes were detected in Levilactobacillus brevis LBA, LBB, and Pediococcus acidilactici CHBI isolated from chicken and sheep intestines respectively. The study identified colistin resistance determinants in lactobacilli from food animals, emphasizing the need for enhanced surveillance and monitoring of resistance spread. These findings underscore colistin resistance as a significant medical concern and should be integrated into India's ongoing antimicrobial resistance monitoring programs.

Resistance to ceftazidime-avibactam and other new β-lactams in Pseudomonas aeruginosa clinical isolates: a multi-center surveillance study.

Multidrug-resistant Pseudomonas aeruginosa infections are a growing threat due to the limited therapeutic options available. Ceftazidime-avibactam (CZA) is among the last-resort antibiotics for the treatment of difficult-to-treat P. aeruginosa infections, although resistance due to the acquisition of transferable β-lactamase genes is increasing. With this work, we report that CZA represents a highly active antipseudomonal β-lactam compound (after cefiderocol), and that metallo-β-lactamases (VIM-type) and extended-spectrum β-lactamases (GES and PER-type) production is the major factor underlying CZA resistance in isolates from Southern Italian hospitals. In addition, we reported that such resistance mechanisms were mainly carried by the international high-risk clones ST111 and ST235.

Colistin-Induced Acute Kidney Injury in the Treatment of Extensively Drug-Resistant Klebsiella Pneumoniae: A Case Report

This case report describes a 59-year-old male with uncontrolled type 2 diabetes mellitus who presented with recurrent urinary tract infections caused by multi-drug resistant Klebsiella pneumoniae. The patient's condition progressed from initial sensitivity to ceftazidime-avibactam to eventual resistance, leaving colistin as the only effective antibiotic. During the 19-day course of colistin therapy (900 mg daily), the patient developed severe acute kidney injury, with serum creatinine rising from 1.3 to 10.1 mg/dL, and colistin-induced peripheral neuropathy. Following discontinuation of colistin, partial renal recovery was observed, with creatinine decreasing to 2.5 mg/dL. This case highlights the challenges in managing extensively drug-resistant infections, the limited treatment options available, and the significant adverse effects associated with last-resort antibiotics like colistin. It underscores the urgent need for new antimicrobial strategies and emphasizes the importance of careful monitoring during treatment with potentially toxic antibiotics.

Characterization of a colistin resistant, hypervirulent hospital isolate of Acinetobacter courvalinii from Canada.

Non-baumannii Acinetobacter spp. are becoming more prevalent in clinical settings including those that present resistance to last-resort antibiotics such as colistin. AB222-IK40 is an Acinetobacter courvalinii strain isolated from the Ottawa Hospital Research Institute located in Ottawa, Canada. To our knowledge, it is the first report of clinical A. courvalinii in Canada. Based on the susceptibility profile, AB222-IK40 is resistant to colistin and non-susceptible to ertapenem. Whole-genome sequencing allowed for genomic investigation into colistin resistance mechanisms. No previously identified mechanism(s) were observed, but a mobile colistin resistance (mcr)-like gene and a UDP-glucose dehydrogenase gene were identified. Based on phylogenomic analyses, the mcr-like gene is an intrinsic phosphoethanolamine transferase. This gene family is implicated in one of the many mechanisms responsible for colistin resistance in Acinetobacter baumannii as well as Acinetobacter modestus. UDP-glucose dehydrogenase is involved in colistin resistance in Enterobacterales and has been shown to be involved in capsule formation in A. baumannii. Global lipidomics revealed greater abundance of phosphatidyl-myo-inositol and lyso-phosphatidyl ethanolamine moieties in the membrane of A. courvalinii than in A. baumannii. Lipidomic profiles showed differences that were probably responsible for the colistin resistance phenotype in AB222-IK40. This isolate was also hypervirulent based on survival assays in Galleria mellonella. As this is the first report of A. courvalinii from a hospital in Canada, this species may be an emerging clinical pathogen, and therefore, it is important to understand this mechanism of its colistin resistance and hypervirulence.

Antimicrobial Resistance Surveillance: Data Harmonisation and Data Selection within Secondary Data Use.

Resistance to last-resort antibiotics is a global threat to public health. Therefore, surveillance and monitoring systems for antimicrobial resistance should be established on a national and international scale. For the development of a One Health surveillance system, we collected exemplary data on carbapenem and colistin-resistant bacterial isolates from human, animal, food, and environmental sources. We pooled secondary data from routine screenings, hospital outbreak investigations, and studies on antimicrobial resistance. For a joint One Health evaluation, this study incorporates epidemiological metadata with phenotypic resistance information and molecular data on the isolate level. To harmonise the heterogeneous original information for the intended use, we developed a generic strategy. By defining and categorising variables, followed by plausibility checks, we created a catalogue for prospective data collections and applied it to our dataset, enabling us to perform preliminary descriptive statistical analyses. This study shows the complexity of data management using heterogeneous secondary data pools and gives an insight into the early stages of the development of an AMR surveillance programme using secondary data.

Colistin resistance in ESBL- and Carbapenemase-producing Escherichia coli and Klebsiella pneumoniae clinical isolates in Cambodia

Despite the critical importance of colistin as a last-resort antibiotic, limited studies have investigated colistin resistance in human infections in Cambodia. This study aimed to investigate the colistin resistance and its molecular determinants among Extended-spectrum beta-lactamase (ESBL)- and carbapenemase-producing (CP) Klebsiella pneumoniae (K. pneumoniae) and Escherichia coli (E. coli) isolated in Cambodia between 2016 and 2020. E. coli (n = 223) and K. pneumoniae (n = 39) were tested for colistin minimum inhibitory concentration (MIC) by broth microdilution. Resistant isolates were subjected to polymerase chain reaction (PCR) for detection of mobile colistin resistance genes (mcr) and chromosomal mutations in the two-component system (TCS). Eighteen isolates (10 K. pneumoniae and 8 E. coli) revealed colistin resistance with a rate of 5.9% in E. coli and 34.8% in K. pneumoniae among ESBL isolates, and 1% in E. coli and 12.5% in K. pneumoniae among CP isolates. The resistance was associated with mcr variants (13/18 isolates, mcr-1, mcr-3, and mcr-8.2) and TCS mutations within E. coli and K. pneumoniae, with the first detection of mcr-8.2 in Cambodia, the discovery of new mutations potentially associated to colistin resistance in the TCS of E. coli (PhoP I47V, PhoQ N352K, PmrB G19R, and PmrD G85R) and the co-occurrence of mcr genes and colistin resistance conferring TCS mutations in 11 of 18 isolates. The findings highlight the presence of colistin resistance in ESBL- and CP- Enterobacteriaceae involved in human infections in Cambodia as well as chromosomal mutations in TCS and the emergence of mcr-8.2 in E. coli and K. pneumoniae. It underscores the need for continuous surveillance, antimicrobial stewardship, and control measures to mitigate the spread of colistin resistance.