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Abstract Introduction The global increase of multidrug-resistant organisms (MDROs) is one of the most urgent public health threats affecting both humans and animals. The One Health concept emphasizes the interconnectedness of human, animal and environmental health and highlights the need for integrated approaches to combat antimicrobial resistance (AMR). Although the sharing of environments and antimicrobial agents between companion animals and humans poses a risk for MDRO transmission, companion animals have been studied to a lesser extent than livestock animals. This study therefore used core genome multilocus sequence typing (cgMLST) to investigate the genetic relationships and putative transmission of MDROs between humans and pets. Methods This descriptive integrated typing study included 252 human isolates, 53 dog isolates and 10 cat isolates collected from 2019 to 2022 at the Charité University Hospital in Berlin, Germany. CgMLST was performed to characterize methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci and multidrug-resistant gram-negative bacteria. The genetic diversity of the MDROs of the different host populations was determined and compared based on sequence type and core genome complex type. Results Within this study the majority of samples from pets and humans was genetically distinct. However, for some isolates, the number of allelic differences identified by cgMLST was low. Two cases of putative household transmission or shared source of VR E. faecium and MDR E. coli between humans and pets were documented. Conclusions The interaction between humans and their pets appears to play a minor role in the spread of the MDROs studied. However, further research is needed. This study emphasizes the importance of comprehensive molecular surveillance and a multidisciplinary One Health approach to understand and contain the spread of MDROs in human and animal populations. Trial Registration The study is registered with the German Clinical Trials Register (DRKS00030009).

Abstract Background Extended-spectrum beta-lactamase (ESBL)-producing Gram-negative bacteria have become a serious threat to global health. Their rapid spread is associated with high mortality due to ineffective antibiotic treatment. To date a regular surveillance of multidrug-resistant (MDR) pathogens in Ethiopia is not established. For this report, published data regarding ESBL-producing bacteria in different health facilities of Ethiopia were reviewed. Methods This study collates data from published information on the rates and clinical implications of infection with ESBL-producing Gram-negative bacteria in Ethiopia. A systematic literature search was conducted using PubMed, PubMed Central, Medline, Science Direct and Google scholar from October 2018 to March 2019. Eligible studies were identified by applying quality criteria. The pooled proportion of ESBL-producing Gram-negative bacteria was estimated based on a random effect model. The publication bias and the variation in proportion estimates attributed to heterogeneity were assessed. Results Fourteen studies with relevant data were included in the review. In total, 1649 Gram-negative bacteria isolated from 5191 clinical samples were included. The pooled proportion estimate of ESBL-producing Gram-negative bacteria was 50% (95% CI: 47.7–52.5%. Data showed a high level of heterogeneity (I2 = 95%, P

Abstract Background A multitude of definitions determining multidrug resistance (MDR) of Gram-negative organisms exist worldwide. The definitions differ depending on their purpose and on the issueing country or organization. The MDR definitions of the European Centre for Disease Prevention and Control (ECDC) were primarily chosen to harmonize epidemiological surveillance. The German Commission of Hospital Hygiene and Infection Prevention (KRINKO) issued a national guideline which is mainly used to guide infection prevention and control (IPC) measures. The Swiss University Hospital Zurich (UHZ) – in absentia of national guidelines – developed its own definition for IPC purposes. In this study we aimed to determine the effects of different definitions of multidrug-resistance on rates of Gram-negative multidrug-resistant organisms (GN-MDRO). Methods MDR definitions of the ECDC, the German KRINKO and the Swiss University Hospital Zurich were applied on a dataset comprising isolates of Escherichia coli, Klebsiella pneumoniae, Enterobacter sp., Pseudomonas aeruginosa, and Acinetobacter baumannii complex. Rates of GN-MDRO were compared and the percentage of patients with a GN-MDRO was calculated. Results In total 11′407 isolates from a 35 month period were included. For Enterobacterales and P. aeruginosa, highest MDR-rates resulted from applying the ‘ECDC-MDR’ definition. ‘ECDC-MDR’ rates were up to four times higher compared to ‘KRINKO-3/4MRGN’ rates, and up to six times higher compared to UHZ rates. Lowest rates were observed when applying the ‘KRINKO-4MRGN’ definitions. Comparing the ‘KRINKO-3/4MRGN’ with the UHZ definitions did not show uniform trends, but yielded higher rates for E. coli and lower rates for P. aeruginosa. On the patient level, the percentages of GN-MDRO carriers were 2.1, 5.5, 6.6, and 18.2% when applying the ‘KRINKO-4MRGN’, ‘UHZ-MDR’, ‘KRINKO-3/4MRGN’, and the ‘ECDC-MDR’ definition, respectively. Conclusions Different MDR-definitions lead to considerable variation in rates of GN-MDRO. Differences arise from the number of antibiotic categories required to be resistant, the categories and drugs considered relevant, and the antibiotic panel tested. MDR definitions should be chosen carefully depending on their purpose and local resistance rates, as definitions guiding isolation precautions have direct effects on costs and patient care.

Abstract Background Enterococcus faecalis is a ubiquitous member of the gut microbiota and has emerged as a life- threatening multidrug-resistant (MDR) nosocomial pathogen. The aim of this study was to survey the prevalence of multidrug-resistant and epidemiologically important strains of E. faecalis in the western region of Saudi Arabia using phenotypic and whole genome sequencing approaches. Methods In total, 155 patients positive for E. faecalis infection were included in this study. The isolates were identified by MALDI-TOF, and screen for antimicrobial resistance using VITEK-2 system. Genome sequencing was performed with paired-end strategy using MiSeq platform. Results Seventeen sequence types (STs) were identified through multilocus sequence typing (MLST) analysis of the E. faecalis genomes, including two novels STs (ST862 and ST863). The most common STs in the Saudi patients were ST179 and ST16 from clonal complex 16 (CC16). Around 96% (n = 149) isolates were MDR. The antibiotics quinupristin/dalfopristin, clindamycin, and erythromycin demonstrated almost no coverage, and high-level streptomycin, gentamycin, and ciprofloxacin demonstrated suboptimal coverage. Low resistance was observed against vancomycin, linezolid, and ampicillin. Moreover, 34 antimicrobial resistance genes and variants, and three families of insertion sequences were found in the E. faecalis genomes, which likely contributed to the observed antimicrobial resistance. Twenty-two virulence factors, which were mainly associated with biofilm formation, endocarditis, cell adherence, and colonization, were detected in the isolates. Conclusions Diverse STs of E. faecalis, including strains associated with common nosocomial infections are circulating in the healthcare facility of Saudi Arabia and carried multi-drug resistance, which has important implications for infection control.

Abstract Background Patients with complicated urinary tract infections (cUTIs) frequently receive broad-spectrum antibiotics. We aimed to determine the prevalence and predictive factors of multidrug-resistant gram-negative bacteria in patients with cUTI. Methods This is a multicenter, retrospective cohort study in south and eastern Europe, Turkey and Israel including consecutive patients with cUTIs hospitalised between January 2013 and December 2014. Multidrug-resistance was defined as non-susceptibility to at least one agent in three or more antimicrobial categories. A mixed-effects logistic regression model was used to determine predictive factors of multidrug-resistant gram-negative bacteria cUTI. Results From 948 patients and 1074 microbiological isolates, Escherichia coli was the most frequent microorganism (559/1074), showing a 14.5% multidrug-resistance rate. Klebsiella pneumoniae was second (168/1074) and exhibited the highest multidrug-resistance rate (54.2%), followed by Pseudomonas aeruginosa (97/1074) with a 38.1% multidrug-resistance rate. Predictors of multidrug-resistant gram-negative bacteria were male gender (odds ratio [OR], 1.66; 95% confidence interval [CI], 1.20–2.29), acquisition of cUTI in a medical care facility (OR, 2.59; 95%CI, 1.80–3.71), presence of indwelling urinary catheter (OR, 1.44; 95%CI, 0.99–2.10), having had urinary tract infection within the previous year (OR, 1.89; 95%CI, 1.28–2.79) and antibiotic treatment within the previous 30 days (OR, 1.68; 95%CI, 1.13–2.50). Conclusions The current high rate of multidrug-resistant gram-negative bacteria infections among hospitalised patients with cUTIs in the studied area is alarming. Our predictive model could be useful to avoid inappropriate antibiotic treatment and implement antibiotic stewardship policies that enhance the use of carbapenem-sparing regimens in patients at low risk of multidrug-resistance.

Abstract Background A high level of antibiotic consumption in France means antimicrobial resistance requires rigorous monitoring. The Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) is a global surveillance study that monitors the in vitro activities of tigecycline and a panel of marketed antimicrobials against clinically important Gram-positive and Gram-negative isolates. Methods Annually clinically relevant strains were prospectively included in the survey through a national network of hospital-based laboratories. MICs were determined locally by broth microdilution using CLSI guidelines. Antimicrobial susceptibility was assessed using European Committee on Antimicrobial Susceptibility Testing breakpoints. Results Thirty-three centres in France collected 26,486 isolates between 2004 and 2016. Enterococcus species were highly susceptible (≥94.4%) to linezolid, tigecycline and vancomycin. Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), were susceptible (≥99.9%) to tigecycline, vancomycin and linezolid. Between 2004 and 2016, 27.7% of S. aureus isolates were MRSA, decreasing from 28.0% in 2013 to 23.5% in 2016. Susceptibility of Streptococcus pneumoniae isolates was 100% to vancomycin, and > 99.0% to levofloxacin, linezolid and meropenem; 3.0% were penicillin-resistant S. pneumoniae (100% susceptibility to vancomycin and linezolid). Escherichia coli isolates were highly susceptible (> 98.0%) to meropenem, tigecycline and amikacin. The rate of extended-spectrum β-lactamase (ESBL) positive E. coli increased from 2004 (3.0%), but was stable from 2012 (23.1%) to 2016 (19.8%). Susceptibility of Klebsiella pneumoniae isolates was 99.4% to meropenem and 96.5% to amikacin. The proportion of ESBL-positive K. pneumoniae isolates increased from 2004 (7.5%) to 2012 (33.3%) and was highest in 2016 (43.6%). A. baumannii was susceptible to meropenem (81.0%) and amikacin (74.9%); none of the 6.2% of isolates identified as multidrug-resistant (MDR) was susceptible to any agents with breakpoints. P. aeruginosa isolates were most susceptible to amikacin (88.5%), and MDR rates were 13.6% in 2013 to 4.0% in 2016; susceptibility of MDR isolates was no higher than 31.4% to amikacin. Conclusions Rates of MRSA decreased slowly, while rates of ESBL-positive E. coli and K. pneumoniae increased from 2004 to 2016. Susceptibility of Gram-positive isolates to vancomycin, tigecycline, meropenem and linezolid was well conserved, as was susceptibility of Gram-negative isolates to tigecycline and meropenem. The spread of MDR non-fermentative isolates must be carefully monitored.

Abstract Background Multidrug-resistant Gram-negative bacteria (MDRGN), including extended-spectrum β-lactamases (ESBLs) and multidrug-resistant glucose-nonfermenting Gram-negative bacilli (nonfermenters), have emerged and spread throughout Southeast Asia. Methods We reviewed and summarized current critical knowledge on the epidemiology and molecular characterization of MDRGN in Southeast Asia by PubMed searches for publications prior to 10 March 2016 with the term related to “MDRGN definition” combined with specific Southeast Asian country names (Thailand, Singapore, Malaysia, Vietnam, Indonesia, Philippines, Laos, Cambodia, Myanmar, Brunei). Results There were a total of 175 publications from the following countries: Thailand (77), Singapore (35), Malaysia (32), Vietnam (23), Indonesia (6), Philippines (1), Laos (1), and Brunei (1). We did not find any publications on MDRGN from Myanmar and Cambodia. We did not include publications related to Shigella spp., Salmonella spp., and Vibrio spp. and non-human related studies in our review. English language articles and abstracts were included for analysis. After the abstracts were reviewed, data on MDRGN in Southeast Asia from 54 publications were further reviewed and included in this study. Conclusions MDRGNs are a major contributor of antimicrobial-resistant bacteria in Southeast Asia. The high prevalence of ESBLs has been a major problem since 2005 and is possibly related to the development of carbapenem resistant organisms in this region due to the overuse of carbapenem therapy. Carbapenem–resistant Acinetobacter baumannii is the most common pathogen associated with nosocomial infections in this region followed by carbapenem-resistant Pseudomonas aeruginosa. Although Southeast Asia is not an endemic area for carbapenem-resistant Enterobacteriaceae (CRE), recently, the rate of CRE detection has been increasing. Limited infection control measures, lack of antimicrobial control, such as the presence of active antimicrobial stewardship teams in the hospital, and outpatient antibiotic restrictions, and travel throughout this region have likely contributed to the increase in MDRGN prevalence.

Background: The widespread application of triclosan contributes to its residual deposition in urine, which provides an environment of long-term exposure to triclosan for the intestinal Escherichia coli. We determined the triclosan and antibiotic resistance characteristics of E. coli strains isolated from urine samples and further investigated the resistance mechanism and molecular epidemic characteristics of triclosan-resistant E. coli isolates., Methods: A total of 200 non-repetitive E. coli strains were isolated from urine samples and then identified. The minimum inhibitory concentrations (MICs) of triclosan and antibiotics, fabI mutation, efflux pump activity, the expression of 14 efflux pump encoding genes, and epidemiological characteristics were determined by the agar dilution method, polymerase chain reaction (PCR), carbonyl cyanide 3-chlorophenylhydrazone (CCCP) inhibition test, quantitative real-time polymerase chain reaction (RT-qPCR), multilocus sequence typing (MLST), and pulse-field gel electrophoresis (PFGE) for all triclosan-resistant isolates. Furthermore, we also investigated the effect of triclosan exposure in vitro on antibiotic susceptibility and the efflux pump encoding gene expressions of triclosan-susceptible strains via serial passage experiments., Results: Of the 200 E. coli isolates, 2.5% (n = 5) were found to be resistant to triclosan, and multidrug resistance (MDR) and cross-resistance phenotypes were noted for these triclosan-resistant strains. The triclosan-sensitive strains also exhibited MDR phenotypes, probably because of the high resistance rate to AMP, CIP, LVX, and GEN. Gly79Ala and Ala69Thr amino acid changes were observed in the triclosan-resistant strains, but these changes may not mediate resistance of E. coli to triclosan, because mutations of these two amino acids has also been detected in triclosan-susceptible strains. Moreover, except for DC8603, all other strains enhanced the efflux pumps activity. As compared with ATCC 25922, except for fabI, increased expressions were noted for all efflux pump encoding genes such as ydcV, ydcU, ydcS, ydcT, cysP, yihV, acrB, acrD, and mdfA among the studied strains with varying PFGE patterns and STs types. Unexpectedly, 5 susceptible E. coli isolates showed rapidly increasing triclosan resistance after exposure to triclosan in vitro for only 12 days, while MDR or cross-resistance phenotypes and the overexpression of efflux pump genes were recorded among these triclosan-induced resistant isolates., Conclusions: This is the first study to report that short-term triclosan exposure in vitro increases triclosan resistance in susceptible E. coli isolates. After acquiring resistance, these strains may present MDR or cross-resistance phenotypes. Moreover, triclosan resistance mainly involves the overexpression of fabI and efflux pumps in E. coli isolates.