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Background: Carbapenem-resistant bacteria are an increasing problem in clinical practice; thus, it is important to identify β-lactamase inhibitors (e.g., relebactam) that can restore carbapenem susceptibility. We report analyses of relebactam enhancement of imipenem activity against both imipenem-nonsusceptible (NS) and imipenem-susceptible (S) Pseudomonas aeruginosa and Enterobacterales. Gram-negative bacterial isolates were collected for the ongoing Study for Monitoring Antimicrobial Resistance Trends global surveillance program. Clinical and Laboratory Standards Institute–defined broth microdilution minimum inhibitory concentrations (MIC) were used to determine the imipenem and imipenem/relebactam antibacterial susceptibilities of P. aeruginosa and Enterobacterales isolates. Results: Between 2018 and 2020, 36.2% of P. aeruginosa (N = 23,073) and 8.2% of Enterobacterales (N = 91,769) isolates were imipenem-NS. Relebactam restored imipenem susceptibility in 64.1% and 49.4% of imipenem-NS P. aeruginosa and Enterobacterales isolates, respectively. Restoration of susceptibility was largely observed among K. pneumoniae carbapenemase-producing Enterobacterales and carbapenemase-negative P. aeruginosa. Relebactam also caused a lowering of imipenem MIC among imipenem-S P. aeruginosa and Enterobacterales isolates from chromosomal Ambler class C β-lactamase (AmpC)–producing species. For both imipenem-NS and imipenem-S P. aeruginosa isolates, relebactam reduced the imipenem MIC mode from 16 μg/mL to 1 μg/mL and from 2 μg/mL to 0.5 μg/mL, respectively, compared with imipenem alone. Conclusions: Relebactam restored imipenem susceptibility among nonsusceptible isolates of P. aeruginosa and Enterobacterales and enhanced imipenem susceptibility among susceptible isolates of P. aeruginosa and isolates from Enterobacterales species that can produce chromosomal AmpC. The reduced imipenem modal MIC values with relebactam may result in a higher probability of target attainment in patients. [ABSTRACT FROM AUTHOR]

The high resistance of K. pneumoniae strains to various antibiotics is remarkable. The most important virulence factors for K. pneumoniae include fimbriae, capsule, lipopolysaccharide, outer membrane proteins, and iron transport molecules. The aim of this study was to investigate the prevalence of capsule (wabG) and fimbriae (fimH) coding genes in MDR K. pneumoniae strains isolated from patients admitted to Isfahan (Iran) hospitals. The antibiotic susceptibility pattern of the isolates was carried out by the disk diffusion method. Definitive confirmation of MDR isolates was done by tracing the 16S-23S ITS gene, and the presence of capsule (wabG) and fimbriae (fimH) genes was investigated in the isolates. Data analysis was done using an independent parametric T-test and one-way analysis of variance (ANOVA). One hundred and two K. pneumoniae isolates were detected in the samples, including urine, respiratory tract, blood, throat, cerebrospinal fluid, direct discharge, wound secretions, pleural fluid, joint fluid, abscess discharge, stool, and sputum. Men were significantly more infected with K. pneumoniae than women. The highest frequency of the isolates was related to urine (40%), followed by the respiratory tract (27%). The largest number of isolates were found in the ICU (37%) and emergency (28%) departments. Out of the 102 isolates of K. pneumoniae, 50 isolates (49%) were MDR, and 50 (49%) were carbapenemresistant. Of the 50 MDR isolates, 48 (96%) and 47 (94%) had fimH and wabG genes, respectively. High frequencies of MDR and carbapenem-resistant strains of K. pneumoniae with a high prevalence of fimH and wabG genes are significant and should be considered by healthcare management. [ABSTRACT FROM AUTHOR]

Uropathogenic Escherichia coli (UPEC) are the strains diverted from the intestinal status and account mainly for uropathogenicity. This pathotype has gained specifications in structure and virulence to turn into a competent uropathogenic organism. Biofilm formation and antibiotic resistance play an important role in the organism’s persistence in the urinary tract. Increased consumption of carbapenem prescribed for multidrug-resistant (MDR) and Extended-spectrum-beta lactamase (ESBL)-producing UPECs, has added to the expansion of resistance. The World Health Organization (WHO) and Centre for Disease Control (CDC) placed the Carbapenem-resistant Enterobacteriaceae (CRE) on their treatment priority lists. Understanding both patterns of pathogenicity, and multiple drug resistance may provide guidance for the rational use of anti-bacterial agents in the clinic. Developing an effective vaccine, adherence-inhibiting compounds, cranberry juice, and probiotics are non-antibiotical approaches proposed for the treatment of drug-resistant UTIs. We aimed to review the distinguishing characteristics, current therapeutic options and promising non-antibiotical approaches against ESBL-producing and CRE UPECs. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this case report is to describe spasticity and encephalopathy that developed in a multiple sclerosis patient following carbapenem administration. Summary: A 55-year-old female with multiple sclerosis developed spasticity and encephalopathy within 24 hours of meropenem and ertapenem administration. This was the second time that she had developed encephalopathy following carbapenem administration. The patient gradually recovered over four days following discontinuation of carbapenem therapy. Conclusion: Carbapenem neurotoxicity, a well-documented adverse effect, has been linked to several risk factors, including central nervous system lesions. Despite this, there is little evidence describing the risk of neurotoxicity in patients with multiple sclerosis. It is important to understand the potential adverse effects of carbapenems in specific patient populations to help guide appropriate treatment of infections. [ABSTRACT FROM AUTHOR]

The aim of this study was to understand the molecular epidemiological characteristics and drug resistance mechanism of carbapenem-resistant Pseudomonas aeruginosa (CRPA) and to provide a theoretical basis for the prevention and treatment of CRPA infection in hospitals. A total of 34 CRPA strains were isolated, and resistance to 13 commonly used antibiotics was detected using the TDR-300B Plus VitEK-2 compact automatic bacterial identification instrument. Then, carbapenemase production was detected using the Carbe NP test. RT-qPCR was used to detect the expression of efflux pump MexA and outer membrane protein OprD, and PCR amplification and sequence analysis were used to detect class Ⅰ integrons carried by drug resistance genes. Our results showed that of the 34 CRPAs, 22 were multi-drug resistant (MDR), and five were extensively drug-resistant (XDR). Sequencing analysis showed that class Ⅰ integron mainly carried aminoglycosides or quinolones resistance genes. Multiple mechanisms play important roles in the formation and development of MDR or XDR. [ABSTRACT FROM AUTHOR]

For people living in developed countries life span is growing at a faster pace than ever. One of the main reasons for such success is attributable to the introduction and extensive use in the clinical practice of antibiotics over the course of the last seven decades. In hospital settings, Klebsiella pneumoniae represents a well-known and commonly described opportunistic pathogen, typically characterized by resistance to several antibiotic classes. On the other hand, the broad wedge of population living in Low and/or Middle Income Countries is increasing rapidly, allowing the spread of several commensal bacteria which are transmitted via human contact. Community transmission has been the original milieu of K. pneumoniae isolates characterized by an outstanding virulence (hypervirulent). These two characteristics, also defined as "pathotypes", originally emerged as different pathways in the evolutionary history of K. pneumoniae. For a long time, the Sequence Type (ST), which is defined by the combination of alleles of the 7 housekeeping genes of the Multi-Locus Sequence Typing, has been a reliable marker of the pathotype: multidrug-resistant clones (e.g. ST258, ST147, ST101) in the Western world and hypervirulent clones (e.g. ST23, ST65, ST86) in the Eastern. Currently, the boundaries separating the two pathotypes are fading away due to several factors, and we are witnessing a worrisome convergence in certain high-risk clones. Here we review the evidence available on confluence of multidrug-resistance and hypervirulence in specific K. pneumoniae clones. [ABSTRACT FROM AUTHOR]

The emergence and spread of carbapenemase genes, colistin resistance genes mcr-1, and tigecycline resistance gene tet(X) represent a significant threat to clinical therapy and public health. In this study, we investigated the presence of carbapenemase genes, mcr-1, and tet(X) in 298 Escherichia coli strains obtained froma teaching hospital inChina. In total, eight (2.68%), six (2.01%), and one (0.34%) E. coli isolates carried blaNDM, mcr-1, and tet(X4), respectively. The blaNDM gene was located on IncX3 (n = 4), F2:A-:B- (n = 3), and F2:A1:B1 (n = 1) plasmids, with high similarity to multiple plasmids belonging to the same incompatibility type from Enterobacteriaceae. Six MCR-producing strains contained mcr-1-carrying IncI2 plasmids, organized similarly to other mcr-1-bearing IncI2 plasmids from animals in China. The blaCTX--M--55/64/132/199 gene located within a typical transposition unit (ISEcp1-blaCTX--M-orf477Δ) was inserted near dnaJ to generate 5-bp direct repeats in four mcr-1-positive plasmids. The tet(X) and another four resistance genes [aadA2, tet(A), floR, and Δlnu(F)] were co-located on an IncX1 plasmid, highly similar to other tet(X4)-carrying IncX1 plasmids from Escherichia and Klebsiella of animal or food origin, except that the conjugative transfer region of IncX1 plasmids was absent in our plasmid. Although a low prevalence of blaNDM, mcr-1, and tet(X) was observed in E. coli from patients in this study, their dissemination associated with some successful pandemic plasmids is of great concern. The continued surveillance of these crucial resistance genes in patients should be strengthened. [ABSTRACT FROM AUTHOR]

The appropriate use of carbapenem is a critical concern for patient safety and public health, and is a national priority. We investigated the nationwide status of carbapenem prescription in patients within their last 14 days of life to guide judicious-use protocols from the previous study comprised of 1350 decedents. Carbapenem use was universally controlled through computerised authorisation system at all centres during the study period. Carbapenem prescribing patterns and their optimality were evaluated. A total of 1201 patients received antimicrobial agents within the last two weeks of their lives, of whom 533 (44.4%) received at least one carbapenem. The median carbapenem treatment duration was seven days. Of the 533 patients receiving carbapenems, 510 (95.7%) patients had microbiological samples drawn and 196 (36.8%) yielded carbapenem-resistant pathogens. A total of 200 (37.5%) patients were referred to infectious disease (ID) specialists. Of the 333 patients (62.5%) who did not have ID consultations, 194 (58.2%) were assessed as "not optimal", 79 (23.7%) required escalation, 100 (30.0%) required de-escalation, and 15 (4.5%) were discontinued. Notwithstanding the existing antibiotic restriction program system, carbapenems are commonly prescribed to patients in their last days of life. [ABSTRACT FROM AUTHOR]

Efflux pumps play an important role in the emergence of antibiotic-resistant Pseudomonas aeruginosa strains. The present study aimed to assess the expression of the MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY-OprM efflux pumps in carbapenem-resistant and multidrug-resistant (MDR) P. aeruginosa strains isolated from clinical specimens between June 2019 and January 2022 in Ardabil city. The presence of efflux pump-encoding genes, i.e. mexA , mexC , mexE , and mexY , was assessed using the polymerase chain reaction (PCR) technique in 48 carbapenem-resistant and MDR P. aeruginosa strains. Real-time reverse transcription PCR was employed to evaluate the expression levels of mexA , mexC , mexE , and mexY genes. All 48 carbapenem-resistant and MDR P. aeruginosa strains harbored efflux pump-encoding genes including mexA , mexC , mexE , and mexY according to the PCR results. Overexpression of the MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY-OprM efflux pumps was detected in 75% (n = 36), 83.3% (n = 40), 10.4% (n = 5) and 41.6% (n = 20) of the clinical isolates of P. aeruginosa, respectively. This study revealed that the presence and overexpression of efflux pumps are associated with the emergence of carbapenem-resistant and MDR P. aeruginosa strains. Therefore, research on efflux pump inhibitors of P. aeruginosa will be a worthwhile endeavor to increase the clinical efficiency of available antibiotics and prevent ensuing treatment failure. [ABSTRACT FROM AUTHOR]

Objective: Pseudomonas aeruginosa is a common cause of nosocomial infections worldwide. Increasing in the emergence and spread of multidrug-resistant (MDR) strains is a serious health concern. The aim of the present study was to determine the antibiotic resistance pattern of P. aeruginosa isolated from clinical samples. Materials and Methods: The current retrospective cross-sectional study was conducted at a tertiary-care hospital in Oman. The data of P. aeruginosa isolates identified during 2015–2019 at Sohar Hospital were retrieved from Al-Shifa computerized data system. The data were systematically analyzed using SPSS 22 software system, IBM Chicago. Descriptive statistics were applied to find frequencies and percentages. Trends were analyzed using a one-sample Chi-square test. Results: A total of 5865 P. aeruginosa strains identified in clinical samples of 4024 patients were studied. The frequency of isolation of P. aeruginosa was more among people aged >60 years (33%). The rate of isolation was significantly high (47%) in pus/wound swabs. The overall resistance of P. aeruginosa was low to moderate (10%–30%) to commonly used anti-pseudomonal drugs. Among, 10% were MDR strains. The lowest resistance (10%) was observed to piperacillin-tazobactam (TAZP), while significantly high resistance (29%–30%) was exhibited by carbapenems. Furthermore, strains isolated from respiratory secretions and urine samples have shown a significantly high percentage of resistance compared to others. Conclusions: Piperacillin-tazobactam is recommended as the drug of choice for treating especially severe Pseudomonas infections. Moderate resistance to carbapenems is an alarming sign. This pattern of resistance suggests the probable overuse of drugs. Therefore, it emphasizes strict antibiotic policy, rapid detection, and continuous monitoring of drug-resistant strains, and timely dissemination of the resistant report to clinicians.

Background: Acinetobacter baumannii can reside in humans without causing infection or symptoms but can opportunistically cause community and nosocomial infections. Few studies from Taiwan have used national-level data to investigate antibiotic resistance rates of A. baumannii infections in the intensive care units (ICUs) of medical centers. Aim: This study determined the number of infection sites of A. baumannii and the resistance rates of carbapenem-resistant A. baumannii (CRAB) infections in ICUs in Taiwan, and identified trends over time, variations of infection site, and factors associated with resistance. Methods: This study used the database provided by Taiwan's Centers for Disease Control. Yearly, Taiwan Nosocomial Infections Surveillance System Surveys from 2008 to 2019 were analyzed, including data on the site of infection and resistance rates of A. baumannii and patient and hospital characteristics. Results: On average, 21 hospitals as medical center/year participated in the survey, and 6803 A. baumannii isolates were identified. All isolates were health care-related infections. The most frequent sites of infection were the urinary tract (50.6%), respiratory tract (19.6%), bloodstream (18.2%), surgical wounds (4.3%), and others (7.4%). Infection rates were the highest in the urinary tract in 2019 (63.6%; P < 0.001). On average, the rate of carbapenem resistance was 66.6% (95% confidence interval: 63.1–70.1) among ICU patients at medical centers. Considerable regional differences were observed, with the highest rates of resistance in the central regions. Higher resistance rates were observed between 2019 and 2020 COVID-19 pandemic (74.2%). Conclusion: This is the first report on the prevalence of health care-related A. baumannii infection in Taiwan in 2008–2019. Several invasive diseases, such as urinary tract infections, are associated with higher rates of carbapenem resistance. The resistance rate of CRAB in Taiwan is exceptionally high. The current big-data-derived findings may inform future surveillance and research efforts in Taiwan.

Carbapenem antibiotics are considered one of the most effective and the last-resort antibiotics for the treatment of infections caused by multidrug-resistant Gram-negative bacteria. However, with the advent of carbapenem resistance, it becomes obvious that quality health-care delivery will be hampered if adequate measure is not put in place. This review assessed the prevalence of carbapenem-resistant Gram-negative bacteria (CR-GNB) and also provided an up-to-date position on carbapenem resistance (CR) in Nigeria. Three electronic databases (Google Scholar, PubMed and African Journal online) were searched for relevant literatures, and 38 articles published between January 2013 and June 2022 that met the criteria for inclusion were recruited into the study. The mean prevalence of CR in Nigeria stands at 21.3%, with the southern and northern regions documenting a mean prevalence of 22.0% and 20.9%, respectively. Most of the reviewed articles were from clinical settings (81.6%), with urine samples (38.7%) constituting the most prevalent clinical sample in which CR-GNB were detected. The preponderance of phenotypic methods (55.3%) over molecular method (44.7%), particularly the use of disk diffusion test breakpoint and Modified Hodge test was documented. The most prevalent carbapenem-resistant bacteria were Escherichia coli (50.0%) and Klebsiella pneumoniae (26.3%). The blaNDM and blaVIM were the major reported carbapenemase-encoded genes, particularly among E. coli, K. pneumoniae and Pseudomonas species. This systematic review revealed a mean prevalence of CR-GNB in Nigeria that required urgent attention. Furthermore, the detection of clinically and epidemiologically important carbapenemase coding genes is of public health importance.

Abstract Background Klebsiella pneumoniae (Kp) Gram-negative bacteria cause nosocomial infections and rapidly acquire antimicrobial resistance (AMR), which makes it a global threat to human health. It also has a comparatively rare hypervirulent phenotype that can lead to severe disease in otherwise healthy individuals. Unlike classic Kp, canonical hypervirulent strains usually have limited AMR. However, after initial case reports in 2015, carbapenem-resistant hypervirulent Kp has increased in prevalence, including in China, but there is limited understanding of its burden in other geographical regions. Methods Here, we examined the largest collection of publicly available sequenced Kp isolates (n=13,178), containing 1603 different sequence types (e.g. ST11 15.0%, ST258 9.5%), and 2174 (16.5%) hypervirulent strains. We analysed the plasmid replicons and carbapenemase and siderophore encoding genes to understand the movement of hypervirulence and AMR genes located on plasmids, and their convergence in carbapenem-resistant hypervirulent Kp. Results We identified and analysed 3034 unique plasmid replicons to inform the epidemiology and transmission dynamics of carbapenem-resistant hypervirulent Kp (n=1028, 7.8%). We found several outbreaks globally, including one involving ST11 strains in China and another of ST231 in Asia centred on India, Thailand, and Pakistan. There was evidence of global flow of Kp, including across multiple continents. In most cases, clusters of Kp isolates are the result of hypervirulence genes entering classic strains, instead of carbapenem resistance genes entering canonical hypervirulent ones. Conclusions Our analysis demonstrates the importance of plasmid analysis in the monitoring of carbapenem-resistant and hypervirulent strains of Kp. With the growing adoption of omics-based technologies for clinical and surveillance applications, including in geographical regions with gaps in data and knowledge (e.g. sub-Saharan Africa), the identification of the spread of AMR will inform infection control globally.

Aim: This study aimed to determine the susceptibility of carbapenem-resistant Gr (-) bacilli isolated from various clinical infections to various antibiotics and identify genes causing carbapenem resistance and their clonal relationships to elucidate the distribution of resistance in community and/or hospital-acquired strains. Material and methods: In this study, antibiotic susceptibilities of 450 carbapenem-resistant Gr (-) bacilli isolated from clinical specimens at Cukurova University, Faculty of Medicine, Balcali Hospital, were investigated using phenotypic methods. The presence of carbapenems and β-lactamase genes were searched using polymerase chain reaction (PCR) and sequence analysis methods. Pulsed-field gel electrophoresis (PFGE) method was used to evaluate the phylogenetic relationship of the isolates. Results: Based on the results, it was determined that 99.23% of the strains had gained resistance to meropenem, whereas 5.38% had developed resistance to colistin. The most dominant carbapenems genes in all isolates were OXA-51, OXA-23-like and OXA-24-like. Conclusion: It was observed that the only antibiotic that could be used safely in carbapenem-resistant Gr (-) bacilli infections was colistin. In addition, when the clonal relationship of the strains was examined, it was found that the clones considered to be closely related persisted, and these clones settled in different clinics of our hospital.

Abstract Background The efficacy of non-carbapenems as an empirical antibiotic for extended-spectrum β-lactamases (ESBL)-producing Escherichia coli and Klebsiella pneumoniae bacteremia in children remains controversial. We compared clinical and microbial outcomes according to the types of empirical antibiotics for treating pediatric patients with ESBL-producing E. coli and K. pneumoniae bacteremia. Methods Data from pediatric patients aged ≤ 18 years who were hospitalized with monomicrobial ESBL-producing E. coli or K. pneumoniae bacteremia at Asan Medical Center Children’s Hospital, Seoul, Korea between January 2014 and May 2019 were analyzed retrospectively. The impact of empirical therapy was assessed as 30-day all-cause mortality and 2-day microbiological outcomes evaluated by the sterility of blood cultures collected on day 2 after empirical antibiotic administration. Logistic regression analysis was used to control for the effects of confounding variables. Results A total of 53 patients with bacteremia caused by ESBL-producing E. coli (n = 29) and K. pneumoniae (n = 24) were included in this study; the median age was 3.6 years, and all had underlying comorbidities. As empirical antibiotics, 27 patients were treated with meropenem, and non-carbapenem agents were administered to 26 patients; 84.6% (22/26) were converted to carbapenem antibiotics as the definitive antibiotic by day 2 after empirical antibiotic administration. Overall, the 30-day all-cause mortality of ESBL-producing E. coli and K. pneumoniae bacteremia was 17.0% (9/53). After adjustment, there was no statistically significant association of use of a non-carbapenem agent as an empirical antibiotic with microbiological failure on day 2 and 30-day all-cause mortality [adjusted odds ratio (OR) 1.0; 95% confidence interval (CI) 0.22–4.88, and adjusted OR 0.1; 95% CI 0.01–1.56]. Conclusions The empirical use of non-carbapenems might not be a risk factor for mortality and early microbiological outcomes in pediatric patients with ESBL-producing E. coli and K. pneumoniae BSI if early transition to appropriate antimicrobial therapy was possible.

Sadia Ishaque,1,2 Beenish Syed,1,3 Sunil Kumar Dodani,4 Sana Anwar5 1Department of Medicine, Liaquat National Hospital, Karachi, Pakistan; 2Department of Infectious Disease Shaheed Mohtarma, Benazir Bhutto Institute of Trauma, Dow University of Health Sciences, Karachi, Pakistan; 3Department of Infectious Diseases, Sindh Infectious Diseases Hospital and Research Center, Karachi, Pakistan; 4Department of Infectious Diseases, Sindh Institute of Urology & Transplantation, Karachi, Pakistan; 5Sana Anwar, Department of Microbiology, Liaquat National Hospital, Karachi, PakistanCorrespondence: Sadia Ishaque, Department of Infectious Disease Shaheed Mohtarma, Benazir Bhutto Institute of Trauma, Dow University of health sciences, Chand Bibi Road, Karachi, Pakistan, Tel +92 300 3750407, Email sadiamir70@gmail.comIntroduction: Antibiotic resistance has become a significant problem in typhoid fever due to the emergence of extensively drug resistant (XDR) Salmonella enterica serovar typhi. In Pakistan, an outbreak of ceftriaxone-resistant typhoid was first reported in November 2016.Methods: A retrospective chart review was conducted at Liaquat National Hospital and Medical University, in Karachi, Pakistan. Patient records were identified from the microbiology laboratory data of all admitted patients who had blood culture positive for XDR Salmonella typhi from January 2017 to December 2019.Results: Out of 254 patients, 179 (70%) were male with an average age of 11.7 ± 10.9 years. Around 190 (74%) patients were treated with combination therapy, 126 (49%) were given azithromycin and meropenem and 61 (24%) received azithromycin and imipenem. A total of 64 (25%) patients received single drug therapy, 33 (12%) were given azithromycin, 23 (9%) meropenem, and 8 (3%) imipenem. Analysis indicated that single drug therapy resulted in an earlier onset of defervescence compared with combination therapy (5.03± 2.98 days vs 3.45± 2.48 days; P < 0.001), with a decreased occurrence of pancytopenia (P < 0.001).Conclusion: Single antimicrobial therapy achieved defervescence earlier than combination therapy, with carbapenems performing better than azithromycin.Keywords: extensive drug resistant, Salmonella typhi, drug therapy, carbapenem, azithromycin

Xiucai Zhang,1 Chao Fang,1 Junfeng Zhang,1 Wang Hua,2 Rong He,1 Mingming Zhou1 1Department of Clinical Laboratory, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, People’s Republic of China; 2Department of Infectious Diseases, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, People’s Republic of ChinaCorrespondence: Mingming Zhou, Department of Clinical Laboratory, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, No. 3333 Binsheng Road, Hangzhou, 310052, People’s Republic of China, Tel +86-571-86670467, Email 6510053@zju.edu.cnBackground: The emergence of carbapenem and colistin co-resistant Escherichia coli poses a huge challenge to infection control. The purpose of this study was to clarify the mechanism of the carbapenems and colistin co-resistance in E. coli strains.Methods: Antimicrobial susceptibility test was carried out by agar dilution methods and colistin resistance was confirmed by broth microdilution methods. Whole genome sequencing was carried out, and resistance genes, sequence types and virulence genes of carbapenems and colistin co-resistance E. coli isolates were analyzed.Results: The results showed that among the 176 carbapenem-resistant Enterobacteriaceae strains, 5 multidrug resistant E. coli strains exhibiting coresistance to carbapenem and colistin. The main mechanism of 5 E. coli strains in this study was generating carbapenem. Four E. coli strains were mcr-positive, while one mcr-negative strain had a new MgrB mutation. The blaNDM-5, blaCTX-M-65, blaOXA-10, blaTEM-1 and mcr-1.1 genes were simultaneously detected in E. coli 20IR1127 strain belonging to ST156 lineage. Other antimicrobial resistance genes encoding aminoglycosides-, sulfonamide-, chloramphenicol-, tetracyclines- and macrolides resistance were also detected.Conclusion: The main mechanisms of carbapenem and colistin resistance were encoded by blaNDM and mcr1.1, meanwhile mgrB mutations also contribute to colistin resistance. To our knowledge, this study is the first to report of E. coli ST156 strain in which the blaNDM-5, blaCTX-M-65, blaOXA-10, blaTEM-1 and mcr1.1 genes coexist. In addition, there is also an E. coli ST457 strain, which carries blaTEM-1, blaNDM-9, blaCTX-M-199 and is positive for mcr1.1 gene.Keywords: Escherichia coli, carbapenem, colistin, co-resistance, WGS

Background: Klebsiella pneumoniae is among the most frequent opportunistic pathogens causing wide range of infections and the emergence and spread of carbapenem resistant Klebsiella pneumoniae are problems currently threatening global health. The present study aimed to determine the prevalence of carbapenem resistant Klebsiella pneumoniae and to detect carbapenem resistance genes in Jos, Nigeria. Methods: A total of 19 clinical specimens were collected from Jos University Teaching Hospital (JUTH) and National Veterinary Research Institute Vom, Jos, Nigeria. Klebsiella pneumoniae was identified by cultural and biochemical methods. Antibiotic susceptibility test was performed using modified Kirby-Bauer disc diffusion technique. Carbapenem resistant Klebsiella pneumoniae isolates were tested for carbapenemase production and blaKPC, blaVIM, and blaNDM genes using Modified Hodges Test and multiplex PCR respectively. Results: Of the 19 clinical specimens examined, 8(42.10%) were positive for Klebsiella pneumonia and most of the isolates were recovered from urine 5(62.50%), followed by sputum 2(25.00%) and isolates from wounds swab recorded the lowest occurrence, 1(12.50%). Antibiotic susceptibility test showed that isolates were highly resistant to gentamicin (62.50%), ceftriaxone (50.00%), amoxicillin/clavulanic acid (62.50%), ciprofloxacin (37.50%), cefepime (62.50%), clarithromycin (50.00%) and meropenem 3(37.50%). Polymerase chain reaction screening for blaKPC, blaVIM, and blaNDM genes which code for carbapenemases among the 3 meropenem resistant Klebsiella pneumoniae isolates were not detected. Conclusion: The expression of high phenotypic antibiotic resistance recorded in this study could be suggestive of other resistance genes which this study was limited for. Therefore, monitoring of carbapenem resistant Klebsiella pneumoniae with the aim of screening other antibiotic resistance genes is strongly recommended. [ABSTRACT FROM AUTHOR]

Avian pathogenic Escherichia coli (APEC) is responsible for significant economic losses in the poultry industry. This study aimed to molecularly detect carbapenem-resistant co-harboring mcr-1 avian pathogenic E. coli in broiler chickens infected with colibacillosis. A total of 750 samples were collected from colibacillosis-infected broilers, and conventional microbiological techniques were used to isolate and identify APEC. MALDI-TOF and virulence-associated genes (VAGs) were used for further identification. Phenotypic carbapenem resistance profiling was followed by molecular detection of carbapenem resistance genes (CRGs) and other resistance genes through PCR using specific primers. Isolates were also subjected to PCR for O typing, followed by allele-specific PCR to detect sequence type (ST) 95. Results showed that 154 (37%) isolates were confirmed as APEC, with 13 (8.4%) isolates found to be carbapenem-resistant (CR)-APEC. Among CR-APEC isolates, 5 (38%) were observed to co-harbor mcr-1. All CR-APEC showed the presence of five markers (ompT, hylF, iutA, iroN, and iss) APEC VAGs, and 89% of CR-APEC isolates displayed O78 type. Furthermore, 7 (54%) CR-APEC isolates were observed with ST95, all displaying O78 type. These results suggest that the improper use of antibiotics in poultry production systems is contributing to the emergence of pathogens such as CR-APEC co-harboring the mcr-1 gene. [ABSTRACT FROM AUTHOR]

The appearance of Pseudomonas aeruginosa strains with multi-resistance to antibiotics is a clinical problem of great relevance. The methods for detecting these resistances are laborious and slow, which is a complication when treating patients promptly. In this work, we developed a simple method for simultaneous detection of several carbapenem resistance genes using a multiplex PCR assay. The PCR assay developed, followed by electrophoretic separation of fragments, allows to simultaneously identify the presence of 6 antibiotic resistance genes: bla-VIM (261 bp), bla-IMP (587 bp), bla-SPM (648 bp), bla-GIM-1 (753 bp), bla-NDM-1 (813 bp) and bla-KPC (882 bp). We analyzed 7 clinical isolates of P. aeruginosa obtained in Chile, finding the resistance genes bla-VIM, bla-IMP, bla-SPM, bla-GIM, and bla-NDM in 5 of them. We found a perfect correlation between the detection of various resistance genes by PCR and the results obtained by antibiograms. Interestingly, 2 of the strains possessed 3 different resistance genes simultaneously. Finally, in this work, we found the presence of 3 genes never described before in clinical isolates of P. aeruginosa in Chile (bla-IMP, bla-SPM, and bla-GIM-1). We developed a rapid multiplex PCR test for the simultaneous detection of up to 6 antibiotic resistance genes of the metallo--lactamase family in P. aeruginosa. [ABSTRACT FROM AUTHOR]

Infectious complications of parietal mesh after prosthetic abdominal wall repair are rare. Their management is complex. Furthermore, the emergence of bacterial resistance, the presence of a foreign material, the need to continue an extended antibiotic therapy, and the choice of an appropriate treatment are crucial. The objective of this study is to access the microbiological epidemiology of infected parietal meshes in order to optimize the empirical antibiotic therapy. Between January 2016 and December 2021, a monocentric and retrospective study was performed in patients hospitalized for infected parietal meshes at Avicenne hospital, in Paris area. Clinical and microbiological data such as antibiotic susceptibility were collected. Twenty-six patients with infected parietal meshes have been hospitalized during this period. Meshes were in preaponevrotic positions (n = 10; 38%), retromuscular (n = 6; 23%) and intraperitoneal (n = 10; 38%). Among the 22 (84.6%) documented cases of infections, 17 (77.3%) were polymicrobial. A total of 54 bacteria were isolated, 48 of which had an antibiogram available. The most frequently isolated bacteria were: Enterobacterales (n = 19), Enterococcus spp. (n = 11) and Staphylococcus aureus (n = 6), whereas anaerobes were poorly isolated (n = 3). Concerning these isolated bacteria, amoxicillin-clavulanic acid, metronidazole-associated cefotaxime, piperacillin-tazobactam and meropenem were susceptible in 45.5%, 68.2%, 63.6%, 77.2%, of cases, respectively. This work highlights that infections of abdominal parietal meshes may be polymicrobial and the association amoxicillin-clavulanic acid cannot be used as a probabilist antibiotic therapy because of the high resistance rate in isolated bacteria. The association piperacillin-tazobactam appears to be a more adapted empirical treatment to preserve carbapenems, a broad-spectrum antibiotic class. [ABSTRACT FROM AUTHOR]

Klebsiella pneumoniae is a multidrug-resistant nosocomial pathogen. Carbapenem resistance is mediated mainly by enzymes carried on transmissible plasmids causing their dissemination among other members of Enterobacteriaceae. This study aimed to molecularly detect carbapenem resistance genes in K. pneumoniae clinical isolates, genotype them using ERIC-PCR, and investigate plasmid transformation of resistant genes by using ERIC-PCR and sequencing. Methods: Antimicrobial resistance of sixty carbapenem-resistant K. pneumoniae strains was evaluated by using the disc diffusion method. Five carbapenemases' genes were amplified by conventional PCR. Genotyping was performed using ERIC-PCR. Gene transformation was performed for the five genes to sensitive isolates. Wild and transformed isolates were genetically investigated using ERIC-PCR and sequencing. Results: Carbapenem resistance in our isolates was associated with high resistance to all tested antibiotics. The 60 K. pneumoniae isolates were divided into 6 resistor types. The prevalence of KPC, IMP, VIM, NDM, and OXA-48 genes were 17%, 63%, 93%, 85% and 100%, respectively. Dendrogram analysis showed 57 distinct patterns, arranged in three clusters. The five genes were transformed successfully into sensitive isolates. ERIC profiles of wild and transformed isolates showed cluster A contained all the wild isolates, and cluster B contained all transformed isolates. Genetic sequences of the 5 genes reflected high genetic similarity with the GenBank reference genes before plasmid transformation; however, a distinguishable decrease of genetic similarity was observed after transformation. Conclusion: Plasmidmediated carbapenem resistance in K. pneumoniae and its dissemination among different strains is a real threat to public health. [ABSTRACT FROM AUTHOR]

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Background Limited data suggest that serious infections caused by Enterobacterales with a moderate to high risk of clinically significant AmpC production can be successfully treated with cefepime if the cefepime minimum inhibitory concentration (MIC) is ≤2 µg/mL. However, isolates with a cefepime-susceptible dose-dependent (SDD) MIC of 4–8 µg/mL should receive a carbapenem due to target attainment and extended-spectrum β-lactamase (ESBL) concerns. Methods This was a retrospective cohort study of hospitalized patients with E. cloacae , K. aerogenes, or C. freundii bacteremia from January 2015 to March 2022 receiving high-dose cefepime or a carbapenem. Cox regression models were used with incorporation of inverse probability of treatment weighting and time-varying covariates. Results Of the 315 patients included, 169 received cefepime and 146 received a carbapenem (ertapenem n = 90, meropenem n = 56). Cefepime was not associated with an increased risk of 30-day mortality compared with carbapenem therapy (adjusted hazard ratio [aHR], 1.45; 95% CI, 0.79–2.14), which was consistent for patients with cefepime SDD isolates (aHR, 1.19; 95% CI, 0.52–1.77). Multivariable weighted Cox models identified Pitt bacteremia score >4 (aHR, 1.41; 95% CI, 1.04–1.92), deep infection (aHR, 2.27; 95% CI, 1.21–4.32), and ceftriaxone-resistant AmpC-E (aHR, 1.32; 95% CI, 1.03–1.59) to be independent predictors associated with increased mortality risk, while receipt of prolonged-infusion β-lactam was protective (aHR, 0.67; 95% CI, 0.40–0.89). Conclusions Among patients with bacteremia caused by Enterobacterales with moderate to high risk of clinically significant AmpC production, these data demonstrate similar risk of 30-day mortality for high-dose cefepime or a carbapenem as definitive β-lactam therapy. [ABSTRACT FROM AUTHOR]

Background: Acinetobacter baumannii can reside in humans without causing infection or symptoms but can opportunistically cause community and nosocomial infections. Few studies from Taiwan have used national-level data to investigate antibiotic resistance rates of A. baumannii infections in the intensive care units (ICUs) of medical centers. Aim: This study determined the number of infection sites of A. baumannii and the resistance rates of carbapenem-resistant A. baumannii (CRAB) infections in ICUs in Taiwan, and identified trends over time, variations of infection site, and factors associated with resistance. Methods: This study used the database provided by Taiwan's Centers for Disease Control. Yearly, Taiwan Nosocomial Infections Surveillance System Surveys from 2008 to 2019 were analyzed, including data on the site of infection and resistance rates of A. baumannii and patient and hospital characteristics. Results: On average, 21 hospitals as medical center/year participated in the survey, and 6803 A. baumannii isolates were identified. All isolates were health care-related infections. The most frequent sites of infection were the urinary tract (50.6%), respiratory tract (19.6%), bloodstream (18.2%), surgical wounds (4.3%), and others (7.4%). Infection rates were the highest in the urinary tract in 2019 (63.6%; P < 0.001). On average, the rate of carbapenem resistance was 66.6% (95% confidence interval: 63.1--70.1) among ICU patients at medical centers. Considerable regional differences were observed, with the highest rates of resistance in the central regions. Higher resistance rates were observed between 2019 and 2020 COVID-19 pandemic (74.2%). Conclusion: This is the first report on the prevalence of health care-related A. baumannii infection in Taiwan in 2008--2019. Several invasive diseases, such as urinary tract infections, are associated with higher rates of carbapenem resistance. The resistance rate of CRAB in Taiwan is exceptionally high. The current big-data-derived findings may inform future surveillance and research efforts in Taiwan. [ABSTRACT FROM AUTHOR]

The rising prevalence of multidrug-resistant (MDR) bacteria, mainly Gram-negative bacteria, challenges their effective treatment. Graphene oxide (GO) represents antibacterial activities; however, the synergistic effect of GO with conventional antibiotics remains unclarified. Here, meropenem-loaded GO (Mrp-GO) was prepared and its physicochemical and biocompatibility properties along with its inhibitory effect against carbapenem-resistant Gram-negative bacteria were evaluated. Cytotoxicity of Mrp-GO on human bone marrow-derived mesenchymal stem cells (hBM-MSCs) was examined as well. The prepared nanoparticles had suitable and acceptable physicochemical properties. The antibacterial activity of Mrp-GO increased in comparison to the GO and Mrp alone. Moreover, the Mrp-GO had low hemolytic effects at the concentrations required for bacterial inhibition. The cell viability of hBM-MSCs at toxic Mrp-GO concentrations for bacterial isolates was almost 90–100%. The combination of nanostructure and conventional antibiotics can be a promising treatment modality against carbapenem-resistant Gram-negative bacteria.

Acinetobacter baumannii is increasingly associated with various epidemics, representing a serious concern due to the broad level of antimicrobial resistance and clinical manifestations. During the last decades, A. baumannii has emerged as a major pathogen in vulnerable and critically ill patients. Bacteremia, pneumonia, urinary tract, and skin and soft tissue infections are the most common presentations of A. baumannii, with attributable mortality rates approaching 35%. Carbapenems have been considered the first choice to treat A. baumannii infections. However, due to the widespread prevalence of carbapenem-resistant A. baumannii (CRAB), colistin represents the main therapeutic option, while the role of the new siderophore cephalosporin cefiderocol still needs to be ascertained. Furthermore, high clinical failure rates have been reported for colistin monotherapy when used to treat CRAB infections. Thus, the most effective antibiotic combination remains disputed. In addition to its ability to develop antibiotic resistance, A. baumannii is also known to form biofilm on medical devices, including central venous catheters or endotracheal tubes. Thus, the worrisome spread of biofilm-producing strains in multidrug-resistant populations of A. baumannii poses a significant treatment challenge. This review provides an updated account of antimicrobial resistance patterns and biofilm-mediated tolerance in A. baumannii infections with a special focus on fragile and critically ill patients.

Infections caused by Robinsoniella peoriensis , particularly bacteremia, are rare, of which only six cases were reported R. peoriensis bloodstream infections. This case report describes an instance of R. peoriensis bacteremia arising while we treated the patient with piperacillin-tazobactam. We treated an 84-year-old female patient with peritoneal carcinoma and febrile neutropenia using piperacillin-tazobactam. The patient's fever subsided. However, she developed a fever again on the fourth day of treatment with piperacillin-tazobactam. Blood cultures taken at this time were positive for R. peoriensis. We substituted meropenem and vancomycin for piperacillin-tazobactam, after which the patient improved. We administered meropenem and vancomycin for 17 days. There is currently no appropriate established treatment for R. peoriensis. In this case, we isolated R. peoriensis from blood cultures using piperacillin-tazobactam, although it was susceptible to piperacillin-tazobactam in vitro. Therefore, monotherapy with penicillins, especially piperacillin-tazobactam, may not be sufficient for R. peoriensis infections, although it was susceptible in vitro. Carbapenem may be effective in the treatment of R. peoriensis bloodstream infections. [ABSTRACT FROM AUTHOR]

Antibiotic resistance in pathogens is a growing threat to human health. Of particular concern is resistance to carbapenem, which is an antimicrobial agent listed as critically important by the World Health Organization. With the global spread of carbapenem-resistant organisms, there is an urgent need for new treatment options. Shewanella algae is an emerging pathogen found in marine environments throughout the world that has increasing resistance to carbapenem. The organism is also a possible antibiotic resistance reservoir in humans and in its natural habitat. The development of CRISPR/Cas9-based methods has enabled precise genetic manipulation. A number of attempts have been made to knock out resistance genes in various organisms. The study used a single plasmid containing CRISPR/Cas9 and recE/recT recombinase to reverse an antibiotic-resistant phenotype in S. algae and showed bla OXA-55 -like gene is essential for the carbapenem resistance. This result demonstrates a potential validation strategy for functional genome annotation in S. algae.

Thanh D Dinh,1,2 Hung N Nguyen,1 Ba Hai Le,1 Thuy TT Nguyen,1 Huong TL Nguyen1 1Department of Clinical Pharmacy, Hanoi University of Pharmacy, Hanoi, Vietnam; 2Phu Tho General Hospital, Việt Trì, Phu Tho Province, VietnamCorrespondence: Huong TL Nguyen, Department of Clinical Pharmacy, Hanoi University of Pharmacy, 13, 15 – Lê Thánh Tông, Hoàn Kiếm, HàNội, 100000, Vietnam, Tel +84904308406, Email huongntl@hup.edu.vnPurpose: The purpose of this study was to characterize the population-based pharmacokinetic (POP-PK) profile of imipenem in Vietnamese adult patients and to assess the probability of target attainment (PTA) of the pharmacokinetic/pharmacodynamic (PK/PD) parameter to determine the optimal dose.Patients and Methods: A POP-PK model of imipenem was developed in patients with severe infection from a 1500-bed general hospital in Vietnam, using MONOLIX 2019. After the initial dose infusion, 6 blood samples per patient were collected to measure plasma imipenem levels. Eight covariates (eg, age, weight) were investigated to ascertain their influence on imipenem’s PK. Monte Carlo simulations were performed to determine the PTA for the time in which the total steady-state imipenem concentrations remained above the MIC (T>MIC) for 40% and 100% of the dosing interval.Results: The best fit to the PK data was a two-compartment model with inter-individual variability (IIV) in clearance (CL), central volume of distribution (Vc), intercompartmental clearance (Q), and peripheral volume of distribution (Vp). Only creatinine clearance was retained as a covariate on CL in the final model. The typical value of CL and Vc were estimated to be 4.79 L/h and 11.1 L, respectively. The between-subject variability in this population was noted to be high (> 38%, especially for IIV on Q at 110%). Prolonged or continuous infusion demonstrated efficacy (40% T>MIC) against bacteria with a MIC of 4mg/L. To achieve 100% T>MIC or bacteria with MIC> 4 mg/L, however, the number of doses must be increased while maintaining the same daily dose for the 3-hour prolonged infusion regimen.Conclusion: A population pharmacokinetic model of imipenem was developed for Vietnamese adult patients with severe illness. By using Monte Carlo simulation, the appropriate dose has been suggested based on the bacterial MIC value and the targeted PK/PD goal.Keywords: imipenem, pharmacokinetic modeling, PK/PD, Monte Carlo, carbapenem

A cross-sectional study was conducted to determine the prevalence of Carbapenem-resistant Gram-negative bacteria (CR-GNB) in animals. The study involves one hundred eighty-four GNB isolates from 214 samples (feces, milk, pus, and uterine discharge) from Buffalo (N=112), Cattle (N=50), and Dog (N=52). Healthy and diseased animals reported to Veterinary Clinical Complex were sampled. Carbapenemase production was evaluated by phenotypic methods and the presence of Metallo β-lactamase genes was assayed by PCR. We observed a 9.78% overall prevalence of CR-GNB in animal sources. CR-GNB was more frequently recovered from companion animals (19.23%) when compared to livestock (4.93%). IMP (44.4%), VIM (38.8%), and OXA-48 (16.66 %) were the main MBLs observed in the study.

BackgroundShewanella algae has been recognized as an emerging human pathogen. However, not much is known about the mechanism of its pathogenesis and its adaptation to a special niche such as the hepatobiliary tract.ResultsIn this study, we isolated the S. algae ACCC strain from human bile and performed whole genome sequencing. S. algae ACCC consists of a circular 4,743,354-bp chromosome with a GC content of 53.08%, within 4080 protein coding sequences. The genome of strain ACCC contains a number of candidate genes which have been reported to be associated with bile adaption, including htpB, exbBD, wecA, galU, adeFGH and phoPQ regulon.ConclusionsOur results highlight the association of S. algae with a rare disease profile. Further studies are needed to shed light on the evolution of pathogenesis and the niche adaptation of S. algae.

BackgroundValproic acid (VPA) is one of the most widely used broad-spectrum antiepileptic drugs, and carbapenems (CBPs) remain the drug of choice for severe infection caused by multidrug-resistant bacteria in critically ill patients. The interaction between VPA and CBPs can lead to a rapid depletion of serum VPA level. This may then cause status epilepticus (SE), which is associated with significant mortality. However, the prognostic impact of drug interactions in critically ill patients remains an under-investigated issue.ObjectiveThe aim of this study was to compare the prognosis of critically ill patients treated with VPA and concomitant CBPs or other broad-spectrum antibiotics.MethodsAdult patients admitted to a medical center intensive care unit between January 2007 and December 2017 who concomitantly received VPA and antibiotics were enrolled. The risk of reduced VPA serum concentration, seizures and SE, mortality rate, length of hospital stay (LOS), and healthcare expenditure after concomitant administration were analyzed after propensity score matching.ResultsA total of 1,277 patients were included in the study, of whom 264 (20.7%) concomitantly received VPA and CBPs. After matching, the patients who received CBPs were associated with lower VPA serum concentration (15.8 vs. 60.8 mg/L; p < 0.0001), a higher risk of seizures (51.2 vs. 32.4%; adjusted odds ratio [aOR], 2.19; 95% CI, 1.48–3.24; p < 0.0001), higher risk of SE (13.6 vs. 4.7%; aOR, 3.20; 95% CI, 1.51–6.74; p = 0.0014), higher in-hospital mortality rate (33.8 vs. 24.9%; aOR, 1.57; 95% CI, 1.03–2.20; p = 0.036), longer LOS after concomitant therapy (41 vs. 30 days; p < 0.001), and increased healthcare expenditure (US$20,970 vs. US$12,848; p < 0.0001) than those who received other broad-spectrum antibiotics.ConclusionThe administration of CBPs in epileptic patients under VPA therapy was associated with lower VAP serum concentration, a higher risk of seizures and SE, mortality, longer LOS, and significant utilization of healthcare resources. Healthcare professionals should pay attention to the concomitant use of VPA and CBPs when treating patients with epilepsy. Further studies are warranted to investigate the reason for the poor outcomes and whether avoiding the co-administration of VPA and CBP can improve the outcomes of epileptic patients.

ABSTRACT: Animal-derived Enterobacteriaceae bacteria such as Escherichia coli (E. coli), Proteus mirabilis (P. mirabilis), and Klebsiella pneumoniae (K. pneumoniae) are important food-borne zoonotic bacilli that exist widely in the broiler-breeding industry. Although carbapenem antibiotics are considered to be the last line of defense against multidrug-resistant bacteria, carbapenem-resistant Enterobacteriaceae (CRE) break through them. In our study, we therefore, examined the prevalence of CRE and characteristics of antimicrobial resistance in 6 conventional broiler-fattening farms in Shandong Province, China. Our study revealed isolation rates of 3.57% (6/168) for carbapenem-resistant E. coli, 10% (5/50) for carbapenem-resistant P. mirabilis, and 3.03% (1/33) for carbapenem-resistant K. pneumoniae. All 12 CRE bacterial strains showed varying degrees of resistance to 27 antibiotics in 8 classes and were multidrug-resistant. The rate of the strains containing blaNDM genes, at 91.67% (11/12), was especially high. Among other results, the carrying rate of integrons in CRE bacteria was 91.67% (11/12), and 2 strains carried both class I and class II integrons, which accelerated the lateral transmission of resistant bacteria. Our first-ever finding of the 3 CRE bacteria E. coli, P. mirabilis, and K. pneumoniae on the same broiler farm suggests that poultry-derived CRE strains may pose a risk to humans. Moreover, our findings from surveillance can inform current understandings of the prevalence and characteristics of multidrug-resistant CRE in Shandong Province and, in turn, help to curb threats to food safety and public health and better prevent and control infectious zoonotic diseases.

TokK is a B12‐dependent radical SAM enzyme involved in the biosynthesis of the β‐lactam antibiotic asparenomycin A. It can catalyze three methylations on different sp3‐hybridized carbon positions to introduce an isopropyl side chain at the β‐lactam ring of pantetheinylated carbapenem. Herein, we report a quantum chemical study of the reaction mechanism of TokK. A stepwise "push‐pull" radical relay mechanism is proposed for each methylation: a 5'‐deoxyadenosine radical first abstracts a hydrogen atom from the substrate in the active site, then methylcobalamin directionally donates a methyl group to the substrate. More importantly, calculations were able to uncover the origin of observed chemoselectivity and stereoselectivity for the first methylation and regioselectivity for the following two methylations. Further detailed distortion/interaction analysis can help to unravel the main factors controlling the selectivities. Our findings of sequential methylations by TokK could have profound implications for studying other B12‐dependent radical SAM enzymes. [ABSTRACT FROM AUTHOR]

Serial perirectal swabs are used to identify colonization of multidrug-resistant bacteria and prevent spread. The purpose of this study was to determine colonization with carbapenem-resistant Enterobacterales (CRE) and vancomycin-resistant Enterococci (VRE). An additional purpose was to establish whether sepsis and epidemic associated with these factors were present in the neonatal intensive care unit (NICU), to which infants with hospital stays exceeding 48 h in an external healthcare center NICU were admitted. Perirectal swab samples were collected in the first 24 h by a trained infection nurse using sterile cotton swabs moistened with 0.9% NaCl from patients admitted to our unit after hospitalization exceeding 48 h in an external center. The primary outcome was positivity in perirectal swab cultures, and the secondary outcomes were whether this caused invasive infection and significant NICU outbreaks. A total of 125 newborns meeting the study criteria referred from external healthcare centers between January 2018 and January 2022 were enrolled. Analysis revealed that CRE constituted 27.2% of perirectal swab positivity and VRE 4.8%, and that one in every 4.4 infants included in the study exhibited perirectal swab positivity. The detection of colonization by these microorganisms, and including them within the scope of surveillance, is an important factor in the prevention of NICU epidemics. [ABSTRACT FROM AUTHOR]

As antibiotic resistance has become a global problem, the intervention of an antimicrobial stewardship team (AST) is warranted. In hematological disorders, infectious complications are crucial owing to abnormal neutrophil function and decreased cell-mediated immunity. Despite the widespread implementation of AST intervention, the effectiveness of stewardship practices for immunocompromised patients remains uncertain. We determined the effect of AST interventions on carbapenem therapy in the department of hematology. Patients admitted to the department and undergoing carbapenem therapy were enrolled. We compared carbapenem use between the pre-AST (April 2016–March 2018) and post-AST (April 2018–March 2021) periods. Factors associated with long-term carbapenem therapy were investigated. Overall, 515 episodes of carbapenem therapy in 264 patients in the department were evaluated. According to the interrupted time series analysis, the number of days of therapy decreased with AST intervention (β = −0.263, p = 0.011). In multivariate analysis, predictive factors associated with long-term carbapenem therapy (>8 days) were outpatient onset, chronic obstructive pulmonary disease, acute myeloid leukemia, multiple myeloma, and infection with resistant bacteria (such as extended spectrum β-lactamases and AmpC) (95% confidence interval, 1.030–2.818, 1.067–66.667, 1.057–2.782, 0.168–0.742, and 1.382–5.750, respectively). The AST intervention reduced carbapenem use in patients with hematological disorders. [ABSTRACT FROM AUTHOR]

Background: Klebsiella pneumoniae (Kp) Gram-negative bacteria cause nosocomial infections and rapidly acquire antimicrobial resistance (AMR), which makes it a global threat to human health. It also has a comparatively rare hypervirulent phenotype that can lead to severe disease in otherwise healthy individuals. Unlike classic Kp, canonical hypervirulent strains usually have limited AMR. However, after initial case reports in 2015, carbapenem-resistant hypervirulent Kp has increased in prevalence, including in China, but there is limited understanding of its burden in other geographical regions. Methods: Here, we examined the largest collection of publicly available sequenced Kp isolates (n=13,178), containing 1603 different sequence types (e.g. ST11 15.0%, ST258 9.5%), and 2174 (16.5%) hypervirulent strains. We analysed the plasmid replicons and carbapenemase and siderophore encoding genes to understand the movement of hypervirulence and AMR genes located on plasmids, and their convergence in carbapenem-resistant hypervirulent Kp. Results: We identified and analysed 3034 unique plasmid replicons to inform the epidemiology and transmission dynamics of carbapenem-resistant hypervirulent Kp (n=1028, 7.8%). We found several outbreaks globally, including one involving ST11 strains in China and another of ST231 in Asia centred on India, Thailand, and Pakistan. There was evidence of global flow of Kp, including across multiple continents. In most cases, clusters of Kp isolates are the result of hypervirulence genes entering classic strains, instead of carbapenem resistance genes entering canonical hypervirulent ones. Conclusions: Our analysis demonstrates the importance of plasmid analysis in the monitoring of carbapenem-resistant and hypervirulent strains of Kp. With the growing adoption of omics-based technologies for clinical and surveillance applications, including in geographical regions with gaps in data and knowledge (e.g. sub-Saharan Africa), the identification of the spread of AMR will inform infection control globally. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance is one of the most pressing concerns of our time. The human diet is rich with compounds that alter bacterial gut communities and virulence‐associated behaviours, suggesting food additives may be a niche for the discovery of novel anti‐virulence compounds. Here, we identify three artificial sweeteners, saccharin, cyclamate and acesulfame‐K (ace‐K), that have a major growth inhibitory effect on priority pathogens. We further characterise the impact of ace‐K on multidrug‐resistant Acinetobacter baumannii, demonstrating that it can disable virulence behaviours such as biofilm formation, motility and the ability to acquire exogenous antibiotic‐resistant genes. Further analysis revealed the mechanism of growth inhibition is through bulge‐mediated cell lysis and that cells can be rescued by cation supplementation. Antibiotic sensitivity assays demonstrated that at sub‐lethal concentrations, ace‐K can resensitise A. baumannii to last resort antibiotics, including carbapenems. Using a novel ex vivo porcine skin wound model, we show that ace‐K antimicrobial activity is maintained in the wound microenvironment. Our findings demonstrate the influence of artificial sweeteners on pathogen behaviour and uncover their therapeutic potential. Synopsis: Artificial sweeteners can inhibit the growth of multidrug‐resistant pathogens, disrupt virulence associated behaviours and potentiate antibiotic activity. In wound models the sweetener, Acesulfame K, shows potential as a topical wound treatment. Artificial sweeteners can significantly impact the growth of bacterial pathogens.Ace‐K can inhibit a range of virulence traits such as biofilm formation, motility and natural transformation.It weakens the bacterial cell membrane leading to loss of morphology and bulge‐mediated cell lysis.It can also potentiate the activity of antibiotics including carbapenems.Ace‐K shows clinical potential as a topical wound therapeutic. [ABSTRACT FROM AUTHOR]

Objectives: The World Health Organization (WHO) mentioned Acinetobacter baumannii as a “priority of concern” in 2017. Acinetobacter baumannii generally infects immunocompromised patients and causes various nosocomial infections in the intensive care unit (ICU) such as bacteremia, meningitis, ventilator-associated pneumonia, other respiratory infections, and surgical site infections. As oxacillinase has weak hydrolysis activity, more work was needed on this class-D beta-lactamase. Hence, the current Systematic review focuses on the A. baumannii’s oxacillinase (Class-D beta-lactamases) enzyme and its variants collected during 2013–2020 in India for complete genome sequencing. Method: This Systematic review has been done according to PRISMA guideline 2020. We have used the Bacterial and Viral Bioinformatic Resource Centre (bv-brc.org) system for comparative genome analysis. The protein Basic Local Alignment Search Tool (BLAST) was used to identify similarities between sequences, in which BLOSUM62 was used as a scoring matrix. Clustal-W was used for multiple sequence alignment. A phylogenetic tree of the blaOXA gene family has been constructed using MEGA version 11. Result: In India during 2013–2020, for genome sequencing of A. baumannii, the highest number of samples was collected from blood (36%), following the ETA (30%). The average G+C % content was 38.95%. Among the 339 A. baumannii isolates, a maximum of 189 (55.75%) strains caused pneumonia, whereas 113 (33.33%) strains were involved in bacteremia. Carbapenems seemed effective, but resistance against them was higher. Among all A. baumannii genomes, bla-OXA-23 had the highest frequency (314; 92.62%), followed by bla-OXA-66 (241; 71.09%) in India. Conclusion: Our findings indicated that a high percentage of A. baumannii strains that produce oxacillinases exist in India, emphasizing the necessity for indigenous molecular surveillance to assist effective management and preventative initiatives. Comparative genomics and next-generation sequencing will offer tremendous potential for tracking and regulating the spread of this dangerous bacterium. [ABSTRACT FROM AUTHOR]

The article provides interim recommendations for the appropriate use of colistin in treating bacterial infections in neonates, infants, and children. Topics discussed include the indications for colistin use, methods for determining minimum inhibitory concentration (MIC) results, and dosing recommendations for patients with renal impairment.

Carbapenem antibiotics are considered one of the most effective and the last‑resort antibiotics for the treatment of infections caused by multidrug‑resistant Gram‑negative bacteria. However, with the advent of carbapenem resistance, it becomes obvious that quality health‑care delivery will be hampered if adequate measure is not put in place. This review assessed the prevalence of carbapenem‑resistant Gram‑negative bacteria (CR‑GNB) and also provided an up‑to‑date position on carbapenem resistance (CR) in Nigeria. Three electronic databases (Google Scholar, PubMed and African Journal online) were searched for relevant literatures, and 38 articles published between January 2013 and June 2022 that met the criteria for inclusion were recruited into the study. The mean prevalence of CR in Nigeria stands at 21.3%, with the southern and northern regions documenting a mean prevalence of 22.0% and 20.9%, respectively. Most of the reviewed articles were from clinical settings (81.6%), with urine samples (38.7%) constituting the most prevalent clinical sample in which CR‑GNB were detected. The preponderance of phenotypic methods (55.3%) over molecular method (44.7%), particularly the use of disk diffusion test breakpoint and Modified Hodge test was documented. The most prevalent carbapenem‑resistant bacteria were Escherichia coli (50.0%) and Klebsiella pneumoniae (26.3%). The blaNDM and blaVIM were the major reported carbapenemase‑encoded genes, particularly among E. coli, K. pneumoniae and Pseudomonas species. This systematic review revealed a mean prevalence of CR‑GNB in Nigeria that required urgent attention. Furthermore, the detection of clinically and epidemiologically important carbapenemase coding genes is of public health importance. [ABSTRACT FROM AUTHOR]

Antibiotic resistance genes can easily be transferred between bacteria in the biofilm. In the dairy industry, many bacterial species forming biofilms on the surfaces of equipment are widely reported. The experiments reported in this research paper aimed to investigate the carbapenem resistance and biofilm formation properties of Enterobacterales isolates which are spoilage microorganisms obtained from raw milk. In addition, the study determined that whether there was a relationship between the biofilm formation ability or the protein spectra of these isolates. In this study, ninety-two Enterobacterales isolates collected from 173 raw milk samples were investigated. Initially, the isolates were identified as Citrobacter braakii (n = 18), Citrobacter freundii (n = 12), Enterobacter asburiae (n = 1), Enterobacter cloacae (n = 3), Escherichia coli (n = 10), Hafnia alvei (n = 18), Klebsiella oxytoca (n = 1), Serratia fonticola (n = 24), Serratia liquefaciens (n = 4), and Serratia marcescens (n = 1) using MALDI-TOF MS. As a result, carbapenem resistance was determined in 6.5% of the isolates by CIM test, MHT, and the disk diffusion methods, but none of them had blaOXA-48, blaKPC, blaNDM-1, blaOXA23, blaOXA-58, blaOXA-51, blaVIM, and blaIMP genes. This may be due to the effect of other resistance mechanisms such as porin loss or increased flow pump activity. Furthermore, biofilm formation (weak and moderate) was detected in 97.8% of the Enterobacterales isolates. The mass spectra of the moderate biofilm producer isolate of Serratia spp. and the mass spectra of the weak biofilm producers of E.coli presented similarities. [ABSTRACT FROM AUTHOR]

ABSTRACT: Objectives: This study investigated the underlying mechanism of the evolution of tigecycline resistance during treatment in a patient infected with Klebsiella pneumoniae harbouring blaKPC-2. Methods: A total of seven clonal K. pneumoniae strains were continuously isolated from a patient during hospitalisation. Antimicrobial resistance in the strains was determined by antimicrobial susceptibility testing. Multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) were performed to explore the homology of the isolates. Whole-genome shotgun (WGS) analysis and cloning experiments were used to investigate the underlying mechanism of the evolution of tigecycline resistance. Results: All of the isolates had a minimum inhibitory concentration (MIC) for tigecycline of 4 µg/mL, except strain FK6768 that had a MIC of 32 µg/mL. Carbapenem-resistant K. pneumoniae strains (FK6614, FK6768 and FK6809) were consecutively isolated from faeces at different times. Antimicrobial susceptibility testing indicated that tigecycline resistance increased in FK6768 and subsequently decreased in FK6809, which attracted our attention. WGS and further bioinformatics analysis showed a homology for the three faecal isolates of >99%. The blaKPC-2 carbapenemase gene and a tet(A) mutation were found in tigecycline-resistant isolate FK6768. Subsequent cloning experiments confirmed the contribution of a tet(A) variant to reduced tigecycline susceptibility. Conclusion: Here we report a K. pneumoniae isolate carrying both tet(A) mutation and the blaKPC-2 gene, which led to increased tigecycline resistance during tigecycline treatment. This is the first report describing tigecycline resistance of K. pneumoniae first increasing and subsequently decreasing in vivo.

ABSTRACT: Objectives: The prevalence and molecular epidemiology of tigecycline resistance in carbapenem-resistant Enterobacter cloacae (CREC) in mainland China is unknown. We aimed to investigate the molecular characteristics and mechanisms of tigecycline-resistant CREC (TCREC) in Southwest China. Methods: We conducted a 5-year retrospective study. TCREC isolates underwent antimicrobial susceptibility testing, PFGE and MLST. We determined the presence of genes, deficiency of outer membrane proteins (OMPs) and expression of efflux pumps using PCR, reverse transcription PCR and SDS-PAGE. Results: A large proportion of CREC isolates (21.7%; 36/166) were TCREC. All isolates were resistant to ertapenem, whereas 67% remained susceptible to imipenem and meropenem. ST88 (10/36; 27.8%) was predominant and was associated with moderate resistance to tigecycline and high resistance to carbapenems, followed by ST256 (3/36; 8.3%), ST78 (2/36; 5.6%), ST557 (2/36; 5.6%) and ST102 (2/36; 5.6%). blaNDM-1 (6/36; 16.7%) was the most common carbapenemase gene, and ST88 (5/6; 83.3%) was the most common type, followed by blaIMP-8 (3/36; 8.3%). Coexistence of extended-spectrum β-lactamase (ESBL) genes and OmpF and/or OmpC loss was found in 27/36 isolates; additionally, increased co-expression of efflux pump genes acrB and oqxA was identified in 25/36 isolates, which may together contribute to co-resistance to carbapenems and tigecycline. Conclusion: Most ST88 strains carried carbapenemases, especially NDM-1. Overexpression of efflux pumps contributed to tigecycline resistance. The presence of carbapenemase and/or ESBL genes and lack of OMPs, but not efflux pump overexpression, may confer carbapenem resistance. Reasonable supervision and management of the epidemic of TCREC will help to stem the transmission of isolates.

Pseudomonas aeruginosa is an adaptable bacteria causing an extensive spectrum of infections and intrinsically resistant to many antibiotics. As antimicrobial resistance has increased due to many resistance mechanisms. This study was done to evaluate the antibiogram of Pseudomonas aeruginosa at a tertiary care centre. Thirty seven isolates were recovered from various specimens for a period of 6 months from June to December 2020 and the disc diffusion method was used for antibiotic susceptibility testing as per CLSI guidelines. Pseudomonas aeruginosa was found to be high (45.9%) in pus/wound than other samples. Antibiotic resistance rate of the isolates were 29.7% to ceftazidime, 16.2% to Piperacillin-tazobactam, 27 % to gentamicin and ciprofloxacin, 16.2% to tobramycin and imipenem, 24.3% to meropenem, 27% to ciprofloxacin, 13.5% to aztreonam, 21.6% to amikacin, 24.3% to cefepime and levofloxacin, 21.6 to tigecycline. All strains were sensitive to colistin. 27% of the organism were found to be multidrug resistance. Hence periodic susceptibility testing can curb the resurgence of these bacterial pathogens.

Meropenem is a potent carbapenem antibiotic frequently used in medical settings. Several studies have confirmed the pervasive presence of these antibiotics in wastewater treatment plants and aquatic environments. However, the effects of these substances on non-target organisms, such as plants, have not been adequately monitored. Thus, this study aimed to assess the short-term impact of meropenem on the growth, photosynthesis, chlorophyll content, and enzyme activity of the macrophyte plant Lemna minor. The methods involved exposing the plant to meropenem under controlled conditions and assessing physiological and biochemical parameters to determine the impact on photosynthetic activity and oxidative stress. These analyses included growth rate, antioxidant enzyme activity, and photosynthetic capacity. The findings suggest that the growth rate of Lemna minor remained unaffected by meropenem at concentrations <200000 μgL−1. However, plants exposed to concentrations >20 μgL−1showed physiological alterations, such as decreased net photosynthesis rate (17%) and chlorophyll concentration (57%), compared to the control group. For acute toxicity assays, the calculated EC 50 7-day and EC 20 7-day were 1135 μgL−1and 33 μgL−1, respectively. In addition, in most treatments tested, meropenem caused an increase in the superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase (APX) activity as a defense mechanism against oxidative stress. Our results suggest that meropenem affects photosynthetic processes and induces oxidative stress in the macrophyte plant Lemna minor. Further studies are needed to assess the physiological and metabolic interactions between antibiotics and primary producers at different long-term trophic levels. [Display omitted] • Meropenem increases CAT, APX, and SOD activity in Lemna minor. • Meropenem induces a reduction in photosynthetic activity in Lemna minor. • Meropenem influences aquatic ecosystems, affecting non-target organisms. [ABSTRACT FROM AUTHOR]