Antimicrobial-resistant Gram-negative Bacteria Research Articles

Hit 'em Where It Hurts: Gram-Negative Bacterial Lipopolysaccharide as a Vaccine Target.

Infections with antimicrobial-resistant (AMR) bacteria pose an increasing threat to the ability to perform surgical procedures, organ transplantation, and treat cancer among many other medical conditions. There are few new antimicrobials in the development pipeline. Vaccines against AMR Gram-negative bacteria may reduce the use of antimicrobials and prevent bacterial transmission. This review traces the origins of lipopolysaccharide (LPS)-based vaccines against Gram-negative bacteria, the role of O polysaccharides and LPS core regions as potential vaccine targets, the development of new vaccine technologies, and their application to vaccines in current development.

High Burden of Intestinal Colonization With Antimicrobial-Resistant Bacteria in Chile: An Antibiotic Resistance in Communities and Hospitals (ARCH) Study.

Antimicrobial resistance is a global threat, heavily impacting low- and middle-income countries. This study estimated antimicrobial-resistant gram-negative bacteria (GNB) fecal colonization prevalence in hospitalized and community-dwelling adults in Chile before the coronavirus disease 2019 pandemic. From December 2018 to May 2019, we enrolled hospitalized adults in 4 public hospitals and community dwellers from central Chile, who provided fecal specimens and epidemiological information. Samples were plated onto MacConkey agar with ciprofloxacin or ceftazidime added. All recovered morphotypes were identified and characterized according to the following phenotypes: fluoroquinolone-resistant (FQR), extended-spectrum cephalosporin-resistant (ESCR), carbapenem-resistant (CR), or multidrug-resistant (MDR; as per Centers for Disease Control and Prevention criteria) GNB. Categories were not mutually exclusive. A total of 775 hospitalized adults and 357 community dwellers were enrolled. Among hospitalized subjects, the prevalence of colonization with FQR, ESCR, CR, or MDR-GNB was 46.4% (95% confidence interval [CI], 42.9-50.0), 41.2% (95% CI, 37.7-44.6), 14.5% (95% CI, 12.0-16.9), and 26.3% (95% CI, 23.2-29.4). In the community, the prevalence of FQR, ESCR, CR, and MDR-GNB colonization was 39.5% (95% CI, 34.4-44.6), 28.9% (95% CI, 24.2-33.6), 5.6% (95% CI, 3.2-8.0), and 4.8% (95% CI, 2.6-7.0), respectively. A high burden of antimicrobial-resistant GNB colonization was observed in this sample of hospitalized and community-dwelling adults, suggesting that the community is a relevant source of antibiotic resistance. Efforts are needed to understand the relatedness between resistant strains circulating in the community and hospitals.

A Narrative Review of Healthcare-Associated Gram-Negative Infections Among Pediatric Patients in Middle Eastern Countries

Gram-negative bacteria (GNB) have become prominent across healthcare and community settings due to factors including lack of effective infection control and prevention (ICP) and antimicrobial stewardship programs (ASPs), GNB developing antimicrobial resistance (AMR), and difficulty treating infections. This review summarizes available literature on healthcare-associated infections (HAIs) in Middle Eastern pediatric patients. Literature searches were performed with PubMed and Embase databases. Articles not reporting data on GNB, HAIs, pediatric patients, and countries of interest were excluded. The searches resulted in 220 publications, of which 49 met the inclusion criteria and 1 additional study was identified manually. Among 19 studies across Egypt reporting GNB prevalence among pediatric patients, Klebsiella species/K.pneumoniae and Escherichiacoli were typically the most common GNB infections; among studies reporting carbapenem resistance and multidrug resistance (MDR), rates reached 86% and 100%, respectively. Similarly, in Saudi Arabia, Klebsiella spp./K.pneumoniae and E.coli were the GNB most consistently associated with infections, and carbapenem resistance (up to 100%) and MDR (up to 75%) were frequently observed. In other Gulf Cooperation Council countries, including Kuwait, Oman, and Qatar, carbapenem resistance and MDR were also commonly reported. In Jordan and Lebanon, E.coli and Klebsiella spp./K.pneumoniae were the most common GNB isolates, and AMR rates reached 100%. This review indicated the prevalence of GNB-causing HAIs among pediatric patients in Middle Eastern countries, with studies varying in reporting GNB and AMR. Most publications reported antimicrobial susceptibility of isolated GNB strains, with high prevalence of extended-spectrum beta-lactamase-producing K.pneumoniae and E.coli isolates. A review of ASPs highlighted the lack of data available in the region. Enhanced implementation of ICP, ASPs, and AMR surveillance is necessary to better understand the widespread burden of antimicrobial-resistant GNB and to better manage GNB-associated HAIs across Middle Eastern countries.

Efficacy of carbapenems versus alternative antimicrobials for treating complicated urinary tract infections caused by antimicrobial-resistant Gram-negative bacteria: protocol for a systematic review and meta-analysis

IntroductionComplicated urinary tract infections (cUTIs) are associated with poor prognosis. The widespread infection of multidrug-resistant Gram-negative uropathogens such as extended-spectrum beta-lactamase-producing bacteria has limited the efficacy of antibiotics used for...

Test Performance and Potential Clinical Utility of the GenMark Dx ePlex Blood Culture Identification Gram-Negative Panel.

The test performance and potential clinical utility of the ePlex blood culture identification Gram-negative (BCID-GN) panel was evaluated relative to matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry on bacterial isolates and conventional antimicrobial susceptibility testing. The majority (106/108, 98.1%) of GN bacteria identified by MALDI were on the BCID-GN panel, and valid tests (107/108, 99.1%) yielded results on average 26.7 h earlier. For all valid tests with on-panel organisms, the positive percent agreement was 102/105 (97.2%) with 3 false negatives and the negative percent agreement was 105/105. Chart review (n = 98) showed that in conjunction with Gram stain results, negative pan-Gram-positive (GP) markers provided the opportunity to discontinue GP antibiotic coverage in 63/98 (64.3%) cases on average 26.2 h earlier. Only 8/12 (66.7%) Enterobacterales isolates with resistance to third-generation cephalosporins harbored the CTX-M gene. In contrast, 8/8 CTX-M+ samples yielded a resistant isolate. Detection of 1 Stenotrophomonas maltophilia (18 h), 1 OXA23/48+ Acinetobacter baumannii (52.4 h), and 3 CTX-M+ Enterobacterales isolates on ineffective treatment (47.1 h) and 1 on suboptimal therapy (72.6 h) would have additionally enabled early antimicrobial optimization in 6/98 (6.1%) patients. IMPORTANCE The GenMark Dx ePlex rapid blood culture diagnostic system enables earlier time to identification of antimicrobial-resistant Gram-negative bacteria causing bloodstream infections. Its ability to rule out Gram-positive bacteria enabled early discontinuation of unnecessary antibiotics in 63/98 (64.3%) cases on average 26.2 h earlier. Detection of bacteria harboring the CTX-M gene as well as early identification of highly resistant bacteria such as Stenotrophomonas maltophilia and Acinetobacter baumannii enabled optimization of ineffective therapy in 6/98 (6.1%) patients. Its implementation in clinical microbiology laboratories optimizes therapy and improves patient care.

Effect of biofilm formation by antimicrobial-resistant gram-negative bacteria in cold storage on survival in dairy processing lines

Antimicrobial-resistant gram-negative bacteria in dairy products can transfer antimicrobial resistance to gut microbiota in humans and can adversely impact the product quality. In this study, we aimed to investigate their distribution in dairy processing lines and evaluate biofilm formation and heat tolerance under dairy processing line-like conditions. Additionally, we compared the relative expression of general and heat stress-related genes as well as spoilage-related gene between biofilm and planktonic cells under consecutive stresses, similar to those in dairy processing lines. Most species of gram-negative bacteria isolated from five different dairy processing plants were resistant to one or more antimicrobials. Biofilm formation by the bacteria at 5 °C increased with the increase in exposure time. Moreover, cells in biofilms remained viable under heat treatment, whereas all planktonic cells of the selected strains died. The expression of heat-shock-related genes significantly increased with heat treatment in the biofilms but mostly decreased in the planktonic cells. Thus, biofilm formation under raw milk storage conditions may improve the tolerance of antimicrobial-resistant gram-negative bacteria to pasteurization, thereby increasing their persistence in dairy processing lines and products. Furthermore, the difference in response to heat stress between biofilm and planktonic cells may be attributed to the differential expression of heat stress-related genes. Therefore, this study contributes to the understanding of how gram-negative bacteria persist under consecutive stresses in dairy processing procedures and the potential mechanism underlying heat tolerance in biofilms.

Oral and Rectal Colonization by Antimicrobial-Resistant Gram-Negative Bacteria and Their Association with Death among Residents of Long-Term Care Facilities: A Prospective, Multicenter, Observational, Cohort Study

Introduction: The prevalence of antimicrobial-resistant bacteria (ARB) in long-term care facilities (LTCFs) remains unclear. Furthermore, the effect of ARB colonization on the clinical outcomes of LTCF residents has not been explored. Methods: We conducted a prospective multicenter cohort study and investigated the residents (N = 178) of six Japanese LTCFs (three Welfare Facilities for the Elderly Requiring Long-term Care and three Geriatric Health Service Facilities) for oral and rectal carriage of ARB. The clinical outcomes of the residents were evaluated based on isolating bacterial strains and subjecting them to whole-genome sequencing. Results: Of the 178 participants, 32 belonging to Geriatric Health Service Facilities with no information on their clinical outcome were excluded, and the remaining 146 were followed up for at most 21 months. Extended-spectrum β-lactamases (ESBL)-producing Enterobacterales and Pseudomonas aeruginosa were detected in 42.7% (n = 76) and 2.8% (n = 5) of the rectal swabs and 5.6% (n = 10) and 3.4% (n = 6) of the oral swabs, respectively. Detection of ARB in the oral and rectal cavities showed remarkable association with enteral nutrition. Further, P. aeruginosa was significantly associated with an increase in mortality of the residents, but there were not significant association between ESBL-producing Enterobacterales and mortality. Core-genome phylogeny of P. aeruginosa revealed a wide-spread distribution of the isolated strains across the phylogeny, which included a cluster of ST235 strains with substantially higher biofilm formation ability than the other isolated P. aeruginosa strains. Discussion/Conclusion: This study is the first to investigate the carriage of both oral and rectal ARB, genomic relatedness and determinants of antimicrobial resistance in isolated strains, and clinical outcomes of LTCF residents. Our study provides the first direct evidence for the burden of antimicrobial resistance in LTCFs.

Occurrence of multidrug resistant Gram-negative bacteria and resistance genes in semi-aquatic wildlife - Trachemys scripta, Neovison vison and Lutra lutra - as sentinels of environmental health

Emergence of antimicrobial resistance (AMR) in bacterial pathogens has been recognized as a major public health concern worldwide. In the present study, antimicrobial resistant Gram-negative bacteria (AMRGNB) and AMR genes were assessed in semi-aquatic wild animals from a highly populated and intensive farming region of Spain, Catalonia. Cloacal/rectal swab samples were collected from 241 animals coming from invasive species Trachemys scripta (n = 91) and Neovison vison (n = 131), and endangered-protected species Lutra lutra (n = 19). Accordingly, 133 (55.2%) isolates were identified as AMRGNB. Escherichia coli and Pseudomonas fluorescens were among the bacteria most frequently isolated in all animal species, but other nosocomial agents such as Klebsiella pneumoniae, Salmonella spp. or Citrobacter freundii, were also prevalent. The phenotypic susceptibility testing showed the highest resistance to β-lactams (91%). Molecular analysis showed 25.3% of turtles (15.4% ESBL/Ampc genes), 21% of Eurasian otters (10.5% ESBL/Ampc genes) and 14.5% of American minks (8.4% ESBL/Ampc genes) were positive to AMR genes. The genotyping frequency was tetM (20.6%), blaCMY-2 (13%), ermB (6.1%), blaCMY-1 (4.6%), blaCTX-M-15 (3.1%) and mcr-4 (0.8%). Turtles had a larger prevalence of AMRGNB and AMR genes than mustelids, but American mink carried mcr-4 colistin-resistance gene. Moreover, cluster analysis of AMR gene distribution revealed that an ESBL/AmpC cluster in a highly populated area comprising big metropolitan regions, and another tetM/emrB cluster in an expended area with highly intensive livestock production. Although the mcr-4 positive case was not included in those clusters, that case was found in a county with a high pig farm density. In conclusion, semi-aquatic wild animals are a good sentinel for environmental contamination with AMRGNB and AMR genes. Therefore, One Health Approach is urgently needed in highly populated regions, and with intensive livestock production like Catalonia.

Screening for antimicrobial-resistant Gram-negative bacteria in hospitalised patients, and risk of progression from colonisation to infection: Systematic review

BackgroundTransmission of antimicrobial-resistant Gram-negative bacteria (AMR-GNB) amongst hospitalised patients can lead to new cases of carriage, infection and outbreaks, hence the need for early carrier identification. We aim to explore two key elements that may guide control policies for colonisation/infection in hospital settings: screening practices on admission to hospital wards and risk of developing infection from colonisation. MethodsWe searched on PubMed, Scopus and Cochrane databases for studies published from 2010 up to 2021 reporting on adult patients hospitalised in high-income countries. ResultsThe search retrieved 11,853 articles. After screening, 100 studies were included. Combining target patient groups and setting type, we identified six screening approaches. The most reported approach was all admitted patients to high-risk (HR) wards (49.4%). The overall prevalence of AMR-GNB was 13.8% (95%CI 9.3–19.0) with significant differences across regions and time. Risk of progression to infection amongst colonised patients was 11.0% (95%CI 8.0–14.3) and varied according to setting and pathogens’ group (p value<0.0001), with higher values reported for Klebsiella species (18.1%; 95%CI 8.9–29.3). ConclusionsWhile providing a comprehensive overview of the screening approaches, our study underlines the considerable burden of AMR-GNB colonisation and risk of progression to infection in hospitals by pathogen, setting and time.

Phenotypic and Genotypic Characteristics of Antimicrobial and Disinfectant Resistance of Gram-negative Bacteria Involved in Early Broiler Chick Mortality

One of the most challenges facing the poultry industry in Egypt is the early mortality among broiler chicks during the first ten days of the rearing cycle, especially which caused by antimicrobial resistant Gram-negative bacteria. This study was conducted for the determination of the prevalence of Gram-negative bacteria involved in early mortality among broiler chicks. Antibiogram profile and antibiotic and disinfectant resistance genes were also performed. Five hundred samples (liver, yolk sac, cecum, spleen, and heart) from freshly dead affected chicks were cultured on different media for isolation of causative agents.by conventional and serological methods. PCR was used for detection of resistance genes. The Bacteriological examination revealed the presence of Salmonella spp., E. coli, and P. aeruginosa in the percentages of 23, 25 and 8%, respectively. Single and mixed infections were observed as 41, and 7%, respectively. 86.9% of Salmonella serovars were resistant to colistin sulphate, 48% of E. coli strains showed resistance against norfloxacin, and 87.5% of P. aeruginosa showed resistance against florfenicol. The mcr1 gene was found in 86.9% of all Salmonella serovar, qnrS gene was detected in 16% of E. coli, and floR gene was present in 100% of P. aeruginosa isolates. PCR screening for qacED1 revealed that all bacterial isolates under test were positive. It was concluded that results of current study assert the existence mcr1, qnrS, floR, and qacED1 genes among (Salmonella spp., E. coli, and P. aeruginosa) which were isolated from early aged broiler dead chicks; that represents a high risk on the poultry industry in Egypt.

Characterization of antimicrobial-resistant Gram-negative bacteria that cause neonatal sepsis in seven low- and middle-income countries

Antimicrobial resistance in neonatal sepsis is rising, yet mechanisms of resistance that often spread between species via mobile genetic elements, ultimately limiting treatments in low- and middle-income countries (LMICs), are poorly characterized. The Burden of Antibiotic Resistance in Neonates from Developing Societies (BARNARDS) network was initiated to characterize the cause and burden of antimicrobial resistance in neonatal sepsis for seven LMICs in Africa and South Asia. A total of 36,285 neonates were enrolled in the BARNARDS study between November 2015 and December 2017, of whom 2,483 were diagnosed with culture-confirmed sepsis. Klebsiella pneumoniae (n = 258) was the main cause of neonatal sepsis, with Serratia marcescens (n = 151), Klebsiella michiganensis (n = 117), Escherichia coli (n = 75) and Enterobacter cloacae complex (n = 57) also detected. We present whole-genome sequencing, antimicrobial susceptibility and clinical data for 916 out of 1,038 neonatal sepsis isolates (97 isolates were not recovered from initial isolation at local sites). Enterobacterales (K. pneumoniae, E. coli and E. cloacae) harboured multiple cephalosporin and carbapenem resistance genes. All isolated pathogens were resistant to multiple antibiotic classes, including those used to treat neonatal sepsis. Intraspecies diversity of K. pneumoniae and E. coli indicated that multiple antibiotic-resistant lineages cause neonatal sepsis. Our results will underpin research towards better treatments for neonatal sepsis in LMICs.

Systematic review on Screening for antimicrobial-resistant Gram-negative bacteria in inpatients

Abstract Background Infections with antimicrobial-resistant Gram-negative bacteria (AMR-GNB) are increasingly being reported worldwide. Early identification of carriage at hospital admission is essential to reduce the risk of onward transmission within the health facility. This systematic review aimed at exploring screening practices for AMR-GNB faecal colonization among patients on admission to hospital in high-income countries and estimating its prevalence. Methods We searched on Pubmed, Scopus and Cochrane databases for studies published from 2010 up to April 2019. We included studies reporting on patients ≥18 years old and hospitalised (excluding long-term care facilities). Results The search retrieved 9496 articles, 85 were included after screening: 10 reported screening activities in outbreak situations (not included in the analysis); 75 in non-outbreak situations. Based on the target patient groups and setting we identified four subsets of screening approaches: all admitted (AA) in high risk (HR) wards (36 studies, 48%), HR patients in HR wards (12, 16%), HR patients in low risk wards (LRW) (11; 15%) and AA - LRW (15, 20%). HR patients-based screening targeted patients with certain clinical conditions (mostly oncologic patients, 37%), travellers 29%, previously hospitalised and individuals with multiple risks 34%. HR wards-based screening was performed mostly in ICU (73%), while LRW-based screening in hospital-wide setting (58%). We investigated the overall prevalence rates of AMR-GNB (15.1%; 95%CI: 9.5-21.6), Klebsiella spp (KB) (4.1%; 3.1-5.3), E. coli (9.6%; 7.7-11.7) P. Aeruginosa (7.6%; 1.7-16.8), A. Baumannii (2.1%; 0.5-4.4) and other Enterobacterales (0.8%; 0.59-1.1). Reported KB-prevalence varied according to screening approaches, with statistically significant higher prevalence in HR wards. Conclusions According to our data, screening for AMR-GNB mostly followed targeted approaches. Overall prevalence of AMR-GNB carriage at hospital admission was considerable. Key messages This systematic review gives un overview on the screening procedures for AMR-GNB faecal colonization among patients on hospital admission in high-income countries. According to our results, overall prevalence of AMR-GNB carriage was considerable (15.1%), varying among specific pathogens but with no significant correlation with screening approaches, except for KB.

Risk of infection in antimicrobial-resistant Gram-negative bacteria carriers: A systematic review

Abstract Background Antimicrobial-resistant Gram-negative bacteria (AMR-GNB) have emerged as important health care-associated pathogens. Infections with AMR-GNB are associated with high patient morbidity and attributable mortality. Colonization is a prerequisite for infection, however the extent to which colonized patients develop infection is unclear. This systematic review explored the risk of developing infection during hospitalisation among AMR-GNB faecal carriers. Also, we investigated the acquisition rate for AMR-GNB colonization among patients not colonized at admission. Methods We searched on PubMed, Scopus and Cochrane databases for studies published from 2010 up to April 2019. We included studies reporting on hospitalised patients ≥18 years old in high-income countries (excluding long-term care facilities). Results Out of 9496 articles, 55 studies fulfilled our inclusion criteria. Forty-two studies reported data from EU/EEA, 6 from USA and 7 from other regions. Almost all studies (n = 45) were conducted in university hospitals. Most studies (n = 41;74.5%) were performed in high-risk wards (ICU, haematology, burn units and transplant units). Out of 55 studies, 8 examined AMR-GNB, 27 Enterobacteriaceae, while the others investigated specific pathogens: Klebsiella spp. (n = 11), E. Coli (n = 2), A. Baumannii (n = 3) and P. Aeruginosa (n = 4). The rate of AMR-GNB carriage acquisition was 10.5% (n = 40 studies; 95% CI:8.2-13.1). The risk of progression to infection among patients colonized at hospital admission was 13.9% (n = 15; 5.4-24.9), while the infection rate in patients who acquired carriage during hospitalization was 23.0% (n = 7; 5.9-45.2). Patients with an undefined time of colonization presented an infection rate of 16.9% (n = 13; 11.2-23.4). Considering these three populations as a whole, the risk of developing infection was 16.0% (11.0-21.0). Conclusions Our results suggest that risk of progression to infection in AMR-GNB colonized patients in hospital setting is high. Key messages The aim of our study was to estimate the risk of progression to infection, during hospital stay, in patients colonized by AMR-GNB at hospital admission in high-income countries. Our results suggest that faecal colonization with AMR-GNB poses a 16.0% risk of subsequent AMR-GNB infection. This risk in higher (23.0%) in patients who acquired colonization during hospitalisation.

Activity of ceftolozane/tazobactam against commonly encountered antimicrobial resistant Gram-negative bacteria in Lebanon.

In view of the continuous rise in Gram-negative bacterial resistance and limited treatment options, Ceftolozane/tazobactam (C/T) is a newly introduced antimicrobial agent in Lebanon for its demonstrated activity against resistant Gram-negative bacteria. However, in vitro data is not available about its activity against commonly isolated bacteria in this country. The analysis included clinical isolates, multidrug-resistant (MDR) and extended-spectrum Beta-lactamases (ESBLs), representing 124 Escherichia coli, 75 Klebsiella pneumoniae and 100 Pseudomonas aeruginosa, identified using the MALDI-TOF. The minimum inhibitory concentration (MIC) for C/T was determined by the Etest (Liofilchem, Roseto degli Abruzzi, Italy). In addition, the disk diffusion (DD) test was used to determine the activity of C/T and of the antimicrobials routinely used to test for such pathogens. The C/T activity against the ESBL producers E. coli and K. pneumoniae isolates were similar (MIC90 value of 1 and 1.5 µg/mL, respectively; susceptibility of 100% and 96%, respectively). However, the activity of C/T against the E. coli and K. pneumoniae MDR isolates was much lower (MIC90 value of 256 and 96 µg/mL, respectively; susceptibility of 54% for each). The C/T MIC90 value for the non-MDR P. aeruginosa isolates was 3 µg/mL and ≥ 256 µg/mL for the MDR P. aeruginosa isolates (susceptibility of 96% vs 42% respectively). Overall, the C/T activities show comparable or higher susceptibility to the routinely used antimicrobials. The high in vitro activity of C/T points out its value as a possible alternative to the antimicrobials currently used for treatment of infections caused by such pathogens and would help in minimizing toxicity and bacterial resistance.

Oral colonisation by antimicrobial-resistant Gram-negative bacteria among long-term care facility residents: prevalence, risk factors, and molecular epidemiology

BackgroundFor residents of long-term care facilities (LTCFs), antimicrobial-resistant bacteria (ARB) are a risk factor, yet their oral colonisation, potentially leading to aspiration pneumonia, remains unclear. This study was undertaken to survey the prevalence, phenotypic characteristics, and molecular epidemiology of antimicrobial-resistant Gram-negative bacteria in the oral cavity of LTCF residents, and to analyse the risk factors for such carriers.MethodsThis study involved 98 residents of a LTCF in Hiroshima City, Japan, aged between 55 and 101 years. Oropharyngeal swabs were collected and plated on screening media for ESBL-producing and carbapenem-resistant bacteria; isolates were identified and tested for antibiotic susceptibility; biofilm formation was tested in vitro; identification of epidemic clones were pre-determined by PCR; resistance genes, sequence types, and whole-genome comparison of strains were conducted using draft genome sequences. Demographic data and clinical characterisations were collected and risk factors analysed.ResultsFifty-four strains from 38% of the residents grew on screening media and comprised predominantly of Acinetobacter spp. (35%), Enterobacteriaceae spp. (22%), and Pseudomonas spp. (19%). All Escherichia coli isolates carried CTX-M-9 group and belonged to the phylogroup B2, O25:H4 ST131 fimH30 lineage. Six Acinetobacter baumannii isolates presented identical molecular characteristics and revealed more biofilm production than the others, strongly suggesting their clonal lineage. One Acinetobacter ursingii isolate displayed extensive resistance to various ß-lactams due to multiple acquired resistance genes. One Pseudomonas aeruginosa isolate showed exceptional resistance to all ß-lactams including carbapenems, aminoglycosides, and a new quinolone, showing a multidrug-resistant Pseudomonas aeruginosa (MDRP) phenotype and remarkable biofilm formation. Genome sequence analysis revealed this isolate was the blaIMP-1-positive clone ST235 in Japan. Strokes (cerebral infarction or cerebral haemorrhage) and percutaneous endoscopic gastrostomy tubes were recognised as risk factors for oral colonisation by ARB in the LTCF residents.ConclusionsARB, as defined by growth on screening agar plates, which carried mobile resistance genes or elements or conferred high biofilm formation, were already prevalent in the oral cavity of LTCF residents. Health-care workers involved in oral care should be aware of antimicrobial resistance and pay special attention to transmission prevention and infection control measures to diminish ARB or mobile resistance elements dissemination in LTCFs.

Antimicrobial activity of POL7306 tested against clinical isolates of Gram-negative bacteria collected worldwide.

POL7306 belongs to a new class of peptidomimetic outer-membrane-protein-targeting antibiotics with a novel mechanism of action. POL7306 is in development for the treatment of infections caused by antimicrobial-resistant Gram-negative bacteria and has demonstrated low cytotoxicity and nephrotoxicity. A total of 891 isolates were collected by the SENTRY Antimicrobial Surveillance Program from 134 medical centres in Europe (n = 424; 41 centres in 18 nations), the USA (n = 411 isolates from 67 centres), the Asia-Pacific region (n = 24; 15 centres in 6 nations) and Latin America (n = 32; 11 centres in 9 nations) and included 558 Enterobacterales, 310 non-fermenters and 23 fastidious organisms. Susceptibility testing was performed using the reference broth microdilution method and the medium was supplemented with 0.002% polysorbate-80 for testing POL7306. Resistant subsets were characterized by WGS. POL7306 demonstrated potent in vitro activity against Enterobacterales [including carbapenem-resistant (MIC50/90, 0.06/0.25 mg/L), ESBL-producing (MIC50/90, 0.06/0.12 mg/L), KPC-producing (MIC50/90, 0.12/0.25 mg/L), MBL-producing (MIC50/90, 0.06/0.25 mg/L), colistin-non-susceptible, mcr-negative (MIC50/90, 0.5/2 mg/L) and mcr-positive (MIC50/90, 0.12/0.25 mg/L) Enterobacterales], Pseudomonas aeruginosa (MIC50/90, 0.25/0.25 mg/L), Acinetobacter baumannii (MIC50/90, 0.06/0.12 mg/L) and Stenotrophomonas maltophilia (MIC50/90, 0.06/0.25 mg/L). POL7306 demonstrated potent activity against a large collection of Gram-negative organisms collected worldwide that included colistin-resistant, XDR and ESBL- and carbapenemase-producing isolates for which there are currently limited treatment options.

Prevalence of Antimicrobial Resistance Genes and Integrons in Commensal Gram-Negative Bacteria in a College Community.

Although the human intestinal microbiome has been shown to harbor antimicrobial drug resistance genes (ARGs), the prevalence of such genes in a healthy population and their impact on extraintestinal infections that occur in that community are not well established. This study sought to identify ARG prevalence and their mobile elements in the intestines of a healthy community population at a California University, and compared these genes to those previously identified among uropathogenic Escherichia coli isolated from patients with urinary tract infection from the same community. We isolated Gram-negative bacteria (GNB) from fecal samples of healthy volunteers and screened them by polymerase chain reaction for class 1 integron cassette sequences and ARGs encoding resistance against ampicillin, trimethoprim-sulfamethoxazole, gentamicin, and colistin. We found antimicrobial-resistant GNB from 83 (81%) of 102 nonredundant rectal swab samples. Seventy-four (72%) of these samples contained β-lactamase genes (blaTEM, blaSHV, blaCTX-M, blaOXA, and blaOXY), dihydrofolate reductase (DHFR) genes (dhfr-A17, dhfr-A12, dhfr-A7, dhfr-A5, dhfr-A21, dhfr-A1, dhfr-A13, and dhfr-7), and aminoglycoside resistance genes (aadA5, aadA2, aadA1, and aadB). Integron sequences were found in 37 (36%) fecal samples. These genes were found in 11 different GNB species. The high prevalence of clinically common ARGs and integrons harbored by GNB in the intestine of a healthy population suggest that human intestines may serve as a major reservoir of these mobile ARGs that appear in E. coli strains causing extraintestinal infections in the same community.

Antimicrobial-resistant Gram-negative colonization in infants from a neonatal intensive care unit in Thailand

SummaryAntimicrobial-resistant Gram-negative bacteria are a major cause of morbidity and mortality in hospitalized neonates in South and South-East Asia. This study aimed to determine the dynamics of colonization with antimicrobial-resistant Gram-negative bacteria amongst patients in a neonatal intensive care unit (NICU) in Thailand. From 97 enrolled patients, 52% were colonized by an extended-spectrum β-lactamase (ESBL) organism at some point during their stay and 64% were colonized by a carbapenem-resistant organism. Rapid acquisition of ESBL-positive and carbapenem-resistant organisms was found. Once colonized with an antibiotic-resistant organism, patients remained colonized for the remainder of their NICU stay.

Temporal trends and patterns in antimicrobial-resistant Gram-negative bacteria implicated in intensive care unit-acquired infections: A cohort-based surveillance study in Istanbul, Turkey

This study assessed trends and patterns in antimicrobial-resistant intensive care unit (ICU)-acquired infections caused by Gram-negative bacteria (GNB) in Istanbul, Turkey. Bacterial culture and antimicrobial susceptibility data were collected for all GNB causing nosocomial infections in five adult ICUs of a large university hospital in 2012-2015. Multiresistance patterns were categorised as multidrug-resistant (MDR), extensively drug-resistant (XDR) and pandrug-resistant (PDR). Temporal patterns and trends were assessed using regression analyses. Of 991 pathogenic GNB recorded, the most frequent were Acinetobacter baumannii (35.3%), Klebsiella spp. (26.7%), Pseudomonas aeruginosa (18.1%) and Escherichia coli (6.7%). The overall infection rate decreased by 41% from 18.4 to 10.9 cases per 1000 patient-days in 2012 compared with 2015 (P<0.001), mostly representing decreases in bloodstream infections and pneumonias by A. baumannii and P. aeruginosa. The XDR proportion in A. baumannii increased from 52.4% in 2012 to 71.7% in 2015, but only one isolate was colistin-resistant. Multiresistance patterns remained stable in Klebsiella, with overall XDR and possible PDR proportions of 14.3% and 1.9%, respectively. A back-to-susceptibility trend was noted for P. aeruginosa in which the non-MDR proportion increased from 53.3% in 2012 to 70.6% in 2015. Moreover, 87.9% of E. coli and 39.5% of Enterobacter isolates were MDR, but none was XDR. Antimicrobial resistance patterns in pathogenic GNB continuously change over time and may not reflect single-agent resistance trends. The proportionate amount of antimicrobial-resistant GNB may persist despite overall decreasing infection rates. Timely regional surveillance data are thus imperative for optimal infection control.

South Asia as a Reservoir for the Global Spread of Ciprofloxacin-Resistant Shigella sonnei: A Cross-Sectional Study.

BackgroundAntimicrobial resistance is a major issue in the Shigellae, particularly as a specific multidrug-resistant (MDR) lineage of Shigella sonnei (lineage III) is becoming globally dominant. Ciprofloxacin is a recommended treatment for Shigella infections. However, ciprofloxacin-resistant S. sonnei are being increasingly isolated in Asia and sporadically reported on other continents. We hypothesized that Asia is a primary hub for the recent international spread of ciprofloxacin-resistant S. sonnei.Methods and FindingsWe performed whole-genome sequencing on a collection of 60 contemporaneous ciprofloxacin-resistant S. sonnei isolated in four countries within Asia (Vietnam, n = 11; Bhutan, n = 12; Thailand, n = 1; Cambodia, n = 1) and two outside of Asia (Australia, n = 19; Ireland, n = 16). We reconstructed the recent evolutionary history of these organisms and combined these data with their geographical location of isolation. Placing these sequences into a global phylogeny, we found that all ciprofloxacin-resistant S. sonnei formed a single clade within a Central Asian expansion of lineage III. Furthermore, our data show that resistance to ciprofloxacin within S. sonnei may be globally attributed to a single clonal emergence event, encompassing sequential gyrA-S83L, parC-S80I, and gyrA-D87G mutations. Geographical data predict that South Asia is the likely primary source of these organisms, which are being regularly exported across Asia and intercontinentally into Australia, the United States and Europe. Our analysis was limited by the number of S. sonnei sequences available from diverse geographical areas and time periods, and we cannot discount the potential existence of other unsampled reservoir populations of antimicrobial-resistant S. sonnei.ConclusionsThis study suggests that a single clone, which is widespread in South Asia, is likely driving the current intercontinental surge of ciprofloxacin-resistant S. sonnei and is capable of establishing endemic transmission in new locations. Despite being limited in geographical scope, our work has major implications for understanding the international transfer of antimicrobial-resistant pathogens, with S. sonnei acting as a tractable model for studying how antimicrobial-resistant Gram-negative bacteria spread globally.