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The global burden associated with antimicrobial resistance is of increasing concern. To evaluate risk factors associated with multidrug-resistant (MDR) infection and its clinical impact in a cohort of patients with healthcare-associated bacteraemic urinary tract infections (BUTIs). This was a prospective, multicentre, post-hoc analysis of patients with healthcare-associated-BUTI (ITUBRAS-2). The primary outcome was MDR profile. Secondary outcomes were clinical response (at 48–72 h and at hospital discharge) and length of hospital stay from onset of BUTI. Logistic regression was used to evaluate variables associated with MDR profile and clinical response. Length of hospital stay was evaluated using multivariate median regression. In all, 443 episodes were included, of which 271 (61.17%) were classified as expressing an MDR profile. In univariate analysis, MDR profile was associated with E. coli episodes (odds ratio (OR): 3.13; 95% confidence interval (CI): 2.11–4.69, P < 0.001) and the extensively drug-resistant (XDR) pattern with P. aeruginosa aetiology (7.84; 2.37–25.95; P = 0.001). MDR was independently associated with prior use of fluoroquinolones (adjusted OR: 2.43; 95% CI: 1.25–4.69), cephalosporins (2.14; 1.35–3.41), and imipenem or meropenem (2.08; 1.03–4.20) but not with prior ertapenem. In terms of outcomes, MDR profile was not associated with lower frequency of clinical cure, but was associated with longer hospital stay. MDR profile was independently associated with prior use of fluoroquinolones, cephalosporins, imipenem, and meropenem, but not with prior ertapenem. MDR-BUTI episodes were not associated with worse clinical cure, although they were independently associated with longer duration of hospital stay. [ABSTRACT FROM AUTHOR]

Scant data are available on the link between armed conflicts and the development and spread of antimicrobial resistance. We performed a systematic review with the aim to summarize the available data on the prevalence and features of antibiotic resistance and the causes of antibiotic resistance development during armed conflicts in the 21st century. Data sources: PubMed and SCOPUS databases were searched from 1 January 2000 to 30 November 2023. Study eligibility criteria: Original articles reporting data on armed conflicts and antimicrobial resistance were included in this systematic review. No attempt was made to obtain information from unpublished studies. No language restriction was applied. Methods of data synthesis: Both quantitative and qualitative information were summarized by means of textual descriptions. Participants: Patients or soldiers deployed in armed conflict zones. Tests: culture-dependent antibiotic sensitivity testing or molecular detection of the genetic determinants of antibiotic resistance after a confirmed diagnosis of bacterial infection. Assessment of risk of bias: To evaluate the quality of the included studies, we adapted the tool recommended by the Joanna Briggs Institute. Thirty-four studies were identified, published between November 2004 and November 2023. The quality of included studies was high and medium in 47% and 53% of the studies, respectively. The included studies reported high infection and colonization rates of multidrug-resistant bacteria. Studies performed during the Eastern Ukraine conflict reported high rates of New Delhi metallo-β-lactamase producers. Our findings confirm that wars lead to a large pool of multidrug-resistant infections that could potentially spread. Infection control in healthcare facilities in conflict zones and proper antimicrobial stewardship are crucial. [ABSTRACT FROM AUTHOR]

Carbapenems and piperacillin/tazobactam (PIPC/TAZ) are commonly used as the initial therapy to treat extended-spectrum β-lactamase (ESBL)-producing Enterobacterales in acute cholangitis. However, the overuse of these antibiotics contributes to the spread of antimicrobial resistance. Cefmetazole (CMZ) is stable to hydrolysis by ESBLs, so it may be an alternative to carbapenems and PIPC/TAZ. However, the effectiveness of CMZ compared with that of carbapenems and PIPC/TAZ as the initial therapy for acute cholangitis is unknown. We conducted a retrospective cohort study at a university hospital between April 1, 2014, and December 31, 2022. Patients with bacteremic acute cholangitis who received CMZ, carbapenems, or PIPC/TAZ as the initial therapy were included. The patients were divided into a CMZ group and a carbapenems or PIPC/TAZ (CP) group to compare patient outcomes. A total of 99 patients (54 in the CMZ group and 45 in the CP group) were analyzed. The baseline characteristics of the patients were similar and 30-day mortality did not differ between groups (4% vs. 7%, P = 0.66). However, the CMZ group had a shorter length of stay (LOS) (8 days vs. 15 days, P < 0.001) and lower mean antibiotic cost (98.92 USD vs. 269.49 USD, P < 0.001) than the CP group. In bacteremic acute cholangitis, initial therapy with CMZ may contribute to a shorter LOS and lower antibiotic costs than treatment with carbapenems and PIPC/TAZ, without worsening patient outcomes. [ABSTRACT FROM AUTHOR]

The accelerating prevalence of extended-spectrum β-lactamase (ESBL)-producing and multidrug-resistance (MDR) Escherichia coli (E. coli) become a public health challenge worldwide. This study aimed to discuss the prevalence of drug-resistant E. coli colonization and analyze its risk factors and clinical characteristics among young infants in Southern Taiwan. Stool samples were collected from young infants, aged less than three months, within three days of their hospitalization from September to December 2019 in a tertiary hospital. A questionnaire was designed for parents to complete. E. coli colonies were selected and analyzed for antimicrobial susceptibility. PCR-based multilocus sequence typing was to detect the presence of sequence type ST131 and bla CTX-M genes. Among 100 enrolled infants, 36% had fecal carriage of E. coli isolates, of which twenty nine (80.5%) were MDR, thirteen (36.1%) were ESBL-producing isolates and five (13.8%) and ten (27.7%) were ST131 and strains carrying CTX-M-14 gene, respectively. Compared to non-ST131 and non-CTX-M-14 gene carrier, isolates of ST131 and CTX-M-14 gene carrier showed a significantly higher resistance rate to cefixime, ceftriaxone, and gentamycin, with p value all <0.05. The prevalence of ESBL-producing and MDR E. coli fecal carriage were both high in young infants. The most common sequence type is ST131, of which all are strains carrying CTX-M-14. Further surveillance and investigation to control for the high prevalence of antimicrobial-resistant E. coli fecal carriage among infants in Taiwan are warranted. [ABSTRACT FROM AUTHOR]

This study compares the clinical and microbiological efficacy of ceftolozane/tazobactam (CTLZ/TAZ) and piperacillin/tazobactam (PIPC/TAZ) for treating complicated cystitis or acute pyelonephritis. Patients who had been treated with empiric antibiotics, CTLZ/TAZ (52 cases) or PIPC/TAZ (47 cases), due to urinary tract infections (UTIs) were eligible for this study. Patients' demographic backgrounds, types of UTIs, and causative microorganisms isolated from urine or blood bacterial cultures were collected. Short-term clinical efficacy at the end of the initial empiric therapy, long-term clinical efficacy including sequential antibiotic treatments (nonrecurrence rate within 1 month after the initial empiric therapy), and microbiological efficacy were retrospectively compared in both CTLZ/TAZ and PIPC/TAZ groups. Complicated UTIs were present in most eligible patients, and no significant difference in the patients' background was observed between the two groups. Escherichia coli and Enterococcus faecalis were the most common microorganisms isolated from urine culture in both groups. The short-term clinical effective rate of CTLZ/TAZ and PIPC/TAZ was 80.8% and 87.2%, respectively. For long-term clinical efficacy, the nonrecurrence rate of UTIs was present in 95.1% and 89.7% of patients with CTLZ/TAZ and PIPC/TAZ, respectively. No significant difference was observed in the short- and long-term effects between the two groups. The microbiological efficacy of the CTLZ/TAZ and PIPC/TAZ groups was 72.7% and 86.0%, respectively. No significant difference in microbiological effects was also observed between the two groups. This study demonstrated the noninferiority of CTLZ/TAZ to PIPC/TAZ, suggesting that CTLZ/TAZ is an alternative antibiotic used as empiric therapy for UTIs. [ABSTRACT FROM AUTHOR]

Extended-spectrum beta-lactamase-producing Enterobacterales (eESBL) have high prevalence in hospitals, but real-time monitoring of nosocomial acquisition through conventional typing methods is challenging. Moreover, patient-to-patient transmission varies between the main species, namely Escherichia coli and Klebsiella pneumoniae , which draws into question the relevance of applying identical preventive measures. To detect eESBL cross-transmission events (CTEs) using the quantitative antibiogram (QA) method in combination with epidemiological data (combined QA method), and to determine the effectiveness of standard or contact precautions for eESBL species. First, a validation set was used to compare the relevance of the combined QA method with a combination of pulsed-field gel electrophoresis and epidemiological data (combined PFGE method). Next, a 4-year retrospective analysis was conducted to detect eESBL CTEs in hospitalized patients. Two species were screened – ESBL E. coli (ESBL-Ec) and ESBL K. pneumoniae (ESBL-Kp). During the study, standard precautions alone were applied to patients with ESBL-Ec, whereas contact precautions were applied for patients with ESBL-Kp. As a proof of concept, use of the combined QA method and the combined PFGE method for the detection of CTEs gave identical results for E. coli , and similar results for at least 75% of K. pneumoniae. Overall, 722 patients with ESBL-Ec isolates and 280 patients with ESBL-Kp isolates were included in the retrospective analysis. Nine and 23 CTEs were identified for E. coli and K. pneumoniae , respectively, involving 20 (2.7%) and 36 (12.8%) patients, respectively. The combined QA method constitutes a rapid tool for epidemiological surveillance to detect CTEs. In the study hospital, standard precautions are sufficient to prevent acquisition of ESBL-Ec, whereas contact precautions must be implemented to prevent acquisition of ESBL-Kp. [ABSTRACT FROM AUTHOR]

The global prevalence of intestinal extended-spectrum β-lactamase–producing Enterobacterales (ESBL-PE) is approximately 17% in communities, with significant variations among regions. This longitudinal study aimed to assess the impact of antibiotic intake on the incidence of intestinal ESBL-PE in Ghanaian pharmacy customers outside of hospitals. Screening for ESBL-PE was performed in four independent pharmacies in Kumasi, Ghana, using rectal swabs and an ESBL-PE–selective medium. Pharmacy customers purchasing antibiotics were recruited, and those buying non-antibiotic drugs served as controls. Participants who were negative for ESBL-PE provided follow-up swabs for up to 28 days. At baseline, 302 (75%) of 404 participants were colonized with ESBL-PE. Sixty-three participants who were negative for ESBL-PE at baseline received per-protocol follow-up, including 28 individuals who took antibiotics and 35 controls. The cumulative proportions of ESBL-PE in the antibiotics and control groups were 71% (20/28) and 54% (19/35) at the first follow-up (p 0.258), 86% (24/28) and 80% (28/35) at the second follow-up (p 0.741) and 86% (24/28) and 94% (33/35) at the third follow-up (p 0.393), respectively. The rate of intestinal ESBL-PE carriage among pharmacy customers outside of hospitals was higher than expected at baseline and further increased during the 28 days of follow-up, irrespective of antibiotic intake. This alarming finding needs to be considered in the antibiotic treatment of outpatients and emphasizes the urgent need for improved prevention strategies, development of new antibiotic drugs and potential future elimination strategies. Further longitudinal studies on ESBL-PE in African communities, also outside of pharmacy settings, are required. [Display omitted] [ABSTRACT FROM AUTHOR]

Long-term care hospitals (LTCHs) are at a high risk for the inflow and spread of antimicrobial resistance (AMR) pathogens. However, owing to limited laboratory resources, little is known about the extent to which AMR organisms are endemic. We performed active surveillance for carbapenem-resistant Enterobacteriaceae (CRE) and extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) in newly admitted patients at Marugame Medical Center, a nearly 200-bedded LTCH located in Kagawa, Japan. From August to December 2021, we tested stool samples from patients wearing diapers and confirmed the genetic variants using specific PCR assays. We also collected clinical variables and compared them between AMR carriers and non-carriers. Stool samples were collected from 75 patients, with a median age of 84 years. CRE strain was not detected, but 37 strains of ESBL-E were isolated from 32 patients (42.7%). During the study period, 4.9% of in-hospital patients (37 per 756 patients) were identified to be ESBL-E carriers in the routine microbiological processing, suggesting that active surveillance detected approximately 9-fold more ESBL-E carriers. The bla CTX-M-9 group was the most common (38.5%), followed by the bla TEM (26.9%). The clinical backgrounds of the ESBL-E non-carriers and carriers were not significantly different. Our active screening demonstrated that nearly half of the patients hospitalized or transferred to a Japanese LTCH were colonized with ESBL-E. We highlight the enforcement of universal basic infection prevention techniques at LTCHs where patients carrying AMR pathogens gather. [ABSTRACT FROM AUTHOR]

• Treatment of multidrug-resistant Gram-negative bacteria is increasingly complex. • ESCMID and IDSA guidelines defined optimal strategies when robust data were available. • However, these guidelines could not address more complex infections due to scarcity of literature. • This 'practical approach' paper aimed to provide guidance for these unmet needs. The emergence of multidrug-resistant Gram-negative bacilli and the development of new antibiotics have complicated the selection of optimal regimens. International guidelines are valuable tools, but are limited by the scarcity of high-quality randomized trials in many situations. A panel of experts from the French and Italian Societies of Infectious Diseases aimed to address unresolved issues in clinical practice based on their experience, an updated literature review and open discussions. The panel reached consensus for the following 'first choices': (i) cefepime for ventilator-acquired pneumonia due to AmpC β-lactamase-producing Enterobacterales; (ii) the β-lactam/β-lactamase inhibitor combination most active in vitro , or cefiderocol combined with fosfomycin, and aerosolized colistin or aminoglycosides, for severe pneumonia due to Pseudomonas aeruginosa resistant to ceftolozane-tazobactam; (iii) high-dose piperacillin-tazobactam (including loading dose and continuous infusion) for complicated urinary tract infections (cUTIs) caused by extended-spectrum β-lactamase-producing Enterobacterales with piperacillin-tazobactam minimum inhibitory concentration (MIC) ≤8 mg/L; (iv) high-dose cefepime for cUTIs due to AmpC β-lactamase-producing Enterobacterales other than Enterobacter spp. if cefepime MIC ≤2 mg/L; (v) ceftolozane-tazobactam or ceftazidime-avibactam plus metronidazole for intra-abdominal infections (IAIs) due to third-generation cephalosporin-resistant Enterobacterales; (vi) ceftazidime-avibactam plus aztreonam plus metronidazole for IAIs due to metallo-β-lactamase-producing Enterobacterales; (vii) ampicillin-sulbactam plus colistin for bloodstream infections (BSIs) caused by carbapenem-resistant Acinetobacter baumannii ; (viii) meropenem-vaborbactam for BSIs caused by Klebsiella pneumoniae carbapenemase-producing Enterobacterales; and (ix) ceftazidime-avibactam plus fosfomycin for neurological infections caused by carbapenem-resistant P. aeruginosa. These expert choices were based on the necessary balance between antimicrobial stewardship principles and the need to provide optimal treatment for individual patients in each situation. [Display omitted] [ABSTRACT FROM AUTHOR]

Salmonella causes foodborne disease outbreaks worldwide and raises concerns about public health and economic losses. To determine prevalence, serovar, antimicrobial resistance patterns, and the presence of extended-spectrum β-lactamase (ESBL) genes in a cross-sectional study, 418 total samples from feces and carcasses (from three slaughterhouses) and pork and cutting boards (from four markets) were collected in a central Thailand province in 2017 and 2018. Of the 418 samples, 272 (65.1%) were positive for Salmonella. The prevalence of Salmonella-positive samples from markets (158 of 178; 88.8%) was significantly higher than that among samples from slaughterhouses (114 of 240; 47.5%) (P , 0.05). A total of 1,030 isolates were identified; 409 were assigned to 45 serovars, with Salmonella Rissen the most common (82 of 409; 20%). Two serovars, Salmonella Cannstatt and Salmonella Braubach, were identified for the first time in Thailand in market and slaughterhouse samples, respectively. Among 180 isolates representing 19 serovars, 133 (73.9%) exhibited multidrug resistance. Screening for ESBL production revealed that 41 (10.3%) of 399 isolates were ESBL positive. The prevalence of ESBL-producing Salmonella isolates was significantly higher among the market isolates (31 of 41; 75.6%) than among the slaughterhouse isolates in (10 of 41; 24.4%) (P , 0.05). In market samples, 24 (77.4%) of 31 isolates were recovered from pork and 7 (22.6%) were recovered from cutting boards. Nine ESBL-producing isolates carried single ESBL genes, either blaTEM (4 of 41 isolates; 9.8%) or blaCTX-M (5 of 41 isolates; 12.2%), whereas 11 (26.8%) carried both blaTEM and blaCTX-M. No ESBL-producing Salmonella isolate carried the blaSHV gene. These results suggest that pigs, their flesh, and cutting boards used for processing pork could be reservoirs for widespread ESBL-producing Salmonella isolates with multidrug resistance and outbreak potential across the food chain [ABSTRACT FROM AUTHOR]

A wide range of bacterial infections occur in coronavirus disease 2019 (COVID-19) patients, particularly in those with severe coronaviral disease. Some of these are community-acquired co-infections. To review recent data that indicate the occurrence of hospital-onset bacterial infections, including with antibiotic-resistant isolates, in COVID-19 patients. Using PubMed, the literature was searched using terms including: 'COVID-19'; 'SARS-CoV-2'; 'bacterial infection'; 'healthcare-associated infection'; 'antibiotic resistance'; 'antimicrobial resistance'; 'multi-drug resistance'; ' Streptococcus '; ' Staphylococcus '; ' Pseudomonas '; ' Escherichia '; ' Klebsiella '; ' Enterococcus '; ' Acinetobacter '; ' Haemophilus '; 'MRSA'; 'VRE'; 'ESBL'; 'NDM-CRE'; 'CR-Ab'; 'VRSA'; 'MDR'. There is a growing number of reports of bacterial infections acquired by patients with severe COVID-19 after hospital admission. Antibiotic-resistant pathogens found to cause healthcare-associated infections (HAIs) in COVID-19 patients include methicillin-resistant Staphylococcus aureus , New Delhi metallo-β-lactamase-producing carbapenem-resistant Enterobacterales, carbapenem-resistant Acinetobacter baumannii , extended-spectrum β-lactamase Klebsiella pneumoniae and vancomycin-resistant enterococci. COVID-19 has impacted bacterial HAIs in a number of ways with an increase in the incidence of New Delhi metallo-β-lactamase-producing carbapenem-resistant Enterobacterales and carbapenem-resistant A. baumannii reported at some hospital sites compared with before the pandemic. Recommended guidelines for antimicrobial stewardship in COVID-19 patient treatment are discussed regarding minimization of empiric broad-spectrum antibiotic use. Other studies have reported a decrease in methicillin-resistant S. aureus and vancomycin-resistant enterococci cases, which has been attributed to enhanced infection prevention and control practices introduced to minimize intra-hospital spread of COVID-19. Poorer outcomes have been observed in hospitalized COVID-19 patients with an antibiotic-resistant infection. Although heightened IPC measures have been accompanied by a reduction in some HAIs at specific sites, in other situations, COVID-19 has been associated with an increase in bacterial HAI incidence. Further research is needed to define the cost–benefit relationship of maintaining COVID-19-related infection prevention and control protocols beyond the pandemic to reduce the burden of HAIs. In addition, the longer-term impact of high usage of certain broad-spectrum antibiotics during the COVID-19 pandemic requires evaluation. [ABSTRACT FROM AUTHOR]

Background: Although sink- and drain-related carbapenemase-producing Enterobacterales transmission has been reported previously, there is limited research regarding the transmission of extended-spectrum β-lactamase (ESBL)-producing Enterobacterales.Aim: To investigate nosocomial ESBL-producing Klebsiella pneumoniae transmission via patient sinks and drains on a general surgical hospital ward.Methods: ESBL-producing K. pneumoniae transmission on a surgical ward at Tokyo Medical University Hospital (built in July 2019) from July 2019 to February 2020 was investigated. Information regarding the relatedness of the isolates from the patients and the environment was provided by whole-genome sequence analysis.Findings: Four clinical isolates of K. pneumoniae (TUM19831, TUM19832, TUM19833 and TUM19834) were detected during the study. TUM19831 was identified prior to moving to the new building and was detected again in the new building. TUM19832 and TUM19833 were detected in July 2019, and TUM19834 was detected in December 2019. TUM19835 and TUM19836 were detected in two different sinks and drains in July 2019, while a further two sinks and drains tested positive for TUM19837 and TUM19838 in February 2020. Whole-genome analysis revealed that all strains were ST307 and CTXM15 sequence types, and the isolates were indistinguishable by genetic analysis. Due to inadequate removal of the slime biofilm coating, the sinks needed to be cleaned again before TUM19837 and TUM19838 could be detected.Conclusions: This study demonstrated the transmission of indistinguishable ESBL-producing K. pneumoniae strains from sinks and drains in the patient area of a general surgical hospital ward. There is a need to recognize this risk and develop optimal management strategies for plumbing systems in hospitals and other healthcare settings. [ABSTRACT FROM AUTHOR]

The frequency of urinary tract infections (UTIs) caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacterales is steadily increasing worldwide. Therefore, we aimed to evaluate the efficacy and appropriate dosing of cefmetazole (CMZ) in invasive urinary tract infection (iUTI) caused by ESBL-producing Escherichia coli (ESBLEC). Patients who developed ESBLEC iUTI and received CMZ between January 2007 and December 2018 were identified, and their medical records were reviewed. The time above minimum inhibitory concentration (MIC) (TAM) was calculated using the MIC value obtained from each patient and its simulated CMZ concentration. Thirty-nine patients were included in the study. The median TAM was 92.6% (interquartile range [IQR], 67.6–100). CMZ was clinically efficacious in 38 (97.4%) patients overall and in 11 out of 12 (91.7%) patients with normal renal function who received CMZ at 1 g every 8 h. In normal renal function, 1 g CMZ infused for over 1 h every 8 h is an efficacious treatment for iUTI caused by ESBLEC with MIC =< 4 mg/L. [ABSTRACT FROM AUTHOR]

Compared to cephalosporin-based prophylaxis, ertapenem prophylaxis lowers the risk of surgical site infection among carriers of extended-spectrum β-lactamase-producing Enterobacterales (ESBL-PEs) undergoing colorectal surgery. We aimed to determine whether ertapenem prophylaxis leads to increased postoperative colonization with carbapenem-resistant Enterobacterales (CREs) and third-generation-cephalosporin-resistant Enterobacterales (3GCR-Es). This study was nested within a quality improvement study of prophylaxis for ESBL-PE carriers undergoing colorectal surgery. Patients were screened 4–6 days after surgery for carriage of ESBL-PEs or other 3GCR-Es and CREs. When CREs were detected, pre- and postsurgical clones were compared using Fourier-transform infrared (FT-IR) spectroscopy. The sample consisted of 56 patients who carried ESBL-PEs before surgery and received cefuroxime/metronidazole prophylaxis (Group 1), 66 who carried ESBL-PEs before surgery and received ertapenem (Group 2), and 103 ESBL-PE non-carriers who received cefuroxime/metronidazole prophylaxis (Group 3). CRE carriage was detected postoperatively in one patient (1.5%) in Group 2 versus eight patients (14.3%) in Group 1 (RD –12.8%; 95%CI –22.4% to –3.1%). For seven out of nine patients, preoperative ESBL-PE and postoperative CRE isolates were compared; in five of them, the pre- and postoperative clones were identical. Postoperative 3GCR-E carriage was detected in 37 patients (56.1%) in Group 2 versus 46 patients in Group 1 (82.1%) (aRD –20.7%, 95%CI –37.3% to –4.1%). Among ESBL-PE carriers undergoing colorectal surgery, detection of short-term postsurgical colonization by CREs and 3GCR-Es was significantly lower among patients who received ertapenem prophylaxis than those who received cephalosporin–metronidazole prophylaxis. Resistance development in a colonizing bacterial clone, rather than carbapenemase acquisition, was the major mechanism of carbapenem resistance. [ABSTRACT FROM AUTHOR]

This study aimed to determine rates and risk factors of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE) acquisition and transmission within households after hospital discharge of an ESBL-PE-positive index patient. Two-year prospective cohort study in five European cities. Patients colonized with ESBL-producing Escherichia coli (ESBL-Ec) or Klebsiella pneumoniae (ESBL-Kp), and their household contacts were followed up for 4 months after hospital discharge of the index case. At each follow up, participants provided a faecal sample and personal information. ESBL-PE whole-genome sequences were compared using pairwise single nucleotide polymorphism-based analysis. We enrolled 71 index patients carrying ESBL-Ec (n = 45), ESBL-Kp (n = 20) or both (n = 6), and 102 household contacts. The incidence of any ESBL-PE acquisition among household members initially free of ESBL-PE was 1.9/100 participant-weeks at risk. Nineteen clonally related household transmissions occurred (case to contact: 13; contact to case: 6), with an overall rate of 1.18 transmissions/100 participant-weeks at risk. Most of the acquisition and transmission events occurred within the first 2 months after discharge. The rate of ESBL-Kp household transmission (1.16/100 participant-weeks) was higher than of ESBL-Ec (0.93/100 participant-weeks), whereas more acquisitions were noted for ESBL-Ec (1.06/100 participant-weeks) compared with ESBL-Kp (0.65/100 participant-weeks). Providing assistance for urinary and faecal excretion to the index case by household members increased the risk of ESBL-PE transmission (adjusted prevalence ratio 4.3; 95% CI 1.3–14.1). ESBL-PE cases discharged from the hospital are an important source of ESBL-PE transmission within households. Most acquisition and transmission events occurred during the first 2 months after hospital discharge and were causally related to care activities at home, highlighting the importance of hygiene measures in community settings. German Clinical Trials Register, DRKS-ID: DRKS00013250. [ABSTRACT FROM AUTHOR]

In this observational study, phenotypic and genotypic patterns of antimicrobial resistance (AMR) in Klebsiella pneumoniae isolated from intramammary infections, clinical mastitis, fresh feces, rectal swabs, animal hindlimbs, and bulk tank milk samples from Brazilian dairy herds were investigated. In addition, we identified specific genetic variants present among extended-spectrum β-lactamase (ESBL) producers. We obtained 169 isolates of K. pneumoniae from 2009 to 2011 on 24 Brazilian dairy farms located in 4 Brazilian states. The AMR profile of all isolates was determined using disk-diffusion assays. The antimicrobial panel included drugs commonly used as mastitis treatment in Brazilian dairy herds (gentamicin, cephalosporins, sulfamethoxazole-trimethoprim, tetracycline) as well as antimicrobials of critical importance for human health (meropenem, ceftazidime, fluoroquinolones). The K. pneumoniae isolates resistant to tetracycline, fluoroquinolones, sulfamethoxazole-trimethoprim, or chloramphenicol were screened for presence of drug-specific AMR genes [ tet , qnr , aac (6')- Ib , floR , catA2 , cm1A , dfr , sul ] using PCR. In addition, we identified ESBL genes present among ESBL-producers by using whole genome sequencing. Genomes were assembled and annotated, and patterns of AMR genes were investigated. Resistance was commonly detected against tetracycline (22.5% of all isolates), streptomycin (20.7%), and sulfamethoxazole-trimethoprim (9.5%). Antimicrobial resistance rates were higher in K. pneumoniae isolated from intramammary infections in comparison with isolates from feces (19.2 and 0% of multidrug resistance in intramammary and fecal isolates, respectively). In contrast, no difference in AMR rates was observed when contrasting hind limbs and isolates from intramammary infections. The genes tetA , sul2 , and floR were the most frequently observed AMR genes in K. pneumoniae resistant to tetracycline, sulfamethoxazole-trimethoprim, and chloramphenicol, respectively. The tetA gene was present exclusively in isolates from milk. The genes bla CTX-M8 and bla SHV-108 were present in 3 ESBL-producing K. pneumoniae , including an isolate from bulk tank milk. The 3 isolates were of sequence type 281 and had similar mobile genetic elements and virulence genes. Our study reinforced the epidemiological importance and dissemination of bla CTX-M-8 pST114 plasmid in food-producing animals in Brazil. [ABSTRACT FROM AUTHOR]

To investigate and explore temporal changes in risk factors of community-onset extended-spectrum β-lactamase (ESBL) Escherichia coli and Klebsiella pneumoniae bacteraemia in a region with low antibiotic resistance. Population-based case–control study including 223 cases hospitalized with a first-time community-onset ESBL-producing E. coli and K. pneumoniae bacteraemia, 2214 non-ESBL E. coli and K. pneumoniae bacteraemia controls, and 2228 population controls in the North Denmark Region between 2007 and 2017. We used a conditional logistic regression to compute crude and adjusted (age, gender and co-morbidity) odds ratios (aORs) and 95% CIs of risk factors and compared selected risk factors between 2007–2011 and 2016–2017. Several conventional risk factors of ESBL E. coli or K. pneumoniae were identified compared with the population controls. Compared with the non-ESBL controls, use of fluoroquinolones (aOR 3.56, 95% CI 2.52–5.05), three or more admissions within the recent year (aOR 2.18, 95% CI 1.45–3.28), three or more antibiotic prescriptions within 15–365 days before the admission (aOR 2.18, 95% CI 1.53–3.10), male sex (aOR 2.01, 95% CI 1.50–2.69), admission within 1–91 days (aOR 1.84, 95% CI 1.37–2.48) and antibiotic within 15–91 days (aOR 1.82, 95% CI 1.37–2.42) inferred the highest risk. Assessment of temporal dynamics between 2007–2011 and 2016–2017 revealed a slight reduction in risk factors associated with direct health-care contact (e.g. hospital admission). Recent and frequent hospitalization, and exposure to antibiotics, especially use of fluoroquinolones, appeared to be associated specifically with ESBL production, and focus and interventions should be directed towards these areas. Our results indicated a dissemination of ESBLs into the community. [ABSTRACT FROM AUTHOR]

The frequency of urinary tract infections (UTIs) caused by community-acquired extended-spectrum β-lactamase (CA-ESBL)-producing Enterobacteriaceae is increasing worldwide. Increased carbapenem use may lead to selection of carbapenem-resistant organisms, resulting in dire consequences for hospitals. We compared the outcomes of non-carbapenem antimicrobial therapy on UTIs caused by CA-ESBL-producing and non-producing Escherichia coli (E. coli) in infants younger than 6 months of age. We conducted a retrospective chart review, from January 2010 to December 2018, in infants (0–6 months old) with diagnosed UTIs caused by CA-ESBL-producing and non-producing E. coli at the Pusan National University Children's Hospital. Chart reviews were completed for patients whose urine sample had been collected using urinary catheterization. We treated all patients using non-carbapenem antimicrobials. Two weeks after therapy completion, clinical states were evaluated. There were 105 and 582 patients diagnosed with UTIs caused by CA-ESBL-producing and non-producing E. coli , respectively. The mean age at diagnosis in ESBL and non-ESBL groups was 2.7 ± 1.6 and 2.8 ± 1.1 months (P = 0.711), respectively. There were no significant differences between ESBL and non-ESBL groups in the duration of fever (1.2 ± 0.5 and 1.2 ± 0.4 days, respectively, P = 0.761) or clinical cure states post therapy (101/105 and 567/582, respectively, P = 0.513). This study found no significant differences in treatment outcomes between ESBL and non-ESBL groups treated with non-carbapenem antimicrobials. Therefore, initially administered non-carbapenem antimicrobials can be continued in patients with UTIs caused by CA-ESBL-producing E. coli who show clinical improvement. [ABSTRACT FROM AUTHOR]

The spread of antibiotic resistance among bacterial strains has been associated with consumption of food contaminated with both pathogenic and nonpathogenic bacteria. The objective of this study was to determine the prevalence of antibiotic resistant Escherichia coli isolates in local and imported retail raw chicken meat in Qatar. A total of 270 locally produced (chilled) and imported (chilled or frozen) whole chicken carcasses were obtained from three Hypermarket stores in Qatar. The 216 E. coli isolates recovered from the chicken samples were subjected to antibiotic susceptibility testing with the disk diffusion method. Extended-spectrum β-lactamase (ESBL) production was evaluated with the double disk synergy test. Isolates harboring colistin resistance were identified with a multiplex PCR assay and DNA sequencing. Nearly 89% (192) of the 216 isolates were resistant to at least one of the 18 antibiotics tested. Isolates from local and imported chicken carcasses had relatively higher resistance to sulfamethoxazole (62% of isolates), tetracycline (59.7%), ampicillin and trimethoprim (52.3% each), ciprofloxacin (47.7%), cephalothin (45.4%), and colistin (31.9%). Less resistance was found to amoxicillin–clavulanic acid (6%), ceftriaxone (5.1%), nitrofurantoin (4.2%), piperacillin-tazobactam (4.2%), cefepime (2.3%), meropenem (1.4%), ertapenem (0.9%), and amikacin (0.9%). Nine isolates (4.2%) were ESBL producers, and 137 (63.4%) were multidrug resistant. The percentages of multidrug-resistant, ESBL-producing, and colistin resistant isolates were significantly higher among isolates from local chilled than from imported chilled and frozen chicken samples. Our findings indicate the high prevalence of antibiotic-resistant E. coli in chicken meat sold at retail in Qatar. [ABSTRACT FROM AUTHOR]

Hospital-acquired infections caused by extended-spectrum β-lactamase (ESBL)–producing Escherichia coli are a global problem. Healthy people can carry ESBL-producing E. coli in the intestines; thus, E. coli from healthy people can potentially cause hospital-acquired infections. Therefore, the transmission routes of ESBL-producing E. coli from healthy persons should be determined. A foodborne outbreak of human norovirus (HuNoV) GII occurred at a restaurant in Shizuoka, Japan, in 2018. E. coli O25:H4 was isolated from some of the HuNoV-infected customers. Pulsed-field gel electrophoresis showed that these E. coli O25:H4 strains originated from one clone. Because the only epidemiological link among the customers was eating food from this restaurant, the customers were concurrently infected with E. coli O25:H4 and HuNoV GII via the restaurant food. Whole genome analysis revealed that the E. coli O25:H4 strains possessed genes for regulating intracellular iron and expressing the flagellum and flagella. Extraintestinal pathogenic E. coli often express these genes on the chromosome. Additionally, the E. coli O25:H4 strains had plasmids harboring nine antimicrobial resistance genes. These strains harbored ESBL-encoding blaCTX-M-14 genes on two loci of the chromosome and had higher ESBL activity. Multilocus sequence typing and fimH subtyping revealed that the E. coli O25:H4 strains from the outbreak belonged to the subclonal group, ST131-fimH30R, which has been driving ESBL epidemics in Japan. Because the E. coli O25:H4 strains isolated in the outbreak belonged to a subclonal group spreading in Japan, foods contaminated with ESBL-producing E. coli might contribute to spreading these strains among healthy persons. The isolated E. coli O25:H4 strains produced ESBL and contained plasmids with multiple antimicrobial resistance genes, which may make it difficult to select antimicrobials for treating extraintestinal infections caused by these strains. [ABSTRACT FROM AUTHOR]

• Molecular characteristics of ESBL-producing Klebsiella pneumoniae were investigated. • CTX-M-15 was the predominant ESBL of K. pneumoniae in Japan. • ESBL-producing hypervirulent K. pneumoniae strains were isolated in Japan. • ESBL-producing hypervirulent K. pneumoniae strains comprised various clones. To provide data on the molecular characteristics of extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae clinical isolates in Japan. A total of 100 clinical isolates of ESBL-producing K. pneumoniae collected throughout Japan between June and July 2018 were studied. ESBL genes were analyzed using PCR and DNA sequencing. Transferability of ESBL genes was investigated by conjugation experiments. Plasmid replicon types, virulence genes (rmpA , rmpA2 , iucA , iroB , and peg-344) associated with hypervirulent K. pneumoniae (hvKp), and capsule types were detected using PCR. Genotyping was performed using multilocus sequence typing. All ESBL-producing isolates carried bla CTX-M genes. The most predominant CTX-M-type identified was CTX-M-15 (n = 55). We identified 24 sequence types (STs) among the CTX-M-15 producers, with ST25 (n = 8) being the most common. Most of the transconjugants carrying bla CTX-M-15 contained the FIIk replicon. Of the 100 ESBL-producing isolates, 31 were hvKp defined by the presence of the virulence genes. These ESBL-producing hvKp isolates belonged to eight STs (STs 23, 25, 36, 65, 86, 268, 412, and 4492), with five capsule types (K1, K2, K20, K57, and undefined). CTX-M-15 was the predominant ESBL among K. pneumoniae isolates from Japan. This study shows that ESBL-producing hvKp strains comprising various clones are emerging in Japan. [ABSTRACT FROM AUTHOR]

Infections as a result of extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) are considered infections with a high public health burden. In this study, we aimed to identify incidences of and risk factors for healthcare-associated infections (HAIs) after rectal colonization with ESBL-producing Escherichia coli (ESBL-EC) or Klebsiella pneumoniae (ESBL-KP). This prospective cohort study was performed in 2014 and 2015. Patients colonized with ESBL-EC or ESBL-KP were monitored for subsequent HAI with ESBL-E and other pathogens. In the case of an ESBL-E infection, rectal and clinical isolates were compared using pulsed-field gel electrophoresis (PFGE), and whole-genome sequencing (WGS) for ESBL-KP isolates. Proportional hazard models were applied to identify risk factors for HAIs, and to analyse competing risks. Among all patients admitted to the hospital during the study period, 13.6% were rectally screened for third-generation cephalosporin-resistant Enterobacterales (3GCREB). A total of 2386 rectal carriers of ESBL-EC and 585 of ESBL-KP were included in the study. Incidence density (ID) for HAI with ESBL-E was 2.74 per 1000 patient days at risk (95% confidence interval (CI) 2.16–3.43) among carriers of ESBL-EC, while it was 4.44 per 1000 patient days at risk (95% CI 3.17–6.04) among carriers of ESBL-KP. In contrast, ID for HAI with other pathogens was 4.36 per 1000 patient days at risk (95% CI 3.62–5.21) among carriers of ESBL-EC, and 5.00 per 1000 patient days at risk (95% CI 3.64–6.69) among carriers of ESBL-KP. Cox proportional hazard regression analyses identified colonization with ESBL-KP (HR = 1.58, 95% CI 1.068–2.325) compared with ESBL-EC as independent risk factor for HAI with ESBL-E. The results were consistent over all competing risk analyses. Clinicians should be aware of the increased risk of ESBL-E infections among patients colonized with ESBL-KP compared with ESBL-EC that might be caused by underlying diseases, higher pathogenicity of ESBL-KP and other factors. [ABSTRACT FROM AUTHOR]

This study was conducted to characterize Escherichia coli strains and evaluate the spread of antimicrobial resistance among these strains from fresh produce and farm environments in Korea. We then conducted phenotypic and genetic studies on antimicrobial-resistant isolates. We determined the genetic epidemiological characteristics of isolates that produced extended-spectrum β-lactamase (ESBL) and confirmed plasmid transfer in isolates that carried blaCTX-M-type genes. E. coli strains were isolated from 8 samples of fresh produce and 152 samples from the farm environment collected from May 2014 to June 2016. Cephalosporin resistance was the most prevalent (61.8%) type of resistance among the isolates. Five ESBL-producing strains with high genetic homology with E. coli of human or livestock origin were identified. Lateral transfer of plasmids harboring blaCTX-M-type genes to transconjugants was successful. Two isolates from Chinese cabbage and from water samples collected from a nearby stream harbored the ISEcp1-blaCTX-M-55-orf477 operon and were confirmed as sequence type 1196 and the same type of plasmid replicon, suggesting that cross-contamination was highly likely. A high-risk clone of sequence type 69 (clonal complex 69) isolates was also recovered from the farm environment. This study provides genetic evidence that antimicrobial resistance factors in E. coli from farm environments originate in the clinic or in livestock, highlighting the fact that good agricultural practices in farming are important to inhibit the spread of antimicrobial resistance to bacteria on fresh produce. E. coli was isolated from 8 fresh produce and 152 environment samples. Cephalosporin resistance was the most common type of antimicrobial resistance in E. coli. Five ESBL-producing E. coli strains were confirmed. ESBL-producing E. coli had high homology with isolates from humans and livestock. Horizontal gene transfer was found in plasmids harboring blaCTX-M. [ABSTRACT FROM AUTHOR]

Classical waterborne pathogens (cholera/typhoid) drove the development of safe water and sanitation during the industrial revolution. Whilst effective against these organisms, other bacteria exploited the potential to form biofilm in the narrow pipes of buildings. 1976 saw the discovery of legionella. Despite evidence dating back to 1967 (including paediatric deaths in Manchester in 1995 from splashes from a sink contaminating parenteral nutrition) it required the deaths of four neonates and the might of the Press in 2011 for the UK medical services to accept waterborne transmission of other Opportunistic Plumbing Premise Pathogens (OPPP). Human nature, a healthcare construction industry largely devoid of interest in water safety, and failures in recognising transmission are major forces hindering progress in preventing infection/deaths from waterborne infections. The advent of highly resistant Gram-negative bacteria is highlighting further deficiencies in modern drainage systems. These bacteria are not thought to have special adaptations promoting their dispersal but purely attract our attention to the well-trodden routes used by sensitive organisms, which go undetected. The O'Neill report warns of the bleak future without effective antibiotics. This paper examines the evidence as to why modern water services/sanitation continue to present a risk to patient safety (and the general public) and also suggests their designs may be flawed if they are to stem the modern equivalent of cholera, the dissemination of antibiotic resistance. [ABSTRACT FROM AUTHOR]

Escherichia coli (E. coli) causes urinary tract infections, pneumonia, surgical site infections, and bloodstream infections and is the important pathogen for both community-acquired and healthcare-associated infections. To investigate the clonality of E. coli is important for infection control and prevention. We aimed to investigate the clonality of clinical E. coli isolates using Cica Geneus E. coli polymerase chain reaction (PCR)-based open-reading frame typing (POT) KIT and clarify the clinical usefulness of this kit. About 124 E. coli isolates obtained from inpatients at Sapporo Medical University Hospital were used. The POT method was used to classify 124 clinical isolates into 87 POT numbers. In addition to the clonality, it was possible to obtain additional information that 20 of the 124 isolates were extended-spectrum β-lactamase (ESBL) producing E. coli (5 isolates of CTX-M-1 group and 15 isolates of CTX-M-9 group) and 13 were sequence type (ST) 131 clone. Furthermore, when these ESBL-producing 20 isolates were compared with pulsed-field gel electrophoresis (PFGE) or multilocus sequence typing (MLST), Simpson's index of diversity was 0.968 in POT method, 0.979 in PFGE, and 0.584 in MLST. POT method had an analytical power similar to that of PFGE. In conclusion, attention should be paid to the difference in the interpretation of the results between the POT method and the PFGE, but POT method may be useful to timely monitor the spread of E. coli in medical facilities. [ABSTRACT FROM AUTHOR]

The aim of the study was to measure the impact of antibiotic exposure on the acquisition of colonization with extended-spectrum β-lactamase-producing Gram-negative bacteria (ESBL-GNB) accounting for individual- and group-level confounding using machine-learning methods. Patients hospitalized between September 2010 and June 2013 at six medical and six surgical wards in Italy, Serbia and Romania were screened for ESBL-GNB at hospital admission, discharge, antibiotic start, and after 3, 7, 15 and 30 days. Primary outcomes were the incidence rate and predictive factors of new ESBL-GNB colonization. Random forest algorithm was used to rank antibiotics according to the risk of selection of ESBL-GNB colonization in patients not colonized before starting antibiotics. We screened 10 034 patients collecting 28 322 rectal swab samples. New ESBL-GNB colonization incidence with and without antibiotic treatment was 22/1000 and 9/1000 exposure-days, respectively. In the adjusted regression analyses, antibiotic exposure (hazard ratio (HR) 2.38; 95% CI 1.29–4.40), age 60–69 years (HR 1.19; 95% CI 1.05–1.34), and spring season (HR 1.25; 95% CI 1.14–1.38) were independently associated with new colonization. Monotherapy ranked higher als combination therapy in promoting ESBL-GNB colonization. Among monotherapy, cephalosporins ranked first followed by tetracycline (second), macrolide (fourth) and cotrimoxazole (seventh). Overall the ranking of cephalosporins was lower when used in combination. Among combinations not including cephalosporins, quinolones plus carbapenems ranked highest (eighth). Among sequential therapies, quinolones ranked highest (tenth) when prescribed within 30 days of therapy with cephalosporins. Impact of antibiotics on selecting ESBL-GNB at intestinal level varies if used in monotherapy or combination and according to previous antibiotic exposure. These finding should be explored in future clinical trials on antibiotic stewardship interventions. NCT01208519. [ABSTRACT FROM AUTHOR]

Antimicrobial residues in milk have been discussed as a possible selector for Enterobacteriaceae that produce extended-spectrum β-lactamases (ESBL) in dairy herds. Such residues are found in waste milk after antibiotic treatment of mastitis, but antibiotic dry cow therapy might also lead to antibiotic residues in colostrum and in milk during early lactation. While it is known that feeding of waste milk selects ESBL bacteria in calves, this was not investigated for colostrum yet, which is supposed to contain much lower antibiotic concentrations than waste milk. In this observational prospective case study on 2 farms, we hypothesized that blanket dry cow treatment with β-lactams would have more selective (here: increasing) effects on ESBL concentrations than selective (here: individually chosen) antibiotic dry cow therapy. Thus, we compared concentrations of ESBL-producing Enterobacteriaceae in feces of calves (n = 50) at 2 dairy farms with different management of antibiotic dry cow therapy. Considerably higher concentrations of ESBL-producing Escherichia coli were observed in blanket antibiotic dry cow therapy on d 3 of the calf's life (7.6 vs. 5.3 log cfu/g of calf feces). Both farms used narrow-spectrum penicillin combined with aminoglycosides for drying off, and the majority of ESBL isolates (93%) were co-resistant to aminoglycosides. No waste milk was fed to calves and no calf was treated with β-lactam antibiotics or aminoglycosides during the first 3 d of life, thus differences were most likely associated with different frequency of antibiotic dry cow therapy on farms (19 of 25 mother cows on farm A, 9 of 25 on farm B). Even though the presumable selection effect of antibiotics used for drying off decreased within the next 3 wk, this result further emphasizes the need for the reduction and prudent use of antibiotic dry cow therapy on farms. [ABSTRACT FROM AUTHOR]

• Long-term-care hospitals are important sources of extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae (KP) infection. • Recent use of urinary catheters and antibiotics are risk factors for ESBL-producing KP. • CTX-M type ESBL genes are prevalent in community-onset KP throughout South Korea. • The most prevalent sequence type among KP isolates was ST23 in South Korea. Although it is essential to know the particular causes of antibiotic-resistant infections in the community, there is lack of evidence regarding risk factors for community-onset extended-spectrum β-lactamase-producing Klebsiella pneumoniae (ESBL-KP) bacteraemia in South Korea. As such, this study aimed to identify risk factors for community-onset ESBL-KP bacteraemia. From May 2016 to April 2017, patients with community-onset KP bloodstream infection (BSI) (n = 408) from six sentinel hospitals participating in the Global Antimicrobial Surveillance System in South Korea were included in this study. Risk factors of ESBL-KP BSI were assessed. Polymerase chain reaction and sequencing to identify genes encoding ESBLs and multi-locus sequence typing were performed. Of the 408 patients with community-onset KP BSI, 70 (17%) had ESBL-KP BSI. Admission to a long-term-care hospital within the previous 3 months [odds ratio (OR) 5.7, 95% confidence interval (CI) 2.1–15.6; P = 0.001], previous use of trimethoprim/sulfamethoxazole (TMP/SMT; OR 11.5, 95% CI 2.7–48.6; P = 0.001) or extended-spectrum cephalosporin (OR 2.2, 95% CI 1.2–3.9; P = 0.01), and previous use of a urinary catheter (OR 2.3, 95% CI 1.1–4.5; P = 0.02) were independent risk factors for community-onset ESBL-KP BSI. ESBL-KP isolates most frequently carried the CTX-M-1 group ESBL (74%, n = 52). The most prevalent sequence type (ST) among the ESBL-KP isolates was ST48 (14%, n = 10). Among non-ESBL-KP isolates, ST23 was most prevalent (21%, n = 70). Previous admission to a long-term-care hospital, use of a urinary catheter and use of TMP/SMT or extended-spectrum cephalosporin within the previous 3 months were identified as risk factors for community-onset ESBL-KP BSI. Strict antibiotic stewardship and infection control measures are needed for long-term-care hospitals. [ABSTRACT FROM AUTHOR]

Extended-spectrum β-lactamase (ESBL)–producing bacteria are spreading rapidly, posing a threat to human and animal health. Contamination of vegetables with antimicrobial-resistant bacteria or those harboring antimicrobial resistance genes or a combination of both presents a potential route of transmission to humans. Therefore, the aim of this study was to determine the prevalence of these bacteria in fresh vegetables in Japan. A total of 130 samples of fresh vegetables were collected from seven supermarkets in Japan. The predominant genus detected was Pseudomonas spp., including 10 ESBL-producing strains, isolated from 10 (7.7%) of the vegetable samples. Two ESBL genes were detected, blaTEM-116 (n = 7) and blaSHV-12 (n = 3), and some of these strains were resistant to multiple antibiotics. Because vegetables are often consumed raw, those contaminated with ESBL producers could represent an important route of transmission to humans in Japan. Thus, more stringent hygiene measures and monitoring are required to prevent transmission via this source. Retail vegetables in Japan are not as frequently contaminated by animal feces. ESBL-producing bacteria were isolated from vegetables (7.7%). Two ESBL genes (blaTEM-116 and blaSHV-12) were detected in vegetables. [ABSTRACT FROM AUTHOR]

• Non-intravenous carbapenem-sparing antibiotics could have a role in ESBL/AmpC-positive bacteraemia. • Use of oral definitive treatment did not show increased mortality. • Trimethoprim/sulfamethoxazole could be used as a non-intravenous stewardship option in this setting. • This strategy could reduce carbapenem use and shorten hospital length of stay. Carbapenems are considered the treatment of choice for extended-spectrum β-lactamase (ESBL)- or AmpC β-lactamase-producing Enterobacteriaceae bacteraemia. Data on the effectiveness of non-intravenous carbapenem-sparing antibiotic options are limited. This study compared the 30-day mortality and clinical failure associated with the use of carbapenems versus alternative non-intravenous antibiotics for the definitive treatment of ESBL/AmpC-positive Enterobacteriaceae bacteraemia. This 12-year retrospective study (2004–2015) included all patients with bacteraemia due to ESBL/AmpC-producing Enterobacteriaceae at a Spanish hospital. Given the lack of randomisation of initial therapies, a propensity score for receiving carbapenems was calculated. There were 1115 patients with a first episode of bacteraemia due to Escherichia coli or Klebsiella pneumoniae , of which 123 (11.0%) were ESBL/AmpC-positive. There were 101 eligible patients: 59 in the carbapenem group and 42 in the alternative treatment group (trimethoprim/sulfamethoxazole 59.5%, quinolones 21.4%). The most frequent sources of infection were urinary (63%) and biliary (15%). Compared with the carbapenem group, patients treated with an alternative regimen had a shorter hospital stay [median (IQR) 7 (5–10) days vs. 12 (9–18) days; P < 0.001]. Use of an alternative non-intravenous therapy did not increase mortality (OR = 0.27, 95% CI 0.05–1.61; P = 0.15). After controlling for confounding factors with the propensity score, the adjusted OR of carbapenem treatment was 4.95 (95% CI 0.94–26.01; P = 0.059). Alternative non-intravenous carbapenem-sparing antibiotics could have a role in the definitive treatment of ESBL/AmpC-positive Enterobacteriaceae bacteraemia, allowing a reduction in carbapenem use. Use of trimethoprim/sulfamethoxazole in this series showed favourable results. [ABSTRACT FROM AUTHOR]

This study was performed to evaluate what percentage of urinary tract infections (UTIs) caused by extended spectrum β-lactamase (ESBL)-producing strains recurs with ESBL-producing strains during follow up and to assess the risk factors for recurrence with ESBL-producing Escherichia coli strains on subsequent first recurrence episode. We enrolled female patients with UTIs caused by ESBL-producing E. coli between May 2012 and December 2015, who were longitudinally followed up for at least 24 months. Among the 206 patients with ESBL positive UTI, 180 completed the study. 60 (60/180, 33.3%) of patient with first episode of UTI caused by ESBL-producing E. coli experienced recurrent UTIs during follow up. Of 60 patients, 43 (43/60, 71.7%) recurred with ESBL-producing E. coli on the first UTI recurrence episode. On multivariate analysis, the time to recurrence and history of cephalosporin usage in the last 6 months were identified as risk factors for recurrence with ESBL-producing E. coli per se (odds ratio [OR] = 0.9, 95% confidence interval [CI] 0.8–1.0, p = 0.030 and OR = 27.0, 95% CI 2.4–299.8, p = 0.007, respectively). These findings show that high proportion of patient with UTI caused by ESBL-producing E. coli recurs with ESBL-producing E. coli on subsequent recurrence episode. While result of antibiotic susceptibility cannot be identified on the visit day empirical treatment should be referred to the antecedent antibiotic resistance profile in patients whose previous UTIs were due to ESBL-producing strains. [ABSTRACT FROM AUTHOR]

Intestinal carriage with extended spectrum β-lactamase Enterobacteriaceae (ESBL-E) and carbapenemase-producing Enterobacteriaceae (CPE) can persist for months. We aimed to evaluate whether oral antibiotics followed by faecal microbiota transplantation (FMT) can eradicate intestinal carriage with ESBL-E/CPE. Randomized, open-label, superiority trial in four tertiary-care centres (Geneva (G), Paris (P), Utrecht (U), Tel Aviv (T)). Non-immunocompromised adult patients were randomized 1: 1 to either no intervention (control) or a 5-day course of oral antibiotics (colistin sulphate 2 × 106 IU 4×/day; neomycin sulphate 500 mg 4×/day) followed by frozen FMT obtained from unrelated healthy donors. The primary outcome was detectable intestinal carriage of ESBL-E/CPE by stool culture 35–48 days after randomization (V4). ClinicalTrials.gov NCT02472600. The trial was funded by the European Commission (FP7). Thirty-nine patients (G = 14; P = 16; U = 7; T = 2) colonized by ESBL-E (n = 36) and/or CPE (n = 11) were enrolled between February 2016 and June 2017. In the intention-to-treat analysis 9/22 (41%) patients assigned to the intervention arm were negative for ESBL-E/CPE at V4 (1/22 not receiving the intervention imputed as positive) whereas in the control arm 5/17 (29%) patients were negative (one lost to follow up imputed as negative) resulting in an OR for decolonization success of 1.7 (95% CI 0.4–6.4). Study drugs were well tolerated overall but three patients in the intervention group prematurely stopped the study antibiotics because of diarrhoea (all received FMT). Non-absorbable antibiotics followed by FMT slightly decreased ESBL-E/CPE carriage compared with controls; this difference was not statistically significant, potentially due to early trial termination. Further clinical investigations seem warranted. [ABSTRACT FROM AUTHOR]

The aim of these guidelines is to provide recommendations for decolonizing regimens targeting multidrug-resistant Gram-negative bacteria (MDR-GNB) carriers in all settings. These evidence-based guidelines were produced after a systematic review of published studies on decolonization interventions targeting the following MDR-GNB: third-generation cephalosporin-resistant Enterobacteriaceae (3GCephRE), carbapenem-resistant Enterobacteriaceae (CRE), aminoglycoside-resistant Enterobacteriaceae (AGRE), fluoroquinolone-resistant Enterobacteriaceae (FQRE), extremely drug-resistant Pseudomonas aeruginosa (XDRPA), carbapenem-resistant Acinetobacter baumannii (CRAB), cotrimoxazole-resistant Stenotrophomonas maltophilia (CRSM), colistin-resistant Gram-negative organisms (CoRGNB), and pan-drug-resistant Gram-negative organisms (PDRGNB). The recommendations are grouped by MDR-GNB species. Faecal microbiota transplantation has been discussed separately. Four types of outcomes were evaluated for each target MDR-GNB:(a) microbiological outcomes (carriage and eradication rates) at treatment end and at specific post-treatment time-points; (b) clinical outcomes (attributable and all-cause mortality and infection incidence) at the same time-points and length of hospital stay; (c) epidemiological outcomes (acquisition incidence, transmission and outbreaks); and (d) adverse events of decolonization (including resistance development). The level of evidence for and strength of each recommendation were defined according to the GRADE approach. Consensus of a multidisciplinary expert panel was reached through a nominal-group technique for the final list of recommendations. The panel does not recommend routine decolonization of 3GCephRE and CRE carriers. Evidence is currently insufficient to provide recommendations for or against any intervention in patients colonized with AGRE, CoRGNB, CRAB, CRSM, FQRE, PDRGNB and XDRPA. On the basis of the limited evidence of increased risk of CRE infections in immunocompromised carriers, the panel suggests designing high-quality prospective clinical studies to assess the risk of CRE infections in immunocompromised patients. These trials should include monitoring of development of resistance to decolonizing agents during treatment using stool cultures and antimicrobial susceptibility results according to the EUCAST clinical breakpoints. [ABSTRACT FROM AUTHOR]

• Community-onset infections due to ESBL-Enterobacteriaceae (ESBL-Ent) are frequently treated with inappropriate therapy. • Inappropriate empirical antibiotic therapy is associated with higher mortality in ESBL-Ent infections. • Previous fluoroquinolone use increases the risk of presenting with ESBL-Ent infection at hospital admission. • Invasive devices and previous combination therapy triple the risk of developing an infection due to ESBL-Ent. The impact of inappropriate empirical antibiotic therapy (IEAT) on the outcome of severe infections due to extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-Ent) remains unclear. Current evidence is limited by study design and lack of confounder control. The main objective of this study was to define the outcome of severe infections due to ESBL-Ent according to clinical parameters and place of infection acquisition. Adult hospitalised patients with ESBL-Ent infections were included in a 3-year multicentre prospective study. Primary outcomes were IEAT rates and crude mortality of severe infections, adjusted by place of acquisition [community-acquired infection (CAI), healthcare-associated infection (HCAI) and hospital-acquired infection (HAI)]. Among 729 patients, 519 (71.2%) were diagnosed with HAI, 176 (24.1%) with HCAI and 34 (4.7%) with CAI. Moreover, 32.9% of patients received IEAT; higher rates of IEAT were observed in pneumonia (23%) and deep surgical site infections (19%). HCAIs were more frequently associated with IEAT than HAIs (48.3% vs. 27.9%; OR = 1.7, 95% CI 1.2–2.4). The overall mortality rate for severe infections (n = 264) was 12.1% and was significantly higher in HCAIs (20%) than HAIs (10%) (RR = 2.3, 95% CI 1.01–5.3). IEAT significantly increased the risk of mortality in bloodstream infections (RR = 8.3, 95% CI 2–46.3). Rates of IEAT and overall mortality of ESBL-Ent severe infections were higher in HCAIs than HAIs. Prompt diagnosis of patients with severe HCAIs due to ESBL-Ent is essential since these infections receive high rates of IEAT and significantly higher mortality than HAIs [ClinicalTrials.gov Identifier: NCT00404625]. [ABSTRACT FROM AUTHOR]

To investigate factors for the recurrence of acute pyelonephritis (APN) caused by extended-spectrum β-lactamase–producing Escherichia coli (ESBL-PE), a retrospective cohort study was performed at a tertiary-care hospital from 2014 through 2016. Among 135 patients who had recovered from APN caused by ESBL-PE, the 1-year cumulative recurrence rates of APN caused by any pathogen or by ESBL-PE specifically were 35.6% and 22.1%, respectively. In a multivariate analysis, infectious disease (ID) consultation was associated with decreased recurrence (95% confidence interval [CI] = 0.24–0.96, P = 0.038 for recurrence caused by any pathogen; and 95% CI = 0.15–0.84, P = 0.019 for recurrence caused by ESBL-PE). History of APN within 1 year was a risk factor for recurrent APN caused by any pathogen (P = 0.011). Microbiological cure was a preventive factor for recurrent APN caused by ESBL-PE (P = 0.024). In conclusion, our data show that ID consultation protects against APN recurrence caused by ESBL-PE. • Acute pyelonephritis (APN) caused by extended-spectrum β-lactamase–producing Escherichia coli (ESBL-PE) is increasing. • Data of the factors associated with APN recurrence caused by ESBL-PE were limited. • The 1-year cumulative recurrence rate of APN caused by ESBL-PE was 22.1%. • Infectious disease (ID) consultation was associated with decreased recurrence. • We should encourage physicians to refer patients with APN for ID consultation. [ABSTRACT FROM AUTHOR]

• In 59.6% of Dutch dairy herds ESBL/AmpC-producing E. coli were found. • ESBL/AmpC-producing E. coli prevalence significantly declined between 2011 and 2013. • Animal prevalence of ESBL/AmpC-producing E. coli is highest in young calves. This study was conducted to assess: (1) a change in between-herd prevalence of extended-spectrum and AmpC β-lactamase-producing Escherichia coli (ESBL/AmpC-EC) between 2011 and 2013, the period during which the antimicrobial policy in animal husbandry in the Netherlands changed significantly, and (2) the prevalence of ESBL/AmpC-EC in individual calves, young stock, and dairy cows in the Netherlands. In 196 randomly selected conventional dairy herds, faecal samples were collected from calves (maximum n = 15), and randomly selected young stock (n = 5) and dairy cows (n = 15). Additionally, fresh faecal samples were collected from five different places on the floors where the dairy cows were housed. Samples were screened for E. coli with non-wild type susceptibility for cefotaxime and isolates were phenotypically confirmed as ESBL/AmpC-producing by disc diffusion, using cefotaxime and ceftazidime with and without clavulanic acid, and cefoxitin. Samples containing ESBL/AmpC-EC were examined semi-quantitatively. In 59.6% of the dairy herds one or more samples tested positive for ESBL/AmpC-EC. The between-herd prevalence based on floor samples in 2013 (18.0%) was significantly lower than the prevalence in 2011 based on comparable samples (32.7%). The individual animal prevalence of ESBL/AmpC-EC, with a minimum shedding level of 103 cfu/g of faeces, was 19.3% in calves, 0.9% in young stock, and 0.8% in dairy cows. Although ESBL/AmpC-EC was found in the majority of dairy herds, the herd prevalence declined significantly between 2011 and 2013. Calves were found to have both, a much higher individual animal prevalence and a higher level of shedding than young stock and cows. [ABSTRACT FROM AUTHOR]

• Use of non-carbapenems to treat ESBL-producing Enterobacteriaceae (ESBL-E) infection is controversial. • No study comparing carbapenem with non-carbapenem agents in ICU patients with sepsis or septic shock due to ESBL-E to date. • Comparison of outcomes for ICU patients with severe ESBL-E infection receiving a carbapenem vs. non-carbapenem antibiotic. • Outcomes did not differ between patients receiving a carbapenem vs. non-carbapenem as definitive treatment. • A randomised controlled trial in ICU patients is merited to evaluate the efficacy of non-carbapenem agents in ESBL-E. The aim of this study was to evaluate the use of non-carbapenem antibiotics to treat severe extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) infections in intensive care unit (ICU) patients. This retrospective observational study conducted in two ICUs compared the outcomes of patients with ESBL-E infections administered a carbapenem or a non-carbapenem antibiotic as their definitive treatment. The primary outcome was treatment failure within 30 days, a composite endpoint of ESBL-E infection recurrence and 30-day mortality. Secondary outcomes included 30-day and in-hospital mortality rates, ESBL-E infection recurrence and infection(s) due to other pathogen(s). Among 107 patients included in the study, 67 received a carbapenem and 40 received a non-carbapenem antibiotic as their definitive treatment. Clinical characteristics of the two groups were similar. Comparing patients given a non-carbapenem antibiotic with those administered a carbapenem, they had similar 30-day treatment failure (43% vs. 61%, respectively; P = 0.06) and ESBL-E infection recurrence rates (25% vs. 22%; P = 0.8), but the former had lower 30-day mortality (23% vs. 45%; P = 0.02) and in-hospital mortality rates (23% vs. 49%; P = 0.005). Secondary infection rates caused by other pathogen(s), including Clostridium difficile , were comparable. Outcomes were comparable regardless of whether or not patients received an empirical carbapenem. For ICU patients with severe ESBL-E infections, treatment with a non-carbapenem antibiotic was not associated with poorer outcomes compared with a carbapenem antibiotic. [ABSTRACT FROM AUTHOR]

European legislation stipulates that food no longer intended for human consumption, due to commercial reasons, manufacturing problems, or some defect, can be used in pet feed. However, the presence of former foodstuffs in pet diets could constitute a public health issue because pets can act as reservoirs of antimicrobial resistance genes. In this study, for the first time, biological hazards due to the presence of Escherichia coli and Salmonella in former foodstuff meat products were evaluated. Among the 112 samples of packaged fresh meat (poultry, pork, and beef) collected from cold storage warehouses of a mass market retailer, the overall prevalence of E. coli and Salmonella, the prevalence of strains with multidrug resistance, the phenotypic and genotypic characteristics of strains that produce extended-spectrum β-lactamase, and the presence of biofilm producers were assessed. A high prevalence of E. coli was observed in former foodstuffs of poultry (100%), pork (100%), and beef (93.3%). Salmonella Derby and Salmonella Typhimurium were found in 11.5% of the poultry samples, and Salmonella Typhimurium was found in 13.3% of the pork samples. Salmonella was not recovered from the beef samples. Multidrug resistance was found in E. coli and Salmonella isolates from poultry, pork, and beef. Overall, 18.2% of E. coli isolates and 20% of Salmonella isolates were resistant to various types of antibiotics with various mechanisms of action. Salmonella isolates from pork are an important source of extended-spectrum β-lactamase production. Both E. coli and Salmonella were carriers of antibiotic resistance marker genes (blaTEM, blaSHV, and blaCTX-M) associated with β-lactamase production in poultry and pork. Approximately 30% of the E. coli isolates from the various types of meat were phenotypically biofilm producers, and all carried the fimH gene. These findings indicate that the use of former foodstuff meat products in pet diets can represent a risk for public health. [ABSTRACT FROM AUTHOR]

In the poultry industry, commercial layer farms play an important role in meeting the protein demand through the supply of eggs. However, the risk of contamination by β-lactamase-producing Escherichia coli in eggs laid by commercial chickens is significant. In this study, we investigated the rate of extended-spectrum β-lactamase (ESBL) and plasmid-mediated AmpC (pAmpC) β-lactamase-producing E. coli isolated from layer hens and characterized their molecular background. Among the 92 cefotaxime-resistant E. coli isolates, 66 (71.7%) were identified as multidrug resistant and 29 showed phenotypic and genotypic characteristics of β-lactamase-producing E. coli. The ESBL/pAmpC genes bla CTX-M-1, bla CTX-M-14, bla CTX-M-15, and bla CMY-2 were detected in 1, 6, 5, and 4 isolates, respectively. The non-ESBL/pAmpC gene bla TEM-1 was found in 16 isolates. Three isolates harbored both bla TEM-1 and bla CTX-M-14 genes. A total of 12 isolates also carried class 1 integrons, with 3 different gene cassette arrangements found in 8 of these isolates. A pulsed-field gel electrophoresis (PFGE) analysis of the 29 β-lactamase-producing E. coli isolates revealed that 4 PFGE patterns were consistent with the β-lactamase gene and layer farm origin, and showed a similar antibiotic resistance pattern. Our results suggest that comprehensive surveillance and more prudent use of third-generation cephalosporins in commercial layer farms is necessary to prevent the dissemination of ESBL/pAmpC-producing E. coli. [ABSTRACT FROM AUTHOR]

Highlights • bla PER extended-spectrum β-lactamase genes were mobilised from Pararheinheimera spp. • A Pararheinheimera branch acquired the bla PER progenitor long ago. • Mobilisation of bla PER genes into pathogens is a recent event. ABSTRACT To investigate the origin of PER extended-spectrum β-lactamases, publicly available sequence databases were searched for bla PER-like genes. Three genomes from Pararheinheimera , a genus associated with water and soil environments, were found to carry bla PER-like genes but lacked the IS CR1 /IS Pa12 /IS Pa13 insertion sequences commonly associated with bla PER in clinical isolates. Sequence analysis revealed 78–96% nucleotide identity and conserved synteny between the clinical mobile genetic elements (MGEs) encoding bla PER-1 and the bla PER locus in the Pararheinheimera genomes. Notably, bla PER genes were only identified in 3 of 21 Pararheinheimera and Rheinheimera genomes, whereas the genetic environment of bla PER genes as found in clinical MGEs was conserved in all Pararheinheimera and Rheinheimera genomes. These findings indicate that bla PER genes were likely acquired by a branch of the Pararheinheimera genus long before the antibiotic era. Later, bla PER genes were mobilised, likely through the involvement of insertion sequences, from one or several Pararheinheimera species, allowing their dissemination into human pathogens. [ABSTRACT FROM AUTHOR]

Highlights • Clinical efficacy of mecillinam is uncertain against ESBL-producing Escherichia coli. • Combination of mecillinam, amoxicillin and clavulanic acid has synergistic activity. • The three-drug combination could be clinically useful for urinary tract infections. ABSTRACT This study aimed to evaluate the potential synergistic and bactericidal effects of mecillinam in combination with amoxicillin and clavulanic acid against extended-spectrum β-lactamase (ESBL)-producing Escherichia coli. Eight clinical E. coli isolates with varying susceptibility to mecillinam [minimum inhibitory concentrations (MICs) of 0.125 mg/L to >256 mg/L] and high-level resistance to amoxicillin (MICs > 256 mg/L) were used. Whole-genome sequencing was performed to determine the presence of β-lactamase genes and mutations in the cysB gene. The activities of single drugs and the combinations of two or three drugs were tested in 24-h time–kill experiments. Population analysis was performed for two strains before and after experiments. Only one strain had a mutation in the cysB gene resulting in an amino acid substitution. With the two-drug combinations, initial killing was observed both with mecillinam and amoxicillin when combined with clavulanic acid. Synergy was observed with mecillinam and clavulanic acid against one strain and with amoxicillin and clavulanic acid against three strains. However, following significant re-growth, a bactericidal effect was found only with amoxicillin and clavulanic acid against two strains. Pre-existing subpopulations with elevated mecillinam MICs were detected before experiments and were selected with mecillinam alone or in two-drug combinations. In contrast, the three-drug combination showed enhanced activity with synergy against six strains, a bactericidal effect against all eight strains, and suppression of resistance during 24-h antibiotic exposure. This combination may be of clinical interest in the treatment of urinary tract infections caused by ESBL-producing E. coli. [ABSTRACT FROM AUTHOR]

Highlights • Newly diagnosed ESBL patients felt there was a lack of information from the attending doctor about ESBL and the consequences for their daily lives. • This insufficient information initially caused fear and anxiety. • To cope, patients searched for information themselves using the Internet and found strategies to enable them to carry on with their lives as before. • Patients were treated respectfully and not in a way that made them feel uncomfortable or stigmatized, and with correct hygiene routines. Background The number of people who become carriers of antibiotic-resistant extended-spectrum β-lactamase (ESBL)–producing bacteria is steadily increasing. A carrier of ESBL can potentially be stressful for individuals, affecting their daily lives. Methods The purpose of this study was to increase the understanding of experiences and consequences of being an ESBL carrier. A modified version of the grounded theory was used to analyze 16 open interviews. Results The analysis resulted in the core category "to handle the new life situation." The results showed a lack of information being passed by attending doctors to study participants about ESBL and the consequences for their daily lives. This insufficient information initially caused fear and anxiety, leading to participants instead searching for information themselves using the Internet. Armed with this information, they developed strategies to continue with their lives as before. As patients they experienced staff that were respectful, showed no stigmatization toward ESBL carriership, and used correct hygiene routines. Conclusions When the information from the attending doctor about ESBL carriers is insufficient, patients often use the Internet to obtain additional information. With the use of this information, patients develop strategies to cope with their lives. [ABSTRACT FROM AUTHOR]

Abstract The number of patients infected with extended-spectrum beta-lactamase (ESBL)-producing organisms has increased dramatically worldwide, and high mortality rates are seen in severely ill patients. This study retrospectively compared the clinical characteristics and outcomes of critically ill patients in an intensive care unit (ICU) at the Tsuyama Chuo Hospital (Okayama, Japan) who were hospitalized for bacteremia caused by ESBL-producing Escherichia coli (ESBL-EC) or non-ESBL-producing E. coli (non-ESBL-EC) between January 2006 and December 2016 (11 years). We analyzed the patients' age, sex, underlying disease(s), sequential organ failure assessment scores, primary focus of bacteremia, empiric antibiotics, rate of appropriateness of empiric antibiotics, and treatment duration, with 28-day mortality being the primary outcome. The study included 24 patients with ESBL-EC bacteremia and 77 with non-ESBL-EC bacteremia. The rate of appropriate initial antibiotic treatment was significantly lower (54.2% vs. 96.1%, respectively; P < 0.01) and the mortality due to bacteremia significantly higher (37.5% vs. 15.6%, respectively; P = 0.04) in the ESBL-EC than in the non-ESBL-EC bacteremia group. A subgroup analysis focusing on patients who were administered appropriate empiric antibiotics showed that the 28-day mortality rate did not differ significantly between the two groups (P = 0.23). To our knowledge, this is the first study to compare the outcomes of patients with ESBL-EC and non-ESBL-EC bacteremia in a Japanese ICU setting. Initial empiric antibiotic therapy covering ESBL-producing pathogens should be considered for critically ill patients in the ICU. [ABSTRACT FROM AUTHOR]

Urinary tract infection (UTI) and bloodstream infection (BSI) caused by extended-spectrum β-lactamase (ESBL)-producing bacteria are important healthcare problems. Appropriate infection management requires the direct detection of organisms in clinical specimens. We assessed the capability of the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry-based MBT STAR-Cepha kit to detect ESBL producers in clinical urine and blood samples. Over a 1-year period, 90 urine samples and 55 positive monomicrobial (Escherichia coli , Klebsiella pneumoniae , Klebsiella oxytoca , or Proteus mirabilis) blood cultures were collected from patients with UTI or BSI at Hamamatsu University Hospital. β-lactamase activity in these samples was directly detected using the MBT STAR-Cepha kit, and the results were compared with those of antimicrobial susceptibility testing and polymerase chain reaction detection assay for the isolates. In receiver operating characteristic curve analysis, the kit assay showed low accuracy in detecting ESBL producers in urine samples (area under the curve [AUC], 0.69). Meanwhile, the AUC for detecting all ESBL-producing bacteria in positive blood cultures was 0.81. The kit assay detected cefotaxime (CTX) resistance (mainly in CTX-M-type ESBL producers) with high accuracy in positive blood cultures; however, it did not accurately detect ESBL producers in urine samples and CTX-susceptible isolates with other ESBL-associated genes (e.g., TEM and SHV types) in positive blood cultures. MBT STAR-Cepha testing can accurately discriminate CTX-resistant ESBL producers in BSI cases and thus can contribute to effective infection management. The results suggest that different sample types, antibiotic resistance profiles, and resistance genes can affect the kit performance. • MALDI-TOF MS-based MBT STAR-Cepha kit detected CTX resistance in positive blood cultures. • The kit detected CTX-resistant ESBL producers in bloodstream infection. • The kit performance needs improvement for detecting ESBL producers in urinary tract infection. [ABSTRACT FROM AUTHOR]

Objectives We quantified the impact of antibiotics prescribed in primary care for urinary tract infections (UTIs) on intestinal colonization by ciprofloxacin-resistant (CIP-RE) and extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE), while accounting for household clustering. Methods Prospective cohort study from January 2011 to August 2013 at primary care sites in Belgium, Poland and Switzerland. We recruited outpatients requiring antibiotics for suspected UTIs or asymptomatic bacteriuria (exposed patients), outpatients not requiring antibiotics (non-exposed patients), and one to three household contacts for each patient. Faecal samples were tested for CIP-RE, ESBL-PE, nitrofurantoin-resistant Enterobacteriaceae (NIT-RE) and any Enterobacteriaceae at baseline (S1), end of antibiotics (S2) and 28 days after S2 (S3). Results We included 300 households (205 exposed, 95 non-exposed) with 716 participants. Most exposed patients received nitrofurans (86; 42%) or fluoroquinolones (76; 37%). CIP-RE were identified in 16% (328/2033) of samples from 202 (28%) participants. Fluoroquinolone treatment caused transient suppression of Enterobacteriaceae (S2) and subsequent two-fold increase in CIP-RE prevalence at S3 (adjusted prevalence ratio (aPR) 2.0, 95% CI 1.2–3.4), with corresponding number-needed-to-harm of 12. Nitrofurans had no impact on CIP-RE (aPR 1.0, 95% CI 0.5–1.8) or NIT-RE. ESBL-PE were identified in 5% (107/2058) of samples from 71 (10%) participants, with colonization not associated with antibiotic exposure. Household exposure to CIP-RE or ESBL-PE was associated with increased individual risk of colonization: aPR 1.8 (95% CI 1.3–2.5) and 3.4 (95% CI 1.3–9.0), respectively. Conclusions These findings support avoidance of fluoroquinolones for first-line UTI therapy in primary care, and suggest potential for interventions that interrupt household circulation of resistant Enterobacteriaceae . [ABSTRACT FROM AUTHOR]

Highlights • Pseudomonas aeruginosa is a major multidrug-resistant pathogen of cystic fibrosis (CF) patients. • β-Lactam resistance mechanisms were evaluated in 123 CF strains of P. aeruginosa. • Overproduction of AmpC chromosomal cephalosporinase and major OprD porin alterations were most prevalent. • No ESBLs or carbapenemases were detected, although these resistance mechanisms are emerging in P. aeruginosa. • Monitoring and controlling the spread of such transferable β-lactamases in CF strains of P. aeruginosa is essential. ABSTRACT Pseudomonas aeruginosa is responsible for chronic respiratory tract colonisation and acute exacerbations in cystic fibrosis (CF) patients. This Gram-negative bacterium often develops multidrug resistance, which represents a therapeutic challenge. The objective of this study was to characterise the phenotypic and genetic β-lactam resistance traits of P. aeruginosa strains isolated from CF patients at Grenoble Alpes University Hospital (Grenoble, France). The susceptibility to β-lactam compounds of 123 P. aeruginosa strains collected from the lower respiratory tract of 45 CF patients between 2010–2014 was evaluated. Genetic analyses focused on characterisation of the presence of carbapenemase- and extended-spectrum β-lactamases (ESBL)-encoding genes as well as alterations in the oprD gene encoding the OprD porin. Among the 123 P. aeruginosa strains evaluated, 25 were susceptible to both ceftazidime (CAZ) and imipenem (IPM), 9 only to IPM and 36 only to CAZ; 53 strains were resistant to both drugs. CAZ resistance could be reverted by cloxacillin in 29 strains, indicating overproduction of cephalosporinase. Genetic analyses performed for 79 P. aeruginosa strains revealed no ESBL- or carbapenemases-encoding genes. Among the 74 IPM-resistant strains, 42 (56.8%) displayed major alterations in the OprD protein sequence. This study shows that in this CF patient cohort, cephalosporinase overproduction and OprD alterations were the main resistance mechanisms of P. aeruginosa to CAZ and IPM, respectively. No genes coding for ESBLs or carbapenemases were detected, but monitoring of the emergence of such resistance genes in CF patients is warranted owing to their ability to rapidly spread by horizontal gene transfer. [ABSTRACT FROM AUTHOR]

Highlights • Extended-spectrum β-lactamase (ESBL) prevalence of 6.2% in ceftazidime-resistant Pseudomonas aeruginosa from Dutch ICUs. • A bla VIM metallo-β-lactamase (MBL) gene was found in 3.1% of isolates resistant to imipenem and/or meropenem. • Most ESBL-producing isolates belonged to clonal complexes known for their successful spread (e.g. CC111 and CC235). • All bla VIM -positive isolates belonged to high-risk international clone ST111. ABSTRACT Pseudomonas aeruginosa is one of the most important causes of infection in intensive care units (ICUs). It is intrinsically resistant to many antimicrobials and easily acquires additional resistance genes via horizontal gene transfer of mobile genetic elements. In this study, 1528 P. aeruginosa isolates obtained from a Dutch national surveillance programme between the years 1998–2011 were analysed for the presence of extended-spectrum β-lactamase (ESBL) genes (bla CTX-M , bla SHV , bla TEM , bla BEL , bla PER , bla VEB and bla OXA-10) and metallo-β-lactamase (MBL) genes (bla IMP , bla VIM and bla NDM). Of the ceftazidime-resistant isolates, 6.2% tested phenotypically positive for ESBL. Moreover, a Verona integron-encoded MBL (VIM) gene was found in 3.1% of isolates that were phenotypically resistant to imipenem and/or meropenem. Multilocus sequence typing (MLST) of ESBL-positive isolates indicated ST1216, ST111 and ST622, with all bla VIM -positive isolates belonging to the ST111 clone. Although the prevalence of ESBL and MBL phenotypes in this Dutch national surveillance collection of >1500 ICU P. aeruginosa isolates was very low, all VIM-producing isolates belonged to the high risk-associated, international, clonal complex CC111, and most ESBL-producing isolates belonged to clonal complexes known for their successful spread, e.g. CC111 and CC235. These data indicate that high-risk clones of P. aeruginosa were present in the Netherlands between 1998–2011 and probably spread unnoticed throughout Dutch hospitals. [ABSTRACT FROM AUTHOR]

Extended-spectrum cephalosporin (ESC)-resistant Salmonella in chicken meat is a significant food safety concern. We previously reported that the prevalence of ESC-resistant Salmonella in chicken meat, giblets, and processed chicken (chicken meat products) increased in Japan between 2005 and 2010, with 27.9% (17/61) of Salmonella isolated from chicken meat products in 2010 showing resistance to ESC. The aims of the present study were to clarify trends in the prevalence of ESC-resistant Salmonella in chicken meat products in Japan between 2011 and 2015, and to determine the genetic profiles of bla -harboring plasmids, including replicon types, using next-generation sequencing. Our results showed that the prevalence of ESC-resistant Salmonella , mainly consisting of AmpC β-lactamase CMY-2-producing isolates, in chicken meat products had increased to 45.5% (10/22) by 2011. However, following the voluntary cessation of ceftiofur use by the Japanese poultry industry in 2012, the prevalence of ESC-resistant Salmonella steadily decreased each year, to 29.2% (7/24), 18.2% (4/22), 10.5% (2/19), and 10.5% (2/19) in 2012, 2013, 2014, and 2015, respectively. Furthermore, no AmpC β-lactamase CMY-2-producing isolates were identified in 2014 and 2015. However, the prevalence of Salmonella enterica subspecies enterica serovar Manhattan isolates harboring a bla TEM-52 -carrying IncX1 plasmid remained steady even after the cessation of ceftiofur use. Therefore, continuous monitoring of ESC resistance amongst Salmonella isolates from chicken meat products is required for food safety. [ABSTRACT FROM AUTHOR]

The principle of empirical therapy for patients with intra-abdominal infections (IAI) should include antibiotics with activity against Enterobacteriaceae and Bacteroides fragilis group species. Coverage of Pseudomonas aeruginosa , Enterobacter cloacae , and Enterococcus faecalis is also recommended for hospital-associated IAI. A nationwide survey was conducted to investigate the antimicrobial susceptibility of pathogens isolated from postoperative IAI. All 504 isolates were collected at 26 institutions and referred to a central laboratory for susceptibility testing. Lower susceptibility rates to ciprofloxacin and cefepime were demonstrated in Escherichia coli . Among E. coli , 24.1% of strains produced extended-spectrum β-lactamase (ESBL). Carbapenems, piperacillin/tazobactam, cephamycins/oxacephem, aminoglycosides, and tigecycline had high activity against E. coli , including ESBL-producing isolates. Among E. cloacae , low susceptibility rates to ceftazidime were demonstrated, whereas cefepime retained its activity. P. aeruginosa revealed high susceptibility rates to all antimicrobials tested except for imipenem. Among B. fragilis group species, low levels of susceptibility were observed for cefoxitin, moxifloxacin, and clindamycin, and high susceptibility rates were observed for piperacillin/tazobactam, meropenem, and metronidazole. Ampicillin, piperacillin, and glycopeptides had good activity against E. faecalis . Imipenem had the highest activity against E. faecalis among carbapenems. In conclusion, we suggested the empirical use of antimicrobials with the specific intent of covering the main organisms isolated from postoperative IAI. Piperacillin/tazobactam, meropenem, or doripenem, are appropriate in critically ill patients. Combination therapy of cefepime (aztreonam in patients with β-lactam allergy) plus metronidazole plus glycopeptides, imipenem/cilastatin or cephamycins/oxacephem plus ciprofloxacin plus metronidazole are potential therapeutic options. [ABSTRACT FROM AUTHOR]