Epidemiology, risk factors, and prediction score of carbapenem resistance among inpatients colonized or infected with 3rd generation cephalosporin resistant Enterobacterales.

In this study, we determined the incidence and risk factors of Carbapenem-resistant Enterobacterales (CRE) acquisition in inpatients with 3rd generation cephalosporin-resistant (3GCR) Enterobacterales at a tertiary-care hospital in Lebanon, and suggested a risk prediction score for it. This is a retrospective matched case-control study of inpatients with 3GCR Enterobacterales that are carbapenem resistant (cases) versus those with carbapenem-sensitive isolates (controls). Data analysis was performed on IBM SPSS program, version 23.0 (Armonk, NY, USA: IBM Corp.). Categorical variables were compared between cases and controls through bivariate analysis and those with statistical significance (P < 0.05) were included in the forward stepwise multiple logistic regression analysis. To develop the CRE acquisition risk score, variables that maintained statistical significance in the multivariate model were assigned a point value corresponding to the odds ratio (OR) divided by the smallest OR identified in the regression model, and the resulting quotient was multiplied by two and rounded to the nearest whole number. Summation of the points generated by the calculated risk factors resulted in a quantitative score that was assigned to each patient in the database. Predictive performance was determined by assessing discrimination and calibration. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated for different cutoffs of the score. The incidence of CRE acquisition significantly increased with time from 0.21 cases/1000 patient-days (PD) in 2015 to 1.89 cases/1000PD in 2019 (r2 = 0.789, P = 0.041). Multivariate analysis of matched data revealed that the history of cerebrovascular disease (OR 1.96; 95% CI 1.04-3.70; P = 0.039), hematopoietic cells transplantation (OR 7.75; 95% CI 1.52-39.36; P = 0.014), presence of a chronic wound (OR 3.38; 95% CI 1.73-6.50; P < 0.001), endoscopy done during the 3 months preceding the index hospitalization (OR 2.96; 95% CI 1.51-4.73; P = 0.01), nosocomial site of acquisition of the organism in question (OR 2.68; 95% CI 1.51-4.73; P = 0.001), and the prior use of meropenem within 3 months of CRE acquisition (OR 5.70; 95% CI 2.61-12.43; P < 0.001) were independent risk factors for CRE acquisition. A risk score ranging from 0 to 25 was developed based on these independent variables. At a cut-off of ≥ 5 points, the model exhibited a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 64.5%, 85.8%, 82%, 70.7% and 75%, respectively. We also showed that only meropenem consumption intensity and CRE acquisition incidence density showed a strong positive correlation(r = 0.798, P = 0.106), unlike imipenem (r = - 0.868, P = 0.056) and ertapenem (r = 0.385, P = 0.522). Patients with a score of ≥ 5 points in our model were likely to acquire CRE. Only meropenem was associated with CRE carriage. Our proposed risk prediction score would help target surveillance screening for CRE amongst inpatients at the time of hospital admission and properly guide clinicians on using anti-CRE therapy.

Carbapenem-resistant Enterobacter cloacae complex in a tertiary Hospital in Northeast China, 2010-2019.

BACKGROUND: Carbapenem-resistant Enterobacter cloacae complex (CREC) is a new emerging threat to global public health. The objective of the study was to investigate the clinical characteristics and molecular epidemiology of CREC infections in the medical center of northeast China. METHODS: Twenty-nine patients were infected/colonized with CREC during a ten-year period (2010-2019) by WHONET analysis. Antibiotic susceptibilities were tested with VITEK 2 and micro broth dilution method (for polymyxin B and tigecycline). Carbapenemase encoding genes, ß-lactamase genes, and seven housekeeping genes for MLST were amplified and sequenced for 18 cryopreserved CREC isolates. Maximum likelihood phylogenetic tree was built with the concentrated sequences to show the relatedness between the 18 isolates. RESULTS: There was a rapid increase in CREC detection rate during the ten-year period, reaching 8.11% in 2018 and 6.48% in 2019. The resistance rate of CREC isolates to imipenem and meropenem were 100.0 and 77.8%, however, they showed high sensitivity to tigecycline, polymyxin B and amikacin. The 30-day crude mortality of CREC infection was 17.4%, indicating that it may be a low-virulence bacterium. Furthermore, molecular epidemiology revealed that ST93 was the predominant sequence type followed by ST171 and ST145, with NDM-1 and NDM-5 as the main carbapenemase-encoding genes. Moreover, E. hormaechei subsp. steigerwaltii and E. hormaechei subsp. oharae were the main species, which showed different resistance patterns. CONCLUSION: Rising detection rate of CREC was observed in a tertiary hospital, which showed heterogeneity in drug resistance patterns, resistance genes, and MLST types. Effective infection prevention and control measures should be taken to reduce the spread of CREC.

Treatment of extended-spectrum ß-lactamases infections: what is the current role of new ß-lactams/ß-lactamase inhibitors?

PURPOSE OF REVIEW: The widespread diffusion of extended-spectrum ß-lactamases (ESBLs)-producing Enterobacteriales currently represents a major threat for public health worldwide. Carbapenems are currently considered the first-line choice for serious ESBL infections. However, the dramatic global increase in ESBL prevalence has led to a significant overuse of carbapenems that has promoted the selection and spread of carbapenemases, which might further prejudicated our ability to treat infections due to multidrug-resistant pathogens. Therefore, strategies to limit the use of carbapenems should be implemented. RECENT FINDINGS: Although piperacillin-tazobactam should no longer be considered an alternative to carbapenems for definitive treatment of bloodstream infections due to ESBL-producing strains, it might still represent an alternative for step-down therapy or for low-to-moderate severity infection originating from urinary or biliary sources and when piperacillin-tazobactam minimum inhibitory concentration of 4 mg/l or less. Ceftazidime-avibactam and ceftolozane-tazobactam are both carbapenem sparing agents that appear interesting alternatives for treatment of serious ESBL infections. New ß-lactams/ß-lactamase inhibitors (BL/BLI), including cefepime-enmetazobactam, ceftaroline fosamil-avibactam, aztreonam-avibactam and cefepime-zidebactam, are also promising agents for treatment of ESBL infections, but further clinical data are needed to establish their efficacy relative to carbapenems. The role of carbapenems/ß-lactamase inhibitors remain to be clarified. SUMMARY: New BL/BLI have distinctive specificities and limitations that require further investigations. Future randomized clinical trials are required to define the best strategy for their administering for ESBL infections.

Hospital Discharge Data Underascertain Enteric Bacterial Infections Among Children.

Many enteric pathogens disproportionately infect children. Hospital discharge data can provide information on severe infections, including cost. However, the diagnosis must be recorded on the discharge record and coded accurately. We estimated the rate of underascertainment in hospital discharge data among children with culture-confirmed Campylobacter, Salmonella, and Escherichia coli O157 infections using linked laboratory and hospital discharge data from an integrated health care organization. We reviewed the International Classification of Diseases, 9th and 10th Revisions, Clinical Modification (ICD-9/10-CM) diagnosis codes on each patient's discharge record. We determined the percentage of patients who had a pathogen-specific diagnosis code (for Campylobacter, Salmonella, or E. coli O157) or nonspecific gastroenteritis code. We included the first admission or positive test and calculated the number of days between specimen submission (outpatient ≤7 days before admission or inpatient) and hospital discharge. Of 65 hospitalized children with culture-confirmed Campylobacter (n = 30), Salmonella (n = 24), or E. coli O157 (n = 11) infections, 55% had that pathogen-specific diagnosis code listed on the discharge record (79% Salmonella, 54% E. coli O157, 37% Campylobacter). The discharge records of the 35 children with a specimen submitted for culture ≥3 days before discharge were 16 times more likely to have a pathogen-specific diagnosis than the records of the 30 children with a specimen submitted <3 days before discharge (83% vs. 23%; odds ratio 15.9, 95% confidence interval: 4.7-53.8). Overall, 34% of records of children with culture-confirmed infection had ≥1 nonspecific gastroenteritis code (Campylobacter 43%, Salmonella 29%, E. coli O157 18%), including 59% of those for children without a pathogen-specific diagnosis (Campylobacter 63%; Salmonella 60%; E. coli O157 40%). This study showed that hospital discharge data under-ascertain enteric illnesses in children even when the infections are culture confirmed, especially for infections that usually have a short length of stay.

Hafnia alvei pneumonia: a rare cause of infection in the multimorbid or immunocompromised.

Hafnia alvei is a rare, poorly understood commensal bacterium which has, on occasion, been shown to infect humans. We present two cases. The first patient presented with a 1-week history of dyspnoea, pleurisy and a productive cough, and the second with a prodrome of fatigue and night sweats. The former had a history of severe chronic obstructive pulmonary disease and the latter had a history of Crohn's disease. Both patients had underlying comorbidities and immunosuppression, but differed in presentation, radiological findings and recovery. This case series aims to remind readers of the broad differential of pathogens that can lead to disease in the immunocompromised and that one should not dismiss atypical cultured bacteria as commensal too hastily.

An investigation of dairy calf management practices, colostrum quality, failure of transfer of passive immunity, and occurrence of enteropathogens among Australian dairy farms.

Calf preweaning morbidity and mortality risks have been reported as high in several countries, with average values approximating 35 and 7%, respectively. However, limited data are available for calf morbidity and mortality risks on Australian dairy farms. The aims of this study were (1) to investigate current calf management practices on dairy farms in Australia and their association with herd-level morbidity and mortality using a questionnaire-based, cross-sectional study; and (2) to estimate the prevalence of common enteropathogens causing diarrhea, the failure of passive transfer of immunity, and poor colostrum quality in a sample of Australian dairy farms. We analyzed 106 completed questionnaires and samples from 23 farms (202 fecal, 253 calf serum, and 221 colostrum samples). Morbidity and mortality risks reported by farmers in preweaned heifers were 23.8 and 5.6%, respectively. These risks were above the Australian dairy industry targets in 75.5 and 66.7% of respondents. The zoonotic pathogens Cryptosporidium spp. and Salmonella spp. were the most prevalent enteropathogens, with a true prevalence of 40.9 and 25.2%, respectively. Salmonella O-group D was present in 67.9% of Salmonella-positive samples, followed by O-groups B (17.9%) and C (10.7%). Failure of transfer of passive immunity (IgG <10 g/L) was observed in 41.9% of calves (mean herd-level prevalence of 36.2%), and only 19.5% of colostrum samples met the standards for immunoglobulin content and microbiological quality. Collectively, these data indicate that there is still considerable room for improvement in calf-rearing practices on Australian dairy farms, particularly with regard to colostrum management and feeding hygiene.

Oral treatment options for patients with urinary tract infections caused by extended spectrum ßeta-lactamase (ESBL) producing Enterobacteriaceae.

INTRODUCTION: Frequent use of different antibiotics to treat urinary tract infections (UTIs) exerts a variety of selective pressure on pathogens which ultimately lead to the antimicrobial resistance. Extended Spectrum ßeta-Lactamase (ESBL) producing Enterobacteriacae causing UTIs, which are usually multidrug resistant organisms, pose a great therapeutic treatment challenge. Rediscovery of forgotten antibiotics such as pivmecillinam, fosfomycin, and nitrofurantoin may be helpful in this situation until the discovery of new agents. The main aim of present study was to determine the prevalence of ESBL producing Enterobacteriacae causing UTIs and their sensitivity profile to determine alternate effective oral treatment options. METHODS: This retrospective study was conducted to determine the prevalence of ESBL producing Enterobacteriacae from urine samples and their sensitivity profile (pivmecillinam, fosfomycin, nitrofurantoin, trimethoprim and ciprofloxacin) from September 2015 to September 2017. RESULTS: A total of 986 organisms were isolated from the urine samples of 680 patients. Approximately 77% isolates were obtained from female patients (526). Of 986 organisms, Escherichia coli was the most common isolated organism (889, 90%); followed by Klebsiella species (71, 7%) and other Enterobacteriacae (26, 3%). Of 889 E. coli, approximately 98%, 96%, and 93% were found to be sensitive to fosfomycin, pivmecillinam and nitrofurantoin respectively. On the other hand pivmecillinam was most effective against Klebsiella species (83%, 59); followed by fosfomycin (62%, 44) and nitrofurantoin (42%, 30). Of 26 other Enterobacteriacae, 23 (88%), and 22 (85%) were sensitive to pivmecillinam and fosfomycin while lower sensitivity rate (15%, 4) was noted against nitrofurantoin. More than 95% of all ESBL producing Enterobacteriacae were sensitive to pivmecillinam, fosfomycin and nitrofurantoin. Trimethoprim and ciprofloxacin were least effective. CONCLUSION: The emergence of multidrug resistant ESBL producing Enterobacteriacae restricts significantly the therapeutic options. This study shows higher sensitivity rates to pivmecillinam, fosfomycin and nitrofurantoin. We recommend their use to treat uncomplicated UTIs due to ESBL producing Enterobacteriacae.

Decreased antibiotic susceptibility of Enterobacteriaceae causing community-acquired urinary tract infections in French Amazonia.

OBJECTIVES: Urinary tract infections (UTIs) have rarely been studied in the Amazon region. We aimed to describe the epidemiology of bacteria causing UTIs in French Guiana. PATIENTS AND METHODS: We performed a monocenter retrospective study of adults consulting at the emergency department of Cayenne Hospital in 2014 with a diagnosis of UTI. The bacterial species and resistance profile were described. RESULTS: Two-hundred-and-eighty-nine patients presenting with UTI were included: 82 (28.4%) presented with cystitis, 166 (57.4%) with pyelonephritis, and 41 (14.2%) with male UTI. E. coli was predominant (74.1%), and had decreased susceptibility to ampicillin, amoxicillin-clavulanic acid, fluoroquinolones, co-trimoxazole, and furans compared with data from metropolitan France. Extended-spectrum beta-lactamases (ESBL) was isolated in 3.1% of E. coli and 31.6% of K. pneumoniae. CONCLUSIONS: Antibiotic susceptibility in UTI is lower than reported in metropolitan France without evidence for an excessive consumption of antibiotics.

Epidemiological situation of enterobacteriaceae resistant to cephalosporins third generation in the region of Mahdia, Tunisia (2002-2014).

OBJECTIVES: To determine the prevalence and to monitor the trends of resistance to broad-spectrum cephalosporins among various species of enterobacteria in the region of Mahdia (Tunisia) from 2002 to 2014. METHODS: A retrospective study was carried out in the microbiology laboratory at Tahar Sfar Teaching Hospital in Mahdia. Data concerning a thirteen-year period (2002-2014). All clinical isolates of enterobacteriaceae were identified with the API 20 E system. Antimicrobial susceptibilities were determined by disk diffusion on Mueller Hinton agar according to CA-SFM recommendations. RESULTS: During the study period, 25040 non-duplicate clinical strains of enterobacteriacae were identified. 2584 (10,3%) clinical isolates showed acquired resistance to third generation cephalosporins (3rdGC). The overall frequency of resistance increased from 8% in 2002 to 16,3% in 2014. This increase was statistically significant. High prevalence rates of 3rdGC resistance have been observed in pediatric (25,1%), in gynecologyobstetrics (21,9%) and medecine (17,4%). E. coli (21,6%), K. pneumoniae (28,6%) and E. cloacae (30,5%) showed high prevalence rates of broad-spectrum cephalosporin resistance. CONCLUSION: The resistance rates ERC3G in our region seems to be increasing. Implementation of infection control measures and identification of the mechanism responsible for third generation cephalosporins resistance are necessary to limit the spreading of these resistant enterobacteriaceae in hospitals and community settings.

Poor clinical outcomes associated with community-onset urinary tract infections due to extended-spectrum cephalosporin-resistant Enterobacteriaceae.

OBJECTIVE: Resistance to extended-spectrum cephalosporins (ESC) among Enterobacteriaceae (EB) is increasingly prevalent. We sought to determine the clinical outcomes associated with community-onset ESC-resistant (ESC-R) EB urinary tract infections (UTIs) in a US health system. DESIGN: Retrospective cohort study.PatientsAll patients presenting to the emergency departments (EDs) or outpatient practices with EB UTIs between 2010 and 2013 were included. Exposed patients had ESC-R EB UTIs. Unexposed patients had ESC-susceptible EB UTIs and were matched to exposed subjects 1:1 on study year. Multivariable logistic regression analyses were performed to evaluate the association between ESC-R EB UTI and the outcomes of clinical failure and inappropriate initial antibiotic therapy (IIAT). RESULTS: A total of 302 patients with community-onset EB UTI were included, with 151 exposed and unexposed. On multivariable analyses, UTI due to an ESC-R EB was significantly associated with clinical failure (odds ratio [OR], 7.07; 95% confidence interval [CI], 3.16-15.82; P<.01). Other independent risk factors for clinical failure included infection with Citrobacter spp and need for hemodialysis. UTI due to an ESC-R EB was also significantly associated with IIAT (OR, 4.40; 95% CI, 2.64-7.33; P<.01). CONCLUSIONS: Community-onset UTI due to an ESC-R EB organism is significantly associated with clinical failure, which may be due in part to IIAT. Further studies are needed to determine which patients in the community are at high risk for drug-resistant infection to help inform prompt diagnosis and appropriate antibiotic prescribing for ESC-R EB.

[Comparative effectivenesss of standard antibiotic therapy and Canephron N asymptomatic bacteriuria in pregnant women].

Current international and Russian clinical guidelines recommend treating asymptomatic bacteriuria in pregnancy to prevent acute gestational pyelonephritis. At the same time, the growing resistance of uropathogens and the risks associated with antibiotic therapy in pregnancy dictate the need to limit the use of antibiotics and seek alternative approaches to antibacterial therapy. MATERIALS AND METHODS: A retrospective analysis was performed on 60 pregnant women who received either a standard antibiotic regimen (n=32) or the herbal preparation Canephron N (n=28). The primary outcomes were the incidence of symptomatic infections (cystitis or pyelonephritis), premature birth and low birth weight delivery, and incidence of persistent/recurrent bacteriuria. RESULTS: In the group of antibiotic therapy, one patient developed cystitis and three had pyelonephritis; in the Canephron N group, cystitis occurred in one patient, no pyelonephritis cases were observed. Among the whole study cohort (n=60), the incidence of symptomatic infections and pyelonephritis was 8.3 and 5.0%, respectively. The incidence of symptomatic infections (cystitis, pyelonephritis) did not differ statistically significantly between the study groups (p=0.2157). There were three and one premature births in the group of antibiotic therapy and the Canephron N group, respectively (p=0,373), and two low birth weight deliveries in each group (p=0.891). Recurrent bacteriuria was registered in 17 patients from the group of antibiotic therapy and in three in the Canephron N group (p=0.0006). CONCLUSIONS: The management of asymptomatic bacteriuria in pregnancy using Canephron N is not inferior to standard antibiotic therapy regarding the incidence of symptomatic infection, premature birth, and low birth weight delivery. Persistent/recurrent bacteriuria was more common in women receiving the antibiotic therapy.

Laboratory investigation of a suspected outbreak caused by Providencia stuartii with intermediate resistance to imipenem at a long-term care facility.

BACKGROUND: Providencia stuartii survives well in natural environment and often causes opportunistic infection in residents of long-term care facilities (LTCFs). Clinical isolates of P. stuartii are usually resistant to multiple antibiotics. The bacterium is also naturally resistant to colistin and tigecycline. Treatment of infections caused by carbapenem-resistant P. stuartii is challenging. METHODS: During a 15-month period in 2013-2014, four isolates (P1, P2, and P3B/P3U) of P. stuartii showing intermediate resistance to imipenem were identified at a regional hospital in southern Taiwan. They were identified from three patients (P1-P3) transferred from the same LTCF for the treatment of the infection. Pulsed-field gel electrophoresis was used to genotype the isolates. Resistance genes/plasmids and outer membrane proteins were investigated by polymerase chain reaction and sequence analysis. RESULTS: Isolates P1 and P3B/P3U demonstrated similar pulsotypes. All isolates were found to have resistance genes (blaCMY-2, qnrD1, aac(6')-Ib-cr) carried on nonconjugative IncA/C plasmids of different sizes. A single point mutation was identified in the chromosomal gyrA (Ser83Ile) and parC (Ser84Ile) genes of all isolates. Various point mutations and insertion/deletion changes were found in their major outer membrane protein gene ompPst1. CONCLUSIONS: Isolates of similar pulsotypes could appear after 15 months and caused urosepsis in another resident of the same LTCF. The bacterium may have persisted in the environment and caused opportunistic infection. As LTCF residents are usually vulnerable to infections, surveillance of multidrug-resistant organisms and infection control intervention that have been established in acute-care hospitals to control infections by resistant organisms are apparently as essential in LTCFs.

Prevalence and drug resistance characteristics of carbapenem-resistant Enterobacteriaceae in Hangzhou, China.

With the abuse of antimicrobial agents in developing countries, increasing number of carbapenem-resistant Enterobacteriaceae (CRE) attracted considerable public concern. A retrospective study was conducted based on 242 CRE strains from a tertiary hospital in Hangzhou, China to investigate prevalence and drug resistance characteristics of CRE in southeast China. Bacterial species were identified. Antimicrobial susceptibility was examined by broth microdilution method or epsilometer test. Resistant ß-lactamase genes were identified by polymerase chain reaction and sequencing. Genotypes were investigated by phylogenetic analysis. Klebsiella pneumoniae and Escherichia coli were the most prevalent types of species, with occurrence in 71.9% and 21.9% of the strains, respectively. All strains exhibited high resistance (> 70%) against ß-lactam antibiotics, ciprofloxacin, trimethoprim-sulfamethoxazole, and nitrofurantoin but exhibited low resistance against tigecycline (0.8%) and minocycline (8.3%). A total of 123 strains harbored more than two kinds of ß-lactamase genes. blaKPC-2, blaSHV-11, blaTEM-1, and blaCTX-M-14 were the predominant genotypes, with detection rates of 60.3%, 61.6%, 43.4%, and 16.5%, respectively, and were highly identical with reference sequences in different countries, indicating potential horizontal dissemination. IMP-4 was the most frequent class B metallo-lactamases in this study. In conclusion, continuous surveillance and effective prevention should be emphasized to reduce spread of CRE.

Activity of Ceftolozane-Tazobactam against Pseudomonas aeruginosa and Enterobacteriaceae Isolates Collected from Respiratory Tract Specimens of Hospitalized Patients in the United States during 2013 to 2015.

The activities of ceftolozane-tazobactam and comparator agents against organisms deemed to be the cause of pneumonia among patients hospitalized in the United States during 2013 to 2015 were evaluated. Organisms included 1,576 Pseudomonas aeruginosa and 2,362 Enterobacteriaceae isolates susceptibility tested using reference broth microdilution methods. Ceftolozane-tazobactam, cefepime, ceftazidime, meropenem, and piperacillin-tazobactam inhibited 96.3%, 84.8%, 83.5%, 80.0%, and 78.6%, respectively, of the P. aeruginosa isolates. Ceftolozane-tazobactam inhibited 77.5 to 85.1% of isolates nonsusceptible to antipseudomonal ß-lactams and 86.6% and 71.0% of the 372 (23.6% overall) multidrug- and 155 (9.8%) extensively drug-resistant isolates tested. The activity of this combination was greater than those of other ß-lactams evaluated against P. aeruginosa groups across all U.S. census divisions. Ceftolozane-tazobactam was active against 90.6% of the Enterobacteriaceae, being less active than only meropenem (95.6% susceptible) among the ß-lactams evaluated. Against 145 Escherichia coli and Klebsiella pneumoniae isolates carrying extended-spectrum-ß-lactamase (ESBL)-encoding genes without carbapenemases, ceftolozane-tazobactam inhibited 82.8% of these isolates and was more active than cefepime and piperacillin-tazobactam (15.2% and 74.3% susceptible, respectively). ESBL genes included in this analysis were mainly blaCTX-M-15-like (89 isolates) and blaCTX-M-14-like (22) genes but also blaSHV (31) and blaTEM (3). Ceftolozane-tazobactam also displayed activity (84.6% susceptible) against 13 isolates harboring acquired AmpC genes. All ß-lactams displayed limited activity against blaKPC-carrying isolates. Ceftolozane-tazobactam was the most active ß-lactam tested against P. aeruginosa isolates from isolates that were the probable cause of pneumonia and displayed in vitro activity against Enterobacteriaceae, including isolates resistant to cephalosporins and carrying ESBL genes.

Inappropriate Empirical Treatment of Uncomplicated Cystitis in Thai Women: Lessons Learned.

A prospective study conducted in a Thai general practice clinic demonstrated a high prevalence (91.3%) of inappropriate empirical antibiotic use in women with uncomplicated cystitis and 42.6% Escherichia coli fluoroquinolone resistance. An annual update of antimicrobial resistance surveillance data of uropathogens may permit targeted treatment of patients in hospital care.

Antimicrobial Use for and Resistance of Zoonotic Bacteria Recovered from Nonhuman Primates.

As a growing threat to human and animal health, antimicrobial resistance (AMR) has become a central public-health topic. Largescale surveillance systems, such as the National Antimicrobial Resistance Monitoring System (NARMS), are now established to monitor and provide guidance regarding AMR, but comprehensive literature on AMR among NHP is sparse. This study provides data regarding current antimicrobial use strategies and the prevalence of AMR in zoonotic bacteria recovered from NHP within biomedical research institutions. We focused on 4 enteric bacteria: Shigella flexneri, Yersinia enterocolitica, Y. pseudotuberculosis, and Campylobacter jejuni. Fifteen veterinarians, 7 biomedical research institutions, and 4 diagnostic laboratories participated, providing susceptibility test results from January 2012 through April 2015. Veterinarians primarily treated cases caused by S. flexneri, Y. enterocolitica, and Y. pseudotuberculosis with enrofloxacin but treated C. jejuni cases with azithromycin and tylosin. All isolates were susceptible to the associated primary antimicrobial but often showed resistance to others. Specifically, S. flexneri isolates frequently were resistant to erythromycin (87.5%), doxycycline (73.7%), and tetracycline (38.3%); Y. enterocolitica isolates to ampicillin (100%) and cefazolin (93.6%); and C. jejuni isolates to methicillin (99.5%) and cephalothin (97.5%). None of the 58 Y. pseudotuber-culosis isolates was resistant to any tested antimicrobial. Notably, resistance patterns were not shared between this study's NHP isolates and human isolates presented by NARMS. Our findings indicate that zoonotic bacteria from NHP diagnostic samples are broadly susceptible to the antimicrobials used to treat the clinical infections. These results can help veterinarians ensure effective antimicrobial therapy and protect staff by minimizing occupational risk.

ESBL/AmpC-producing Enterobacteriaceae in households with children of preschool age: prevalence, risk factors and co-carriage.

OBJECTIVES: ESBL/AmpC-producing Enterobacteriaceae are an emerging public health concern. As households with preschool children may substantially contribute to the community burden of antimicrobial resistance, we determined the prevalence, risk factors and co-carriage of ESBL/AmpC-producing bacteria in preschool children and their parents. METHODS: From April 2013 to January 2015, each month 2000 preschool children were randomly selected from Dutch population registries. The parents were invited to complete an epidemiological questionnaire and to obtain and send a faecal sample from the selected child and from one parent. Samples were tested for ESBL/AmpC-producing bacteria. Logistic regression was used to identify risk factors for ESBL/AmpC carriage in children and parents, and findings were internally validated by bootstrapping. RESULTS: In total, 1016 families were included and ESBL/AmpC prevalence was 4.0% (95% CI 3.2%-5.0%); 3.5% (95% CI 2.5%-4.8%) in children and 4.5% (95% CI 3.4%-6.0%) in parents. Attending a daycare centre (DCC) was the only significant risk factor for children (OR 2.1, 95% CI 1.0-4.3). For parents, the only significant risk factor was having one or more children attending DCCs (OR 2.2, 95% CI 1.2-4.8). For parents of ESBL/AmpC-positive children the OR for ESBL/AmpC carriage was 19.7 (95% CI 9.2-42.4). Co-carriage of specific ESBL/AmpC genotypes in child and parent occurred more often than expected by chance (14.6% versus 1.1%, P < 0.001). CONCLUSIONS: In this study, intestinal carriage with ESBL/AmpCs was detected in ∼4% of households with preschool children. DCC attendance was a risk factor in both children and parents and co-carriage of specific genotypes frequently occurred in child-parent pairs. These findings suggest household transmission or/and family-specific exposure to common sources of ESBL/AmpC-producing bacteria.

Carbapenemase-producing Enterobacteriaceae in the UK: a national study (EuSCAPE-UK) on prevalence, incidence, laboratory detection methods and infection control measures.

OBJECTIVES: To estimate UK prevalence and incidence of clinically significant carbapenemase-producing Enterobacteriaceae (CPE), and to determine epidemiological characteristics, laboratory methods and infection prevention and control (IPC) measures in acute care facilities. METHODS: A 6 month survey was undertaken in November 2013-April 2014 in 21 sentinel UK laboratories as part of the European Survey on Carbapenemase-Producing Enterobacteriaceae (EuSCAPE) project. Up to 10 consecutive, non-duplicate, clinically significant and carbapenem-non-susceptible isolates of Escherichia coli or Klebsiella pneumoniae were submitted to a reference laboratory. Participants answered a questionnaire on relevant laboratory methods and IPC measures. RESULTS: Of 102 isolates submitted, 89 (87%) were non-susceptible to ≥1 carbapenem, and 32 (36%) were confirmed as CPE. CPE were resistant to most antibiotics, except colistin (94% susceptible), gentamicin (63%), tigecycline (56%) and amikacin (53%). The prevalence of CPE was 0.02% (95% CI = 0.01%-0.03%). The incidence of CPE was 0.007 per 1000 patient-days (95% CI = 0.005-0.010), with north-west England the most affected region at 0.033 per 1000 patient-days (95% CI = 0.012-0.072). Recommended IPC measures were not universally followed, notably screening high-risk patients on admission (applied by 86%), using a CPE 'flag' on patients' records (70%) and alerting neighbouring hospitals when transferring affected patients (only 30%). Most sites (86%) had a laboratory protocol for CPE screening, most frequently using chromogenic agar (52%) or MacConkey/CLED agars with carbapenem discs (38%). CONCLUSIONS: The UK prevalence and incidence of clinically significant CPE is currently low, but these MDR bacteria affect most UK regions. Improved IPC measures, vigilance and monitoring are required.

A prospective study of treatment of carbapenem-resistant Enterobacteriaceae infections and risk factors associated with outcome.

BACKGROUND: To describe the clinical and microbiological data of carbapenem-resistant Enterobacteriaceae (CRE) infections, the treatment used, hospital- and infection-related mortality, and risk factors for death. METHODS: A prospective cohort conducted from March 2011 to December 2012. Clinical, demographic, and microbiological data such as in vitro sensitivity, clonality, carbapenemase gene mortality related to infection, and overall mortality were evaluated. Data were analyzed using Epi Info version 7.0 (CDC, Atlanta, GA, USA) and SPSS (Chicago, IL, USA). RESULTS: One hundred and twenty-seven patients were evaluated. Pneumonia, 52 (42 %), and urinary tract infections (UTI), 51 (40.2 %), were the most frequent sites of infection. The isolates were polyclonal; the Bla KPC gene was found in 75.6 % of isolates, and 27 % of isolates were resistant to colistin. Mortality related to infection was 34.6 %, and was higher among patients with pneumonia (61.4 %). Combination therapy was used in 98 (77.2 %), and monotherapy in 22.8 %; 96.5 % of them were UTI patients. Shock, age, and dialysis were independent risk factors for death. There was no difference in infection-related death comparing colistin-susceptible and colistin-resistant infections (p = 0.46); neither in survival rate comparing the use of combination therapy with two drugs or more than two drugs (p = 0.32). CONCLUSIONS: CRE infection mortality was higher among patients with pneumonia. Infections caused by colistin-resistant isolates did not increase mortality. The use of more than two drugs on combination therapy did not show a protective effect on outcome. The isolates were polyclonal, and the bla KPC gene was the only carbapenemase found. Shock, dialysis, and age over 60 years were independent risk factors for death.