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Background: Patients with cirrhosis are at high risk of Clostridium difficile infection (CDI). Rifaximin is commonly used in cirrhotic patients as prophylaxis for hepatic encephalopathy (HE). Several studies have demonstrated the efficacy of rifaximin in the treatment of CDI; however, resistance to rifaximin has also been reported. Few studies have assessed the risk of developing CDI in cirrhotic patients receiving rifaximin. Our objective was to assess the incidence and characteristics of CDI in patients with cirrhosis, especially in those who received rifaximin., Methods: We assessed the incidence and clinical characteristics of CDI in cirrhotic patients over a 6-year period in our hospital. Medical charts were retrospectively reviewed. Ribotyping and antimicrobial susceptibility testing of all strains against rifaximin were performed., Results: A total of 388 cirrhotic patients were included, of whom 127 patients had at least 1 episode of diarrhea in which a sample was sent to the laboratory. CDI was detected in 46 patients. Fourteen patients (30.4%) were receiving rifaximin as prophylaxis for HE. The main ribotypes detected were 001 (30.4%), followed by 014 (19.6%). Resistance to rifaximin was 34.1% overall, and 84.6% in patients who had received rifaximin. Multivariate analysis showed that rifamycin therapy and ribotype 001 were significant risk factors for having a rifaximin-resistant C. difficile strain., Conclusions: A high percentage of CDI cases were detected in cirrhotic patients receiving rifaximin, mostly owing to selection of rifaximin-resistant C. difficile strains. Clinicians should be aware of the risk of CDI in cirrhotic patients, even in those receiving rifaximin.

An outbreak of Clostridium difficile infection (CDI) caused by ribotype 027 (B1/NAP1) began in our hospital in November 2014, and produced 141 episodes in the following months. The aim of this study is to describe this outbreak, assess risk factors for recurrence of CDI-027 and to analyze the implementation of a novel treatment strategy. This is a prospective study of all patients with CDI-027, from November 2014 to November 2015. The epidemiological data were collected daily for each patient. We compared clinical characteristics and treatment between patients with and without recurrence of CDI-027. Interestingly, liver cirrhosis was present in 22% of the patients, and most of them received prophylaxis for hepatic encephalopathy with rifaximin. Patients were also taking antimicrobial drugs (93.6%) and proton pump inhibitors (80.1%). Overall, 27 (23.5%) patients had a first recurrence of CDI-027. Liver cirrhosis increased the risk of recurrence (44.4% vs 14.8%). Patients treated with a prolonged oral vancomycin regimen vs the conventional regimen (oral metronidazole or 10 days of vancomycin) had fewer recurrences (8.6 versus 44.7% [p ≤ 0.01]; OR, 0.91; 95% CI, 0.028-0.294) and less attributable mortality (0% versus 7.1%; p = 0.058). We report an outbreak of CDI-027, mainly in patients with liver cirrhosis. Recurrence of CDI-027 was more common in those patients. A novel approach involving high-dose prolonged vancomycin taper as a first-line treatment, together with a bundle of outbreak measures, seemed to reduce the number of cases of CDI-027, recurrences, and attributable mortality. Nevertheless, this approach warrants further investigation.

Linezolid serum trough ( C min ) and peak ( C max ) levels were determined prospectively in 90 patients. Adequate exposure was defined as a C min of 2 to 8 mg/liter. Therapy was empirical (73.3%) or targeted (26.7%). Wide interindividual variability in linezolid C min levels was recorded (0.1 to 25.2 μg/ml). Overall, 65.5% of the patients had out-of-range, 41.1% had subtherapeutic, and 24.4% had supratherapeutic trough levels. We did not find a correlation between abnormal levels and adverse events, in-hospital mortality, or overall poor outcome., (Copyright © 2017 American Society for Microbiology.)

The closer contact with wildlife due to the growing human population and the destruction of natural habitats emphasizes the need of gaining insight into the role of animals as source of antimicrobial resistance. Here, we aim at characterizing the antimicrobial resistance genes and phylogenetic distribution of commensal Escherichia coli from 62 wild mammals. Isolates exhibiting resistance to ≥1 antibiotic were detected in 25.8% of the animals and 6.4% carried an extended-spectrum beta-lactamase (ESBL)/AmpC-producing E. coli. Genetic mechanisms involved in third-generation cephalosporin resistance were as follows: (i) hyperproduction of chromosomal AmpC (hedgehog), (ii) production of acquired CMY-2 β-lactamase (hedgehog), (iii) production of SHV-12 and CTX-M-14 ESBLs (n = 2, mink and roe-deer). ESBL genes were transferable by conjugation, and blaCMY-2 was mobilized by a 95kb IncI1 plasmid. The distribution of the phylogenetic groups in the E. coli collection studied was B1 (44.6%), B2 (24.6%), E (15.4%), A (4.6%) and F (3.1%). Five isolates (7.7%) were cryptic Escherichia clades (clade IV, 4 mice; clade V, 1 mink). ESBL/AmpC-E. coli isolates showed different sequence types (STs): ST1128/B1, ST4564/B1 (new), ST4996/B1 (new) and a non-registered ST. This study contributes to better understand the E. coli population and antimicrobial resistance flow in wildlife and reports new AmpC-E. coli STs and a first described ESBL-producing Escherichia clade V isolate., (© FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

To get a better insight into the role of birds as reservoirs of extended-spectrum β-lactamase (ESBL) and plasmidic AmpC β-lactamase (pAmpC) Escherichia coli producers, 100 fecal samples belonging to 15 different wild avian species from Northern Spain were analyzed. Cefotaxime-resistant (CTX R ) E. coli isolates were identified in 16 of the 100 tested birds, which corresponded to 9 animal species (Gyps fulvus-griffon vulture, Larus michahellis-yellow-legged gull, Milvus migrans-black kite, Milvus milvus-red kite, Ciconia ciconia-white stork, Sturnus unicolor-spotless starling, Aquila chrysaetos-golden eagle, Cuculus canorus-common cuckoo, Tyto alba-barn owl). Fifteen isolates harbored ESBL or pAmpC-encoding genes (number of isolates): bla SHV-12 (9), bla CTX-M-1 (3), bla CTX-M-14 (2), and bla CMY-2 (1). The last CTX R isolate presented a -42-point-mutation in the chromosomal ampC promoter. Eleven out of 15 ESBL/pAmpC E. coli isolates were multiresistant (most common resistance phenotype: β-lactams-quinolones-tetracycline-sulfamethoxazole/trimethoprim). A plasmid-mediated quinolone resistance determinant (qnrS1) was identified in one E. coli from a barn owl. High genetic diversity was observed among ESBL/pAmpC E. coli isolates, with 12 different sequence types (STs), including several strains of STs frequently detected among human clinical isolates (ST38/D, ST131/B2, ST155/B1, ST10/A). The ST131 isolate belonged to the emergent ciprofloxacin-resistant H30R subclone. This study reveals a high percentage of bird as carriers of ESBL/pAmpC E. coli isolates in Spain, highlighting the elevated rate among storks, kites, and vultures. Wild birds can contribute to the global spread of ESBL/pAmpC-producing E. coli in natural ecosystems.

Purpose: Despite the high concentration of patients with known risk factors for Clostridium difficile infection (CDI) in intensive care units (ICUs), data on ICU patients are scarce. The aim of this study was describe the incidence, clinical characteristics, and evolution of CDI in critically ill patients., Materials and Methods: From 2003 to 2012, adult patients admitted to an ICU (A-ICU) and positive for CDI were included and classified as follows: pre-ICU, if the positive sample was obtained within ±3 days of ICU admission; in-ICU, if obtained after 3 days of ICU admission and up to 3 days after ICU discharge., Results: We recorded 4095 CDI episodes, of which 328 were A-ICU (8%). Episodes of A-ICU decreased from 19.4 to 8.7 per 10000 ICU days of stay (P < .0001). Most A-ICU CDIs (66.3%) were mild to moderate. Pre-ICU episodes accounted for 16.2% and were more severe complicated than in-ICU episodes (11% vs 0%; P = .020). Overall mortality was 28.6%, and CDI-attributable mortality was only 3%., Conclusion: The incidence of A-ICU CDI has decreased steadily over the last 10 years. A significant proportion of A-ICU CDI episodes are pre-ICU and are more severe than in-ICU CDI episodes. Most episodes of A-ICU CDI were nonsevere, with low associated mortality., (Copyright © 2015 Elsevier Inc. All rights reserved.)

We studied the molecular mechanisms of linezolid resistance in 9 isolates of toxigenic Clostridium difficile with high linezolid MICs. The activity of linezolid was determined against 891 clinical isolates of toxigenic C. difficile. The MIC50 and MIC90 of linezolid were 0.75 μg/ml and 1.5 μg/ml, respectively. Nine strains (1%) showed high linezolid MICs (6 μg/ml to 16 μg/ml) and also were resistant to clindamycin, erythromycin, and chloramphenicol. These strains were selected for molecular studies: sequencing of domain V of the 23 rRNA gene, detection of the cfr methyltransferase gene, and sequencing of the ribosomal protein genes rplC and rplD. Molecular relatedness between strains was assessed using PCR ribotyping and MLVA (multilocus variable-number tandem-repeat analysis) typing. The strains belonged to ribotypes 001 (2/9), 017 (6/9), and 078 (1/9). MLVA showed that strains of ribotype 001 and 017 belonged to the same clonal complex in each ribotype. We did not detect mutations in the 23S rRNA gene. The cfr gene was detected in 7 of 9 strains. Sequencing of cfr amplicons revealed a similarity of 100% to a fragment of transposon Tn6218 of C. difficile, which was annotated as a putative chloramphenicol/florfenicol resistance protein. We were unable to detect mechanisms of resistance to linezolid in the 2 strains belonging to ribotype 001. While the relevance of our results lies in the detection of the cfr gene as a possible mechanism of resistance to linezolid in C. difficile, our findings should be assessed by further investigations to characterize these possible cfr genes and their contribution to linezolid resistance., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Clostridium difficile is an emerging pathogen for humans and animals and there is concern about the possibility that livestock might serve as a reservoir of epidemic strains. In Spain, ribotype 078 is one of the most prevalent in human episodes of C. difficile infection, but the distribution of this and other ribotypes in animals is yet unknown. We present the first report on the ribotype distribution and antimicrobial susceptibility of C. difficile in swine in Spain. A total of 144 isolates were PCR ribotyped, and their MIC values for 13 antimicrobial agents were determined using the Etest. Toxins A and B production was assessed using a commercial immunoassay and, in the case of toxin B, a specific cytotoxicity test. Our results show a high prevalence of the toxigenic 078 ribotype (94.4%) and multidrug resistance (49.3%) among the studied isolates. A minority of isolates (5.6%) belonged to a mostly non-toxinogenic ribotype. All isolates were resistant to the fluoroquinolone ciprofloxacin, but susceptible to daptomycin, linezolid, meropenem, rifampicin, teicoplanin, tigecycline, metronidazole and vancomycin. Resistance to clindamycin, ertapenem, erythromycin and moxifloxacin was common (≥27.8% in all cases). Resistance rates for the different antibiotics tested were in all cases independent from the ribotype of isolates and the host's condition (diarrheic or non-diarrheic), but erythromycin and moxifloxacin resistance was associated with the geographic origin of isolates. Metronidazole heteroresistance was found among animal isolates of C. difficile. Our results highlight the role of livestock as a potential source of epidemic multidrug resistant strains in Spain., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Clostridium difficile infection (CDI) is one of the main causes of diarrhoea associated with antimicrobial therapy. Antibiotics with good 'in vitro' activity against C. difficile could protect patients from developing CDI. In this study, the potential of linezolid to protect patients with ventilator-associated pneumonia (VAP) from developing CDI was assessed. Over a 4-year period, a cohort of patients who developed VAP following major heart surgery (MHS) in Gregorio Marañón General Hospital (Madrid, Spain) was retrospectively analysed. Patients were divided into those who developed CDI in the post-operative period and those who did not. Variables associated with the development of CDI were analysed, including the role of antimicrobial therapy. Overall, 1934 patients underwent MHS; 90 patients were excluded due to intra-operative or early post-operative (first 48h) death, leaving a study population of 1844 patients, of which 105 cases had VAP. Complete clinical data were available in 91 cases. CDI occurred in 22 patients (24.2%). When comparing VAP cases with and without CDI, EuroSCORE and overall antibiotics prescribed were not significantly different. Patients with chronic renal failure (CRF) were more prone to develop CDI than those without CRF (32% vs. 13%; P=0.04), and patients without [corrected] CDI received more doses of linezolid than those with [corrected] CDI [12.4±9.7 defined daily doses (DDDs) vs. 6.7±4.0 DDDs; P=0.007]. Multivariate analysis confirmed that receiving more DDDs of linezolid protects from developing CDI (hazard ratio=0.908, 95% confidence interval 0.83-0.99; P=0.04). This work is retrospective and addresses a very particular population, but it is the first to suggest the potential impact of linezolid against CDI., (Copyright © 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

Clostridium difficile is the most frequently identified enteric pathogen in patients with nosocomially acquired, antibiotic-associated diarrhea. The drugs most commonly used to treat diseases associated with C. difficile are metronidazole and vancomycin. Most clinical laboratories assume that all C. difficile isolates are susceptible to metronidazole and vancomycin. We report on the antimicrobial susceptibilities of 415 C. difficile isolates to metronidazole and vancomycin over an 8-year period (1993 to 2000). The overall rate of resistance to metronidazole at the critical breakpoint (16 microg/ml) was 6.3%. Although full resistance to vancomycin was not observed, the overall rate of intermediate resistance was 3.1%. One isolate had a combination of resistance to metronidazole and intermediate resistance to vancomycin. Rates of resistance to metronidazole and vancomycin were higher among isolates from human immunodeficiency virus-infected patients. Molecular typing methods proved the absence of clonality among the isolates with decreased susceptibilities to the antimicrobials tested.

We examined the in vitro activity of linezolid against Clostridium difficile, including isolates with reduced susceptibility to metronidazole or vancomycin. The MIC at which 50% of the isolates were inhibited (MIC50) and MIC90 were 0.5 and 2 microg/ml, respectively (range, 0.03 to 4 microg/ml). MICs were always

The in vitro activity of LY333328 was compared with those of vancomycin and teicoplanin against 425 gram-positive clinical isolates, including a variety of multiply resistant strains. LY333328 at

Susceptibility testing of Eikenella corrodens is usually performed by a Mueller-Hinton sheep blood agar dilution (AD) method. However, this method is impractical for testing only a few strains. We compared AD with the broth microdilution method using Haemophilus test medium (HTM) in order to determine the susceptibility of 36 clinical isolates of E. corrodens to eight antimicrobial agents. MICs obtained by the HTM method yielded 95.5 and 84% agreement (within 2 and 1 log2 dilutions, respectively) with those obtained by AD. The HTM method with incubation in CO2 for 48 h was highly reproducible and constitutes an easy alternative for antimicrobial susceptibility testing of E. corrodens.