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Assessment of vancomycin-resistant Enterococcus faecium (VREfm) prevalence upon hospital admission and analysis of risk factors for colonization.From 2014 to 2018, patients were recruited within 72 hours of admission to seven participating German university hospitals, screened for VREfm and questioned for potential risk factors (prior multidrug-resistant organism detection, current/prior antibiotic consumption, prior hospital, rehabilitation or long-term care facility stay, international travel, animal contact and proton pump inhibitor [PPI]/antacid therapy). Genotype analysis was done using cgMLST typing. Multivariable analysis was performed.In 5 years, 265 of 17,349 included patients were colonized with VREfm (a prevalence of 1.5%). Risk factors for VREfm colonization were age (adjusted OR [aOR], 1.02; 95% CI, 1.01-1.03), previous (aOR, 2.71; 95% CI, 1.87-3.92) or current (aOR, 2.91; 95% CI, 2.60-3.24) antibiotic treatment, prior multidrug-resistant organism detection (aOR, 2.83; 95% CI, 2.21-3.63), prior stay in a long-term care facility (aOR, 2.19; 95% CI, 1.62-2.97), prior stay in a hospital (aOR, 2.91; 95% CI, 2.05-4.13) and prior consumption of PPI/antacids (aOR, 1.29; 95% CI, 1.18-1.41). Overall, the VREfm admission prevalence increased by 33% each year and 2% each year of life. 250 of 265 isolates were genotyped and 141 (53.2%) of the VREfm were the emerging ST117. Multivariable analysis showed that ST117 and non-ST117 VREfm colonized patients differed with respect to admission year and prior multidrug-resistant organism detection.Age, healthcare contacts and antibiotic and PPI/antacid consumption increase the individual risk of VREfm colonization. The VREfm admission prevalence increase in Germany is mainly driven by the emergence of ST117.

Objectives: The aim of this study was to quantify the time delay between screening and initiation of contact isolation for carriers of extended-spectrum beta-lactamase (ESBL)–producing Enterobacterales (ESBL-E). Methods: This study was a secondary analysis of contact isolation periods in a cluster-randomized controlled trial that compared 2 strategies to control ESBL-E (trial no. ISRCTN57648070). Patients admitted to 20 non-ICU wards in Germany, the Netherlands, Spain, and Switzerland were screened for ESBL-E carriage on admission, weekly thereafter, and on discharge. Data collection included the day of sampling, the day the wards were notified of the result, and subsequent ESBL-E isolation days. Results: Between January 2014 and August 2016, 19,122 patients, with a length of stay ≥2 days were included. At least 1 culture was collected for 16,091 patients (84%), with a median duration between the admission day and the day of first sample collection of 2 days (interquartile range [IQR], 1–3). Moreover, 854 (41%) of all 2,078 ESBL-E carriers remained without isolation during their hospital stay. In total, 6,040 ESBL-E days (32% of all ESBL-E days) accrued for patients who were not isolated. Of 2,078 ESBL-E-carriers, 1,478 ESBL-E carriers (71%) had no previous history of ESBL-E carriage. Also, 697 (34%) were placed in contact isolation with a delay of 4 days (IQR, 2–5), accounting for 2,723 nonisolation days (15% of ESBL-E days). Conclusions: Even with extensive surveillance screening, almost one-third of all ESBL-E days were nonisolation days. Limitations in routine culture-based ESBL-E detection impeded timely and exhaustive implementation of targeted contact isolation.

Objectives 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). Methods 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. Results 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. Conclusions 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.

ObjectivesTo analyse the rectal carriage rate and the molecular epidemiology of vancomycin-resistant Enterococcus faecium (VREfm) recovered from patients upon hospital admission.MethodsAdult patients were screened at six German university hospitals from five different federal states upon hospital admission for rectal colonization with VREfm between 2014 and 2018. Molecular characterization of VREfm was performed by WGS followed by MLST and core-genome MLST analysis.ResultsOf 16350 patients recruited, 263 were colonized with VREfm, with increasing prevalence rates during the 5 year study period (from 0.8% to 2.6%). In total, 78.5% of the VREfm were vanB positive and 20.2% vanA positive, while 1.2% harboured both vanA and vanB. The predominant ST was ST117 (56.7%) followed by ST80 (15%), ST203 (10.9%), ST78 (5.7%) and ST17 (3.2%). ST117/vanB VREfm isolates formed a large cluster of 96 closely related isolates extending across all six study centres and four smaller clusters comprising 13, 5, 4 and 3 isolates each. In contrast, among the other STs inter-regional clonal relatedness was rarely observed.ConclusionsTo our knowledge, this is the largest admission prevalence and molecular epidemiology study of VREfm. These data provide insight into the epidemiology of VREfm at six German university hospitals and demonstrate the remarkable inter-regional clonal expansion of the ST117/vanB VREfm clone.

[Objectives] We aimed to evaluate different interventions to reduce multidrug-resistant Enterobacteriaceae (MDR-E) infection/colonization., [Methods] A systematic review and meta-analysis evaluating interventions for prevention of MDR-E infection/colonization among hospitalized adult patients. The co-primary outcomes were mortality and MDR-E infections. PubMed, Cochrane library, and LILACS databases were searched up till December 2019, as well as grey literature sources. We included randomized controlled trials and observational studies. Infection/colonization/acquisition outcomes were reported per patient-days as pooled incidence ratios (IRs) with 95% confidence intervals (CIs). Interrupted time series (ITS) analysis studies were reported separately., [Results] Sixty-three studies were included, 16 RCTs, 33 observational studies, and 14 ITS. For the intervention of antimicrobial stewardship program (ASP), 23 studies were included. No differences in mortality or MDR-E infections were observed with ASP, however, MDR-E colonization was significantly reduced (IR 0.69, 95% CI 0.57–0.82). Seventeen studies examined decolonization without significant difference in outcomes. Other interventions were scarcely represented. Among 14 ITS publications, most evaluating ASP, 11 showed benefit of the intervention., [Conclusions] ASP is an effective measure in preventing MDR-E colonization. Decolonization did not show significant benefit in reducing infection or colonization. Studies are needed to evaluate the cost effectiveness of ASP and assess bundles of interventions., This publication was made possible by grants from following national funding agencies: Germany BMBF 01KI1704A (Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Institute of Hygiene and Environmental Medicine); 01KI1704B (Helmholtz Center for Infection Research GmbH) and 01KI1704C (Martin-Luther-University Halle-Wittenberg, medical faculty, Institute of medical epidemiology, biostatistics and informatics); the Netherlands ZonMw grant number 547001005 (Julius centre, University Medical centre Utrecht); Israel CSO-MOH grant number 3000013820 (Rabin Medical Center, Beilinson Hospital / Department of Medicine), and Poland National Science centre Poland, Unisono: 2016/22/Z/ST1/00690 (University of Warsaw, Faculty of Mathematics, Informatics and Mechanics, Institute of Applied Mathematics and Mechanics and Department of Microbiology, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University); within the 3rd JPI ARM framework (Joint Programming Initiative on Antimicrobial Resistance) cofound grant no. 681055 for the consortium EMerGE-Net (Effectiveness of infection control strategies against intra- and inter-hospital transmission of Multidrug-resistant Enterobacteriaceae).

Objectives To assess the admission prevalence of third-generation cephalosporin-resistant Enterobacterales (3GCREB) and to assess whether risk factors vary by β-lactamase genotype. Methods Adult patients were recruited within 72 h of admission to general wards of six university hospitals in 2014 and 2015. Rectal swabs were screened for 3GCREB and isolates were analysed phenotypically and genotypically. Patients were questioned on potential risk factors. Multivariable analyses were performed to identify risk factors for 3GCREB colonization and for specific β-lactamases. Results Of 8753 patients screened, 828 were 3GCREB positive (9.5%). Eight hundred and thirteen isolates were available for genotyping. CTX-M-15 was the most common ESBL (38.0%), followed by CTX-M-1 (22.5%), CTX-M-14 (8.7%), CTX-M-27 (7.5%) and SHV-ESBL (4.4%). AmpC was found in 11.9%. Interestingly, 18 Escherichia coli isolates were AmpC positive, 12 of which (67%) contained AmpC on a gene of plasmid origin [CMY (n = 10), DHA (n = 2)]. Risk factors for 3GCREB colonization varied by genotype. Recent antibiotic exposure and prior colonization by antibiotic-resistant bacteria were risk factors for all β-lactamases except CTX-M-14 and CTX-M-27. Travel outside Europe was a risk factor for CTX-M-15 and CTX-M-27 [adjusted OR (aOR) 3.49, 95% CI 2.88–4.24 and aOR 2.73, 95% CI 1.68–4.43]. A previous stay in a long-term care facility was associated with CTX-M-14 (aOR 3.01, 95% CI 1.98–4.59). A preceding hospital stay in Germany increased the risk of CTX-M-15 (aOR 1.27, 95% CI 1.14–1.41), while a prior hospital stay in other European countries increased the risk of SHV-ESBL colonization (aOR 3.85, 95% CI 1.67–8.92). Conclusions The detection of different ESBL types is associated with specific risk factor sets that might represent distinct sources of colonization and ESBL-specific dissemination routes.

Background In addition to an overall rise in vancomycin-resistant Enterococcus faecium (VREfm), an increase in certain strain types marked by sequence type (ST) and cluster type (CT) has been reported in Germany over the past few years. Outbreak analyses at Charité - Universitätsmedizin Berlin revealed the frequent occurrence of VREfm ST117 CT71 isolates in 2017 and 2018. To investigate whether ST117 CT71 have emerged in recent years or whether these strains have been circulating for a longer time, we retrospectively analyzed non-outbreak strains that occurred between 2008 and 2018 to identify frequent STs and CTs. Methods In total, 120 VREfm isolates obtained from clinical and surveillance cultures from the years 2008, 2013, 2015, and 2018 were analyzed. Thirty isolates per year comprising the first 7–8 non-outbreak isolates of each quarter of the respective year were sequenced using whole genome sequencing. MLST and cgMLST were determined as well as resistance genes and virulence factors. Risk factors for VREfm ST117 were analyzed in a multivariable analysis with patient characteristics as possible confounders. Results The percentage of VREfm of type ST117 increased from 17% in 2008 to 57% in 2018 (p = 0.012). In 2008, vanA genotype accounted for 80% of all ST117 isolates compared to 6% in 2018. VanB CT71 first appeared in 2018 and predominated over all other ST117 at 43% (p The set of resistance genes (msrC, efmA, erm(B), dfrG, aac(6′)-Ii, gyrA, parC and pbp5) and virulence factors (acm, esp, hylEfm, ecbA and sgrA) in CT71 was also found in other ST117 non-CT71 strains, mainly in CT36. The study population did not differ among the different calendar years analyzed in terms of age, gender, length of stay, or ward type (each p > 0.2). Conclusion This study revealed an increase in ST117 strains from 2008 to 2018, accompanied by a shift toward CT71 strains with the vanB genotype in 2018. We did not detect resistance or virulence traits in CT71 that could confer survival advantage compared to other CTs among ST117 strains. To date, it is not clear why ST117 and in particular strain type ST117 CT71 predominates over other strains.

Background: The ST131 Escherichia coli clone is associated with the global dissemination of ESBLs. It has been hypothesized that ST131 could take advantage of better colonizing abilities. However, the data on colonization prevalence of ESBL-ST131 in European hospitals are scarce. Objectives: To assess the prevalence of the ST131 clone and its microbiological characteristics among colonizing ESBL-producing E. coli (ESBL-Ec) from hospitalized patients in four European hospitals (Berlin, Geneva, Madrid and Utrecht) during the R-GNOSIS study. Methods: ESBL-Ec isolates (n = 688) were obtained from rectal swabs of hospitalized patients from March 2014 to February 2015 using selective media. The ST131 clone and its subclones were sought using PCR and positive isolates were further studied. blaESBL genes were characterized (PCR and sequencing), antibiotic susceptibility testing was performed, clonal relationships were studied by PFGE and fimH allele and O type (PCR) were assessed. Results: ST131 prevalence was 20.5% (141/688); C1/H30R1 isolates were significantly more prevalent in Geneva (49%) and C2/H30Rx in Madrid (67%). C1/H30R1 isolates showed less resistance to amikacin than C2/H30Rx (4% versus 35%) and all were susceptible to penicillin/inhibitor combinations. CTX-M-15 was the most common enzyme (49%) followed by CTX-M-27 (27%). C1/H30R1 isolates were significantly associated with CTX-M-27 (72%) and all of these isolates belonged to the C1-M27 clade. Moreover, C2/H30Rx isolates and CTX-M-15 were also significantly related (88%). Conclusions: The predominance of C2/H30Rx-CTX-M-15 in Madrid and C1/H30R1-CTX-M-27 in Geneva demonstrates a changing epidemiology of ESBLs in Europe caused by ST131 subclones; in particular, the emergence of the C1-M27 clade in Europe.

Background Infections caused by third generation cephalosporin-resistant Enterobacteriaceae (3GCREB) are an increasing healthcare problem. We aim to describe the 3GCREB infection incidence and compare it to prevalence upon admission. In addition, we aim to describe infections caused by 3GCREB, which are also carbapenem resistant (CRE). Methods In 2014–2015, we performed prospective 3GCREB surveillance in clinically relevant patient specimens (screening specimens excluded). Infections counted as hospital-acquired (HAI) when the 3GCREB was detected after the third day following admission, otherwise as community-acquired infection (CAI). Results Of 578,420 hospitalized patients under surveillance, 3367 had a 3GCREB infection (0.58%). We observed a similar 3GCREB CAI and HAI incidence (0.28 and 0.31 per 100 patients, respectively). The most frequent pathogen was 3GCR E. coli, in CAI and HAI (0.15 and 0.12 per 100 patients). We observed a CRE CAI incidence of 0.006 and a HAI incidence of 0.008 per 100 patients (0.014 per 1000 patient days). Conclusions Comparing the known 3GCREB admission prevalence of the participating hospitals (9.5%) with the percentage of patients with a 3GCREB infection (0.58%), we conclude the prevalence of 3GCREB in university hospitals to be about 16 times higher than suggested when only patients with 3GCREB infections are considered. Moreover, we find the HAI and CAI incidence caused by CRE in Germany to be relatively low.

Background Vancomycin-resistant enterococci (VRE) are among the most common antimicrobial-resistant pathogens causing nosocomial infections. Although antibiotic use has been identified as a risk factor for VRE, it remains unclear which antimicrobial agents particularly facilitate VRE selection. Here, we assessed whether use of specific antimicrobial agents is independently associated with healthcare-associated (HA) VRE rates in a university hospital setting in Berlin, Germany. Methods We conducted the study between January 2014 and December 2015 at the Charité-university hospital of Berlin, Germany. From the hospital pharmacy, we extracted data for all antibacterials for systemic use (anatomical therapeutic chemical (ATC)-classification J01) and calculated ward specific antibiotic consumption in defined daily doses (DDDs) per 100 patient-days (PD). We used the microbiology laboratory database to identify all patients with isolation of invasive or non-invasive VRE and calculated HA-VRE incidence as nosocomial VRE-cases per 100 patients and HA-VRE incidence density as nosocomial VRE-cases per 1000 PD. We defined VRE isolates as hospital-acquired if they were identified three days or later after hospital admission and otherwise as community-acquired (CA-VRE). We performed univariable and multivariable regression analyses to estimate the association of the frequency of HA-VRE per month with antibiotic use and other parameters such as length of stay, type of ward or presence of at least one CA-VRE on ward. In a second analysis, we considered only patients with VRE infections. Results We included data from 204,054 patients with 948,380 PD from 61 wards. Overall, 1430 VRE-cases were identified of which 409 (28.6%) were considered hospital-acquired (HA). We found that carbapenem use in the current month and prior-month use of glycopeptides increased the risk for HA-VRE by 1% per 1 DDD/100 PD and 3% per 1 DDD/100 PD, respectively. However, when only VRE from clinical samples were considered, only glycopeptide use showed a statistically significant association. In both models, detection of at least one patient with CA-VRE on a ward in the current month significantly increased the risk of HA-VRE, thereby indicating nosocomial spread of VRE. Conclusions Our findings suggest that the risk of HA-VRE is associated with specific antimicrobial agents. Prudent use of these antimicrobial agents might reduce nosocomial VRE rates. That appearance of at least one CA-VRE case on the ward increased the risk of HA-VRE detection highlights the importance of strict hand hygiene practices to interrupt person-to-person transmission of VRE.

OBJECTIVES This study aimed to determine the prevalence of and risk factors for colonization with extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) and methicillin-resistant Staphylococcus aureus (MRSA) in very low birth weight (VLBW

Objectives: To discern the relevance of ST648 extended-spectrum β-lactamase (ESBL)-producing Escherichia coli as a putative new group of multiresistant and extraintestinal pathogenic strains in animals, its frequency, ESBL types, antimicrobial resistance patterns and virulence gene (VG) profiles should be determined and compared with ST131 strains from the same collection of strains. Methods: ESBL-producing E. coli isolates (n=1152), consecutively sampled from predominantly dogs, cats and horses between 2008 and 2011, were assigned to a phylogenetic group by PCR. Partial multilocus sequence typingwas performed for group D and B2 strains and strains presumed to be D-ST648 and B2-ST131 were fully typed. ESBL genes and extraintestinal pathogenic E. coli (ExPEC)-like VGs were characterized by PCR and sequence analysis and antimicrobial resistance was determined by broth dilution. Clonal analysis was done by PFGE. Results: Forty (3.5%) ESBL-producing E. coli were determined as D-ST648, whereas B2-ST131 isolates occurred less frequently (2.8%). Although the predominant ESBL type in both groups was CTX-M-15 (72.5% versus 46.9%), ST648 strains from companion animals and horses displayed a lower variety of ESBL types (CTX-M-1,-3,-14,-15 and-61 versus CTX-M-1,-2,-14,-15,-27 and-55 and SHV-12). In contrast to ST131 strains, a higher proportion of ST648 strains showed resistance to most non-b-lactam antibiotics. Overall, VGs were less abundant in ST648 strains, although some strains had VG profiles comparable to those of ST131 strains. ExPEC-associated serotype O1:H6 was predominant (46.8%) among the ST648 strains. Some PFGE clusters comprised ST648 isolates from pets, horses and wild birds and humans included from previous studies. Conclusions: Our findings demonstrate that certain subgroups of E. coli D-ST648-CTX-M may represent a novel genotype that combines multiresistance, extraintestinal virulence and zoonotic potential. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

As part of the multicentre Antibiotic Therapy Optimisation Study (ATHOS), minimum inhibitory concentrations (MICs) were determined for cephalosporins alone and in combination with the β-lactamase inhibitors tazobactam, clavulanic acid and avibactam against third-generation cephalosporin-resistant Escherichia coli, Klebsiella spp. and Enterobacter spp. isolates collected in German hospitals. MIC50/90 values were 0.25–4 mg/L for cefepime/tazobactam, 0.25–2 mg/L for ceftazidime/avibactam, 0.125–0.5 mg/L for ceftaroline/avibactam, 0.5–4 mg/L for cefpodoxime/clavulanic acid and 0.25–1 mg/L for aztreonam/avibactam, depending on the underlying resistance mechanism and organism. Based on in vitro testing, β-lactam antibiotics play an important role in the treatment of infections due to β-lactamase-producing organisms.

Background We report on an outbreak in a surgical, interdisciplinary intensive care unit (ICU) of a tertiary care hospital. We detected a cluster of ICU patients colonized or infected with multidrug-resistant Pseudomonas aeruginosa. We established an outbreak investigation team, performed an exploratory epidemiological analysis and initiated an epidemiology-based intervention. Methods As part of the outbreak investigation, we performed microbiological examinations of the sinks in the patient rooms and a retrospective case-control study. All patients admitted to the outbreak ICU between January 2012 and February 2014 were included. Cases were patients colonized with the outbreak strain. Controls were patients with a different Pseudomonas aeruginosa strain. Risk factors were evaluated using multivariable conditional logistic regression analysis. Strain typing was performed using the repetitive element-based polymerase chain reaction (rep-PCR) DiversiLab system. Results The outbreak strain was found in the sinks of five (of 16) patient rooms. Altogether 21 cases and 21 (randomly selected) controls were included. In the univariate analysis, there was no significant difference in baseline data of the patients. In the multivariate analysis, stay in a room with a colonized sink (Odds Ratio[OR] 11.2, p = 0.007) and hemofiltration (OR 21.9, p = 0.020) were independently associated with an elevated risk for colonization or infection by the outbreak strain. In a subsequent evaluation of the work procedures associated with hemofiltration, we found that the ultra-filtrate bags had been on average five times per day emptied in the sinks of the patient rooms and were used multiple for the same patient. We exchanged the traps of the contaminated sinks and eliminated work procedures involving sinks in patient rooms by implementation of single use bags, which are emptied outside patient rooms to reduce splash water at the sinks. In the 20 month follow-up period, the outbreak strain was detected only once, which indicated that the outbreak had been ceased (incidence 0.75% vs. 0.04%, p

To determine the prevalence of extended-spectrum β-lactamase (ESBL) production in Enterobacteriaceae in retail chicken meat in Germany.A total of 399 chicken meat samples from nine supermarket chains, four organic food stores and one butcher's shop in two geographically distinct regions (Berlin and Greifswald) were screened for ESBL production using selective agar. Phenotypic ESBL isolates were tested for bla(TEM), bla(CTX-M) and bla(SHV) genes using PCR and DNA sequencing. Antibiotic coresistances were determined and strain typing was performed using PCR-based phylogenetic grouping and XbaI-PFGE.A total of 185 confirmed ESBL isolates were obtained from 175 samples (43.9%) from all tested sources. The majority of isolates were Escherichia coli producing ESBL types SHV-12 (n = 82), CTX-M-1 (n = 77) and TEM-52 (n = 16). No differences could be observed in the prevalence of ESBL producers between organic and conventional samples. 73.0% of the ESBL producers showed coresistance to tetracycline, 35.7% to co-trimoxazole and 7.6% to ciprofloxacin. Strain typing of selected E. coli isolates from Berlin revealed identical macrorestriction patterns for several isolates from samples taken from the same stores.This is the first comprehensive study from Germany showing a high prevalence of TEM-, CTX-M- and SHV-type ESBLs in Enterobacteriaceae isolated from retail chicken meat. The high rate of coresistance to different classes of antibiotics in the ESBL producers might reflect the common veterinary usage of these and related substances. There is an urgent need to further evaluate the role of poultry in the transmission of highly resistant ESBL-producing bacteria in humans.

Infection control personnel performing surveillance activities noticed a cluster of patients with isolates of carbapenem-resistant Pseudomonas aeruginosa (CRPA) in the surgical intensive care unit (SICU) of a German University Hospital. An outbreak investigation including a descriptive analysis, a case-control study comparing 15 CRPA case patients with 18 patients with carbapenem-susceptible P. aeruginosa, environmental sampling and pulsed-field gel electrophoresis (PFGE) typing of P. aeruginosa isolates was carried out. Fifteen patients acquired CRPA in the SICU during the outbreak period between 1 July 2006 and 31 October 2006 and PFGE typing of 11 available patient isolates revealed two outbreak strains as well as sporadic CRPA isolates. Both outbreak strains were resistant to penicillins, cephalosporins, carbapenems, aminoglycosides and quinolones, and remained susceptible only to colistin. The most likely mode of transmission was cross-transmission between patients during postoperative wound care with abdominal and/or thoracic drains (odds ratio: 64.33; 95% confidence interval: 5.32-999) and therapy with quinolones (48.37; 3.71-999) being independent risk factors for acquisition of CRPA. No further clusters of CRPA cases were observed after implementation of contact isolation precautions and after healthcare workers were made aware of the likely mode of transmission. This study shows the complex epidemiology of CRPA in a SICU including cross-transmission of two CRPA strains related to postoperative wound care.

Several randomized controlled trials (RCTs) have examined the influence of oral chlorhexidine (CHX) in preventing nosocomial lower respiratory tract infection (LRTI). Most have failed to demonstrate a reduction in the incidence of LRTI. The present meta-analysis summarizes the effect of oral CHX on the development of LRTI. RCTs were identified through searching PubMed, MEDLINE and the Cochrane Central Register of Controlled Trials databases. Those describing the use of chlorhexidine for oral decontamination and reporting the incidence of LRTI as a study outcome were included in the meta-analysis. Seven RCTs met the inclusion criteria; pooling the results from these reveals a reduction in the relative risk (RR) of LRTI in the CHX group [RR(random): 0.58, 95% confidence interval (CI): 0.45-0.74; and RR(fixed): 0.56, CI95: 0.44-0.72, respectively]. Further analyses showed that this result applied only to patients ventilated for up to 48h (RR(random): 0.58, CI95: 0.45-0.74; and RR(fixed): 0.56, 95% CI: 0.44-0.72). Oral CHX should be included among preventive measures performed to reduce nosocomial LRTI. Whether it has an impact on the development of LRTI in patients requiring mechanical ventilation for a longer period of time remains unresolved.

The usefulness and applicability of isolation precautions were questioned for extended-spectrum beta-lactamase (ESBL)-producing strains of Enterobacteriaceae in the endemic setting. We performed a surveillance programme for ESBL-positive organisms and the infection control management of patients colonized or infected with these organisms. Between 1 January 2002 and 31 December 2004, a total of 147 cases of ESBL-producing strains of Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis from 123 patients were noted. The overall incidence of ESBL-producing-strain-positive cases was 0.12/1000 patient-days. The proportion of referred cases was 35% (N=51); 65% of cases (N=96) were acquired in our institution. Infections developed in 57 cases (38.8%), of which 36 (63.3%) were nosocomial. Contact isolation precautions were carried out for 79.6% of the cases, with a median duration of contact isolation precautions for 14 days (range: 0-144). The contact isolation precautions resulted in 2985 isolation days in total, i.e. 995 isolation days per year. Typing by pulsed-field gel electrophoresis showed clonal diversity in 94.2% of the isolates from patients. Seven patient-to-patient transmissions were noted. Only in 10 cases (6.8%) was colonization with ESBL-producing strains cleared. Considering the large number of immunocompromised patients treated in our institution (>1500 bone marrow or solid organ transplantations performed during 2002-2004), we will continue to isolate patients who are colonized or infected with ESBL-producing organisms.

The outcome of infections occurring at different anatomic sites caused by ESBL-producing E. coli or K. pneumoniae was retrospectively analysed for a 3-y period. 23 cases were compared to 46 controls with infections caused by third-generation cephalosporin-susceptible strains matched by age, severity of illness and duration of hospitalization before onset of infection. Only 27.8% of cases received appropriate empirical antimicrobial therapy compared with 79.6% of controls (OR(paired)=0.053, p=0.001). This did not result in higher costs of antibiotic therapy, a longer median post-infection hospital stay or higher mortality in cases of patients with urinary tract or wound infections. In cases of patients with respiratory tract and bloodstream infections (RTI/BSI), median costs of definitive antibiotic treatment were significantly higher than in controls (325 vs 58.9 Euros, p=0.002). Moreover, more case patients with RTI/BSI had a post-infection stay exceeding the 75th percentile of 15 d on ICU and of 18 d in hospital, respectively (50% vs 6.67%, p=0.034). There was no difference in in-hospital mortality between case and control patients with RTI/BSI (25% vs 20%, p=1.0).

Background Carbapenemase-producing Enterobacteriaceae (CPE) have become a major problem for healthcare systems worldwide. While the first reports from European hospitals described the introduction of CPE from endemic countries, there is now a growing number of reports describing outbreaks of CPE in European hospitals. Here we report an outbreak of Carbapenem-resistant K. pneumoniae in a German University hospital which was in part associated to duodenoscopy. Findings Between December 6, 2012 and January 10, 2013, carbapenem-resistant K. pneumoniae (CRKP) was cultured from 12 patients staying on 4 different wards. The amplification of carbapenemase genes by multiplex PCR showed presence of the bla OXA-48 gene. Molecular typing confirmed the identity of all 12 isolates. Reviewing the medical records of CRKP cases revealed that there was a spatial relationship between 6 of the cases which were located on the same wards. The remaining 6 cases were all related to endoscopic retrograde cholangiopancreatography (ERCP) which was performed with the same duodenoscope. The outbreak ended after the endoscope was sent to the manufacturer for maintenance. Conclusions Though the outbreak strain was also disseminated to patients who did not undergo ERCP and environmental sources or medical personnel also contributed to the outbreak, the gut of colonized patients is the main source for CPE. Therefore, accurate and stringent reprocessing of endoscopic instruments is extremely important, which is especially true for more complex instruments like the duodenoscope (TJF Q180V series) involved in the outbreak described here.

Background. It is unknown whether rising incidence rates of nosocomial bloodstream infections (BSIs) caused by antibiotic-resistant bacteria (ARB) replace antibiotic-susceptible bacteria (ASB), leaving the total BSI rate unaffected. Methods. We investigated temporal trends in annual incidence densities (events per 100 000 patient-days) of nosocomial BSIs caused by methicillin-resistant Staphylococcus aureus (MRSA), ARB other than MRSA, and ASB in 7 ARB-endemic and 7 ARB-nonendemic hospitals between 1998 and 2007. Results. 33 130 nosocomial BSIs (14% caused by ARB) yielded 36 679 microorganisms. From 1998 to 2007, the MRSA incidence density increased from 0.2 to 0.7 (annual increase, 22%) in ARB-nonendemic hospitals, and from 3.1 to 11.7 (annual increase, 10%) in ARB-endemic hospitals (P = .2), increasing the incidence density difference between ARB-endemic and ARB-nonendemic hospitals from 2.9 to 11.0. The non-MRSA ARB incidence density increased from 2.8 to 4.1 (annual increase, 5%) in ARB-nonendemic hospitals, and from 1.5 to 17.4 (annual increase, 22%) in ARB-endemic hospitals (P < .001), changing the incidence density difference from −1.3 to 13.3. Trends in ASB incidence densities were similar in both groups (P = .7). With annual increases of 3.8% and 5.4% of all nosocomial BSIs in ARB-nonendemic and ARB-endemic hospitals, respectively (P < .001), the overall incidence density difference of 3.8 increased to 24.4. Conclusions. Increased nosocomial BSI rates due to ARB occur in addition to infections caused by ASB, increasing the total burden of disease. Hospitals with high ARB infection rates in 2005 had an excess burden of BSI of 20.6 per 100 000 patient-days in a 10-year period, mainly caused by infections with ARB. Funding Agencies|Netherlands Organization of Scientific Research|VICI NWO 918.76.611|Oxford National Institute for Health Research Biomedical Research Centre||Novartis||3M||Roche||Optimer Pharmaceuticals||Cepheid||bioMerieux||Astellas||Basilea||Bayer||Pfizer||Gilead||MSD||Oxoid||Wyeth||Siemens||Bruker

The purpose of this study was to determine the prevalence of extended-spectrum β-lactamase (ESBL) and vancomycin-resistant enterococci (VRE) colonisation among healthy infection control personnel and to determine risk factors for ESBL or VRE colonisation within this group.Participants were recruited at an infection control symposium in 2011. Volunteers were asked to perform a rectal swab and to fill in questionnaires on risk factors of ESBL or VRE carriage (report on diet, contact with domestic or production animals, travel, hospital stay and antibiotic use all within the last 12 months). Rectal swabs were inoculated onto ESBL and VRE chromogenic agar; species identification and susceptibility testing was done by using a VITEK 2 system. In the multivariable analysis, a logistic regression with stepwise forward variable selection was performed.Two hundred and thirty people participated in the study, i.e. 36 % of the symposium attendees (231/639). No VRE faecium or faecalis were isolated, whereas ESBL were isolated from 8 out of 231 individuals, i.e. 3.5 % (95 % confidence interval 1.5-6.7). In the multivariable analysis, travel to Greece or Africa and contact with pets were independently associated with ESBL positivity. The odds ratios were as follows: travel to Greece 15.2, travel to Africa 14.8 and for having a pet animal 6.7.This is the first report showing that contact with pets increases by almost seven-fold the chance to be colonised with ESBL Escherichia coli. A colonisation rate of 3.5 % with ESBL-producing enterobacteriaceae among infection control personnel is of concern and reflects probably less an occupational health risk but the reservoir of and the expansion into the community, especially in persons with pet animals and travel history to high-endemicity countries.

We report an infection with a linezolid-resistant S. aureus in a patient with a left ventricular assist system. Linezolid should be used with caution when invasive devices or foreign materials are in place or therapeutic courses last longer than 14 d. Previous cases of linezolid-resistant S. aureus are summarized.

Little information is available on prevalence of extended-spectrum-betalactamase-producing Enterobacteriaceae (ESBL-E) with and without additional resistance to fluoroquinolones. In Germany, Enterobacteriaceae are classified according to their susceptibility to four classes of antimicrobial substances. Only organisms resistant to acylureidopenicillins, 3rd and 4th generation cephalosporins and fluoroquinolones are labelled as “multidrug–resistant”.

The systemic inflammatory response of the body to invading microorganisms, termed sepsis, leads to profound activation of the complement system. Pathophysiological concepts suggest that complement activation occurs very early in this syndrome. Thus, we discuss whether the determination of concentrations of the complement components C3a, C5a, and C3 in plasma as well as of the C3a/C3 ratio might be helpful to diagnose sepsis early. For this purpose, 33 patients from an intensive care unit were monitored for 10 days. In comparison with healthy donors, C3a levels and the C3a/C3 ratio of intensive-care-unit patients were significantly elevated (P < 0.0001) on admission. In contrast, C3 levels were significantly reduced (P < 0.0001) but increased during the study. C5a levels in the plasma of healthy donors and patients were identical. Twenty-two of 33 patients fulfilled microbiological and clinical criteria of sepsis. Eleven patients had signs of systemic inflammatory response syndrome but no microbiological evidence of sepsis. The groups could be differentiated from each other by their C3a levels or their C3a/C3 ratios during the first 24 h after the clinical onset of sepsis (P < 0.05). Septic patients in shock had higher C3a levels than normotensive septic patients, although the differences were not significant. Nonsurvivors had significantly higher C3a levels on admission than survivors (P = 0.0185). No differences were found between septic patients who developed adult respiratory distress syndrome and those who did not. Thus, determination of C3a concentrations in plasma may prove useful (i) to diagnose sepsis early, (ii) to differentiate between patients with sepsis and those with systemic inflammatory response syndrome, and (iii) to assess prognosis.