ORCID Profile
0000-0003-1449-5780
Current Organisations
Universität zu Köln
,
Carl von Ossietzky Universität Oldenburg
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Publisher: Cambridge University Press (CUP)
Date: 05-04-2018
DOI: 10.1017/ICE.2018.63
Abstract: To compare the epidemiology, clinical characteristics, and mortality of patients with bloodstream infections (BSI) caused by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (ESBL-EC) versus ESBL-producing Klebsiella pneumoniae (ESBL-KP) and to examine the differences in clinical characteristics and outcome between BSIs caused by isolates with CTX-M versus other ESBL genotypes As part of the INCREMENT project, 33 tertiary hospitals in 12 countries retrospectively collected data on adult patients diagnosed with ESBL-EC BSI or ESBL-KP BSI between 2004 and 2013. Risk factors for ESBL-EC versus ESBL-KP BSI and for 30-day mortality were examined by bivariate analysis followed by multivariable logistic regression. The study included 909 patients: 687 with ESBL-EC BSI and 222 with ESBL-KP BSI. ESBL genotype by polymerase chain reaction lification of 286 isolates was available. ESBL-KP BSI was associated with intensive care unit admission, cardiovascular and neurological comorbidities, length of stay to bacteremia days from admission, and a nonurinary source. Overall, 30-day mortality was significantly higher in patients with ESBL-KP BSI than ESBL-EC BSI (33.7% vs 17.4% odds ratio, 1.64 P =.016). CTX-M was the most prevalent ESBL subtype identified (218 of 286 polymerase chain reaction-tested isolates, 76%). No differences in clinical characteristics or in mortality between CTX-M and non–CTX-M ESBLs were detected. Clinical characteristics and risk of mortality differ significantly between ESBL-EC and ESBL-KP BSI. Therefore, all ESBL-producing Enterobacteriaceae should not be considered a homogeneous group. No differences in outcomes between genotypes were detected. ClinicalTrials.gov. Identifier: NCT01764490. Infect Control Hosp Epidemiol 2018 :660–667
Publisher: Informa UK Limited
Date: 02-01-2019
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1016/J.CMI.2018.12.029
Abstract: Colonization and infection with third-generation cephalosporin-resistant Escherichia coli (3GCR-EC) are frequent in haematological and oncological patients. In this high-risk setting, German guidelines recommend single-room contact precautions (SCP) for patients with 3GCR-EC that are non-susceptible to fluoroquinolones (F3GCR-EC). However, this recommendation is controversial, as evidence is limited. We performed a prospective, multicentre cohort study at four haematology and oncology departments assessing the impact of SCP on hospital-acquired colonization or bloodstream infection (BSI) with F3GCR-EC. Two sites performed SCP for F3GCR-EC patients including single rooms, gloves and gowns (SCP sites), and two did not (NCP sites). Active screening for 3GCR-EC was performed and isolates were characterized with molecular typing methods including whole genome sequencing and core genome multiple locus sequence typing to assess patient-to-patient transmission. Potential confounders were assessed by competing-risk regression analysis. Within 12 months, 1386 patients at NCP sites and 1582 patients at SCP sites were included. Hospital-acquisition of F3GCR-EC was observed in 22/1386 (1.59%) and 16/1582 (1.01%) patients, respectively (p 0.191). There were 3/1386 (0.22%) patients with BSI caused by F3GCR-EC at NCP sites and 4/1582 (0.25%) at SCP sites (p 1.000). Patient-to-patient transmission occurred in three cases at NCP and SCP sites each (p 1.000). The number of patients needed to screen in order to prevent one patient-to-patient transmission of F3GCR-EC was determined to be 3729. Use of SCP had no significant impact on hospital-acquisition or patient-to-patient transmission of F3GCR-EC in this high-risk setting.
Publisher: Oxford University Press (OUP)
Date: 16-03-2020
DOI: 10.1093/JAC/DKAA052
Abstract: To assess the admission prevalence of third-generation cephalosporin-resistant Enterobacterales (3GCREB) and to assess whether risk factors vary by β-lactamase genotype. 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. 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). 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.
Publisher: Elsevier BV
Date: 11-2018
DOI: 10.1016/J.IJANTIMICAG.2018.06.018
Abstract: There are few data in the literature regarding sepsis or septic shock due to extended-spectrum β-lactamases (ESBL)-producing Enterobacteriaceae (E). The aim of this study was to assess predictors of outcome in septic patients with bloodstream infection (BSI) caused by ESBL-E. Patients with severe sepsis or septic shock and BSI due to ESBL-E were selected from the INCREMENT database. The primary endpoint of the study was the evaluation of predictors of outcome after 30 days from development of severe sepsis or septic shock due to ESBL-E infection. Three cohorts were created for analysis: global, empirical-therapy and targeted-therapy cohorts. 367 septic patients were analysed. Overall mortality was 43.9% at 30 days. Escherichia coli (62.4%) and Klebsiella pneumoniae (27.2%) were the most frequent isolates. β-lactam/β-lactamase inhibitor (BLBLI) combinations were the most empirically used drug (43.6%), followed by carbapenems (29.4%). Empirical therapy was active in vitro in 249 (67.8%) patients, and escalation of antibiotic therapy was reported in 287 (78.2%) patients. Cox regression analysis showed that age, Charlson Comorbidity Index, McCabe classification, Pitt bacteremia score, abdominal source of infection and escalation of antibiotic therapy were independently associated with 30-day mortality. No differences in survival were reported in patients treated with BLBLI combinations or carbapenems in empirical or definitive therapy. BSI due to ESBL-E in patients who developed severe sepsis or septic shock was associated with high 30-day mortality. Comorbidities, severity scores, source of infection and antibiotic therapy escalation were important determinants of unfavorable outcome.
Publisher: Oxford University Press (OUP)
Date: 27-02-2018
DOI: 10.1093/JAC/DKY040
Abstract: Fluoroquinolone resistance (FQR) in third-generation cephalosporin-resistant Enterobacteriaceae (3GCRE) presents serious limitations to antibiotic therapy. The aim of this study was to investigate whether the FQR proportion among 3GCRE differs between community-acquired (CA) and hospital-acquired (HA) isolates. In a prospective observational study covering 2014 and 2015, we monitored the occurrence of 3GCRE in adult hospitalized patients in six German university hospitals. 3GCRE clinical isolates were sub ided into CA and HA. Multivariable analysis identified factors associated with in vitro non-susceptibility to ciprofloxacin. The dataset included 5721 3GCRE isolates of which 52.9% were HA and 52.7% exhibited FQR. Interestingly, the FQR proportion was higher in CA 3GCRE than in HA 3GCRE (overall, 60.1% versus 46.2%, respectively, P < 0.001). Multivariable analysis adjusting for age confirmed community acquisition as a risk factor for FQR [adjusted rate ratio (aRR) 1.33, 95% CI 1.17-1.53]. Escherichia coli and Klebsiella spp. were associated with a much higher FQR proportion than other Enterobacteriaceae species (aRR 8.14, 95% CI 6.86-9.65 and aRR 7.62 with 95% CI 6.74-8.61, respectively). The high FQR proportion observed among CA 3GCRE, particularly in E. coli and Klebsiella spp., indicates that selection pressure in the outpatient setting needs to be addressed with antibiotic stewardship and other interventions in order to limit further spread of MDR.
Publisher: American Society for Microbiology
Date: 07-2016
DOI: 10.1128/AAC.00365-16
Abstract: The spread of extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-E) is leading to increased carbapenem consumption. Alternatives to carbapenems need to be investigated. We investigated whether β-lactam/β-lactamase inhibitor (BLBLI) combinations are as effective as carbapenems in the treatment of bloodstream infections (BSI) due to ESBL-E. A multinational, retrospective cohort study was performed. Patients with monomicrobial BSI due to ESBL-E were studied specific criteria were applied for inclusion of patients in the empirical-therapy (ET) cohort (ETC 365 patients), targeted-therapy (TT) cohort (TTC 601 patients), and global cohort (GC 627 patients). The main outcome variables were cure/improvement rate at day 14 and all-cause 30-day mortality. Multivariate analysis, propensity scores (PS), and sensitivity analyses were used to control for confounding. The cure/improvement rates with BLBLIs and carbapenems were 80.0% and 78.9% in the ETC and 90.2% and 85.5% in the TTC, respectively. The 30-day mortality rates were 17.6% and 20% in the ETC and 9.8% and 13.9% in the TTC, respectively. The adjusted odds ratio (OR) (95% confidence interval [CI]) values for cure/improvement rate with ET with BLBLIs were 1.37 (0.69 to 2.76) for TT, they were 1.61 (0.58 to 4.86). Regarding 30-day mortality, the adjusted OR (95% CI) values were 0.55 (0.25 to 1.18) for ET and 0.59 (0.19 to 1.71) for TT. The results were consistent in all subgroups studied, in a stratified analysis according to quartiles of PS, in PS-matched cases, and in the GC. BLBLIs, if active in vitro , appear to be as effective as carbapenems for ET and TT of BSI due to ESLB-E regardless of the source and specific species. These data may help to avoid the overuse of carbapenems. (This study has been registered at ClinicalTrials.gov under registration no. NCT01764490.)
Publisher: Oxford University Press (OUP)
Date: 06-08-2014
DOI: 10.1093/JAC/DKU305
Abstract: Bloodstream infections (BSIs) caused by enterobacteria remain a leading cause of mortality in patients with chemotherapy-induced neutropenia. The rate and type of colonization and infection with ESBL-producing Enterobacteriaceae (ESBL-E) and their mode of transmission in German cancer centres is largely unknown. We performed a prospective, observational study at five German university-based haematology departments. Participating sites screened for intestinal ESBL-E colonization within 72 h of admission, every 10 ± 2 days thereafter and before discharge. Three of the five centres performed contact isolation for patients colonized or infected with ESBL-E. Molecular characterization of resistance mechanisms and epidemiological typing of isolates by repetitive extragenic palindromic PCR (rep-PCR) and PFGE was performed to assess strain transmission between patients. Between October 2011 and December 2012, 719 hospitalizations of 497 haematological high-risk patients comprising 20,143 patient-days were analysed. Mean duration of in-hospital stay was 36.6 days (range: 2-159 days). ESBL-E were identified from screening s les (82.8% Escherichia coli and 14.6% Klebsiella pneumoniae) in 55/497 patients (11.1% range by centre: 5.8%-23.1%). PFGE and rep-PCR revealed only a single case of potential cross-transmission among two patients colonized with K. pneumoniae. Six episodes of BSI with ESBL-E were observed. Multivariate analysis revealed previous colonization with ESBL-E as the most important risk factor for BSI with ESBL-E (OR 52.00 95% CI 5.71-473.89). Even though BSI with ESBL-E is still rare in this high-risk population, colonization rates are substantial and vary considerably between centres. In-hospital transmission of ESBL-E as assessed by molecular typing was the exception.
Publisher: Oxford University Press (OUP)
Date: 17-06-2016
DOI: 10.1093/JAC/DKW216
Abstract: The objectives of this study were to prospectively assess the rectal carriage rate of third-generation cephalosporin-resistant Enterobacteriaceae (3GCREB) in non-ICU patients on hospital admission and to investigate resistance mechanisms and risk factors for carriage. Adult patients were screened for 3GCREB carriage at six German tertiary care hospitals in 2014 using rectal swabs or stool s les. 3GCREB isolates were characterized by phenotypic and molecular methods. Each patient answered a questionnaire about potential risk factors for colonization with MDR organisms (MDROs). Univariable and multivariable risk factor analyses were performed to identify factors associated with 3GCREB carriage. Of 4376 patients, 416 (9.5%) were 3GCREB carriers. Escherichia coli was the predominant species (79.1%). ESBLs of the CTX-M-1 group (67.3%) and the CTX-M-9 group (16.8%) were the most frequent β-lactamases. Five patients (0.11%) were colonized with carbapenemase-producing Enterobacteriaceae. The following risk factors were significantly associated with 3GCREB colonization in the multivariable analysis (P < 0.05): centre previous MDRO colonization (OR = 2.12) antibiotic use within the previous 6 months (OR = 2.09) travel outside Europe (OR = 2.24) stay in a long-term care facility (OR = 1.33) and treatment of gastroesophageal reflux disease (GERD) (OR = 1.22). To our knowledge, this is the largest admission prevalence study of 3GCREB in Europe. The observed prevalence of 9.5% 3GCREB carriage was higher than previously reported and differed significantly among centres. In addition to previously identified risk factors, the treatment of GERD proved to be an independent risk factor for 3GCREB colonization.
Publisher: Oxford University Press (OUP)
Date: 06-01-2017
DOI: 10.1093/JAC/DKW513
Publisher: Oxford University Press (OUP)
Date: 19-01-2017
DOI: 10.1093/JAC/DKW577
Abstract: As part of the multicentre Antibiotic Therapy Optimisation Study, MIC values of 19 non-β-lactam agents were determined for third-generation cephalosporin-resistant Escherichia coli , Klebsiella species and Enterobacter species (3GCREB) isolates collected in German hospitals. A total of 328 E. coli , 35 Klebsiella spp. (1 Klebsiella oxytoca and 34 Klebsiella pneumoniae ) and 16 Enterobacter spp. (1 Enterobacter aerogenes and 15 Enterobacter cloacae ) isolates were submitted to broth microdilution antimicrobial susceptibility testing with the MICRONAUT system. MICs of fluoroquinolones (levofloxacin and moxifloxacin), aminoglycosides (gentamicin, tobramycin, amikacin, streptomycin, neomycin and paromomycin), tetracyclines (tetracycline, minocycline and tigecycline), macrolides (erythromycin, clarithromycin and azithromycin) and miscellaneous agents [trimethoprim/sulfamethoxazole, chlor henicol, nitrofurantoin, colistin and fosfomycin intravenous (iv)] were determined and reviewed against 2016 EUCAST breakpoints. The MIC of levofloxacin was >2 mg/L for 128 of 328 E. coli and 8 of 35 Klebsiella spp., but only 1 of 16 Enterobacter spp. Rates of resistance to trimethoprim/sulfamethoxazole were high (>70%), except for Enterobacter spp. Rates of resistance to colistin and fosfomycin iv were still low. About 20% of the tested isolates were resistant to chlor henicol. Only 1 (of 328) E. coli isolate had an MIC of amikacin >16 mg/L and only 33 of 328 E. coli and 1 of 35 Klebsiella spp. had an MIC of tobramycin >4 mg/L, whereas average gentamicin MICs were in general more elevated. A tigecycline MIC >2 mg/L was only found for 1 of 16 Enterobacter spp., but in none of the E. coli or Klebsiella spp. isolates. Our study gives insight into previously unreported non-β-lactam MIC distributions of 3GCREB isolates.
Publisher: Springer Science and Business Media LLC
Date: 18-09-2019
DOI: 10.1186/S12915-019-0692-Y
Abstract: The selection pressure exercised by antibiotic drugs is an important consideration for the wise stewardship of antimicrobial treatment programs. Treatment decisions are currently based on crude assumptions, and there is an urgent need to develop a more quantitative knowledge base that can enable predictions of the impact of in idual antibiotics on the human gut microbiome and resistome. Using shotgun metagenomics, we quantified changes in the gut microbiome in two cohorts of hematological patients receiving prophylactic antibiotics one cohort was treated with ciprofloxacin in a hospital in Tübingen and the other with cotrimoxazole in a hospital in Cologne. Analyzing this rich longitudinal dataset, we found that gut microbiome ersity was reduced in both treatment cohorts to a similar extent, while effects on the gut resistome differed. We observed a sharp increase in the relative abundance of sulfonamide antibiotic resistance genes (ARGs) by 148.1% per cumulative defined daily dose of cotrimoxazole in the Cologne cohort, but not in the Tübingen cohort treated with ciprofloxacin. Through multivariate modeling, we found that factors such as in idual baseline microbiome, resistome, and plasmid ersity liver/kidney function and concurrent medication, especially virostatic agents, influence resistome alterations. Strikingly, we observed different effects on the plasmidome in the two treatment groups. There was a substantial increase in the abundance of ARG-carrying plasmids in the cohort treated with cotrimoxazole, but not in the cohort treated with ciprofloxacin, indicating that cotrimoxazole might contribute more efficiently to the spread of resistance. Our study represents a step forward in developing the capability to predict the effect of in idual antimicrobials on the human microbiome and resistome. Our results indicate that to achieve this, integration of the in idual baseline microbiome, resistome, and mobilome status as well as additional in idual patient factors will be required. Such personalized predictions may in the future increase patient safety and reduce the spread of resistance. ClinicalTrials.gov, NCT02058888 . Registered February 10 2014
Publisher: Springer Science and Business Media LLC
Date: 27-12-2018
DOI: 10.1186/S13756-018-0452-8
Abstract: 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). 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). 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). 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.
Publisher: Elsevier BV
Date: 2017
DOI: 10.1016/J.DIAGMICROBIO.2016.09.012
Abstract: As part of the multicenter Antibiotic Therapy Optimisation Study-the largest study on the prevalence of third-generation cephalosporin-resistant Enterobacteriaceae carriage upon hospital admission-minimum inhibitory concentration values were generated for icillin/sulbactam, amoxicillin/clavulanic acid, piperacillin/tazobactam, mecillinam, mecillinam/clavulanic acid, and temocillin against third-generation cephalosporin-resistant Escherichia coli, Klebsiella species and Enterobacter species.
Publisher: Elsevier BV
Date: 02-2017
DOI: 10.1016/J.IJANTIMICAG.2016.10.013
Abstract: 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. MIC
Location: Germany
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Axel Hamprecht.