ORCID Profile
0000-0003-0837-6945
Current Organisation
Albert-Ludwigs-Universität Freiburg
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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: 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: Frontiers Media SA
Date: 19-07-2021
Abstract: Background: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is used for critically ill patients requiring hemodynamic support but has been shown to induce an inflammatory response syndrome potentially leading to severe complications and poor outcome. Monocytes are comprised of different subsets and play a central role in the innate immune system. The unique small binding proteins, Designed Ankyrin Repeat Protein “F7” and single chain variable fragment “MAN-1,” specifically detect the activated conformation of the leukocyte integrin Mac-1 enabling the highly sensitive detection of monocyte activation status. The aim of this study was to characterize monocyte function and heterogeneity and their association with outcome in VA-ECMO patients. Methods: VA-ECMO patients were recruited from the ICUs of the University Hospital in Freiburg, Germany. Blood was s led on day 0 and day 3 after VA-ECMO placement, after VA-ECMO explantation and from healthy controls. Monocyte subset distribution, baseline activation and stimulability were analyzed by flow cytometry using the unique small binding proteins F7 and MAN-1 and the conventional activation markers CD163, CD86, CD69, and CX3CR1. Furthermore, expression of monocyte activation markers in survivors and non-survivors on day 0 was compared. Simple logistic regression was conducted to determine the association of monocyte activation markers with mortality. Results: Twenty two patients on VA-ECMO and 15 healthy controls were recruited. Eleven patients survived until discharge from the ICU. Compared to controls, baseline monocyte activation was significantly increased, whereas stimulability was decreased. The percentage of classical monocytes increased after explantation, while the percentage of intermediate monocytes decreased. Total, classical, and intermediate monocyte counts were significantly elevated compared to controls. On day 0, baseline binding of F7 was significantly lower in non-survivors than survivors. The area under the ROC curve associated with mortality on day 0 was 0.802 ( p = 0.02). Conclusions: Distribution of monocyte subsets changes during VA-ECMO and absolute classical and intermediate monocyte counts are significantly elevated compared to controls. Monocytes from VA-ECMO patients showed signs of dysfunction. Monocyte dysfunction, as determined by the unique tool F7, could be valuable for predicting mortality in patients receiving VA-ECMO and may be used as a novel biomarker guiding early clinical decision making in the future.
Publisher: Springer Science and Business Media LLC
Date: 10-01-2022
DOI: 10.1038/S41467-021-27595-9
Abstract: The quality and persistence of children’s humoral immune response following SARS-CoV-2 infection remains largely unknown but will be crucial to guide pediatric SARS-CoV-2 vaccination programs. Here, we examine 548 children and 717 adults within 328 households with at least one member with a previous laboratory-confirmed SARS-CoV-2 infection. We assess serological response at 3–4 months and 11–12 months after infection using a bead-based multiplex immunoassay for 23 human coronavirus antigens including SARS-CoV-2 and its Variants of Concern (VOC) and endemic human coronaviruses (HCoVs), and additionally by three commercial SARS-CoV-2 antibody assays. Neutralization against wild type SARS-CoV-2 and the Delta VOC are analysed in a pseudotyped virus assay. Children, compared to adults, are five times more likely to be asymptomatic, and have higher specific antibody levels which persist longer (96.2% versus 82.9% still seropositive 11–12 months post infection). Of note, symptomatic and asymptomatic infections induce similar humoral responses in all age groups. SARS-CoV-2 infection occurs independent of HCoV serostatus. Neutralization responses of children and adults are similar, although neutralization is reduced for both against the Delta VOC. Overall, the long-term humoral immune response to SARS-CoV-2 infection in children is of longer duration than in adults even after asymptomatic infection.
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: Informa UK Limited
Date: 09-2020
DOI: 10.2147/CLEP.S256735
Publisher: Elsevier BV
Date: 10-2022
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: 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.
No related grants have been discovered for Klaus Kaier.