Showing papers by "Ulrich Vogel published in 2020"

Hospital preparedness for mass critical care during SARS-CoV-2 pandemic.

Abstract: Mass critical care caused by the severe acute respiratory syndrome corona virus 2 pandemic poses an extreme challenge to hospitals The primary goal of hospital disaster preparedness and response is to maintain conventional or contingency care for as long as possible Crisis care must be delayed as long as possible by appropriate measures Increasing the intensive care unit (ICU) capacities is essential In order to adjust surge capacity, the reduction of planned, elective patient care is an adequate response However, this involves numerous problems that must be solved with a sense of proportion This paper summarises preparedness and response measures recommended to acute care hospitals

Comprehensive integrated NGS-based surveillance and contact-network modeling unravels transmission dynamics of vancomycin-resistant enterococci in a high-risk population within a tertiary care hospital.

Abstract: Vancomycin-resistant E faecium (VRE) are an important cause of nosocomial infections, which are rapidly transmitted in hospitals To identify possible transmission routes, we applied combined genomics and contact-network modeling to retrospectively evaluate routine VRE screening data generated by the infection control program of a hemato-oncology unit Over 1 year, a total of 111 VRE isolates from 111 patients were collected by anal swabs in a tertiary care hospital in Southern Germany All isolated VRE were whole-genome sequenced, followed by different in-depth bioinformatics analyses including genotyping and determination of phylogenetic relations, aiming to evaluate a standardized workflow Patient movement data were used to overlay sequencing data to infer transmission events and strain dynamics over time A predominant clone harboring vanB and exhibiting genotype ST117/CT469 (n = 67) was identified Our comprehensive combined analyses suggested intra-hospital spread, especially of clone ST117/CT469, despite of extensive screening, single room placement, and contact isolation A new interactive tool to visualize these complex data was designed Furthermore, a patient-contact network-modeling approach was developed, which indicates both the periodic import of the clone into the hospital and its spread within the hospital due to patient movements The analyzed spread of VRE was most likely due to placement of patients in the same room prior to positivity of screening We successfully demonstrated the added value for this combined strategy to extract well-founded knowledge from interdisciplinary data sources The combination of patient-contact modeling and high-resolution typing unraveled the transmission dynamics within the hospital department and, additionally, a constant VRE influx over time

Invasive Haemophilus influenzae Infections in Germany After the Introduction of Routine Childhood Immunization, 2001-2016.

Abstract: Introduction Haemophilus influenzae (Hi) serotype b (Hib) vaccination was introduced in Germany in 1990. This study presents a comprehensive overview on the burden of invasive Hi infections for 2001-2016, including serotype-distribution and ampicillin resistance. Materials and Methods Nationwide data from statutory disease surveillance (2001-2016) were linked with laboratory surveillance data (2009-2016). Besides descriptive epidemiology, statistical analyses included multiple imputation to estimate secular trends. Results In 2001-2016, 4,044 invasive Hi infections were reported. Mean incidence was 3.0 per million inhabitants, higher in males (3.2 vs. 2.9 in females) and in age groups <1 year (15.2) and ≥80 years (15.5). Non-typeable Hi (NTHi) caused 81% (n=1,545) of cases in 2009-2016. Of capsulated cases, 69% were serotype f and 17% serotype b. Of Hib cases eligible for vaccination, 10% (3/29) were fully vaccinated. For 2009-2016, significant increasing trends were observed for NTHi and Hif infections in age groups <5 years and ≥60 years and for ampicillin resistance in NTHi. Conclusions This is one of the most comprehensive Hi data analyses since the introduction of Hib vaccines. NTHi and Hif cause an increasing disease burden among elderly patients and infants. Ampicillin resistance in NTHi must be considered in the treatment of invasive Hi infections.

Structural and mechanistic basis of capsule O-acetylation in Neisseria meningitidis serogroup A.

Abstract: O-Acetylation of the capsular polysaccharide (CPS) of Neisseria meningitidis serogroup A (NmA) is critical for the induction of functional immune responses, making this modification mandatory for CPS-based anti-NmA vaccines. Using comprehensive NMR studies, we demonstrate that O-acetylation stabilizes the labile anomeric phosphodiester-linkages of the NmA-CPS and occurs in position C3 and C4 of the N-acetylmannosamine units due to enzymatic transfer and non-enzymatic ester migration, respectively. To shed light on the enzymatic transfer mechanism, we solved the crystal structure of the capsule O-acetyltransferase CsaC in its apo and acceptor-bound form and of the CsaC-H228A mutant as trapped acetyl-enzyme adduct in complex with CoA. Together with the results of a comprehensive mutagenesis study, the reported structures explain the strict regioselectivity of CsaC and provide insight into the catalytic mechanism, which relies on an unexpected Gln-extension of a classical Ser-His-Asp triad, embedded in an α/β-hydrolase fold. Neisseria meningitidis capsular polysaccharide (CPS) is a major virulence factor and vaccine formulations against Neisseria meningitidis serogroup A (NmA) contain O-acetylated CPS. Here, the authors provide mechanistic insights into CPS O-acetylation in NmA by determining the crystal structure of the O-acetyltransferase CsaC and NMR measurements further reveal that the CsaC-mediated reaction is regioselective for O3 and that the O4 modification results from spontaneous O-acetyl migration.

Molecular epidemiology of imipenem resistance in invasive Haemophilus influenzae infections in Germany in 2016.

Abstract: BACKGROUND The carbapenems imipenem and meropenem play an important role in the empirical anti-infective treatment of critically ill patients. Carbapenem resistance in Haemophilus influenzae (Hi) has rarely been reported. OBJECTIVES We provide prevalence data for resistance to carbapenems from laboratory surveillance of invasive Hi infections in Germany in 2016. METHODS Phenotypic susceptibility testing against ampicillin, amoxicillin/clavulanate, cefotaxime and imipenem was carried out on 474 isolates from blood and CSF. The isolates were collected as part of the national laboratory surveillance programme. Imipenem-resistant strains were further tested for meropenem susceptibility. Molecular analysis was done by ftsI sequencing to detect mutations in PBP3, by acrR sequencing to detect alterations in the regulatory protein of the AcrAB-TolC efflux pump and by MLST. RESULTS No resistance to meropenem was detected. Cefotaxime resistance was rare (n = 3; 0.6%). Imipenem resistance was found in 64 strains (13.5%) using gradient agar diffusion and was confirmed in 26 isolates by broth microdilution (5.5%). Imipenem resistance occurred predominantly in Hi that were β-lactamase negative but ampicillin resistant and in those that were β-lactamase positive but nevertheless amoxicillin/clavulanate resistant. This finding suggested a β-lactamase-independent mechanism. Accordingly, sequence analysis of PBP3 identified previously described mutations. MLST of the imipenem-resistant strains, which were all non-typeable Hi, revealed a high diversity. CONCLUSIONS We conclude that imipenem, but not meropenem, resistance is frequent in Hi. It is likely to be supported by PBP3 mutations.

Recurrent invasive meningococcal infections - quantifying the risk, Germany, 2002 to 2018

Abstract: Introduction Invasive meningococcal disease (IMD) is a rare condition with a high case fatality rate While most patients suffer from one single episode in life, there is anecdotal evidence for recurrent infection Aim The German National Reference Laboratory for Meningococci and Haemophilus influenzae (NRZMHi) analysed IMD cases from 2002 to 2018 to retrospectively quantify the risk of recurrent infection Methods Recurrent IMD was defined as detection of Neisseria meningitidis in a sample of the same patient more than 30 days after the first episode of IMD Results Among 5,854 patients with a median observation period of 94 years, 14 suffered a second IMD episode and one patient a third one The risk of a recurrent IMD was 294 per 100,000 person-years for survivors of the first episode Rare serogroups (Y, W, E and Z) were more common in patients with recurrent IMD (p < 00001) Discussion Patients surviving IMD were at least at a 50-fold risk of another IMD episode compared with the general population The study most likely underestimated the risk of recurrent infection Increased risk may be due to undiagnosed complement deficiencies The high risk of re-infection argues for vaccination of patients who have survived IMD

Susceptibility of invasive Neisseria meningitidis strains isolated in Germany to azithromycin, an alternative agent for post-exposure prophylaxis.

Abstract: BACKGROUND Post-exposure prophylaxis (PEP) for close contacts of invasive meningococcal disease (IMD) cases is recommended in most countries to avoid secondary cases by eradicating supposed meningococcal colonization. Currently, rifampicin, ciprofloxacin and ceftriaxone are recommended in many countries including Germany. Azithromycin has been shown to eradicate meningococcal colonization. OBJECTIVES To assess the azithromycin susceptibility of invasive Neisseria meningitidis isolates. METHODS A subset of German invasive meningococcal isolates from 2006-18 was selected for this study. Azithromycin MIC was determined using broth microdilution and agar gradient diffusion. RESULTS Azithromycin MICs as determined by broth microdilution ranged from <0.003 to 2 mg/L (median 0.50 mg/L, Q75 1 mg/L). All isolates were susceptible to azithromycin according to the CLSI breakpoint (95% CI 0.0%-1.5%). There was no significant correlation between MICs determined by broth microdilution and agar gradient diffusion. Nevertheless, the two methods were consistent regarding the categorization of all isolates as susceptible. CONCLUSIONS Azithromycin is an eligible antibiotic for PEP of IMD close contacts. It is approved for adults as well as children and may even be used in pregnancy. Because of easier application and lower toxicity, it might be an alternative to rifampicin and ciprofloxacin, as we found no resistant isolates. Since a gonococcal gene associated with elevated azithromycin MICs has been reported in N. meningitidis, careful monitoring of the emergence of resistant strains is nevertheless necessary for meningococci. Lack of concordance of MICs between broth microdilution and agar gradient diffusion needs to be considered.

Low efficacy of vaccination against serogroup B meningococci in patients with atypical hemolytic uremic syndrome

Abstract: Background: The C5 complement inhibitor eculizumab is first-line treatment in atypical hemolytic uremic syndrome (aHUS) going along with a highly increased risk of meningococcal infections. Serogroup B meningococci (MenB) are the most frequently encountered cause for meningococcal infections in Europe. Efficacy of the protein-based MenB-vaccine Bexsero in aHUS has not been determined and testing is only possible in patients off-treatment with eculizumab as a human complement source is required. Methods: Patients with aHUS were vaccinated with two doses of the protein-based MenB-vaccine Bexsero. Serum bactericidal antibody (SBA) titers against factor H binding protein (fHbp) of MenB were determined in 14 patients with aHUS off-treatment with eculizumab. Results: Only 50% of patients showed protective human serum bactericidal antibody (hSBA) titers (≥1:4) against MenB following two vaccinations. Bactericidal antibody titers were relatively low (≤1:8) in three of seven patients with protective titers. While 71% of patients were on immunosuppressive treatment for either thrombotic microangiopathy or renal transplantation at either first or second vaccination, all four patients not receiving any immunosuppressive treatment showed protective bactericidal antibody response. Time between second vaccination and titer measurement was not significantly different between patients with protective titers compared with those with non-protective titers, while time between first and second vaccination was significantly longer in patients with protective titers going along with a tendency for reduction in immunosuppressive treatment. Conclusions: Efficacy of vaccination against MenB is insufficient in patients with aHUS. Response to vaccination seems to be hampered by immunosuppression. Therefore, implementation of adequate antibiotic prophylaxis seems pivotal.

Discriminative Potential of the Vitek MS In Vitro Diagnostic Device Regarding Haemophilus influenzae and Haemophilus haemolyticus.

Abstract: Haemophilus influenzae can cause respiratory and invasive infections ([1][1]), whereas H. haemolyticus (Hh) is generally considered apathogenic ([2][2]) and is rarely associated with disease ([3][3]). Since both species colonize the upper respiratory tract, their distinction is crucial in routine