Impact of single-room contact precautions on acquisition and transmission of vancomycin-resistant enterococci on haematological and oncological wards, multicentre cohort-study, Germany, January−December 2016

Background Evidence supporting the effectiveness of single-room contact precautions (SCP) in preventing in-hospital acquisition of vancomycin-resistant enterococci (haVRE) is limited. Aim We assessed the impact of SCP on haVRE and their transmission. Methods We conducted a prospective, multicentre cohort study in German haematological/oncological departments during 2016. Two sites performed SCP for VRE patients and two did not (NCP). We defined a 5% haVRE-risk difference as non-inferiority margin, screened patients for VRE, and characterised isolates by whole genome sequencing and core genome MLST (cgMLST). Potential confounders were assessed by competing risk regression analysis. Results We included 1,397 patients at NCP and 1,531 patients at SCP sites. Not performing SCP was associated with a significantly higher proportion of haVRE; 12.2% (170/1,397) patients at NCP and 7.4% (113/1,531) patients at SCP sites (relative risk (RR) 1.74; 95% confidence interval (CI): 1.35–2.23). The difference (4.8%) was below the non-inferiority margin. Competing risk regression analysis indicated a stronger impact of antimicrobial exposure (subdistribution hazard ratio (SHR) 7.46; 95% CI: 4.59–12.12) and underlying disease (SHR for acute leukaemia 2.34; 95% CI: 1.46–3.75) on haVRE than NCP (SHR 1.60; 95% CI: 1.14–2.25). Based on cgMLST and patient movement data, we observed 131 patient-to-patient VRE transmissions at NCP and 85 at SCP sites (RR 1.76; 95% CI: 1.33–2.34). Conclusions We show a positive impact of SCP on haVRE in a high-risk population, although the observed difference was below the pre-specified non-inferiority margin. Importantly, other factors including antimicrobial exposure seem to be more influential.

The First Dimeric Derivatives of the Glycopeptide Antibiotic Teicoplanin

Various dimeric derivatives of the glycopeptide antibiotic teicoplanin were prepared with the aim of increasing the activity of the parent compound against glycopeptide-resistant bacteria, primarily vancomycin-resistant enterococci. Starting from teicoplanin, four covalent dimers were prepared in two orientations, using an α,ω-bis-isothiocyanate linker. Formation of a dimeric cobalt coordination complex of an N-terminal L-histidyl derivative of teicoplanin pseudoaglycone has been detected and its antibacterial activity evaluated. The Co(III)-induced dimerization of the histidyl derivative was demonstrated by DOSY experiments. Both the covalent and the complex dimeric derivatives showed high activity against VanA teicoplanin-resistant enterococci, but their activity against other tested bacterial strains did not exceed that of the monomeric compounds.

Molecular Epidemiology of Vancomycin-Resistant Enterococci Bloodstream Infections in Germany: A Population-Based Prospective Longitudinal Study

Vancomycin-resistant enterococci (VRE) pose a public health challenge worldwide. While VRE bloodstream infections (VREBI) increase in Germany and Europe, population-based molecular data are scarce. We aimed to analyze the molecular epidemiology, demographic aspects, and geographical distribution of VREBI in the German Federal State of North-Rhine–Westphalia (NRW), located in the German–Dutch–Belgian border area, representing over 20% of Germany’s population. VREBI isolates were collected from hospitals across NRW between 2016 and 2019. Demographic data were gathered and anonymized upon sample collection. Multilocus sequence typing (MLST) and identification of glycopeptide resistance were carried out. Epidemiological analysis and geographical mapping were performed. Single VREBI isolates from 755 patients were analyzed. In total, 38.9% were female, and 80.0% were aged ≥ 60 years. The VREBI incidence per 100,000 inhabitants nearly tripled, from 0.52 (2016) to 1.48 (2019), particularly in male patients aged ≥ 50 years. The proportion of vanB reached 83% (n = 202/243) in 2018, overtaking vanA as the predominant glycopeptide resistance determinant, detected in close relation with ST117 isolates. The proportion of MLST sequence type (ST) 117 peaked in 2018, at 78.2% (n = 190/243). The major role of these emerging strains in invasive infections in central Europe requires novel strategies for their diagnosis, treatment, and prevention.

Prevalence of Vancomycin-Resistant Enterococci and Antimicrobial Residues in Wastewater and Surface Water

Due to the extensive use of antimicrobial agents in human and veterinary medicine, residues of various antimicrobials get into wastewater and, subsequently, surface water. On the one hand, a combination of processes in wastewater treatment plants aims to eliminate chemical and biological pollutants; on the other hand, this environment may create conditions suitable for the horizontal transfer of resistance genes and potential selection of antibiotic-resistant bacteria. Wastewater and surface water samples (Morava River) were analyzed to determine the concentrations of 10 antibiotics and identify those exceeding so-called predicted no-effect environmental concentrations (PNECs). This study revealed that residues of five of the tested antimicrobials, namely ampicillin, clindamycin, tetracycline, tigecycline and vancomycin, in wastewater samples exceeded the PNEC. Vancomycin concentrations were analyzed with respect to the detected strains of vancomycin-resistant enterococci (VRE), in which the presence of resistance genes, virulence factors and potential relationship were analyzed. VRE were detected in 16 wastewater samples (11%) and two surface water samples (6%). The PNEC of vancomycin was exceed in 16% of the samples. Since the detected VRE did not correlate with the vancomycin concentrations, no direct relationship was confirmed between the residues of this antimicrobials and the presence of the resistant strains.

The evaluation of vancomycin-resistant enterococci and carbapenamase producing Klebsiella colonization among ICU-Hospitalized Patients

Background: Multi-drug resistant organisms, especially Vancomycin-Resistant Enterococcus (VRE) and Carbapenam Resistant Klebsiella pneumoniae (KPC), are serious health threat. Early detection of resistant bacteria colonization amongpatients in intensive care units (ICUs) not only enables effective treatment but more importantly prevents disease and limits transmission. Therefore, we aimed to to assess the frequency of VRE and KPC colonization via rectal swab sampling. Methods: The study was carried out in ICUs of a tertiary hospital. Two rectal swab samples were collected within the first 24 hours of admission and another one was taken every subsequent 15 days to test for for VRE and KPC carriage. Results: A total 316 rectal swab samples taken from 230 patients. Forty-seven patients were screened at least 2 times. 183 patients were not further screened due to discharge, exitus or transfer to other wards. Thirty-six patients (16%) were determinedto be VRE (+). The most frequently isolated strain was E. faecium (80.5%) and its most common genotype was VanA (87.5%). Seven patients (3%) were identified as KPC (+). OXA-48 type crbapenamase was confirmed in all KPC isolates. Conclusion: This study shows that VRE and KPC colonization continues to be a serious threat in ICUs. Keywords: Carbapenam resistant klebsiella pneumoniae; vancomycin-resistant enterococci; intensive care units.

Utility of bile esculin azide agar for screening of stool samples for vancomycin resistant enterococci from patients with gut colonization

Background: Due to increased prevalence of vancomycin resistant enterococci (VRE) in hospital settings as an important nosocomial pathogen, microbiology laboratories should be prepared with test protocol for prompt detection and reporting of these resistant organisms. This helps in appropriate treatment of patients without delay and implementation of infection control measures in order to prevent spread of such infections. With this background present study was conducted to demonstrate utility of bile esculin azide agar with vancomycin (BEAV) for screening of enterococci for vancomycin drug resistance.Methods: Over a period of one year 200 stool samples were collected from hospitalized patients in a tertiary care hospital. Samples were inoculated on bile esculin azide agar with vancomycin (6ug/ml) to screen for vancomycin drug resistance in enterococci isolated from stool samples. Vancomycin drug resistance was confirmed by agar dilution method.Results: Out of 200 stool samples collected from hospitalized patients, 13 (6.5%) samples showed growth on bile esculin azide agar with vancomycin (6 µg/ml). Of these 13 isolates, 12 (92.3%) isolates were confirmed as VRE by agar dilution method and demonstrated minimum inhibitory concentration (MIC) of ≥32 µg/ml and all 12 isolates were identified as E. faecium. One (7.7%) isolate grown on BEAV was identified as E. gallinarum and showed MIC value of 8 µg/ml.Conclusions: Present study recommends use of bile esculin azide agar with vancomycin (6 µg/ml) as a screening medium for isolation of VRE from stool samples which usually carries mixed commensal flora of gastrointestinal tract.

Oxandrastins: Antibacterial Meroterpenes from an Australian Mud Dauber Wasp Nest-Associated Fungus, Penicillium sp. CMB-MD14

The ethyl acetate extract of an ISP-2 agar cultivation of the wasp nest-associated fungus Penicillium sp. CMB-MD14 exhibited promising antibacterial activity against vancomycin-resistant enterococci (VRE), with a bioassay guided chemical investigation yielding the new meroterpene, oxandrastin A (1), the first andrastin-like metabolite with an extra oxygenation at C-2. A culture media optimisation strategy informed a scaled-up rice cultivation that yielded 1, together with three new oxandrastins B–D (2–4), two known andrastins C (5) and F (6), and a new meroterpene of the austalide family, isoaustalide F (7). Structures of 1–7 were assigned based on detailed spectroscopic analysis and chemical interconversion. A GNPS molecular networking analysis of the rice cultivation extract detected the known austalides B (8), H (9), and H acid (10), tentatively identified based on molecular formulae and co-clustering with 7. That the anti-VRE properties of the CMB-MD14 extract were exclusively attributed to 1 (IC50 6.0 µM, MIC99 13.9 µM), highlights the importance of the 2-OAc and 3-OAc moieties to the oxandrastin anti-VRE pharmacophore.