Rate of antibiotic prescriptions in German outpatient care - are the guidelines followed or are they still exceeded?

Aim: The consequences of antibiotic overuse are substantial. We combined and analyzed the infection diagnoses and antibiotic prescribing practices of physicians in outpatient settings. Recommendations for targeting policy efforts to focused areas are given. Methods: Antibiotic prescriptions and infections diagnosed were provided by a German statutory health insurance provider over a 12-month period. Antibiotic use was expressed as prescriptions per 100 patients. Results: 2,594,000 patient-physician contacts within twelve months were analyzed. A median of 6.5 antibiotics was prescribed to 100 patients. Antibiotic use in private practice showed large variations between and within medical specialties (the upper quarter of physicians who prescribed above the 75th percentile of all prescriptions, at a rate of approximately 43%), by season (antibiotic prescription was 50% higher in winter than in summer) and a considerable proportion of the antibiotics prescribed did not conform with the recommendations of national guidelines. Fluoroquinolones, predominantly ciprofloxacin, were among the top three antibiotics prescribed by all physicians (except pediatricians), although national guidelines do not recommend these agents for uncomplicated respiratory or urinary tract infections. Respiratory tract infections headed the list for the prescription of antibiotics. Conclusions: Antibiotics were still not prescribed appropriately in respect to indication and selection (often unnecessary and/or too broad). We recommend focusing on I) high/over-prescribers, because improved and appropriate antibiotic prescription by this group would result in an over-proportionally lower antibiotic prescription rate, II) respiratory tract infections, because they represent the vast majority of infections treated in primary care and III) intelligent implementation strategies of guidelines

Usefulness of screening for Candida auris colonisation in international patients admitted to a large university hospital

Introduction Candida auris is an emerging pathogen in health care-associated infections. In contrast to many other countries with rising numbers of C. auris, only seven cases have been reported in Germany from 2015 to 2017, mostly from patients who received prior medical treatment abroad. We therefore established a mandatory screening for C. auris colonisation at our tertiary care centre for all patients who were admitted as international patients or previously hospitalised in a foreign country within the past 6 months. Methods Colonisation of patients was assessed using a previously established screening protocol for multidrug resistant bacteria. Since 2017, all screening samples were additionally analysed for C. auris using CHROMagar Candida (CHROMagar, Paris, France). Yeast isolates were identified using matrix-assisted laser ionisation time-of-flight (MALDI TOF), except for C. albicans (identified by the typical green colour on chromogenic agar). Data were analysed retrospectively. Results Our study cohort included 655 patients and an overall number of 1399 samples. Fifty-three patients were colonised with Candida species (C. albicans, n = 37; C. glabrata, n = 14; others n = 9). No case of C. auris was detected. Candida spp. were mainly detected from respiratory samples (5.4% positive) and gastrointestinal specimen (5.2%). Laboratory costs were 14,689 euro and analyses resulted in 98.7 h of additional technician's work. Conclusion No colonisation with C. auris was detected among patients with previous hospitalisation abroad. Universal C. auris screening of patients with any contact to foreign health care does not seem to be cost-effective in our setting and more targeted screening strategies have to be developed

Molds and More: Rare Fungal Infections in Preterm Infants <24 Weeks of Gestation

Background: Extreme immature infants are at an increased risk of fungal infection due to immaturity of the skin barrier and the immune system. Besides Candida infections, in particular, Aspergillus may cause life-threatening diseases in preterm infants. Frequently, Aspergillus primarily affects the skin and may cause extensive damage. Methods: We searched our hospital database for fungal infections other than Candida in preterm infants treated between 2015 and 2020 at our level III neonatal intensive care unit of the University Hospital of Cologne. Results: In total, 13 preterm infants were identified. Of these, 11 had cutaneous Aspergillosis, one infant had severe enterocolitis caused by Aspergillus and Rhizopus and one had invasive intraabdominal Trichosporon mucoides infection. All infants were born <24 weeks of gestation, were delivered due to premature labor or chorioamnionitis, and had received prenatal steroids and/or hydrocortisone. Voriconazole and liposomal Amphotericin B were first-line treatments and the length of treatment varied between 3 and 148 days. Two infants died associated with severe infection. Liver toxicity was observed in six infants treated with Voriconazole. Therapeutic drug management for Voriconazole was performed in four infants. Target levels were not achieved by the doses that are recommended. Conclusions: Rare fungal infections, predominantly cutaneous Aspergillosis affects the most immature preterm infants and may cause severe disease. Treatment with Voriconazole has a high rate of liver toxicity and target levels are difficult to achieve in extremely immature infants

Characterization of a vancomycin-resistant Enterococcus faecium isolate and a vancomycin-susceptible E. faecium isolate from the same blood culture

Objectives: To characterize two Enterococcus faecium isolates with different resistance phenotypes obtained from the same blood culture. Methods: The isolates were identified by MALDI-TOF MS and antimicrobial susceptibility testing (AST) was performed using a VITEK (R) 2 AST P592 card and Etest. WGS was performed on the MiSeq and MinION sequencer platforms. Core-genome MLST (cgMLST) and seven-Loci MLST were performed. Plasmid anaLysis was performed using S1-PFGE followed by Southern-blot hybridization. Results: Both E. faecium isolates were ST203. AST revealed that one was a vancomycin-resistant E. faecium (VREfm) isolate and the other was a vancomycin-susceptible E. faecium (VSEfm) isolate. The VREfm isolate harboured the vanA gene cluster as part of a Tn1546-type transposon encoded on a 49 kb multireplicon (repl, rep2 and rep7a) plasmid (pAML0157.1). On the same plasmid, ant(6)-Ia, cat-Like and erm(B) were encoded. The VSEfm isolate harboured a rep2 plasmid (pAML0158.1), 12 kb in size, which was present in full length as part of pAML0157.1 from the VREfm isolate. The vanA-encoding pAML0157.1 was a chimera of the rep2 pAML0158.1 and a second DNA segment harbouring vanA, ant(6)-Ia, erm(B) and cat-Like, as well as the replicons repl and rep7a. By cgMLST analysis, the VREfm and VSEfm isolates were identical. Conclusions: Our results demonstrate that the VREfm and VSEfm blood culture isolates represented ST203 and were identical. The investigated heterogeneous resistance phenotypes resulted from the acquisition or Loss of plasmid segments in the enterococcal isolates. These data illustrate that mobile genetic elements may contribute to the spread of vancomycin resistance among enterococci and to the genotypic and phenotypic variation within clonal isolates

The role and regulation of Moraxella catarrhalis-induced human beta-defensin 3 expression in human pulmonary epithelial cells

Background: Bacterial colonisation with Moraxella catarrhalis may partly sustain chronic inflammation in the lower airways of patients with chronic obstructive pulmonary disease (COPD). In addition, this bacterium causes infectious exacerbations of COPD, which often necessitate treatment with antibiotics. Antimicrobial peptides are the body's own antibiotic substances with bactericidal and bacteriostatic, as well as immunomodulatory function. In particular, human beta-defensin 3 (hBD-3) exerts an antimicrobial effect against an extraordinarily broad spectrum of pathogens. We therefore investigated the role of hBD-3 in infections of pulmonary epithelial cells with M. catarrhalis. Methods: The antimicrobial activity of hBD-3 vs. M. catarrhalis was evaluated in an antimicrobial susceptibility assay. We analyzed hBD-3 secretion of M. catarrhalis-infected pulmonary epithelial cells using ELISA. The role of M. catarrhalis-specific virulence factors, toll-like receptors (TLR) 2 and 4, MAPK pathways, and transcription factors AP-1 and NF-kappa B in the induction and regulation of hBD-3 expression were explored with specific inhibitors, small interference RNA, Western Blot, and chromatin immunoprecipitation (ChIP) assays. Results: HBD-3 exhibited a strong bactericidal effect against M. catarrhalis. M. catarrhalis induced hBD-3 expression in pulmonary epithelial cells, which was dependent on M. catarrhalis membranous lipoolygosaccharide (LOS), while the surface proteins UspA1 and UspA2 were not involved. Gene silencing of TLR2, but not TLR4, led to a reduced hBD-3 secretion after stimulation with M. catarrhalis or M. catarrhalis LOS. Inhibition of MAPKs ERK1/2 and JNK, but not p38, reduced hBD-3 secretion. HBD-3 expression was mediated through the recruitment of AP-1 to the hBD-3 gene promoter and was independent of NF-kappa B. Conclusion: The immune response of pulmonary epithelial cells towards M. catarrhalis involves secretion of hBD-3, which has a bactericidal effect against this pathogen. Binding of M. catarrhalis virulence factor LOS to TLR2 causes an ERK1/2- and JNK-dependent induction of AP-1-related transcription of the hBD-3 gene, resulting in the production and secretion of hBD-3. (C) 2015 Published by Elsevier Inc

Bacterial inhibition of phosphatidylcholine synthesis triggers apoptosis in the brain

Streptococcus pneumoniae is the most common cause of bacterial meningitis of high mortality and morbidity. Neurological sequelae include paralysis, mental retardation, and learning disorders. In humans, neurons of the hippocampus undergo apoptosis as a result of meningitis. Phosphatidylcholine (PtdCho) is an essential component of mammalian cell membranes and PtdCho deficiency, either due to chemicals or altered nutrition, leads to apoptosis, especially in hippocampal neurons. We show that apoptosis of a variety of brain cells after pneumococcal infection arises from inhibition of PtdCho biosynthesis, the first such activity described for a bacterium. Apoptosis inhibitors did not prevent the bacterial-dependent inhibition of PtdCho biosynthesis. Supplementation with exogenous lyso-phosphatidylcholine prevents cell death and treatment of mice with cytidine diphosphocholine attenuates hippocampal damage during meningitis, even after the onset of infection. We conclude that bacterial inhibition of PtdCho biosynthesis activates an apoptotic cascade that is a causative event in pathogenesis and amenable to therapeutic intervention

Bacterial Inhibition of Phosphatidylcholine Synthesis Triggers Apoptosis in the Brain

Streptococcus pneumoniae is the most common cause of bacterial meningitis of high mortality and morbidity. Neurological sequelae include paralysis, mental retardation, and learning disorders. In humans, neurons of the hippocampus undergo apoptosis as a result of meningitis. Phosphatidylcholine (PtdCho) is an essential component of mammalian cell membranes and PtdCho deficiency, either due to chemicals or altered nutrition, leads to apoptosis, especially in hippocampal neurons. We show that apoptosis of a variety of brain cells after pneumococcal infection arises from inhibition of PtdCho biosynthesis, the first such activity described for a bacterium. Apoptosis inhibitors did not prevent the bacterial-dependent inhibition of PtdCho biosynthesis. Supplementation with exogenous lyso-phosphatidylcholine prevents cell death and treatment of mice with cytidine diphosphocholine attenuates hippocampal damage during meningitis, even after the onset of infection. We conclude that bacterial inhibition of PtdCho biosynthesis activates an apoptotic cascade that is a causative event in pathogenesis and amenable to therapeutic intervention

Viral Load Dynamics in SARS-CoV-2 Omicron Breakthrough Infections

To determine viral dynamics in Omicron breakthrough infections, we measured severe acute respiratory syndrome coronavirus 2 RNA in 206 double-vaccinated or boostered individuals. During the first 3 days following the onset of symptoms, viral loads were significantly higher (cycle threshold [Ct], 21.76) in vaccinated compared to boostered (Ct, 23.14) individuals (P = .029). However, by performing a longitudinal analysis on 32 individuals over 14 days, no difference in the viral load trajectory was observed between double-vaccinated and boostered patients. Our results indicate that booster immunization results in a reduction in detectable viral loads without significantly changing viral load dynamics over time. This study provides longitudinal data upon Omicron breakthrough infections in double-vaccinated and boostered individuals. While peak viral loads were reduced in boostered individuals, no difference was observed for the duration of SARS-CoV-2 detection between both groups

High admission prevalence of fluoroquinolone resistance in third-generation cephalosporin-resistant Enterobacteriaceae in German university hospitals

Objectives: 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. Methods: 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 subdivided into CA and HA. Multivariable analysis identified factors associated with in vitro non-susceptibility to ciprofloxacin. Results: 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). Conclusions: 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