Characterization of antimicrobial use and co-infections among hospitalized patients with COVID-19: a prospective observational cohort study.

PURPOSE: To investigate antimicrobial use and primary and nosocomial infections in hospitalized COVID-19 patients to provide data for guidance of antimicrobial therapy. METHODS: Prospective observational cohort study conducted at Charité-Universitätsmedizin Berlin, including patients hospitalized with SARS-CoV-2-infection between March and November 2020. RESULTS: 309 patients were included, 231 directly admitted and 78 transferred from other centres. Antimicrobial therapy was initiated in 62/231 (26.8%) of directly admitted and in 44/78 (56.4%) of transferred patients. The rate of microbiologically confirmed primary co-infections was 4.8% (11/231). Although elevated in most COVID-19 patients, C-reactive protein and procalcitonin levels were higher in patients with primary co-infections than in those without (median CRP 110 mg/l, IQR 51-222 vs. 36, IQR 11-101, respectively; p < 0.0001). Nosocomial bloodstream and respiratory infections occurred in 47/309 (15.2%) and 91/309 (29.4%) of patients, respectively, and were associated with need for invasive mechanical ventilation (OR 45.6 95%CI 13.7-151.8 and 104.6 95%CI 41.5-263.5, respectively), extracorporeal membrane oxygenation (OR 14.3 95%CI 6.5-31.5 and 16.5 95%CI 6.5-41.6, respectively), and haemodialysis (OR 31.4 95%CI 13.9-71.2 and OR 22.3 95%CI 11.2-44.2, respectively). The event of any nosocomial infection was significantly associated with in-hospital death (33/99 (33.3%) with nosocomial infection vs. 23/210 (10.9%) without, OR 4.1 95%CI 2.2-7.3). CONCLUSIONS: Primary co-infections are rare, yet antimicrobial use was frequent, mostly based on clinical worsening and elevated inflammation markers without clear evidence for co-infection. More reliable diagnostic prospects may help to reduce overtreatment. Rates of nosocomial infections are substantial in severely ill patients on organ support and associated with worse patient outcome.

Incidence of healthcare-associated Clostridioides difficile infections and association with ward-level antibiotic consumption in a German university hospital: an ecological study.

OBJECTIVES: Clostridioides difficile infection (CDI) is one of the most important healthcare-associated infections. We aimed to describe the incidence density of healthcare-associated CDI (HA-CDI) in Germany's largest hospital and to identify associations with ward-level antimicrobial consumption. METHODS: We used surveillance data on CDI and antimicrobial consumption from 2014 to 2017 and analysed a potential association by means of multivariable regression analysis. RESULTS: We included 77 wards with 404998 admitted patients and 1850862 patient-days. Six hundred and seventy-one HA-CDI cases were identified, resulting in a pooled mean incidence density of 0.36/1000 patient-days (IQR = 0.34-0.39). HA-CDI incidence density on ICU and haematological-oncological wards was about three times higher than on surgical wards [incidence rate ratio (IRR) = 3.00 (95% CI = 1.96-4.60) and IRR = 2.78 (95% CI = 1.88-4.11), respectively]. Ward-level consumption of third-generation cephalosporins was the sole antimicrobial risk factor for HA-CDI. With each DDD/100 patient-days administered, a ward's HA-CDI incidence density increased by 2% [IRR = 1.02 (95% CI = 1.01-1.04)]. Other risk factors were contemporaneous community-associated CDI cases [IRR = 1.32 (95% CI = 1.07-1.63)] and CDI cases in the previous month [IRR = 1.27 (95% CI = 1.07-1.51)]. Furthermore, we found a significant decrease in HA-CDI in 2017 compared with 2014 [IRR = 0.68 (95% CI = 0.54-0.86)]. CONCLUSIONS: We confirmed that ward-level antimicrobial use influences HA-CDI and specifically identified third-generation cephalosporin consumption as a risk factor.

Antibiotic prescribing behavior among general practitioners - a questionnaire-based study in Germany.

BACKGROUND: This study investigates the barriers and facilitators of the use of antibiotics in acute respiratory tract infections by general practitioners (GPs) in Germany. METHODS: A multidisciplinary team designed and pre-tested a written questionnaire addressing the topics awareness of antimicrobial resistance (7 items), use of antibiotics (9 items), guidelines/sources of information (9 items) and sociodemographic factors (7 items), using a five-point-Likert-scale ("never" to "very often"). The questionnaire was mailed by postally to 987 GPs with registered practices in eastern Germany in May 2015. RESULTS: 34% (340/987) of the GPs responded to this survey. Most of the participants assumed a multifactorial origin for the rise of multidrug resistant organisms. In addition, 70.2% (239/340) believed that their own prescribing behavior influenced the drug-resistance situation in their area. GPs with longer work experience (> 25 years) assumed less individual influence on drug resistance than their colleagues with less than 7 years experience as practicing physicians (Odds Ratio [OR] 0.32, 95% Confidence Interval [CI] 0.17-0.62; P < 0.001). 99.1% (337/340) of participants were familiar with the "delayed prescription" strategy to reduce antibiotic prescriptions. However, only 29.4% (74/340) answered that they apply it "often" or "very often". GPs working in rural areas were less likely than those working in urban areas to apply delayed prescription. CONCLUSION: The knowledge on factors causing antimicrobial resistance in bacteria is good among GPs in eastern Germany. However measures to improve rational prescription are not widely implemented yet. Further efforts have to be made in order to improve rational prescription of antibiotic among GPs. Nevertheless, there is a strong awareness of antimicrobial resistance among the participating GPs.

Chlorhexidine and octenidine susceptibility of bacterial isolates from clinical samples in a three-armed cluster randomised decolonisation trial.

BACKGROUND: Routine use of chlorhexidine or octenidine for antiseptic bathing may have unintended consequences. Our analysis aimed to assess the phenotypic susceptibility of bacterial isolates from clinical samples to chlorhexidine and octenidine collected from intensive care units (ICU) that routinely used 2% chlorhexidine-impregnated wash cloths or 0.08% octenidine wash mitts (intervention) or water and soap (control) for daily patient care. METHODS: This study was conducted within the context of a three armed cluster-randomised controlled decolonisation trial (Registration number DRKS00010475, registration date August 18, 2016). Bacterial isolates were collected prior to and at the end of a 12-month-intervention period from patients with ≥ 3 days length of stay at an ICU assigned to one of two intervention groups or the control group. Phenotypic susceptibility to chlorhexidine and octenidine was assessed by an accredited contract research laboratory determining minimal inhibitory concentrations (MIC) as percentage of extraction solutions used. MIC were reported as estimated concentrations in µg/ml derived from the chlorhexidine and octenidine extraction solutions. Statistical analyses including generalized estimating equation models were applied. RESULTS: In total, 790 ICU-attributable bacterial isolates from clinical samples (e.g. blood, urine, tracheal aspirate) were eligible for all analyses. Pathogens included were Staphylococcus aureus (n = 155), coagulase-negative staphylococci (CoNS, n = 122), Escherichia coli (n = 227), Klebsiella spp. (n = 150) and Pseudomonas aeruginosa (n = 136). For all species, chlorhexidine and octenidine MIC did not increase from baseline to intervention period in the antiseptic bathing groups. For proportions of bacterial isolates with elevated chlorhexidine / octenidine MIC (≥ species-specific chlorhexidine / octenidine MIC50), adjusted incidence rate ratios (aIRR) showed no differences between the intervention groups and the control group (intervention period). CONCLUSION: We found no evidence for reduced phenotypic susceptibilities of bacterial isolates from clinical samples to chlorhexidine or octenidine in ICUs 12 months after implementation of routine antiseptic bathing with the respective substances.

Phorbol ester enhances KAI1 transcription by recruiting Tip60/Pontin complexes.

Down-regulation of the KAI1 (CD82) metastasis suppressor is common in advanced human cancer, but underlying mechanism(s) regulating KAI1 expression are only now being elucidated. Recent data provide evidence that low levels of KAI1 mRNA in LNCaP cells are caused by binding of beta-catenin/Reptin complexes to a specific motif in the proximal promoter, which prevents binding of Tip60/Pontin activator complexes to the same motif, thus inhibiting transcription. Here, we explored a pathway by which phorbol 12-myristate 13-acetate (PMA) up-regulates KAI1 transcription in LNCaP prostate cancer cells. Pretreatment with specific inhibitors showed that induction of KAI1 by PMA uses classic isoforms of protein kinase C (cPKC), is independent of Ras and Raf, and requires activation of MEK1/2 and ERK1/2, but does not involve p38MAPK. Induction of KAI1 transcription by PMA was associated with enhanced overall acetylation of histones H3 and H4, but only acetylation of H3 was blocked by a PKC inhibitor. Chromatin immunoprecipitation showed that PMA induces recruitment of Tip60/Pontin activator complexes to NFkappaB-p50 motifs in the proximal promoter, and this was blocked by a PKC inhibitor. These changes were not associated with differences in overall levels of Tip60, Pontin, beta-catenin, or Reptin protein expression but with PMA-induced nuclear translocation of Tip60.