Sarah Victoria Walker

Background: Intravenous-to-oral switch (IVOS) is considered safe in selected patients with bloodstream infection (BSI) and provides operational advantages. Still, it is underused in many clinical settings. We evaluated IVOS patterns, associated factors, and clinical outcomes in patients with BSI. Methods: Secondary data were analyzed from 2 prospective, multicenter cohort studies recruiting patients with BSI. IVOS was assessed on day 3 and 7 after positive blood culture. Eligibility for IVOS was based on infectious focus, clinical safe-switch criteria, and antimicrobial susceptibility. Risk factors for non-IVOS were studied using multivariable logistic regression. Results: Among 3824 patients, 2770 were included in the secondary analysis, and 742 (19.4%) were eligible and evaluable for IVOS. By day 7, 240 patients (32.3%) underwent IVOS. Switch occurred on the day of discharge in 107 patients (44.6%), and 1 day before discharge in 46 (19.2%). The most commonly used oral agents were ciprofloxacin (75 patients [31.3%]), sultamicillin (56 [23.3%]), and cefuroxime axetil (27 [11.3%]). Barriers to IVOS on multivariable analysis included diabetes (odds ratio, 0.57 [95% confidence interval, .38–.88]; P = .01), chronic kidney disease (0.64 [.41–.99]; P = .048), Pitt bacteremia score ≥2 on day 3 (0.43 [.19–.97]; P = .04), and septic shock before day 7 (0.31 [.11–.87]; P = .03), while urogenital focus (2.22 [1.50–3.28]; P < .001) and 2 study centers were positively associated with IVOS. IVOS was associated with shorter length of stay (7 vs 12 days; P < .001) and a lower 28-day mortality rate. Conclusions: In clinically stable patients with BSI, IVOS was infrequently implemented. Barriers to IVOS should be addressed as part of antimicrobial stewardship programs.

Purpose: To analyze the longitudinal epidemiology and antimicrobial resistance (AMR) patterns of Gram-negative bloodstream infections (BSI) in Germany. Methods: Post-hoc analysis of prospectively documented BSI due to Escherichia coli, Klebsiella spp., Enterobacter spp., Pseudomonas aeruginosa and Acinetobacter baumannii from six university hospitals between 2016 and 2020. In a subanalysis 1228 episodes of BSI (E. coli N = 914, Klebsiella spp. N = 314) were analyzed for clinical endpoints and risk factors. Results: E. coli was the most prevalent cause of BSI, with 5412 cases, followed by Klebsiella spp. (2148 cases), P. aeruginosa (789 cases), Enterobacter spp. (696 cases), and A. baumannii (31 cases). BSI incidence rates were particularly high in haematology/oncology, with E. coli BSI reaching 13.9 per 1000 admissions. Most (58%) of the BSI episodes were community-acquired. A notable finding was the moderate increase of third-generation cephalosporin resistant Enterobacterales (3GCREB) for E. coli from 13.9% in 2016 to 14.4% in 2020 and a decrease for Klebsiella spp. from 16.5% in 2016 to 11.1% in 2020 corresponding to extended-spectrum betalactamase (ESBL) phenotype. In our analysis, the 3GCREB phenotype was not associated with a higher risk of death or discharge with sequelae for E. coli and Klebsiella spp. Conclusion: Our study provides longitudinal data on Gram-negative BSI in Germany on a clinical basis for the first time. These data underscores the critical need for ongoing surveillance and more pathogen-related clinical data.

To assess incidence rates of surgical site infections (SSI) by MRSA and to determine related factors and clinical outcome compared to MSSA, including country-specific, institutional and patient determinants. We performed a subgroup analysis of the Europe-wide SALT (NCT03353532) study population with MRSA SSI from 14 centres in France, Germany, Italy, Spain and the UK. An overall MRSA SSI incidence of 0.06% (n = 104) was found in 178 903 patients undergoing invasive surgery in 2016. Frequently observed comorbidities were chronic cardiovascular disease, diabetes and solid tumours. Compared to the overall MRSA SSI incidence, incidence rates were significantly higher in Spain (58 of 67 934 cases) and lower in Germany (16 of 46 443 cases; both P < 0.05). Centres with antibiotic stewardship (ABS) and infectious disease (ID) consultation programmes (n = 3/14) had lower MRSA rates (17 of 43 556 cases versus 61 of 83 048 cases, P < 0.05). In bivariate analyses, MRSA SSI patients were significantly older, had higher BMI and more comorbidities compared to MSSA (P < 0.05 each). Surgery performed between 6:00 and 12:00 pm led to higher MRSA proportions among S. aureus SSI (17 of 104 cases versus 62 of 640 cases, P < 0.05). This study shows low overall and country-specific incidence rates of MRSA SSI in Europe. We could show significant differences between countries as well as between centres with established ABS and ID consultation programmes were observed. The number of those programmes seems too small against this background.

For many, coffee is the elixir of life. But is it also a cradle of life?Sarah Victoria Walker and colleaguespeer into the depths of the hospital coffee machine

Purpose: Bone and joint infections are an important and increasing problem. Whether intraoperatively detected bacteria should be considered relevant or not is often difficult to assess. This retrospective cohort study analyzes the relevance of C. acnes cultured from deep intraoperative specimens. Methods: All deep tissue samples collected intraoperatively between 2015 and 2020 from a quartiary care provider were evaluated for detection of C. acnes and its therapeutical consequences. Infection rates were determined according to a standardized definition and protocol and analyzed in dependence of patient’s demographic data (age and gender), operative parameters (type of surgery, body region/location of surgery, and impression of the surgeon), and initiated therapy. Results: In 270 cases of more than 8500 samples, C. acnes was detected. In 30%, the detection was considered an infection. The number of samples taken and tested positive for C. acnes correlated significantly with its classification as a cause of infection. If more than one sample of the patient was positive, the detection was significantly more likely to be treated as infection (p < 0.001). In 76% of cases, a consultation to the infectious diseases (ID) department took place regarding the classification of the pathogen detection and the therapy to be carried out. Almost all of the tested isolates demonstrated the wild-type susceptibility for penicillin and clindamycin. Conclusion: Intraoperative detection of skin-colonizing bacteria such as C. acnes is not always synonymous with infection. In particular, if other examination results contradict an infection (pathological sample without evidence of an infectious event, detection of malignant cells, etc.), the situation must be considered in a very differentiated manner. Interdisciplinary boards, for example, are suitable for this purpose. Care should be taken to obtain a sufficiently large number of tissue samples for microbiological examination to be able to better classify the result.

To analyse the influence of antibiotic consumption on healthcare-associated healthcare onset (HAHO) Clostridioides difficile infection (CDI) in a German university hospital setting. Monthly ward-level antibiotic consumption measured in DDD/100 patient days (pd) and CDI surveillance data from five university hospitals in the period 2017 through 2019 were analysed. Uni- and multivariable analyses were performed with generalized estimating equation models. A total of 225 wards with 7347 surveillance months and 4 036 602 pd participated. With 1184 HAHO-CDI cases, there was a median incidence density of 0.17/1000 pd (IQR 0.03–0.43) across all specialties, with substantial differences among specialties. Haematology-oncology wards showed the highest median incidence density (0.67/1000 pd, IQR 0.44–1.01), followed by medical ICUs (0.45/1000 pd, IQR 0.27–0.73) and medical general wards (0.32/1000 pd, IQR 0.18–0.53). Multivariable analysis revealed carbapenem (mostly meropenem) consumption to be the only antibiotic class associated with increased HAHO-CDI incidence density. Each carbapenem DDD/100 pd administered increased the HAHO-CDI incidence density by 1.3% [incidence rate ratio (IRR) 1.013; 95% CI 1.006–1.019]. Specialty-specific analyses showed this influence only to be valid for haematological-oncological wards. Overall, factors like ward specialty (e.g. haematology-oncology ward IRR 2.961, 95% CI 2.203–3.980) or other CDI cases on ward had a stronger influence on HAHO-CDI incidence density (e.g. community-associated CDI or unknown association case in same month IRR 1.476, 95% CI 1.242–1.755) than antibiotic consumption. In the German university hospital setting, monthly ward-level carbapenem consumption seems to increase the HAHO-CDI incidence density predominantly on haematological-oncological wards. Furthermore, other patient-specific factors seem to be equally important to control HAHO-CDI.

Five commercially available selective agar were evaluated regarding sensitivity and specificity to detect vancomycin-resistant Enterococcus (E.) faecium. Altogether 187 E. faecium strains were included, comprising 119 van-carrying strains (phenotypically vancomycin-resistant n = 105; phenotypically vancomycin-susceptible VVE-B n = 14) and 68 vancomycin-susceptible isolates. Limit of detection was calculated for each selective agar for pure cultures, stool suspensions and artificial rectal swabs. After 24-h incubation sensitivity ranged between 91.6% and 95.0%. It increased in 2 out of 5 agar after 48-h incubation. Specificity ranged between 94.1% and 100% and was highest after 24 h in 4 out of the 5 agar. Sensitivity of van-carrying phenotypically vancomycin-resistant strains was higher after 24 h (97.1–100%) and 48 h (99.1–100%) when compared to van-carrying strains that tested vancomycin-susceptible (50.0–57.1% after both incubation periods). Overall, chromID VRE, CHROMagar VRE and Brilliance VRE demonstrated the highest detection rates after 24 h. Detection rates of Chromatic VRE and VRESelect improved after 48 h. Adjustment of incubation time depending on the applied media may be advised. As detection of VVE-B was impeded with all selective agar, screening for vancomycin-resistant enterococci relying solely on selective media would not be recommended for critical clinical samples, but rather in combination with molecular methods to improve detection of these strains. Furthermore, stool samples were demonstrated to be superior to rectal swabs and should be favoured, if possible, in screening strategies.

Species within the Enterobacter cloacae complex (ECC) include globally important nosocomial pathogens. A three-year study of ECC in Germany identified Enterobacter xiangfangensis as the most common species (65.5%) detected, a result replicated by examining a global pool of 3246 isolates. Antibiotic resistance profiling revealed widespread resistance and heteroresistance to the antibiotic colistin and detected the mobile colistin resistance (mcr)−9 gene in 19.2% of all isolates. We show that resistance and heteroresistance properties depend on the chromosomal arnBCADTEF gene cassette whose products catalyze transfer of L-Ara4N to lipid A. Using comparative genomics, mutational analysis, and quantitative lipid A profiling we demonstrate that intrinsic lipid A modification levels are genospecies-dependent and governed by allelic variations in phoPQ and mgrB, that encode a two-component sensor-activator system and specific inhibitor peptide. By generating phoPQ chimeras and combining them with mgrB alleles, we show that interactions at the pH-sensing interface of the sensory histidine kinase phoQ dictate arnBCADTEF expression levels. To minimize therapeutic failures, we developed an assay that accurately detects colistin resistance levels for any ECC isolate.

To analyse the epidemiology and population structure of third-generation cephalosporin-resistant (3GCR) and carbapenem-resistant (CR) Klebsiella pneumoniae complex isolates, patients were screened for rectal colonisation with 3GCR/CR K. pneumoniae complex on admission to six German university hospitals (2016–2019). Also collected were 3GCR/CR and susceptible K. pneumoniae isolates from patients with bloodstream infections (2016–2018). Whole-genome sequencing was performed followed by multilocus sequencing typing (MLST), core-genome MLST, and resistome and virulome analysis. The admission prevalence of 3GCR K. pneumoniae complex isolates during the 4-year study period was 0.8%, and 1.0 bloodstream infection per 1000 patient admissions was caused by K. pneumoniae complex (3GCR prevalence, 15.1%). A total of seven K. pneumoniae complex bloodstream isolates were CR (0.8%). The majority of colonising and bloodstream 3GCR isolates were identified as K. pneumoniae, 96.7% and 98.8%, respectively; the remainder were K. variicola and K. quasipneumoniae. cgMLST showed a polyclonal population of colonising and bloodstream isolates, which was also reflected by MLST and virulome analysis. CTX-M-15 was the most prevalent extended-spectrum beta-lactamase, and 29.7% of the colonising and 48.8% of the bloodstream isolates were high-risk clones. The present study provides an insight into the polyclonal 3GCR K. pneumoniae population in German hospitals.