In vitro susceptibility to 19 agents other than ß-lactams among third-generation cephalosporin-resistant Enterobacteriaceae recovered on hospital admission.

Objectives: As part of the multicentre Antibiotic Therapy Optimisation Study, MIC values of 19 non-ß-lactam agents were determined for third-generation cephalosporin-resistant Escherichia coli , Klebsiella species and Enterobacter species (3GCREB) isolates collected in German hospitals. Methods: A total of 328 E. coli , 35 Klebsiella spp. (1 Klebsiella oxytoca and 34 Klebsiella pneumoniae ) and 16 Enterobacter spp. (1 Enterobacter aerogenes and 15 Enterobacter cloacae ) isolates were submitted to broth microdilution antimicrobial susceptibility testing with the MICRONAUT system. MICs of fluoroquinolones (levofloxacin and moxifloxacin), aminoglycosides (gentamicin, tobramycin, amikacin, streptomycin, neomycin and paromomycin), tetracyclines (tetracycline, minocycline and tigecycline), macrolides (erythromycin, clarithromycin and azithromycin) and miscellaneous agents [trimethoprim/sulfamethoxazole, chloramphenicol, nitrofurantoin, colistin and fosfomycin intravenous (iv)] were determined and reviewed against 2016 EUCAST breakpoints. Results: The MIC of levofloxacin was >2 mg/L for 128 of 328 E. coli and 8 of 35 Klebsiella spp., but only 1 of 16 Enterobacter spp. Rates of resistance to trimethoprim/sulfamethoxazole were high (>70%), except for Enterobacter spp. Rates of resistance to colistin and fosfomycin iv were still low. About 20% of the tested isolates were resistant to chloramphenicol. Only 1 (of 328) E. coli isolate had an MIC of amikacin >16 mg/L and only 33 of 328 E. coli and 1 of 35 Klebsiella spp. had an MIC of tobramycin >4 mg/L, whereas average gentamicin MICs were in general more elevated. A tigecycline MIC >2 mg/L was only found for 1 of 16 Enterobacter spp., but in none of the E. coli or Klebsiella spp. isolates. Conclusions: Our study gives insight into previously unreported non-ß-lactam MIC distributions of 3GCREB isolates.

[Osteosynthesis-associated infections : Epidemiology, definition and diagnosis]. / Osteosyntheseassoziierte Infektionen : Epidemiologie, Definition und Diagnostik.

Osteosynthesis-associated infections occur in 1-5% after closed and in up to 30% after open fractures. There are three different descriptions of implant-associated infections after fracture fixation, which are crucial for the selection of the adequate treatment strategy; temporal appearance from the index surgery (early versus late), pathogenesis of the infection (exogenous, hematogenous and contiguous from an adjacent focus), duration of infection symptoms (acute versus chronic). Diagnosis of osteosynthesis-associated infection is challenging, as chronic low-grade infections often present only with unspecific and subtle clinical symptoms. History, clinical evaluation, imaging, histopathlogical and microbiological examination build the cornerstones of diagnostics in implant-associated infections. A new onset of rest pain, early loosening of the prosthesis or mechanically unexplained, nonunion should raise suspicion for infection and prompt further evaluation. Percutaneous sinus tracts, purulent wound secretion and skin erosions with visibility of the implant confirm the implant-associated infection. Elevated C­reactive protein value in blood is a supportive argument for infection, but is neither sensitive nor specific for infection. Imaging plays a key role to detect nonunions, infectious callus, sequester, peri-implant osteolysis and extraosseous and intramedullary involvement. Through microbiological and histopathological examination of intraoperative tissue samples, as well as sonication of explanted implants the causative pathogen is identified in most cases.

Colonization with third-generation cephalosporin-resistant Enterobacteriaceae on hospital admission: prevalence and risk factors.

OBJECTIVES: The objectives of this study were to prospectively assess the rectal carriage rate of third-generation cephalosporin-resistant Enterobacteriaceae (3GCREB) in non-ICU patients on hospital admission and to investigate resistance mechanisms and risk factors for carriage. METHODS: Adult patients were screened for 3GCREB carriage at six German tertiary care hospitals in 2014 using rectal swabs or stool samples. 3GCREB isolates were characterized by phenotypic and molecular methods. Each patient answered a questionnaire about potential risk factors for colonization with MDR organisms (MDROs). Univariable and multivariable risk factor analyses were performed to identify factors associated with 3GCREB carriage. RESULTS: Of 4376 patients, 416 (9.5%) were 3GCREB carriers. Escherichia coli was the predominant species (79.1%). ESBLs of the CTX-M-1 group (67.3%) and the CTX-M-9 group (16.8%) were the most frequent ß-lactamases. Five patients (0.11%) were colonized with carbapenemase-producing Enterobacteriaceae. The following risk factors were significantly associated with 3GCREB colonization in the multivariable analysis (P < 0.05): centre; previous MDRO colonization (OR = 2.12); antibiotic use within the previous 6 months (OR = 2.09); travel outside Europe (OR = 2.24); stay in a long-term care facility (OR = 1.33); and treatment of gastroesophageal reflux disease (GERD) (OR = 1.22). CONCLUSIONS: To our knowledge, this is the largest admission prevalence study of 3GCREB in Europe. The observed prevalence of 9.5% 3GCREB carriage was higher than previously reported and differed significantly among centres. In addition to previously identified risk factors, the treatment of GERD proved to be an independent risk factor for 3GCREB colonization.

[Periprosthetic infections of the hip joint : Clinical approach]. / Periprothetischer Infekt des Hüftgelenks : Klinisches Vorgehen.

BACKGROUND: Increasing rates of periprosthetic joint infections (PJI) will present orthopedic surgeons and the health care system with challenges in the next few years. New concepts in diagnostic and surgical pathways allow specialized centers to offer differentiated therapy of PJI. AIM: This article presents an overview of recent treatment concepts for PJI of the hip emphasizing diagnosis and the clinical approach. METHOD: A selective literature search was performed focusing on evidence-based concepts including diagnostics, surgical treatment, and biofilm active antibiotics. RESULTS: PJI of the hip are classified as mature biofilm or immature biofilm infections. The most important step in the diagnostic procedure is to identify the pathogen and its antimicrobial susceptibility. Preoperative joint aspiration and leukocyte count, differentiation, and microbiological culture should be standard. Arthroscopic biopsy may be necessary to identify the pathogen. Depending on the biofilm maturity and the antimicrobial susceptibility, implant retention or two-stage revisions should be performed. Combination of surgical therapy and biofilm-active antibiotics are of utmost importance for successful treatment. DISCUSSION: PJI represents a significant challenge for the orthopedic surgeon. Evidence-based and standardized clinical pathways are necessary for accurate and rapid diagnosis as well as patient-specific treatment concepts.

The Bcr-Abl mutations T315I and Y253H do not confer a growth advantage in the absence of imatinib.

Mutations in the Bcr-Abl kinase domain are a frequent cause of imatinib resistance in patients with advanced CML or Ph+ ALL. The impact of these mutations on the overall oncogenic potential of Bcr-Abl and on the clinical course of the disease in the absence of imatinib is presently unclear. In this study, we analyzed the effects of the Bcr-Abl P-loop mutation Y253H and the highly imatinib resistant T315I mutation on kinase activity in vitro and transforming efficiency of Bcr-Abl in vitro and in vivo. Immunoprecipitated Bcr-AblY253H and Bcr-AblT315I proteins displayed similar kinase activities and substrate phosphorylation patterns as Bcr-Abl wildtype. We directly compared the proliferative capacity of mutant to wildtype Bcr-Abl in primary BM cells in vitro and in a murine transplantation model of CML by using a competitive repopulation assay. The results implicate that in the absence of imatinib, there is no growth advantage for cells carrying Bcr-AblT315I or Bcr-AblY253H compared to Bcr-Ablwt, whereas imatinib treatment clearly selects for leukemic cells expressing mutant Bcr-Abl both in vitro and in vivo. Thus, the analysed Bcr-Abl mutants confer imatinib resistance, but do not induce a growth advantage in the absence of imatinib.

The use of proton pump inhibitors and the spectrum and number of biliary pathogens in patients with acute cholangitis.

BACKGROUND: Knowledge of the bacterial spectrum for acute cholangitis is essential for adequate empiric antibiotic treatment. AIM: To analyse the relation of proton pump inhibitors (PPI) with biliary pathogens in patients with acute cholangitis. METHODS: This retrospective study identified 278 patients with 318 acute cholangitis episodes using an endoscopic database. The relationship between PPI and microbiological outcomes was assessed by logistic and poisson regression analysis for binary and count data. RESULTS: In total, 882 pathogens were isolated, of which, 120 cholangitis episodes occurred with PPI; 198 cholangitis episodes without PPI. Multivariate poisson regression analysis showed that PPI use resulted in a 23% increase in the number of biliary pathogens [3.14 vs. 2.55 (Δ = 0.59), P < 0.01], whereas stent therapy, previous interventional procedures (endoscopic retrograde cholangiography/percutaneous transhepatic cholangiography), genesis, age and sex showed no significant association with the number of biliary pathogens. Significantly, more cholangitis episodes with more than one pathogen isolated occurred during PPI treatment [103/120 (86%) vs. 151/198 (76%), P = 0.04]. Analysis of intrinsic anti-microbial resistance patterns was performed: Anti-microbial combination therapies were significantly more required to cover all isolated pathogens in cholangitis episodes with PPI than in cholangitis episodes without PPI (44/120 vs. 46/198, P = 0.01). Additionally, PPI use was associated with a significantly higher incidence of oropharyngeal flora in the biliary tract (53/120 vs. 61/198, P = 0.02). CONCLUSIONS: Proton pump inhibitors seem to influence biliary pathogens by increasing the number and broadening the spectrum of biliary pathogens. However, the findings of this hypothesis-generating study need to be tested by confirmatory studies.