Isavuconazole (ISA) is a triazole antifungal agent recommended for treatment of invasive aspergillosis or mucormycosis. The objective of this study was to evaluate ISA levels in a real world setting in a mixed patient cohort including patients with non-malignant diseases and extracorporeal treatments, and to correlate findings with efficacy and safety outcomes. We investigated 33 ISA treatment courses in 32 adult patients with hematological and other underlying diseases and assessed the clinical response, side effects and ISA trough plasma concentrations. ISA treatment led to complete and partial response in 87% of patients and was well tolerated. The median ISA plasma concentration was 3.05 µg/mL (range 1.38–9.1, IQR 1.93–4.35) in patients without renal replacement therapy (RRT) or extracorporeal membrane oxygenation (ECMO) and significantly lower in patients with RRT including cases with additional ECMO or Cytosorb^® adsorber therapy (0.88 µg/mL, range 0.57–2.44, IQR 0.71–1.21). After exclusion of values obtained from four patients with ECMO or Cytosorb^® adsorber the median concentration was 0.91 µg/mL (range 0.75–2.44, IQR 0.90–1.36) in the RRT group. In addition to previous recommendations we propose to monitor ISA trough plasma concentrations in certain circumstances including RRT, other extracorporeal treatments and obesity.

Anaerobic bacteria play an important role in human infections. Bacteroides spp. are some of the 15 most common pathogens causing nosocomial infections. We present antimicrobial susceptibility testing (AST) results of 114 Gram-positive anaerobic isolates and 110 Bacteroides-fragilis-group-isolates (BFGI). Resistance profiles were determined by MIC gradient testing. Furthermore, we performed disk diffusion testing of BFGI and compared the results of the two methods. Within Gram-positive anaerobes, the highest resistance rates were found for clindamycin and moxifloxacin (21.9% and 16.7%, respectively), and resistance for beta-lactams and metronidazole was low (<1%). For BFGI, the highest resistance rates were also detected for clindamycin and moxifloxacin (50.9% and 36.4%, respectively). Resistance rates for piperacillin/tazobactam and amoxicillin/clavulanic acid were 10% and 7.3%, respectively. Two B. fragilis isolates were classified as multi-drug-resistant (MDR), with resistance against all tested beta-lactam antibiotics. The comparative study of 109 BFGI resulted in 130 discrepancies in 763 readings (17%) with a high number of Very Major Errors (VME) and Major Errors (ME). In summary, resistance rates, with the exception of clindamycin and moxifloxacin, are still low, but we are facing increasing resistance rates for BFGI. Surveillance studies on a regular basis are still recommended.

Healthcare-associated infections (HCAI) are a common cause for residents’ mortality and morbidity associated with a significant socio-economic burden. Data on HCAIs in Austrian long-term care facilities are scare. Therefore, we evaluated the incidence rate of HCAIs per 1000 resident days in four LTC facilities in Graz, Austria, characterized the spectrum of HCAIs and the use of antimicrobial substances. We conducted a prospective surveillance study from 1 January to 31 December 2018 in four LTCFs of the Geriatric Health Centre of the City of Graz (total of 388 beds). Nursing staff collected data on HCAIs once a week using an electronic reporting system. During the 12-month surveillance period, 252 infections of 165 residents were recorded. The overall incidence rate of HCAIs was 2.1 per 1000 resident days. Urinary tract infections were the most commonly recorded HCAIs (49%, 124/252, 1.03 per 1000 resident days), followed by skin and soft tissue infections and respiratory tract infections. Beta-lactams (ATC class J01C) were prescribed most frequently (63/212), followed by fluoroquinolones (J01M; 54/212). In conclusion, the overall incidence rate for HCAIs was relatively low at 2.1 per 1000 resident days. Our real-life data can serve as a basis for future antimicrobial stewardship and infection prevention interventions.

Molecular techniques including the sequencing of fungal-specific DNA targets are increasingly used in the diagnosis of suspected invasive fungal infections. In contrast to established biomarkers like galactomannan or 1-3-β-d-glucan, the clinical impact of these methods remains unknown. We retrospectively investigated the impact of ITS1-sequencing on antifungal treatment strategies in 71 patients (81 samples) with suspected invasive fungal infections. ITS-sequencing either confirmed already ongoing antifungal therapy (19/71 patients, 27%), led to a change in antifungal therapy (11/71, 15%) or supported the decision to withhold antifungal treatment (34/71, 48%) (in seven of 71 patients, ITS-sequencing results were obtained postmortem). ITS-sequencing results led to a change in antifungal therapy in a relevant proportion of patients, while it confirmed therapeutic strategies in the majority. Therefore, ITS-sequencing was a useful adjunct to other fungal diagnostic measures in our cohort.

Interleukin (IL) 17A plays a decisive role in anti-Candida host defense. Previous data demonstrated significantly increased IL-17A values in candidemic patients. We evaluated levels and time courses of IL-17A, and other cytokines suggested to be involved in Candida-specific immunity (IL-6, IL-8, IL-10, IL-17F, IL-22, IL-23, interferon-γ, tumor necrosis factor-α, Pentraxin-related protein 3, transforming growth factor-β) in patients with invasive candidiasis (IC) compared to bacteremic patients (Staphylococcus aureus, Escherichia coli) and healthy controls (from previous 4 days up to day 14 relative to the index culture (−4; 14)). IL-17A levels were significantly elevated in all groups compared to healthy controls. In IC, the highest IL-17A values were measured around the date of index sampling (−1; 2), compared to significantly lower levels prior and after sampling the index culture. Candidemic patients showed significantly higher IL-17A values compared to IC other than candidemia at time interval (−1; 2) and (3; 7). No significant differences in IL-17A levels could be observed for IC compared to bacteremic patients. Candidemic patients had higher IL-8, IL-10, IL-22, IFN-γ, PTX3 and TNF-α values compared to non-candidemic. Based on the limited discriminating competence between candidemia and bacteremia, IL-17A has to be considered a biomarker for blood stream infection rather than invasive Candida infection.

Background: A variety of rapid molecular PCR tests has been developed and commercialised that interrogate the junction site between the staphylococcal core genome, and the mobile genetic element (SCC mec ) which harbours the gene responsible for methicillin-/beta-lactam-resistance. Aim: The purpose of the present study was to investigate why a clinical MRSA isolate yielded false negative test results with widely used, commercial orfX /SCC mec junction site PCR tests. Methods: A collection of isolates that belonged to the same epidemic strain as the index isolate were investigated with commercial MRSA assays and all isolates were sequenced in order to explain this observation. Results: It was found that isolates of the epidemic “European CC1-MRSA-IV” clone, which likely originated in South-Eastern Europe and subsequently spread to Western Europe, generally exhibit this behaviour. The failure of the assays was attributable to a characteristic large insertion in the orfX /SCC mec integration site presumably targeted by such tests. In contrast to MW2 (GenBank BA000033.2 , a CC1 “USA400” strain which also harbours SCC mec IVa), the European CC1 clone harbours an insertion of ca . 5,350 nucleotides adjacent to orfX . This sequence starts with a novel SCC terminal sequence alternate to dcs and encodes six different hypothetical proteins (E7MHX1, ydiL 2, C5QAP8, A8YYX4, npd- SCC, H4AYD7; nucleotide positions 280,690–286,024 of GenBank RBVO000005.1). An SCC mec element with the same insertion was previously found in a Staphylococcus epidermidis isolate (GenBank MH188467.1 ) suggesting transfer between staphylococcal species. Conclusion: In order to ensure the reliability of molecular MRSA tests, it is vital to monitor the emergence of new SCC mec junction sites, not only in Staphylococcus aureus but also in coagulase-negative staphylococci.