Invasive Pulmonary Aspergillosis in Critically Ill Patients with Hantavirus Infection, Austria.

We investigated a cohort of 370 patients in Austria with hantavirus infections (7.8% ICU admission rate) and detected 2 cases (cumulative incidence 7%) of invasive pulmonary aspergillosis; 1 patient died. Hantavirus-associated pulmonary aspergillosis may complicate the course of critically ill patients who have hemorrhagic fever with renal syndrome.

Vaccination acceptance and its associated factors in patients on hemodialysis in Austria: A nationwide survey.

BACKGROUND: Vaccines are essential in disease prevention among patients on chronic hemodialysis (HD). However, during the coronavirus disease 2019 pandemic, there has been an increased rate of vaccination hesitancy. A better understanding of patients' opinions may help identify a more targeted approach to increase vaccination rates. MATERIALS AND METHODS: Questionnaires with 43 questions based on the recommendations of the Strategic Advisory Group of Experts (SAGE) on Immunization Working Group on Vaccine Hesitancy were administered to patients during routine HD sessions at different dialysis centers in Austria. RESULTS: In total, 347 patients participated in this study. Approximately 81% of the patients were aged > 54 years, and 65% were men. Further, 53% of patients were receiving HD from private units. In ~ 72% of patients, the dialysis physicians were the source of vaccination information. Meanwhile, the source of information in 28% of patients was the primary care physician (28%), and 18% of patients obtained vaccination details from the internet. The number of younger (aged < 55 years) patients who were more likely to use online content as the main source of information was significantly higher than that of older patients (32 vs. 15%, p = 0.001). Furthermore, the number of older patients who wanted to receive more information from the dialysis physician was significantly higher than that of younger patients (57 vs. 38%, p = 0.009). Only 65% of patients had a good understanding of the mechanisms of action of vaccines. The younger population (aged 18 - 54 years) had a higher number of individuals with a good understanding of vaccine mechanisms than the older population (78 vs. 62%, p = 0.016). Moreover, 86% of the whole population wanted to complete the recommended vaccinations. However, only 39% of respondents had sufficient information about the vaccination plan in Austrian. CONCLUSION: Numerous patients receiving HD wanted to obtain more information from their dialysis physicians. Increased awareness among providers and targeted communication might increase vaccination rates.

Poor Prognosis for Puumala Virus Infections Predicted by Lymphopenia and Dyspnea.

We investigated a prospective cohort of 23 patients who had Puumala virus infection in Austria to determine predictors of infection outcomes. We reviewed routinely available clinical and laboratory parameters collected when patients initially sought care. Low absolute lymphocyte count and dyspnea were parameters associated with a severe course of infection.

Human Tularemia Epididymo-Orchitis Caused by Francisella tularensis Subspecies holartica, Austria.

A previously healthy man in Austria had tularemia epididymo-orchitis develop, leading to unilateral orchiectomy. Francisella tularensis subspecies holartica was detected by 16S rRNA gene sequencing analysis of inflamed granulomatous testicular tissue. Clinicians should suspect F. tularensis as a rare etiologic microorganism in epididymo-orchitis patients with relevant risk factors.

Treatment options for multidrug-resistant Gram-negatives in urinary tract infections.

PURPOSE OF REVIEW: Infections due to multidrug-resistant (MDR) Gram-negative bacteria are challenging to treat because of limited treatment options and potential side effects of less frequently used anti-infectives. In the past few years, several new antimicrobial agents effective against MDR Gram-negatives have become available. This review focuses on the treatment options for complicated urinary tract infections (cUTIs) caused by MDR Gram-negatives. RECENT FINDINGS: The novel combinations, betalactam or carbapenem and betalactamase inhibitor, ceftazidime/avibactam and meropenem/vaborbactam, are effective for infections caused by KPC-carbapenemase-producing pathogens. Imipenem/relebactam, another carbapenem/betalactamase inhibitor combination, has been approved for the treatment of cUTI. However, data on the efficacy of imipenem/relebactam against carbapenem-resistant pathogens is still limited. Ceftolozane/tazobactam is mainly used for the treatment of MDR Pseudomonas aeruginosa infections. For the treatment of cUTI caused by extended-spectrum betalactamases producing Enterobacterales aminoglycosides or intravenous fosfomycin should be considered. SUMMARY: To ensure prudent use and to avoid the development of resistance to novel anti-infective substances, an interdisciplinary approach, including urologists, microbiologists, and infectious disease physicians, is strongly advised.

Implementation of rapid antimicrobial susceptibility testing combined with routine infectious disease bedside consultation in clinical practice (RAST-ID): a prospective single-centre study.

OBJECTIVES: Recently, EUCAST released guidelines for rapid antimicrobial susceptibility testing (RAST) directly from positive blood culture bottles. The aim of our prospective single-centre clinical study was to assess the proportion of readable results and errors compared with routine antimicrobial susceptibility testing and the clinical consequences drawn by infectious disease (ID) physicians from RAST results during same-day bedside consultation. METHODS: All positive blood cultures suitable for RAST from January to December 2019 were included and RAST results at 4 and 6 h compared with standard disc diffusion. The real-life impact of RAST on clinical decisions was assessed during same-day ID bedside consultation. RESULTS: The proportion of readable RAST results was significantly higher after 6 h of incubation compared with after 4 h (881/930 versus 642/847; P < 0.0001). Major and very major errors were rare (17/642 after 4 h and 12/881 after 6 h; P = 0.087). ID consultation was performed in 134 patients after the RAST result. Antimicrobial treatment was changed in 73 patients and 84 additional measures (i.e. imaging studies, surgery, additional resistance testing) were ordered in 62 patients. CONCLUSIONS: RAST according to EUCAST methods was easy to implement with a low number of major and very major errors after 6 h of incubation. ID physicians performing bedside consultations frequently used this information to change antimicrobial treatment and recommended additional measures.

T2Candida magnetic resonance in patients with invasive candidiasis: Strengths and limitations.

T2Candida enables detection of five Candida species in whole blood within approximately 5 hours. Routinely drawn EDTA blood samples were prospectively stored and tested with T2Candida in patients with invasive candidiasis identified by routine index blood or sterile site cultures. T2Candida was compared to diagnostic blood and sterile site cultures and also performed with samples obtained prior and after collection of index cultures. T2Candida was evaluated with 133 samples of 32 patients with candidemia and 22 patients with deep-seated invasive candidiasis. In the candidemic group 28/32 (87.5%) patients had at least one positive T2Candida result at any time point. A total of 17/25 (68%) candidemic patients had a positive T2Candida sample that was drawn concurrently to the index blood culture. In the per patient analysis 17/18 (94.4%) candidemic patients with matched T2Candida samples and peripheral blood cultures at any timepoint had a positive T2Candida test. T2Candida revealed discordant Candida species identification in two candidemic patients. Six of 22 (27.3%) deep-seated IC patients had a positive T2Candida result. Despite advanced time-to-results the clinical value of T2Candida in diagnosing candidemia seems to be limited by missing blood culture positive cases. Positivity rates of T2Candida increased when serial T2Candida samples were tested. In patients with suspected deep-seated invasive candidiasis T2Candida might act as a blood based adjunct to sterile site cultures.

An epidemic CC1-MRSA-IV clone yields false-negative test results in molecular MRSA identification assays: a note of caution, Austria, Germany, Ireland, 2020.

We investigated why a clinical meticillin-resistant Staphylococcus aureus (MRSA) isolate yielded false-negative results with some commercial PCR tests for MRSA detection. We found that an epidemic European CC1-MRSA-IV clone generally exhibits this behaviour. The failure of the assays was attributable to a large insertion in the orfX/SCCmec integration site. To ensure the reliability of molecular MRSA tests, it is vital to monitor emergence of new SCCmec types and junction sites.

Antifungal Prophylaxis with Posaconazole Delayed-Release Tablet and Oral Suspension in a Real-Life Setting: Plasma Levels, Efficacy, and Tolerability.

We continuously determined posaconazole plasma concentrations (PPCs) in 61 patients with hematological malignancies receiving posaconazole (PCZ) delayed-release tablets (DRT; 48 patients; median duration of intake, 92 days) and PCZ oral solution (OS; 13 patients; median duration of intake, 124 days). PCZ DRT and OS antifungal prophylaxis was efficient and well tolerated. Thirty-four of 48 patients (71%) receiving DRT always had PPCs of >0.7 mg/liter, while 14 of 48 patients (29%) had at least one PPC of ≤0.7 mg/liter. In patients receiving OS, 4 of 13 patients (31%) always had PPCs of >0.7 mg/liter, 6 of 13 patients (46%) had at least one PPC of ≤0.7 mg/liter, and 3 (23%) patients never reached a PPC of 0.7 mg/liter. In patients with at least one determined PPC, the mean proportion of all PPCs of >0.7 mg/liter was 91% for PCZ DRT, whereas it was 52% for PCZ OS (P = 0.001). In the per sample analysis, PPCs were significantly more likely to be >0.7 mg/liter in patients receiving DRT than in patients receiving OS (PPCs were >0.7 mg/liter in 91.4% [297/325] of patients receiving DRT versus 70.3% [85/121] of patients receiving OS; P < 0.001). Patients receiving PCZ DRT had higher proportions of PPCs of >0.7 mg/liter than patients receiving OS both in the per patient and in the per sample analyses. Two patients (3%) had side effects during PCZ prophylaxis, and one (2%) had fungal breakthrough infection. Therapeutic drug monitoring enables detection of extended periods of PPCs of ≤0.7 mg/liter (e.g., due to nonadherence or graft-versus-host disease), which may also be associated with the loss of protective intracellular PCZ concentrations, regardless of the PCZ formulation.

Invasive aspergillosis in patients with underlying liver cirrhosis: a prospective cohort study.

The aim of this study was to determine the prevalence of invasive aspergillosis (IA) in patients with liver cirrhosis and the performance of serum galactomannan (GM) screening. Patients with decompensated liver cirrhosis and patients with compensated liver cirrhosis presenting with fever and/or respiratory symptoms were prospectively enrolled. All patients were screened by serum GM twice weekly irrespective of clinical signs and symptoms. Positive serum GM triggered work-up consisting of chest computed tomography and in case of pathological findings bronchoscopy. 150 patients were included in the study. Two (1.3%) had probable, one (0.7%) had possible, and 147 (98%) had no evidence of IA. Both patients with probable IA had compensated liver cirrhosis. Sensitivity for serum GM screening for probable versus no IA was 0.5 (95% CI, 0.09-0.91), specificity 0.97 (95% CI: 0.92-0.99), negative predictive value 0.99 (95% CI, 0.96-0.99) and positive predictive value (PPV) 0.17 (95% CI, 0.01-0.64). PPV was 0.5 (95% CI, 0.03-0.98) in patients with clinical suspicion of IA. In conclusion, prevalence of IA in patients with liver cirrhosis seems to be low. Targeted GM testing in case of clinical suspicion of IA may be associated with markedly higher PPVs when compared to universal GM screening in patients with liver cirrhosis.

Primary resistance of Helicobacter pylori is still low in Southern Austria.

OBJECTIVES: We determined primary and secondary resistance rates of H. pylori in different regions of Austria and potential bacterial and host factors associated with resistance. METHODS: In a prospective multicentre study H. pylori was cultivated from biopsies and susceptibility testing was performed according to EUCAST. Resistance to clarithromycin and levofloxacin was determined by sequencing of the resistance-determining regions of 23S rRNA and gyrA genes. cagA, vacA and babA2 genotypes were determined. RESULTS: A total of 1266 patients were included. 178 isolates were cultured: 128 from patients without prior eradication therapy, 50 from patients after failed eradication. Primary resistance to clarithromycin, levofloxacin and metronidazole were 17.2%, 9.4% and 10.2%, respectively. Secondary resistance to clarithromycin, levofloxacin and metronidazole were 64%, 18% and 44%, respectively. Prior eradication was associated with a higher risk of clarithromycin as well as metronidazole resistance (OR=8.1; 95% CI 3.8-17.1 and OR 5.7; 95% CI 2.5-13, respectively). CONCLUSION: Primary resistance to both clarithromycin and levofloxacin was markedly lower in Southern Austria than recently reported.

Elevated levels of interleukin 17A and kynurenine in candidemic patients, compared with levels in noncandidemic patients in the intensive care unit and those in healthy controls.

BACKGROUND: The interplay between Candida species and pattern recognition receptors, interleukins, kynurenine, and T cells has been studied in murine and ex vivo human studies, but data are lacking from patients with invasive fungal infections. Interleukin 17A (IL-17A) is considered an important component in host defense against Candida infections and is modulated by Candida-induced impairment of tryptophan-kynurenine metabolism. METHODS: Dectin-1, Toll-like receptor 2, and Toll-like receptor 4 expression; regulatory T cell (Treg) percentages; and interleukin 6, interleukin 10, IL-17A, interleukin 22, interleukin 23, interferon γ, kynurenine, and tryptophan levels were determined in candidemic patients and compared to levels in noncandidemic patients who are in the intensive care unit (ICU) and receiving antibiotic therapy and those in healthy controls, both with and without Candida colonization. RESULTS: Candidemic patients had significantly higher IL-17A and kynurenine levels, compared with noncandidemic patients, including Candida-colonized ICU patients and healthy controls. Within candidemic patients, time-dependent elevation of IL-17A and kynurenine levels was detected. IL-17A areas under the curve for differentiation between patients with early candidemia and those without candidemia (ICU patients, including Candida-colonized patients, and healthy controls) were between 0.94 (95% confidence interval [CI], .89-.99) and 0.99 (95% CI, .99-1). CONCLUSIONS: Candidemic patients had significantly higher IL-17A and kynurenine levels, compared with noncandidemic patients. The statistically significant association between IL-17A and kynurenine levels and candidemia suggests their potential as biomarkers for anticipation of invasive candidiasis. CLINICAL TRIALS REGISTRATION: NCT00786903.

Contaminated handwashing sinks as the source of a clonal outbreak of KPC-2-producing Klebsiella oxytoca on a hematology ward.

We investigated sinks as possible sources of a prolonged Klebsiella pneumonia carbapenemase (KPC)-producing Klebsiella oxytoca outbreak. Seven carbapenem-resistant K. oxytoca isolates were identified in sink drains in 4 patient rooms and in the medication room. Investigations for resistance genes and genetic relatedness of patient and environmental isolates revealed that all the isolates harbored the blaKPC-2 and blaTEM-1 genes and were genetically indistinguishable. We describe here a clonal outbreak caused by KPC-2-producing K. oxytoca, and handwashing sinks were a possible reservoir.

Prevalence of emm types and antimicrobial susceptibility of Streptococcus dysgalactiae subsp. equisimilis in Austria.

OBJECTIVES: An increase of severe infections caused by Streptococcus dysgalactiae subsp. equisimilis (SDSE) similar to infections caused by Streptococcus pyogenes has been reported over the last years. Little is known about infections with SDSE in Austria. Therefore, we investigated a collection of 113 SDSE invasive and non-invasive isolates from different infection sites and type of infections as well as patients' characteristics. METHODS: The isolates were phenotypically identified and emm typed using the enlarged emm database from the Centers for Disease Control and Prevention. Additionally, 13 antimicrobial agents were tested using EUCAST guidelines and virulence genes were investigated. RESULTS: Severe SDSE infections were most common in elderly men with underlying diseases especially diabetes mellitus. With VitekMS identification of SDSE isolates was successful to the species level only. Emm typing revealed 24 different emm types, one new type and one new subtype. StG485, stG6, stC74a, stG643, and stG480 were the predominant types in this study, stC74a and stG652 in invasive infections and stG643, stC74a and stG485 in non-invasive infections. Resistance was observed to tetracycline (62%), macrolides (13%) with one M phenotype, and clindamycin (12%) presenting 6 constitutive MLS(B) phenotypes and 8 inducible MLS(B) phenotypes. Levofloxacin resistance was detected only in one isolate. All isolates tested for virulence genes were positive for scpA, ska, saga and slo. Superantigenic genes were negative except speG(dys) (positive 17/34; 50%). CONCLUSION: This paper presents the first report of SDSE infections in Austria. Severe SDSE infections were found mainly in elderly men with underlying diseases. SDSE isolates demonstrated substantial emm type diversity without association with infections site or invasiveness. Analysis of virulence genes showed no significant difference between invasive and non-invasive infections.

Detection of central venous catheter-related bloodstream infections in haematooncological patients.

BACKGROUND: Catheter-related bloodstream infections (CRBSIs) are currently detected in patients with clinically suspicion. The aim of our study was to evaluate whether CRBSIs could be anticipated and detected in a subclinical stage by peptide nucleic acid fluorescence in situ hybridization (PNA FISH) using universal hybridization probes or acridine orange leucocyte cytospin (AOLC) tests in haematooncological patients with central venous catheters (CVCs) in situ. MATERIALS AND METHODS: Peptide nucleic acid fluorescence in situ hybridization and AOLC tests using blood samples from one CVC lumen/port chamber in haematooncological patients were continuously performed. These results were compared to those obtained from routinely performed CRBSI diagnostic tests. RESULTS: One hundred and eighty-two patients with 342 catheter periods were investigated. Seventeen CRBSI cases were detected in 6466 CVC days by routine measures resulting in a CRBSI rate of 2.6/1000 catheter days. Two of 17 showed positive PNA FISH tests, and five positive AOLC test results before the diagnosis were established with routine measures. The screening revealed further seven patients with positive universal PNA FISH tests and 10 positive AOLC tests without symptoms indicative for infection and were therefore considered not to have CRBSI. CONCLUSIONS: Sampling of only one CVC lumen/port chamber screening for CRBSI in haematooncological patients seems not to be a useful tool for anticipative diagnosis of CRBSI. Reasons for false-negative results might include origin of CRBSIs from the other CVC lumina not sampled for screening, and false-positive results might origin from catheter colonization without subsequent spread of micro-organisms into the peripheral bloodstream.

The Toxin-Producing Pathobiont Klebsiella oxytoca Is Not Associated with Flares of Inflammatory Bowel Diseases.

BACKGROUND: Alterations in the intestinal microbiota are thought to be involved in the pathogenesis of inflammatory bowel diseases (IBD). Klebsiella oxytoca is an intestinal pathobiont that can produce a cytotoxin (tillivaline). AIM: We aimed to elucidate the pathogenetic relevance of toxin-producing K. oxytoca in patients with IBD flares and investigated the clonal relationship of K. oxytoca isolates from IBD patients using multilocus sequence typing (MLST). METHODS: Fecal samples of 235 adult IBD patients were collected from January 2008 to May 2009 and were tested for K. oxytoca, C. difficile toxin, and other pathogens by standard microbiological methods. Clinical data and disease activity scores were collected. K. oxytoca isolates were tested for toxin production using cell culture assays. A total of 45 K. oxytoca isolates from IBD patients, healthy, asymptomatic carriers and from patients with antibiotic-associated hemorrhagic colitis in part from our strain collection were tested for their clonal relationship using MLST. RESULTS: The prevalence of K. oxytoca in IBD overall was 4.7%. Eleven K. oxytoca isolates were detected. Two of 11 isolates were tested positive for toxin production. There was no significant difference in the distribution of K. oxytoca isolates between the groups (active vs. remission in UC and CD). MLST yielded 33 sequence types. K. oxytoca isolates from IBD did not cluster separately from isolates from asymptomatic carriers. CONCLUSIONS: Our data demonstrate that toxin (tilivalline)-producing K. oxytoca is not associated with IBD flares.

Novel tests for diagnosis of invasive aspergillosis in patients with underlying respiratory diseases.

RATIONALE: Invasive pulmonary aspergillosis has been increasingly reported in nonneutropenic patients, including those with underlying respiratory diseases. OBJECTIVES: We compared the diagnostic performances of galactomannan, 1,3-ß-D-glucan, and Aspergillus-specific lateral-flow device tests with that of conventional culture by using bronchoalveolar lavage fluid samples from patients with underlying respiratory diseases. METHODS: We analyzed 268 bronchoalveolar lavage samples from 221 patients with underlying respiratory diseases (and without hematologic malignancy or previous solid organ transplantation) that were collected for routine microbiological workup between February 2012 and May 2014 at the University Hospital of Graz, Austria. Invasive pulmonary aspergillosis was defined according to European Organization of Research and Treatment of Cancer/Mycoses Study Group criteria modified for patients with respiratory diseases. MEASUREMENTS AND MAIN RESULTS: Thirty-one patients (14%) had probable or proven, 25 possible, and the remaining 165 patients no invasive pulmonary aspergillosis. Probable/proven aspergillosis was associated with a significantly higher (P = 0.034) 30-day mortality rate of 32%. Sensitivities, specificities, and diagnostic odd ratios differed markedly between galactomannan (cut-off 0.5: optical density index, 0.97, 0.81, 124.4; cut-off 1.0: 0.97, 0.93, 422.1; cut-off 3.0: 0.61, 0.99, 109.8), ß-D-glucan (cut-off 80 pg/ml: 0.90, 0.42, 6.57; cut-off 200 pg/ml: 0.70, 0.61, 3.7), lateral-flow device tests (0.77, 0.92, 41.8), and mycological culture (0.29, 0.97, 14). CONCLUSIONS: Probable or proven invasive pulmonary aspergillosis was diagnosed in 14% of our study population and associated with significantly higher 30-day mortality rates. Although the performance of ß-D-glucan was limited by low specificity and that of mycological culture by low sensitivity, the Aspergillus lateral-flow device seems to be a promising alternative to galactomannan testing, which remains the diagnostic gold standard for aspergillosis. Clinical trial registered with www.clinicaltrials.gov (NCT 02058316).

Genotypes of Klebsiella oxytoca isolates from patients with nosocomial pneumonia are distinct from those of isolates from patients with antibiotic-associated hemorrhagic colitis.

Klebsiella oxytoca acts as a pathobiont in the dysbiotic human intestinal microbiota, causing antibiotic-associated hemorrhagic colitis (AAHC), but it also infects other organs, resulting in pneumonia and urinary tract and skin infections. The virulence of K. oxytoca is still poorly understood. The production of a specific cytotoxin has been linked to AAHC pathogenesis. To investigate the clonal relationships of K. oxytoca with regard to clinical origin and virulence attributes, we established a multilocus sequence typing (MLST) method and analyzed 74 clinical K. oxytoca isolates from asymptomatic carriers and patients with AAHC, respiratory infections, and other infections. The isolates were phenotypically characterized, typed, and compared phylogenetically based on the sequences of seven housekeeping genes. MLST analysis yielded 60 sequence types, 12 of which were represented by more than one isolate. The phylogenetic tree distinguished clusters of K. oxytoca isolates between patients with AAHC and those with respiratory infections. Toxin-positive and -negative strains were observed within one sequence type. Our findings indicate that AAHC isolates share a genetic background. Interestingly, K. oxytoca isolates from nosocomial pneumonia showed a different genetic clustering, suggesting that these strains do not originate from the intestines or that they are specialized for respiratory tract colonization. Our results further indicate a polyphyletic origin and possible horizontal transfer of the genes involved in K. oxytoca cytotoxin production. This work provides evidence that K. oxytoca isolates colonizing the two main clinically relevant habitats (lower gastrointestinal [GI] tract and respiratory tract) of the human host are genetically distinct. Applications of this MLST analysis should help clarify the sources of nosocomial infections.

Serum 1,3-beta-d-glucan for antifungal treatment stratification at the intensive care unit and the influence of surgery.

The purpose of this study was to evaluate a preemptive approach with serum 1,3-beta-d-glucan (BDG) as a marker for treatment stratification of systemic antifungal (AF) therapy in patients with clinical suspected invasive fungal infections (IFI) at intensive care units (ICU), and the impact of surgical procedures. A total of 66 ICU patients with clinical suspected IFI were included in this retrospective analysis. Serum BDG testing was performed prior to initiation of AF treatment and in addition to routine diagnostic measures. Based on the BDG results the initial clinical decision whether or not to start systemic AF therapy was re-evaluated. Impact of surgical procedures on clinical utility of serum BDG was evaluated in a sub-group of 25 patients who had undergone surgical procedures prior to BDG evaluation. BDG test results led to discontinuation of AF therapy in 13 patients, and initiation of AF therapy in seven patients. In 46 patients the clinical decision was confirmed by BDG. The majority of suspected, probable and proven IFI cases (10/13, 77%) was predicted by the test. BDG testing turned out positive in 9/25 (36%) of patients that had undergone recent surgery and levels correlated with clinical findings. Serum BDG evaluation seems to be a promising tool to guide AF therapy in ICU patients even after recent surgical procedures.

Implementation of an antimicrobial stewardship program for urinary tract infections in long-term care facilities: a cluster-controlled intervention study.

BACKGROUND: Widespread inappropriate use of antimicrobial substances drives resistance development worldwide. In long-term care facilities (LTCF), antibiotics are among the most frequently prescribed medications. More than one third of antimicrobial agents prescribed in LTCFs are for urinary tract infections (UTI). We aimed to increase the number of appropriate antimicrobial treatments for UTIs in LTCFs using a multi-faceted antimicrobial stewardship intervention. METHODS: We performed a non-randomized cluster-controlled intervention study. Four LTCFs of the Geriatric Health Centers Graz were the intervention group, four LTCFs served as control group. The main components of the intervention were: voluntary continuing medical education for primary care physicians, distribution of a written guideline, implementation of the project homepage to distribute guidelines and videos and onsite training for nursing staff. Local nursing staff recorded data on UTI episodes in an online case report platform. Two blinded reviewers assessed whether treatments were adequate. RESULTS: 326 UTI episodes were recorded, 161 in the intervention group and 165 in the control group. During the intervention period, risk ratio for inadequate indication for treatment was 0.41 (95% CI 0.19-0.90), p = 0.025. In theintervention group, the proportion of adequate antibiotic choices increased from 42.1% in the pre-intervention period, to 45.9% during the intervention and to 51% in the post-intervention period (absolute increase of 8.9%). In the control group, the proportion was 36.4%, 33.3% and 33.3%, respectively. The numerical difference between intervention group and control group in the post-intervention period was 17.7% (difference did not reach statistical significance). There were no significant differences between the control group and intervention group in the safety outcomes (proportion of clinical failure, number of hospital admissions due to UTI and adverse events due to antimicrobial treatment). CONCLUSIONS: An antimicrobial stewardship program consisting of practice guidelines, local and web-based education for nursing staff and general practitioners resulted in a significant increase in adequate treatments (in terms of decision to treat the UTI) during the intervention period. However, this difference was not maintained in the post-intervention phase. Continued efforts to improve the quality of prescriptions further are necessary. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov NCT04798365.