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Abstract Background Pseudomonas aeruginosa (PA) bloodstream infection (BSI) is a common healthcare-associated complication linked to antimicrobial resistance and high mortality. Ongoing clinical trials are exploring novel anti-virulence agents, yet studies on how bacterial virulence affects PA infection outcomes is conflicting and data from real-world clinical populations is limited. Methods We studied a multicentre cohort of 773 adult patients with PA BSI consecutively collected during 7-years from sites in Europe and Australia. Comprehensive clinical data and whole-genome sequencing of all bacterial strains were obtained. Results Based on the virulence genotype, we identify several virulence clusters, each showing varying proportions of multidrug-resistant phenotypes. Genes tied to biofilm synthesis and epidemic clones ST175 and ST235 are associated with mortality, while the type III secretion system is associated with septic shock. Adding genomic biomarkers to machine learning models based on clinical data indicates improved prediction of severe outcomes in PA BSI patients. Conclusions These findings suggest that virulence markers provide prognostic information with potential applications in guiding adjuvant sepsis treatments.

The aim of this study was to assess the use of antibiotics in hospitals and different departments over 14 years (2006–2019) and the impact of various national activities related to this, including national audits of the use of antibiotics for systemic use. The consumption of antibiotics for systemic use (J01) from all Slovenian hospitals (n = 29) and five departments (internal medicine, surgery, ICU (medicine, surgery), paediatrics and gynaecology/obstetrics) was collected. Total hospital consumption was expressed as the number of defined daily doses (DDDs) per 1000 inhabitants per day (DID), the number of DDDs/100 bed days and the number of DDDs/100 admissions. Over 14 years, J01 hospital consumption increased by 13.8%, expressed in DDDs/100 bed days (p = 0.002). In 2019, compared to 2006, the consumption of J01, expressed in DDD/100 bed days, increased from 19.9% to 33.1% in all departments, except intensive care units. J01 consumption expressed in DDD/100 admissions increased by 7.0% to 39.4% in all but paediatric wards (where it decreased by 12.7%). In all years, we observed large variations in the consumption of antibiotics in departments of the same type. The effectiveness of audit interventions aimed at optimizing antibiotic consumption exhibited notable variation across hospitals, with specialized facilities generally demonstrating superior outcomes compared to general hospitals.

The COVID-19 pandemic has strained healthcare systems globally. Shortages of hospital beds, reassignment of healthcare workers to COVID-19-dedicated wards, an increased workload, and evolving infection prevention and control measures have potentially contributed to the spread of multidrug-resistant bacteria (MDRB). To determine the impact of the COVID-19 pandemic at the University Medical Center Ljubljana, a tertiary teaching hospital, we analyzed the monthly incidence of select bacterial species per patient from 2018 to 2022. The analysis was performed for all isolates and for MDRB isolates. The data were analyzed separately for isolates from all clinical samples, from blood culture only, and from clinical and surveillance samples. Our findings revealed an increased incidence density of patients with Enterococcus faecium, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa isolates from clinical samples during the COVID-19 period in the studied hospital. Notably, the incidence density of MDRB isolates—vancomycin-resistant E. faecium, extended-spectrum betalactamase-producing K. pneumoniae, and betalactam-resistant P. aeruginosa—from clinical samples increased during the COVID-19 period. There were no statistically significant differences in the incidence density of patients with blood culture MDRB isolates. We observed an increase in the overall MDRB burden (patients with MDRB isolates from both clinical and surveillance samples per 1000 patient days) in the COVID-19 period in the studied hospital for vancomycin-resistant E. faecium, carbapenem-resistant K. pneumoniae, and betalactam-resistant P. aeruginosa and a decrease in the methicillin-resistant S. aureus burden.

Chronic osteomyelitis in adults is a complex condition that requires prolonged and intensive antimicrobial therapy, but evidence on optimal selection and duration of antibiotics is limited. A review of PubMed and Ovid Embase databases was conducted to identify systematic reviews, meta-analyses, retrospective and randomised controlled trials (RCTs) on antibiotic treatment outcomes in adults with chronic osteomyelitis. Three main areas of interest were investigated: short-term versus long-term antibiotic therapy, oral versus parenteral antibiotic therapy, and combination antibiotic therapy with rifampicin versus without rifampicin. A total of 36 articles were identified and findings were synthesised using a narrative review approach. The available literature suffers from limitations, including a lack of high-quality studies, inconsistent definitions, and varying inclusion/exclusion criteria among studies. Most studies are open-labelled and lack blinding. Limited high-quality evidence exists that oral therapy is non-inferior to parenteral therapy and that shorter antibiotic duration might be appropriate in low-risk patients. Studies on the impact of rifampicin are inconclusive. Further well-designed studies are needed to provide more robust evidence in these areas.

Background:Sepsis is one of the most serious bacterial infections. The diagnosis of sepsis is clinical. Microbiologists can detect bacteremia, which however is not present in all septic patients, by the procedure called blood culture.Methods:Blood culture is a semi-automated procedure of culturing blood in liquid media to detect and identify the causative agents. It is important to take 2 to 3 blood cultures with adequate volume of blood. The new, faster methods for bacterial identification from positive blood cultures and molecular methods for the detection of bacterial DNA directly from a blood sample are also becoming available.Results:In the years 2006 to 2011, the number of blood cultures obtained from patients in the University Medical Centre in Ljubljana, Institute of Oncology and the General hospital of Trbovlje (from 2007) was constantly increasing, from 18,404 in 2006 to 25,214 in 2011. The number of patients with positive blood culture/s increased from 1,033 in 2006 to 1,396 in 2011. The rate of blood culture positivity ranged from 10.9 % to 12.3 %. The ratio between gram-positive and gram-negative bacteria was approximately 50:50 %. In all the years under study, Escherichia coliwas the most frequent pathogenic isolate (19.2 % to 22.9 %), followed by Staphylococcus aureus(15.3 % to 17.4 %). Klebsiellaspp. represented 5.3 % to 8.3 % of isolates, Pseudomonas aeruginosa1.8 % to 3.4 %, Streptococcus pneumoniae2.9 % to 4.7 %, Enterococcusspp. 5.4 % to 8.1 %, anaerobes 2.1 % to 3.2 %. Coagulase-negative staphylococci decreased from 23.3 % to 16.9 %. Today, bacteria are identified by the fast and accurate method of mass spectrometry. Bacteria can alternativelly be detected directly from blood by the molecular tests.Conclusions:Blood culture is a very common procedure, its rate of positivity is stable. Among bacteria, the number and the proportion of pathogenic bacteria such as E. coli, S. aureusand S. pneumoniaeis increasing and the proportion of contaminants is decreasing

Background. The soluble interleukin-2 receptor(s-IL-2R) is a soluble cytokine receptor which directly reflectsthe levels of the IL-2 receptor on lymphocytes T, which, alongwith the IL-2 itself, is important for the specific immune response. The aim of the study. We attempted to prove diagnostic andprognostic significance of s-IL-2R in sepsis cases.Patients and methods. In the period of three years we examined64 healthy blood donors and subjects in systematic healthexaminations and examined 50 septic patients with clinicaland laboratory symptoms of sepsis treated in units for the intensivetherapy of adults at the Clinic for Infectious Diseasesand Febrile States at the Clinic Centre of Ljubljana. The assayfor s-IL-2R was performed with a kit from Eurogenetics (Belgium).Results. We proved that the median concentration of s-IL-2R inseptic patients with positive and negative blood culture aresignificantly higher than healthy subjects (p < 0.05) and werealso significantly higher in the blood of dead patients than inthe blood of survivors (p < 0.05). The mean concentration ofs-IL-2R did not differ in septic patients with positive blood culturefrom those with negative blood culture and did not differfor gram negative pathogens from those for gram positive pathogens.Time dynamics showed the increase levels of s-IL-2Rfor the first 48 hours.Conclusions. s-IL-2R levels are elevated in adults with sepsis.Elevation of s-IL-2R are significantly associated with death.

We report a case of human Dirofilaria repens infection in a woman in Slovenia who had concomitant pleural and subcutaneous manifestations of the infection. This case report illustrates the clinical course of a severe symptomatic parasitic infection that had multisystemic manifestations.

Abstract Background Tuberculous meningitis (TBM) represents a diagnostic and management challenge to clinicians. The “Thwaites’ system” and “Lancet consensus scoring system” are utilized to differentiate TBM from bacterial meningitis but their utility in subacute and chronic meningitis where TBM is an important consideration is unknown. Methods A multicenter retrospective study of adults with subacute and chronic meningitis, defined by symptoms greater than 5 days and less than 30 days for subacute meningitis (SAM) and greater than 30 days for chronic meningitis (CM). The “Thwaites’ system” and “Lancet consensus scoring system” scores and the diagnostic accuracy by sensitivity, specificity, and area under the curve of receiver operating curve (AUC-ROC) were calculated. The “Thwaites’ system” and “Lancet consensus scoring system” suggest a high probability of TBM with scores ≤4, and with scores of ≥12, respectively. Results A total of 395 patients were identified; 313 (79.2%) had subacute and 82 (20.8%) with chronic meningitis. Patients with chronic meningitis were more likely caused by tuberculosis and had higher rates of HIV infection (P

Izhodišče: Nezapletene okužbe sečil so ena najpogostejših okužb pri zdravih mladih ženskah. Za zdravljenje tovrstnih okužb izberemo antibiotike ozkega spektra z delovanjem na najpogostejše povzročitelje. Ker je zdravljenje nezapletenih okužb spodnjih sečil večinoma izkustveno, smo v raziskavi ocenili, kakšna je občutljivost najpogostejših povzročiteljev za peroralne betalaktamske antibiotike in ali so primerni za izkustveno zdravljenje nezapletenih okužb sečil v primerih, kadar ne moremo uporabiti antibiotikov izbire. Metode: Iz teoretične porazdelitve pogostosti različnih vrst povzročiteljev okužb sečil in deležev občutljivosti resničnih izolatov urinokultur pri ženskah smo z uporabo matematičnega modela izračunali oceno skupne občutljivosti za peroralne betalaktamske antibiotike. Rezultati: Ocenjena skupna občutljivost za ampicilin je bila slaba (50 %), za cefalosporine prve, druge in tretje generacije pa med 88 % in 90 %. Zaključek: Matematični model za oceno občutljivosti je zanimivo orodje, s katerim lahko napovemo klinično učinkovitost antibiotikov na podlagi lokalne občutljivosti in pogostosti povzročiteljev. Na podlagi naših rezultatov ugotavljamo, da so med betalaktamskimi antibiotiki za zdravljenje cistitisa najprimernejši cefalosporini prve generacije.

Studies suggest that the incidence of coinfections in patients with the coronavirus disease 2019 (COVID-19) is low, but a large number of patients receive antimicrobials during hospitalisation. This may fuel a rise in antimicrobial resistance (AMR). We conducted a multicentre point-prevalence survey in seven tertiary university hospitals (in medical wards and intensive care units) in Croatia, Italy, Serbia and Slovenia. Of 988 COVID-19 patients, 521 were receiving antibiotics and/or antifungals (52.7%; range across hospitals: 32.9–85.6%) on the day of the study. Differences between hospitals were statistically significant (χ2 (6, N = 988) = 192.57, p < 0.001). The majority of patients received antibiotics and/or antifungals within 48 h of admission (323/521, 62%; range across hospitals: 17.4–100%), their most common use was empirical (79.4% of prescriptions), and pneumonia was the main indication for starting the treatment (three-quarters of prescriptions). The majority of antibiotics prescribed (69.9%) belonged to the “Watch” group of the World Health Organization AWaRe classification. The pattern of antimicrobial use differed across hospitals. The data show that early empiric use of broad-spectrum antibiotics is common in COVID-19 patients, and that the pattern of antimicrobial use varies across hospitals. Judicious use of antimicrobials is warranted to prevent an increase in AMR.

“Antimicrobial stewardship” is a strategy that promotes the responsible use of antimicrobials. The objective of this paper is to focus on consolidated and more recent improvements in clinical strategies that should be adopted in hospitalized patients to ameliorate their infectious diseases’ outcome and to reduce the antibiotic resistance risk through judicious use of antibiotics. We present 13 common clinical scenarios, the respective suggested interventions and the explanations of the supporting evidence, in order to help clinicians in their decision-making process. Strategies including the choice of antibiotic and dose optimization, antibiotic spectrum narrowing (de-escalation), shortening of duration, shift to oral route or outpatient parenteral antibiotic (including elastomeric pumps), and biomarkers are described and discussed.

Summary: Background: The Global Point Prevalence Survey (Global-PPS) established an international network of hospitals to measure antimicrobial prescribing and resistance worldwide. We aimed to assess antimicrobial prescribing and resistance in hospital inpatients. Methods: We used a standardised surveillance method to collect detailed data about antimicrobial prescribing and resistance from hospitals worldwide, which were grouped by UN region. The internet-based survey included all inpatients (adults, children, and neonates) receiving an antimicrobial who were on the ward at 0800 h on one specific day between January and September, 2015. Hospitals were classified as primary, secondary, tertiary (including infectious diseases hospitals), and paediatric hospitals. Five main ward types were defined: medical wards, surgical wards, intensive-care units, haematology oncology wards, and medical transplantation (bone marrow or solid transplants) wards. Data recorded included patient characteristics, antimicrobials received, diagnosis, therapeutic indication according to predefined lists, and markers of prescribing quality (eg, whether a stop or review date were recorded, and whether local prescribing guidelines existed and were adhered to). We report findings for adult inpatients. Findings: The Global-PPS for 2015 included adult data from 303 hospitals in 53 countries, including eight lower-middle-income and 17 upper-middle-income countries. 86 776 inpatients were admitted to 3315 adult wards, of whom 29 891 (34·4%) received at least one antimicrobial. 41 213 antimicrobial prescriptions were issued, of which 36 792 (89·3%) were antibacterial agents for systemic use. The top three antibiotics prescribed worldwide were penicillins with β-lactamase inhibitors, third-generation cephalosporins, and fluoroquinolones. Carbapenems were most frequently prescribed in Latin America and west and central Asia. Of patients who received at least one antimicrobial, 5926 (19·8%) received a targeted antibacterial treatment for systemic use, and 1769 (5·9%) received a treatment targeting at least one multidrug-resistant organism. The frequency of health-care-associated infections was highest in Latin America (1518 [11·9%]) and east and south Asia (5363 [10·1%]). Overall, the reason for treatment was recorded in 31 694 (76·9%) of antimicrobial prescriptions, and a stop or review date in 15 778 (38·3%). Local antibiotic guidelines were missing for 7050 (19·2%) of the 36 792 antibiotic prescriptions, and guideline compliance was 77·4%. Interpretation: The Global-PPS showed that worldwide surveillance can be accomplished with voluntary participation. It provided quantifiable measures to assess and compare the quantity and quality of antibiotic prescribing and resistance in hospital patients worldwide. These data will help to improve the quality of antibiotic prescribing through education and practice changes, particularly in low-income and middle-income countries that have no tools to monitor antibiotic prescribing in hospitals. Funding: bioMérieux.

Background: The antibiotic surgical prophylaxis (ASP) is very important as it can decrease the incidence of surgical infections. However, selection pressure of antibiotics is an important driver of antimicrobial resistance and may stimulate development of post-operative infections with resistant bacteria. This study aims to explore the level of compliance of ASP in daily practice with the set guidelines. Methods: Consecutive patients treated in the years 2011 and 2012 in UKCL were included in this retrospective study. Their medical records were reviewed and the results compared against the US Guidelines published in 2013. The following parameters were included in the study: application of an antibiotic prior to surgery, the appropriateness of the antibiotic and its dosage, application time and the number of doses applied. Results: Altogether 451 surgical procedures from 8 different UKCL's surgical units were analyzed. Patients age ranged from 18 to 97 years. Total compliance with the recommendations of ASP was achieved in 26 % of the cases. Antibiotic prophylaxis was applied in 87 % (range 62–100 %) of procedures with the indicated ASP. Appropriate choice of antibiotic reached 95 % (range 46–100 %). The lowest score was observed for the number of doses applied; the average compliance across 8 units was 46 %. Overall, the ASP was compliant with guidelines in 26 %. Conclusion: The study revealed that there is much space for improvement regarding the studied parameters of the ASP, in particular with regard to the appropriate number of doses of antibiotics administered. The prescribing and administrating of ASP in accordance with the recommendations depend strongly on the awareness and education of health care personnel as well as on supervision, feedback and supportive and blameless organization with good interpersonal communication.

Aspergillus osteomyelitis is a rare manifestation of invasive aspergillosis which accounts for 1.8% to 5.6% of all invasive aspergillosis forms. As other forms of invasive aspergillosis, it predominantly occurs in immunosupressed patients with well established risk factors, but there are increasing reports of invasive aspergillosis cases in patients without traditional risk factors such as patients with chronic obstructive pulmonary disease on inhalatory corticosteroid therapy or patients with liver cirrhosis. We present a case of Aspergillus spondylodiscitis in a patient without other risk factors for invasive aspergillosis than liver cirrhosis and diabetes mellitus successfully treated with a 4-month course of voriconasole.

Abstract: Background.Evidence based recommendations for antibiotic prophylaxis in abdominal surgery are prepared to reduce postoperative complications and to reduce inappropriate prophylactic antibiotic prescribing. The original guidline address risk factors for surgical site infection (SSI), benefits and risks of antibiotic profilaxis and indications for surgical antibiotic profilaxis.Update of recommendations is an opportunity to expand and review the evidence supporting recommendations. Recommendations for common surgical procedures in abdominal surgery in adults are included in this guideline.Surgical antibiotic prophylaxis is and adjunct to, not a substitue for, good surgical tecnique. Antibiotic prophylactic should be regarded as one component of an effective policy for the control of healthcare-associated infection.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most important antibiotic-resistant bacteria causing nosocomial infections in the world. A first-line treatment for infections with MRSA continues to be vancomycin. Due to its increased consumption, three MRSA phenotypes with reduced susceptibility to vancomycin (hVISA, VISA, VRSA) have emerged. We wanted to know to what extent these phenotypes occur in the University Medical Centre Ljubljana.Material and methods: We tested susceptibility to vancomycin of 101 MRSA isolates obtained from blood samples of patients admitted to the University Medical Centre Ljubljana between August 2005 and September 2010; the isolates were stored in the database of the Laboratory of blood cultures at the Institute of Microbiology and Immunology. We carried out Etests to determine the minimum inhibitory concentration (MIC) and Etest macro-method to identify heterogeneous vancomycin-intermediate S. aureus strains (hVISA).Results: 100 MRSA isolates were susceptibile to vancomycin with Etest, and one was vancomycin-intermediate S. aureus (VISA). With Etest macro-method, four isolates were additionally characterized as hVISA. Average MIC values of vancomycin show a minimal growth over the years.Conclusions: hVISA and VISA isolates from blood samples are still rare in the University Medical Centre Ljubljana. MIC values will have to be closely monitored in the future. At the same time, we will have to reduce the use of vancomycin.

Introduction: The selection of perioperative prophylactic antibiotic is based on the expected bacterial flora in the site of the surgical procedure and its susceptibility to antibiotics. Recent reports on coagulase-negative staphylococci, typical representatives of skin flora, showed their resistance to methicillin. We may wonder whether cefazolin is still the antibiotic of choice for surgical prophylaxis in clean surgical procedures.Patients and methods: In a prospective study we included patients who underwent surgical treatment for various types of injuries. Three swab samples were taken in each patient.The first sample was taken from the incision site before the operating field was prepared. The second swab was taken after the operating field preparation and the third was taken at the end of the operation. The results of microbial growth and the susceptibility to antibiotics were recorded. The incidence of a wound infection in patients included in the study was followed prospectively. In the case of infection, the bacteria isolated intraoperatively during the surgical revision were compared to the bacteria isolated perioperatively at the time of the first surgery. All patients received cefazolin in a single dose of 1 to 2 grams according to their weight pre-operatively. The antibiotic was administered 20 minutes before the incision. No additional antibiotic dose was given after surgery.Results: Before the operating field was prepared, swabs were sterile in two patients (6.4 %), at the end of preparation the swabs remained sterile in 22 (71 %) patients and at the end of surgery in 13 (42 %) out of the 31 injured patients. There were no methicillin-resistant swab cultures after operative field preparation, but at the end of surgery in four patients (13 %) the swab cultures grew methicillin resistant Staphylococcus epidemidis. Bacillus sp. was isolated in five patients (16.1 %) after operative field preparation and in two patients (6.4 %) at the end of surgery. The susceptibility of the Bacillus sp. was not determined because of the lack of standardized testing method.Conclusion: In a pilot study we found a large proportion (4/31) of patients in whom colonization of the operative field with cefazolin-resistant bacteria developed during the surgical procedure. The result of our pilot study challenges the guidelines recommending cefazolin for surgical prophylaxis in clean surgery. Further studies in larger patient population are needed.

Postoperative infections increase morbidity and mortality of patients undergoing neurosurgical operations. Correct application of prophylactic antibiotics before, during and after surgery is therefore crucial. In this manuscript we present the first Slovenian guidelines that give details on recommended prophylactic regimen and its correct dosing for different types of neurosurgical operations.

Pneumococcal pneumonia causes significant morbidity and mortality among adults. Given limitations of diagnostic tests for non-bacteremic pneumococcal pneumonia, most studies report the incidence of bacteremic or invasive pneumococcal disease (IPD), and thus, grossly underestimate the pneumococcal pneumonia burden. We aimed to develop a conceptual and quantitative strategy to estimate the non-bacteremic disease burden among adults with community-acquired pneumonia (CAP) using systematic study methods and the availability of a urine antigen assay.We performed a systematic literature review of studies providing information on the relative yield of various diagnostic assays (BinaxNOW® S. pneumoniae urine antigen test (UAT) with blood and/or sputum culture) in diagnosing pneumococcal pneumonia. We estimated the proportion of pneumococcal pneumonia that is bacteremic, the proportion of CAP attributable to pneumococcus, and the additional contribution of the Binax UAT beyond conventional diagnostic techniques, using random effects meta-analytic methods and bootstrapping. We included 35 studies in the analysis, predominantly from developed countries. The estimated proportion of pneumococcal pneumonia that is bacteremic was 24.8% (95% CI: 21.3%, 28.9%). The estimated proportion of CAP attributable to pneumococcus was 27.3% (95% CI: 23.9%, 31.1%). The Binax UAT diagnosed an additional 11.4% (95% CI: 9.6, 13.6%) of CAP beyond conventional techniques. We were limited by the fact that not all patients underwent all diagnostic tests and by the sensitivity and specificity of the diagnostic tests themselves. We address these resulting biases and provide a range of plausible values in order to estimate the burden of pneumococcal pneumonia among adults.Estimating the adult burden of pneumococcal disease from bacteremic pneumococcal pneumonia data alone significantly underestimates the true burden of disease in adults. For every case of bacteremic pneumococcal pneumonia, we estimate that there are at least 3 additional cases of non-bacteremic pneumococcal pneumonia.

BACKGROUND External ventricular drainage (EVD) is the most common method of treatment for patients with increased intracranial pressure due to acute hydrocephalus. The most frequent complications of EVD are infections of the central nervous system. Earlier studies indicated numerous risk factors, although the results of studies regarding the impacts of individual factors on the occurrence of infections differ. Our research was aimed at finding the risk factors for infection in patients with an inserted EVD, treated at the Department of Neurosurgery of University Medical Centre (UMC) Ljubljana. METHODS In the article we describe a retrospective research of EVDs inserted in the period from January 2000 to January 2009. Forty-eight cases of EVDs met the study inclusion criteria. Among them, there were 10 cases with an infection which occurred during inserted EVD. We recorded, compared and evaluated information about the patient, the EVD and infections. RESULTS The duration of the drainage was confirmed as a risk factor for EVD infections (p = 0.004). The infection occurred on average on day 8.9 ± 5.4. The shares of subarachnoid and intraventricular hemorrhage, previous neurosurgical procedures, EVD manipulations, number of successive drainages and duration of hospitalization were greater in the cases of infected EVDs. In the cases of EVD exchange, the average day of change in group without infection was day 10.9 ± 5.8 (p = 0.030). Among infectious agents, Gram-positive bacteria prevailed. CONCLUSIONS Strict asepsis is advised during insertion and handling of EVD and a prophylactic exchange of EVD on day 10 of insertion. Risk factors in our study do not differ from findings in other studies. Therefore it is suggested that prophylactic measures against drain-related infection should be developed and implemented and their efficacy confirmed in a prospective study.