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.

European society of clinical microbiology and infectious diseases guidelines for coronavirus disease 2019: an update on treatment of patients with mild/moderate disease.

SCOPE: Despite the large availability of vaccines, coronavirus disease 2019 (COVID-19), induced by severe acute respiratory syndrome coronavirus 2, continues to be a major threat for health-care providers and fragile people. A number of options are now available for outpatients with mild-to-moderate COVID-19 at the risk of disease progression for the prevention of deaths or hospitalization. METHODS: A European Society of Clinical Microbiology and Infectious Diseases COVID-19 guidelines task force was established by the European Society of Clinical Microbiology and Infectious Diseases Executive Committee. A small group was established, half appointed by the chair and the remaining selected based on an open call. Each panel met virtually once a week. For all decisions, a simple majority vote was used. A long list of clinical questions using the population, intervention, comparison, outcome format was developed at the beginning of the process. For each population, intervention, comparison, outcome, two panel members performed a literature search, with a third panelist involved in case of inconsistent results. Voting was based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RECOMMENDATIONS: In this update, we focus on anti-viral agents, monoclonal antibodies (mAbs) and other treatment options proposed for patients with mild or moderate COVID-19 who are at the risk of hospitalization or death. Although the use of anti-virals is recommended, especially nirmatrelvir/ritonavir and remdesivir or, alternatively, molnupirarvir, the administration of mAbs against the spike protein strictly depends on circulating variants or the ability to test timely for variants and sub-variants. At the time of writing (April-June 2022), the only active mAb was tixagevimab/cilgavimab given the predominance of the Omicron BA.2, BA.3, BA.4 and BA.5 sub-lineages in Europe. However, considering that the epidemiological scenario is extremely dynamic, constant monitoring of variants of concern is mandatory.

Spinal Surgery Site Infection Leading to Implant Loosening Is Influenced by the Number of Prior Operations.

STUDY DESIGN: Retrospective Cohort Study. OBJECTIVES: Spinal surgery site infection and chronic implant infection are possible causes for ongoing pain, implant loosening, and failed back surgery syndrome. Evidence of chronic infection was found in 29.1% of revision cases but is also found in a considerable number of degenerative cases without prior surgery. Infection mechanisms and possible clinical correlations are unclear. METHODS: Retrospective analysis of standardized surgery site screening (swab, tissue samples, implant sonication) in 181 cases without clinical evidence of preoperative surgery site infection. RESULTS: Screening results of cases without prior spinal surgery (n = 49, 10.2% positive) were compared to cases with prior spine surgery without implant placement (e.g. micro discectomy) (n = 21, 23.8% positive), revision cases following singular spinal fusion (n = 73, 23.2% positive), and cases with multiple revisions (n = 38, 50.0% positive). Propionibacterium spp. detection rate increased to 80% in positive cases with multiple revisions. Implants in place during revision surgery had a significantly higher infection rate (32.4%) compared to no implant (14.2%, p = 0.007). Positive cases had a significantly higher pain level prior to surgery compared to negative cases (p = 0.019). Laboratory parameters had no predictive value. Logistic regression revealed that previous spinal surgeries (odds ratio [OR] 1.38 per operation, p < 0.001) and male sex (OR 1.15, p = 0.028) were independent predictive factors for infection. CONCLUSIONS: Previous spinal surgery is a risk factor for chronic surgery site infection, leading to chronic pain, implant loosening, and revision. The presence of Propionibacterium spp. was correlated with chronic implant loosening and was more likely with cumulative surgeries.

Longitudinal Evaluation of Plasma Cytokine Levels in Patients with Invasive Candidiasis.

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-ß) 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.

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.

Isavuconazole Treatment in a Mixed Patient Cohort with Invasive Fungal Infections: Outcome, Tolerability and Clinical Implications of Isavuconazole Plasma Concentrations.

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.

Serum 1,3-Beta-D-Glucan Values During and After Laparoscopic and Open Intestinal Surgery.

BACKGROUND: 1,3-beta-D Glucan (BDG) assay has good accuracy for distinguishing patients with invasive fungal infections from patients without. Some procedures and medications affect BDG levels, resulting in false-positive BDG results. The extent of intestinal surgery on BDG kinetics is unknown. We evaluated the influence of laparoscopic and open intestinal surgery on peri- and postsurgical serum BDG values. METHODS: BDG was determined in 346 samples from 50 patients undergoing laparoscopic (24) or open (26) intestinal surgery at the following time points: after insertion of arterial but before skin incision, after skin incision but before dissection of the intestinal mucosa, after completion of anastomosis, after completion of skin sutures, in the evening after surgery, day 2 after surgery, 4-5 days after surgery. RESULTS: BDG was positive (ie, concentration ≥80 pg/mL) in 54% to 61% of patients during laparoscopic and open surgery (highest rates after completion of skin sutures). BDG was still positive in 12% (open) to 17% (laparoscopic) of patients without any suspected or proven fungal infection or anastomotic leakage 4-5 days after surgery. After completion of gut anastomosis, the BDG increase was higher in open compared with laparoscopic intestinal surgery. CONCLUSIONS: The value of positive BDG tests in the perioperative setting up to 5 days postsurgery seems to be limited due to BDG elevations from intestinal surgical procedures.

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.

Mycobiome in the Lower Respiratory Tract - A Clinical Perspective.

Recently the paradigm that the healthy lung is sterile was challenged and it is now believed that the lungs harbor a diverse microbiota also contributing to the pathogenesis of various diseases. Most of the research studies targeting the respiratory microbiome have focused on bacteria and their impact on lung health and lung diseases. Recently, also the mycobiome has gained attention. Lower respiratory tract (LRT) diseases (e.g., cystic fibrosis) and other diseases or conditions (e.g., HIV infection, lung transplantation, and treatment at intensive care units) have been investigated with regard to possible involvement of mycobiome in development or progression of diseases. It has been shown that diversities of mycobiome in the LRT vary in different populations and conditions. It has been proposed that the mycobiome diversity associated with LRT can vary with different stages of diseases. Overall, Candida was the dominant fungal genus in LRT samples. In this review, we summarize the recent findings regarding the human LRT mycobiome from a clinical perspective focussing on characterization of investigated patient groups and healthy controls as well as sampling techniques. From these data, clinical implications for further studies or routine practice are drawn. To obtain clinically relevant answers efforts should be enhanced to collect well characterized and described patient groups as well as healthy individuals for comparative data analysis and to apply thorough sampling techniques. We need to proceed with elucidation of the role of mycobiota in healthy LRT and LRT diseases to hopefully improve patient care.

suPAR remains uninfluenced by surgery in septic patients with bloodstream infection.

Surgical trauma induces activation of the immune system and may cause an increase of inflammatory biomarkers tested postoperatively in septic patients treated for bloodstream infection. The aim of this study was to determine the impact of surgical interventions on the novel sepsis biomarker soluble urokinase plasminogen activator receptor (suPAR) and to compare results with those of routine laboratory parameters CRP, PCT, and IL-6 in patients with culture-proven bloodstream infection. Forty-six adult patients with positive blood culture undergoing minor or major surgical intervention were investigated, 12 blood culture positive patients served as control group. Blood was collected 24 hours before and after surgical intervention for determination of the sepsis biomarkers suPAR, CRP, PCT, and IL-6. Within the surgical study cohort, a non-significant increase of suPAR, CRP, and PCT was observed postoperatively (p 0.642; p 0.773; p 0.087). In contrast, a slight decrease of IL-6 (p 0.599) was observed. A significant correlation was calculated for the pre- and postoperative difference of CRP (p 0.028) and PCT (p 0.008) and type of surgical intervention received: after minor surgical intervention only PCT decreased significantly (p<0.001), while after major surgical interventions no significant differences were observed for all biomarkers evaluated. In the control group, a significant decrease of CRP (p 0.005) and PCT (p 0.005) was observed. In patients treated adequately for bloodstream infections, postoperative suPAR levels remained uninfluenced of the surgical trauma and might therefore be a reliable parameter for postoperative infectious monitoring. After minor surgical intervention, PCT seems to be the most reliable parameter.

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.

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.

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).

Impact of structured personal on-site patient education on low posaconazole plasma concentrations in patients with haematological malignancies.

Low posaconazole plasma concentrations (PPCs) are associated with breakthrough invasive mould infections among patients with haematological malignancies. This study evaluated the influence of structured personal on-site patient education on low PPCs. The study was conducted from July 2012 to May 2013 at the Division of Hematology, Medical University Hospital of Graz (Graz, Austria). PPCs were measured in all patients with haematological malignancies receiving the drug prophylactically. Concentrations above the target of 0.5 mg/L were defined as satisfactory and those below this concentration as low. In patients with low PPCs, structured personal on-site education regarding the intake of posaconazole (e.g. intake with fatty/acid food, prevention of nausea and vomiting) was performed. In total, 258 steady-state PPCs were measured in 65 patients [median PPC 0.59 mg/L, interquartile range 0.25-0.92 mg/L; 141/258 (54.7%) satisfactory]. Diarrhoea was the strongest predictor of low PPCs in the multivariate analysis. Initial steady-state PPCs were sufficient in 29 patients and low in 36 patients. Of the 36 patients with low initial steady-state PPCs, 8 were either discharged or antifungal therapy was modified before a follow-up PPC was obtained; in the remaining 28 patients, personal on-site education was performed. In 12/28 patients (43%) the personal on-site education led to sufficient levels, whilst in 16 (57%) PPCs stayed below the target, although increasing from <0.2 mg/L to >0.3 mg/L in 6 of these patients. In conclusion, personal education appears to be a promising tool to increase low PPCs.

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.

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.

Neurocysticercosis in a European traveler returning from India primarily suspected as neoplasia.

A woman with a history of cured breast cancer and multiple trips to India presented with a cervical nodule. Primarily suspected as metastasis of breast cancer, histopathology, however, showed the scolex of Taenia solium. Although the patient was neurologically asymptomatic neuroimaging showed multiple cysts. During treatment with praziquantel, albendazole, and dexamethason the patient developed seizures.

Microbiological screening for earlier detection of central venous catheter-related bloodstream infections.

BACKGROUND: Catheter-related bloodstream infections (CRBSIs) are currently detected with a reactive diagnostic policy, that is, application of tests to patients with clinically suspected CRBSI. The aim of our study was to evaluate whether CRBSIs could be anticipated in an earlier stage by microbiological screening using peptide nucleic acid fluorescence in situ hybridization (PNA FISH) with universal hybridization probes or acridine-orange leucocyte cytospin (AOLC) tests in haemodialysis and haematological patients with CVCs in situ compared with routine test. MATERIALS AND METHODS: Peptide nucleic acid fluorescence in situ hybridization (PNA FISH) and AOLC tests using blood samples from both CVC lines in patients undergoing haemodialysis were performed three times a week and from one CVC line in haematological patients were performed daily. Results were compared with those obtained from routinely performed CRBSI diagnostic tests. RESULTS: One hundred fifteen patients with 139 catheter periods were investigated. The mean observation time per catheter period was 25 days (IQR 13.5-43.5), resulting in 5615 CVC days with a total of 4839 tested blood samples. Five CRBSI cases were detected by routine measures resulting in a CRBSI rate of 0.9/1000 catheter days. Four of five CRBSIs could be anticipated by positive PNA FISH and AOLC tests 2-8 days before the diagnosis was established with routine measures. CONCLUSIONS: The proactive anticipative strategy using microscopic examination of CVC blood samples to anticipate CRBSI in an earlier stage compared with routine measures is a new diagnostic approach in patients with CVCs and a high risk of developing CRBSI.

Potential factors for inadequate voriconazole plasma concentrations in intensive care unit patients and patients with hematological malignancies.

Voriconazole plasma concentrations (VPCs) vary widely, and concentrations outside the therapeutic range are associated with either worse outcome in invasive aspergillosis (IA) or increased toxicity. The primary goal of this cohort study conducted in a real-life setting was to identify potential factors associated with inadequate VPCs in ICU patients and patients with hematological malignancies. Within a period of 12 months, trough VPCs were obtained and analyzed with high-performance liquid chromatography, and the adequate range was defined as 1.5 to 5.5 mg/liter. VPCs of <1.5 mg/liter were defined as low, whereas VPCs of >5.5 mg/liter were defined as potentially toxic. A total of 221 trough VPCs were obtained in 61 patients receiving voriconazole, and 124/221 VPCs (56%) were found to be low. Multivariate analysis revealed that low VPCs were significantly associated with clinical failure of voriconazole, prophylactic use, younger age, underlying hematological malignancy, concomitant proton pump inhibitor (PPI) (pantoprazole was used in 88% of the patients), and absence of side effects. Low VPCs remained an independent predictor of clinical failure of voriconazole. The defined adequate range was reached in 79/221 (36%) VPCs. In 18 samples (8%), potentially toxic levels were measured. Multivariate analysis revealed higher body mass index (BMI), absence of hematological malignancy, therapeutic application, and diarrhea as factors associated with potentially toxic VPCs. Neurotoxic adverse events occurred in six patients and were mostly associated with VPCs in the upper quartile of our defined adequate range. In conclusion, potential factors like younger age, prophylaxis, underlying hematological malignancy, BMI, and concomitant PPI should be considered within the algorithm of voriconazole treatment.

Diagnostic accuracy of soluble urokinase plasminogen activator receptor (suPAR) for prediction of bacteremia in patients with systemic inflammatory response syndrome.

OBJECTIVES: Soluble urokinase plasminogen activator receptor (suPAR) serum concentrations have recently been described to reflect the severity status of systemic inflammation. In this study, the diagnostic accuracy of suPAR, C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6) to predict bacteremia in patients with systemic inflammatory response syndrome (SIRS) was compared. METHODS: A total of 132 patients with SIRS were included. In 55 patients blood cultures had resulted positive (study group 1, Gram positive bacteria: Staphylococcus aureus and Streptococcus spp., n=15; study group 2, Gram-negative bacteria, n=40) and 77 patients had negative blood culture results (control group, n=77). Simultaneously with blood cultures suPAR, CRP, PCT, IL-6 and white blood count (WBC) were determined. RESULTS: SuPAR values were significantly higher in study group 1 (median 8.11; IQR 5.78-15.53; p=0.006) and study group 2 (median 9.62; IQR 6.52-11.74; p<0.001) when compared with the control group (median 5.65; IQR 4.30-7.83). ROC curve analysis revealed an AUC of 0.726 for suPAR in differentiating SIRS patients with bacteremia from those without. The biomarkers PCT and IL-6 showed comparable results. Regarding combinations of biomarkers multiplying suPAR, PCT and IL-6 was most promising and resulted in an AUC value of 0.804. Initial suPAR serum concentrations were significantly higher (p=0.028) in patients who died within 28 days than in those who survived. No significant difference was seen for PCT, IL-6 and CRP. CONCLUSION: In conclusion, suPAR, IL-6 and PCT may contribute to predicting bacteremia in SIRS patients.