Prognostic significance of plasma cytomegalovirus (CMV) DNA load in immunocompetent patients with CMV pneumonia: A retrospective cohort study.

Cytomegalovirus (CMV) pneumonia, often presented as pneumonitis, is characterized by respiratory failure and large interstitial infiltrates visible on chest radiographs. This retrospective cohort study investigates the predictive significance of plasma CMV DNA load on the short- and long-term mortality among immunocompetent patients diagnosed with CMV pneumonia. The study included 61 immunocompetent patients suspected of having CMV pneumonia, treated with intravenous ganciclovir after positive CMV DNA results from bronchoalveolar lavage or plasma. Our multivariate Cox regression analysis identified several independent predictors of mortality. Having idiopathic pulmonary fibrosis (IPF) significantly increased the risk of in-hospital mortality (HR: 7.27, 95% CI: 1.62-32.52, p = 0.009), as did shorter durations of antiviral therapy (HR: 0.90, 95% CI: 0.84-0.97, p = 0.005) and higher CMV DNA levels (>3870 IU/mL; HR: 9.63, 95% CI: 2.32-39.98, p = 0.002). High CMV DNA levels (>5154 IU/mL) were also predictors of 30-day mortality (HR: 9.39, 95% CI: 2.20-40.01, p = 0.002). For 1-year mortality, the presence of IPF (HR: 2.96, 95% CI: 1.08-8.06, p = 0.034), hypersensitivity pneumonia (HP) (HR: 4.30, 95% CI: 1.57-11.78, p = 0.005), shorter duration of total antiviral therapy (HR: 0.95, 95% CI: 0.93-0.99, p = 0.010), and higher CMV DNA levels (>327 IU/mL) (HR: 3.36, 95% CI: 1.33-8.47, p = 0.010) were identified as independent determinants. The study reveals that IPF increases short and long-term mortality risks, while HP increases long-term mortality. Extended antiviral treatment duration results in a 10% reduction in in-hospital mortality for each additional day of treatment. Furthermore, elevated viral loads are associated with higher mortality rates, highlighting the necessity for careful monitoring.

An evaluation of a Stenotrophomonas maltophilia outbreak due to commercial arterial blood gas collection kit.

BACKGROUND: Stenotrophomonas maltophilia is a gram-negative bacterium that can cause hospital infections and outbreaks within hospitals. This study aimed to evaluate an outbreak of Stenotrophomonas maltophilia, caused by ready-to-use commercial syringes containing liquid lithium and heparin for arterial blood gas collection in a university hospital. METHODS: Upon detecting an increase in Stenotrophomonas maltophilia growth in blood cultures between 15.09.2021 and 19.11.2021, an outbreak analysis and a case-control study (52 patients for the case group, 56 patients for the control group) were performed considering risk factors for bacteremia. Samples from possible foci for bacteremia were also cultured. Growing bacteria were identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. The genetic linkage and clonal relationship isolates were investigated with pulsed-field gel electrophoresis (PFGE) in the reference laboratory. RESULTS: In the case-control study, the odds ratio for the central venous catheter [3.38 (95% confidence interval [CI]: 1.444, 8.705 ; p = 0.006)], for surgery [3.387 (95% confidence interval [CI]: 1.370, 8.373 ; p = 0.008)] and for arterial blood gas collection history [18.584 (95% confidence interval [CI]:4.086, 84.197; p < 0.001)] were identified as significant risk factors. Stenotrophomonas maltophilia growth was found in ready-to-use commercial syringes used for arterial blood gas collection. Molecular analysis showed that the growths in the samples taken from commercial syringes and the growths from blood cultures were the same. It was decided that the epidemic occurred because the method for sterilization of heparinized liquid preparations were not suitable. After discontinuing the use of the kits with this lot number, the outbreak was brought under control. CONCLUSIONS: According to our results, disposable or sterile medical equipment should be included as a risk factor in outbreak analyses. The method by which injectors containing liquids, such as heparin, are sterilized should be reviewed. Our study also revealed the importance of the cooperation of the infection control team with the microbiology laboratory.

Surveillance of carbapenem-resistant Klebsiella pneumoniae and Escherichia coli in perianal swab samples.

Our study aimed to detect carbapenem-resistant Klebsiella pneumoniae (CRKP) and/or carbapenem-resistant Escherichia coli in perianal swab samples, exploring their link to bloodstream infections (BSIs) in a tertiary-care university hospital. CRKP-related BSIs ranged from 3.7% to 9.58%, emphasizing the need to understand local risk factors for effective infection control.

Impact of posaconazole prophylaxis and antifungal treatment on BAL GM performance in hematology malignancy patients with febrile neutropenia: a real life experience.

BACKGROUND: Diagnostic accuracy of galactomannan measurements is highly variable depending on the study population, diagnostic procedures, and treatment procedures. We aimed to evaluate the effect of posaconazole prophylaxis and empiric antifungal treatment upon diagnostic accuracy of GM measurements in bronchoalveolar lavage (BAL), bronchial lavage (BL), and serum in hematological malignancy population. METHODS: Patients hospitalized in a single tertiary care center with hematologic malignancies undergoing fiberoptic bronchoscopy (FOB) with a preliminary diagnosis of IPA were retrospectively included. RESULTS: In all the study population (n = 327), AUC for BAL, BL, and serum GM were as follows: 0.731 [0.666-0.790], 0.869 [0.816-0.912], and 0.610 [0.540-0.676] with BL samples having the best diagnostic value. GM measurements in patients under posaconazole prophylaxis (n = 114) showed similar diagnostic performance. While specificity was similar between patients with and without posaconazole prophylaxis, sensitivity of GM measurements was lower in patients with prophylaxis. Analyses with patient classified according to antifungal treatment at the time of FOB procedure (n = 166) showed a decreased diagnostic accuracy in serum GM and BAL GM measurements related with the duration of treatment. However, BAL, BL, and serum GM measurements presented similar sensitivity and specificity in higher cut-off values in longer durations of antifungal treatment. CONCLUSION: Our study shows that posaconazole prophylaxis and active short-term (3 days) antifungal treatment do not significantly affect overall diagnostic performance of GM measurements in bronchoalveolar lavage and bronchial lavage samples. However, using different cut-off values for patients receiving active treatment might be suggested to increase sensitivity.

Effects of COVID-19 pandemic on healthcare-associated infections, antibiotic resistance and consumption rates in intensive care units.

Purpose: This paper aimed to evaluate the effects of the COVID-19 pandemic on healthcare-associated infections (HAIs), antibiotic resistance and consumption rates in intensive care units (ICUs) of a tertiary care university hospital. Patients and Methods: Between 1 January 2018 and 31 December 2021, adult patients diagnosed with HAIs in ICUs were investigated retrospectively. Patients were divided into pre-pandemic (2018-2019) and pandemic periods (2020-2021). Antibiotic consumption index was calculated via using the formula of (total dose (grams)/defined daily dose (DDD) x total patient days) x1000. A p value below 0.05 was accepted as statistically significant. Results: The incidence of HAIs (per 1000 patient days) in the ICU of COVID-19 patients was 16.59, while it was 13.42 in the other ICUs during the pandemic period (p=0.107). The bloodstream infection (BSI) incidence was 3.32 in the pre-pandemic period and 5.41 in the pandemic period in ICUs other than the ICU of COVID-19 patients (p<0.001). In the pandemic period, the BSI incidence rate was significantly higher in the ICU of COVID-19 patients than in the other ICUs (14.26 vs 5.41, p<0.001). Central venous catheter bloodstream infections incidence rate was 4.72 in the pre-pandemic and 7.52 in the pandemic period in ICUs other than the ICU of COVID-19 patients (p=0.0019). During the pandemic period, the bacteraemia episode rates of Acinetobacter baumannii (5.375 vs 0.984, p<0.001), Enterococcus spp. (1.635 vs 0.268, p<0.001) and Stenotrophomonas maltophilia (3.038 vs 1.297, p=0.0086) in the ICU of COVID-19 patients were significantly found higher than others. The extended-spectrum beta-lactamase (ESBL) positivity rates for Klebsiella pneumoniae and Escherichia coli were 61% and 42% in the pre-pandemic period; 73% and 69% in the pandemic period in ICUs other than the ICU of COVID-19 patients (p>0.05). In the pandemic period, the ESBL positivity rates for K. pneumoniae and E. coli were 83% and 100% in the ICU of COVID-19 patients, respectively. Meropenem (p<0.001), teicoplanin (p<0.001) and ceftriaxone (p<0.001) consumptions were increased while ciprofloxacin (p=0.003) consumption was decreased in all ICUs after the pre-pandemic period. Conclusions: BSI and CVCBSI incidence rates were significantly increased in all ICUs after the COVID-19 pandemic in our hospital. Bacteraemia episode rates of A. baumannii, Enterococcus spp. and S. maltophilia in ICU of COVID-19 patients were significantly found higher than others. In addition, meropenem, teicoplanin and ceftriaxone consumptions were increased in all ICUs after the COVID-19 pandemic.

Remdesivir treatment for patients with moderate to severe COVID-19.

BACKGROUND: Remdesivir, which was first developed for the treatment of Ebola disease but failed to meet expectations, has become hope in the fight against the COVID-19 pandemic. This study aimed to evaluate risk factors for mortality and prognosis of adult moderate/severe COVID-19 patients treated with remdesivir, and safety and tolerability of 5 days of remdesivir treatment. METHODS: This multicenter prospective observational study was conducted in 14 centers in Turkey. Pregnancy or breastfeeding, multiorgan failure, or usage of vasopressors for septic shock, ALT > 5 × the upper limit of the normal range, or eGRF <30 mL/min or dialysis and receiving favipiravir were the exclusion criteria of the study. RESULTS: Among 500 patients, 494 patients were included in the study. On admission, 392 (79.3%) patients had moderate and 102 (20.6%) patients had severe COVID-19. The 28-day mortality was 10.1%. The median of the scores of the seven-category ordinal scale assessed on days 0, 3, 5, 7 were 4 and 3 on day 14. When the survival status of the patients was evaluated according to the time between the remdesivir start date and the end date of the symptoms, no statistically significant difference was found between the medians of the groups (p = 0.404). In multivariable analysis, age (OR, 1.05; 95%CI, 1.02-1.08; p = 0.003), SpO2 level on admission (OR, 3.03; 95%CI, 1.35-6.81; p = 0.007), heart rate (OR, 2.48; 95%CI, 1.01-6.07; p = 0.047), follow-up site at the hospital (clinic/ICU) (OR, 26.4; 95%CI, 11.6-60.17; p < 0.001) were independently associated with increased mortality. Grade 3 adverse event (AE) was observed in 4 (0.8%) patients. None of the patients experienced grade 4 or 5 AEs. DISCUSSION: Remdesivir is a safe and well-tolerated drug and older age, low SpO2 level on admission, tachycardia, and ICU admission are independently associated with increased mortality among patients with moderate/severe COVID-19 receiving remdesivir treatment.

Tocilizumab treatment in COVID-19: A prognostic study using propensity score matching.

BACKGROUND: The potential role of interleukin-6 (IL-6) in coronavirus disease 2019 (COVID-19) pneumonia provides the rationale for investigating IL-6 signaling inhibitors. OBJECTIVES: To evaluate and report treatment responses to tocilizumab (TCZ) in COVID-19 patients and compare mortality outcomes with those of standard care. MATERIAL AND METHODS: Patients hospitalized with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, diagnosed with reverse transcription polymerase chain reaction (RT-PCR) between March 2020 and April 2021, were enrolled in this single-center retrospective cohort study. Propensity score matching was performed in order to reduce confounding effects secondary to imbalances in receiving TCZ treatment. RESULTS: A total of 364 patients were included in this study. Two hundred thirty-six patients received standard care, while 128 patients were treated with TCZ in addition to standard care (26 (20.3%) patients received a dose of 400 mg intravenously once, while 102 (79.7%) patients received a total dose of 800 mg intravenously). In the propensity score-matched population, less noninvasive mechanical ventilation (p = 0.041) and mechanical ventilation support (p = 0.015), and fewer deaths (p = 0.008) were observed among the TCZ-treated patients. The multivariate adjusted Cox regression model showed a significantly higher survival rate among TCZ patients compared to controls (hazard ratio (HR): 0.157, 95% confidence interval (95% CI): 0.026-0.951; p = 0.044). The hazard ratio for mortality in the TCZ group was 0.098 (95% CI: 0.030-0.318; p = 0.0001 using log-rank test). CONCLUSIONS: This study determined that TCZ treatment in COVID-19 patients was associated with better survival, reduced need for mechanical ventilation and reduced hospital-associated mortality.

An outbreak of Ralstonia insidiosa bloodstream infections caused by contaminated heparinized syringes.

INTRODUCTION: Ralstonia insidiosa, a gram-negative waterborne bacteria able to survive and grow in any type of water source, can cause nosocomial infections, and are considered emerging pathogens of infectious diseases in hospital settings. In this study, we report an outbreak of R. insidiosa at our center related to contaminated heparinized syringes. MATERIAL AND METHODS: The present study was conducted in a tertiary care university hospital in Turkey. An outbreak analysis was performed between September 2021 and December 2021. Microbiological samples were obtained from environmental sources and from patient blood cultures. Species identification was performed using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). To investigate the clonality of strains, all confirmed isolates were sent to the National Reference Laboratory and pulsed-field gel electrophoresis (PFGE) was used to perform molecular typing. RESULTS: Seventeen R. insidiosa isolates were identified from the blood cultures of 13 patients from various wards and intensive care units. Isolates from seven patient blood cultures and two heparinized blood gas syringes were characterized by PFGE. All isolates were found to belong to the same clone of R. insidiosa. CONCLUSION: R. insidiosa was identified as the cause of a nosocomial infection outbreak in our hospital, which was then rapidly controlled by the infection-control team. When rare waterborne microorganisms grow in blood or other body fluid cultures, clinicians and the infection-control team should be made aware of a possible outbreak.

Evaluation of Using Empiric Glycopeptides in Accordance with the IDSA Guidelines in Hematologic Malignancy Patients with Febrile Neutropenia.

Background: This study aimed to evaluate the effects of the appropriate use of empiric glycopeptide therapy in hematologic malignancy patients with febrile neutropenia (FN). Materials and Methods: Patients with FN who were hospitalized in our clinic and started empiric glycopeptide therapy were retrospectively analyzed. Empiric glycopeptide treatment initial indications were determined according to 7 specific criteria in the IDSA guidelines. In addition, the duration of glycopeptide use according to initial indications, causative pathogens in culture positivity, frequency of VRE infection, and the mortality rate was identified. Results: 87 patients were included. Of these, 102 episodes of FN were analyzed. Appropriate use of glycopeptides was observed in 98% of patients. The most common initial indication for glycopeptide was skin or soft-tissue infection, with 52% (n = 53). The mean duration of glycopeptide use was 11 (2-22) days. The time of glycopeptide use was longer in patients with catheter-related infections than in those with severe mucositis and hemodynamic instability (p = 0,041/p = 0,016). The duration of glycopeptide use was shorter in patients with consolidation therapy than in those without consolidation therapy. The mortality rate in culture-positive patients was significantly higher than in culture-negative patients (p = 0.041). At 72 h, glycopeptide therapy was discontinued in 8 of 79 FN episodes within culture-negative patients. Conclusion: This study showed that the mortality rate was higher in culture-positive patients. Additionally, glycopeptides should be discontinued early with no evidence of gram-positive infection.

The Age-Dependent Role of Th22, Tc22, and Tc17 Cells in the Severity of Pneumonia in COVID-19 Immunopathogenesis.

Coronavirus disease 2019 (COVID-19) has clinical manifestations ranging from mild symptoms to respiratory failure, septic shock, and multi-organ failure. Lymphocytes are divided into different subtypes based on their cytokine production pattern. In this study, we investigated the role of cytokine expressions of CD4+ T (T helper [Th]1, Th2, Th17, Th22) and CD8+ T cell subtypes (T cytotoxic [Tc]1, Tc2, Tc17, Tc22) in the pathogenesis of COVID-19. Peripheral blood mononuclear cells (PBMCs) were extracted with Ficoll by density gradient centrifugation from blood samples of 180 COVID-19 patients (children and adults) and 30 healthy controls. PBMCs were stimulated with PMA and Ionomycin and treated with Brefeldin A in the fourth hour, and a 10-colored monoclonal antibody panel was evaluated at the end of the sixth hour using flow cytometry. According to our findings, the numbers of Th22 (CD3+, CD4+, and interleukin [IL]-22+) and Tc22 (CD3+, CD8+, IL-22+) cells increased in adult patients regardless of the level of pneumonia (mild, severe, or symptom-free) as compared with healthy controls (p < 0.05). In addition, the number of Tc17 (CD3+, CD8+, and IL-17A+) cells increased in low pneumonia and severe pneumonia groups compared with the healthy controls (p < 0.05). Both IL-22 and IL-17A production decreased during a follow-up within 6 weeks of discharge. Our findings suggest that the increase in only IL-22 expressed Tc22 cells in the 0-12 age group with a general symptom-free course and higher levels of Th22 and Tc22 in uncomplicated adult cases may indicate the protective effect of IL-22. On the contrary, the association between the severity of pneumonia and the elevation of Tc17 cells in adults may reveal the damaging effect of IL-22 when it is co-expressed with IL-17.

Prognostic factors for COVID-19 patients.

INTRODUCTION: Determining prognostic factors in patients with coronavirus disease (COVID-19) can have great impact on treatment planning and follow-up strategies. Herein, we aimed to evaluate prognostic factors and clinical scores for confirmed COVID-19 patients in a tertiary-care hospital in the Bursa region of Turkey. METHODOLOGY: Patients who had been diagnosed with COVID-19 microbiologically and/or radiologically between March and October 2020 in a tertiary-care university hospital were enrolled retrospectively. Adult patients (≥ 18 years) with a clinical spectrum of moderate, severe, or critical illness were included. The dependent variable was 30-day mortality and logistic regression analysis was used to evaluate any variables with a significant p value (< 0.05) in univariate analysis. RESULTS: A total of 257 patients were included in the study. The mortality rate (30-day) was 14.4%. In logistic regression analysis, higher scores on sequential organ failure assessment (SOFA) (p < 0.001, odds ratio (OR) = 1.86, 95% CI = 1.42-2.45) and CURB-65 pneumonia severity criteria (p = 0.001, OR = 2.60, 95% CI = 1.47-4.57) were found to be significant in predicting mortality at admission. In deceased patients, there were also significant differences between the baseline, day-3, day-7, and day-14 results of D-dimer (p = 0.01), ferritin (p = 0.042), leukocyte (p = 0.019), and neutrophil (p = 0.007) counts. CONCLUSIONS: In our study of COVID-19 patients, we found that high SOFA and CURB-65 scores on admission were associated with increased mortality. In addition, D-dimer, ferritin, leukocyte and neutrophil counts significantly increased after admission in patients who died.

Association of SARS-CoV-2 cycle threshold (Ct) values with clinical course and serum biomarkers in COVID-19 patients.

INTRODUCTION: Our knowledge has gaps regarding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication levels and its association to severity of Coronavirus disease 2019 (COVID-19). The aim of this study was to investigate the association of SARS-CoV-2 viral load with disease severity and serum biomarkers in COVID-19 patients. METHODOLOGY: Viral load was determined via cycle threshold (Ct) values of SARS-CoV-2 real-time reverse transcriptase-polymerase chain reaction (RT-PCR) in 214 adult patients. Ct values were compared with clinical severity, biochemical and hematological biomarkers. RESULTS: Clinical course of the disease was mild (49.1%), moderate (40.2%), and severe (10.7%). Median Ct value was 28.2 (IQR: 22.2-33.8) during the first week of the disease. Ct values were lower within five days after symptom onset [lowest Ct value on the third day (median: 24, IQR: 20.6-32.3)], but they increased significantly during the second and third weeks. No association was detected between admission Ct values and disease severity. Gender, age, co-morbidity, and mortality did not differ significantly in patients with low (≤ 25) and high (> 25) Ct values. White blood cell, neutrophil, platelet, and especially lymphocyte counts, were significantly lower in patients with low Ct values. CONCLUSIONS: No definitive/clear correlation between SARS-CoV-2 viral load and severity and mortality was found in the studied COVID-19 patients. However, neutrophil, platelet, and especially lymphocyte count were significantly lower in patients with a high viral load.

Comparison of SARS-CoV-2 Antibodies and Six Immunoassays in Pediatric and Adult Patients 12 Weeks After COVID-19.

Introduction Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific humoral immune persistence has been proposed to be affected by patients' characteristics. Moreover, available conflicting assay results are needed to be settled through comparative research with defined clinical specimens. Methods This prospective study investigated SARS-CoV-2-specific antibodies among 43 adults and 34 children at a mean of 12 weeks after the onset of COVID-19 symptoms using six serological assays and compared their performance. We used two Euroimmun (Euroimmun, Luebeck, Germany), two automated Roche Elecsys (Basel, Switzerland), and two rapid immuno-chromatographic Ecotest (Matrix Diagnostics, Assure Tech. (Hangzhou) Co., L, China) assays to investigate SARS-CoV-2 antibodies. Results The findings showed that the Roche Elecsys anti-S total test yielded the best positivity/sensitivity (children 94.1% and adults 93.0%; p = 0.877) while five immunoglobulin IgG targeting assays had similar positivity/sensitivity between children (88.2% to 94.1%) and adults (88.4% to 93.0%) (p > 0.05). Although IgM positivity was relatively low (p < 0.001), it was found in the majority of our pediatric and adult patients (67.6% and 86.0%, respectively; p = 0.098). SARS-CoV-2 S IgG titers were found to be higher among males in pediatric and adult groups compared to females (p = 0.027 and p = 0.041, respectively). Furthermore, we observed significantly higher antibody titers among pneumonia patients (p = 0.001). Conclusion Overall, we concluded SARS-CoV-2 antibody persistence over an average of 12 weeks after the onset of COVID-19 symptoms. While automated Roche Elecsys total antibody assays yielded the best sensitivity (> 90%) and five assays targeting IgG had acceptable performance. Patients with pneumonia and males have higher antibody titers. The effect of antibody persistence on re-infections should be monitored in longitudinal studies.

Assessment of CD39 expression in regulatory T-cell subsets by disease severity in adult and juvenile COVID-19 cases.

COVID-19 is a disease characterized by acute respiratory failure and is a major health problem worldwide. Here, we aimed to investigate the role of CD39 expression in Treg cell subsets in COVID-19 immunopathogenesis and its relationship to disease severity. One hundred and ninety COVID-19 patients (juveniles, adults) and 43 volunteers as healthy controls were enrolled in our study. Flow cytometric analysis was performed using a 10-color monoclonal antibody panel from peripheral blood samples. In adult patients, CD39+ Tregs increased with disease severity. In contrast, CD39+ Tregs were decreased in juvenile patients in an age-dependent manner. Overall, our study reveals an interesting profile of CD39-expressing Tregs in adult and juvenile cases of COVID-19. Our results provide a better understanding of the possible role of Tregs in the mechanism of immune response in COVID-19 cases.

Healthcare-Associated Stenotrophomonas maltophilia Bacteraemia: Retrospective Evaluation of Treatment and Outcome.

Introduction Stenotrophomonas maltophilia (SM) is one of the common gram-negative pathogens that cause nosocomial infections. The aim of the present study is to evaluate the treatment and outcome of SM bacteraemia. Materials and Methods We retrospectively evaluated antimicrobial treatment in adult patients with nosocomial SM bacteraemia, with the 14th and 30th-day mortality as the outcome. Results In total, 140 adult patients with SM bacteraemia who were diagnosed between January 1, 2002, and December 31, 2016 were enrolled in the present study. Seventy-one (50.7%) patients were in the intensive care unit (ICU). The 14th and the 30th-day mortality rates were 32.9% (n=46) and 45.7% (n=64), respectively. Female sex (OR, 7.47; 95% CI 1.61-34.47, p<0.01), steroid use within the last month (OR, 10.2; 95% CI 1.27-82.27, p=0.029), Pittsburgh bacteraemia score (PBS) ≥4 (OR, 39.9; 95% CI 4.96-321.32, p<0.001) and solid organ malignancy (OR, 9.6; 95% CI 1.73-53.72, p<0.01) were independent risk factors for 14th day mortality. Removal of the catheter was an independent protective factor for both 14th (OR, 0.05; 95% CI 0.22-0.010, p<0.001) and 30th day (OR, 0.039;95% CI 0.164-0.009, p<0.001) mortality. We did not detect any difference between treatment regimens including trimethoprim-sulfamethoxazole (TMP/SMX) or levofloxacin in terms of mortality. We found that TMP/SMX and levofloxacin combination did not significantly improve patient prognosis. Conclusion  Due to the high mortality rates associated with nosocomial SM bacteraemia, adequate antibiotic therapy should be initiated immediately in the suspicion of infection, and prompt removal of any indwelling central venous catheter is important.

Propensity Score and Desirability of Outcome Ranking Analysis of Ertapenem for Treatment of Nonsevere Bacteremic Urinary Tract Infections Due to Extended-Spectrum-Beta-Lactamase-Producing Enterobacterales in Kidney Transplant Recipients.

There are scarce data on the efficacy of ertapenem in the treatment of bacteremia due to extended-spectrum-beta-lactamase (ESBL)-producing Enterobacterales (ESBL-E) in kidney transplant (KT) recipients. We evaluated the association between treatment with ertapenem or meropenem and clinical cure in KT recipients with nonsevere bacteremic urinary tract infections (B-UTI) caused by ESBL-E. We performed a registered, retrospective, international (29 centers in 14 countries) cohort study (INCREMENT-SOT, NCT02852902). The association between targeted therapy with ertapenem versus meropenem and clinical cure at day 14 (the principal outcome) was studied by logistic regression. Propensity score matching and desirability of outcome ranking (DOOR) analyses were also performed. A total of 201 patients were included; only 1 patient (treated with meropenem) in the cohort died. Clinical cure at day 14 was reached in 45/100 (45%) and 51/101 (50.5%) of patients treated with ertapenem and meropenem, respectively (adjusted OR 1.29; 95% CI 0.51 to 3.22; P = 0.76); the propensity score-matched cohort included 55 pairs (adjusted OR for clinical cure at day 14, 1.18; 95% CI 0.43 to 3.29; P = 0.74). In this cohort, the proportion of cases treated with ertapenem with better DOOR than with meropenem was 49.7% (95% CI, 40.4 to 59.1%) when hospital stay was considered. It ranged from 59 to 67% in different scenarios of a modified (weights-based) DOOR sensitivity analysis when potential ecological advantage or cost was considered in addition to outcome. In conclusion, targeted therapy with ertapenem appears as effective as meropenem to treat nonsevere B-UTI due to ESBL-E in KT recipients and may have some advantages.

Conventional Amphotericin B Associated Nephrotoxicity in Patients With Hematologic Malignancies.

INTRODUCTION:  Amphotericin B (AmB-d) is one of the most effective therapeutic options against frequently life-threatening systemic fungal infections in patients with hematologic malignancies. However, significant adverse effects including nephrotoxicity associated with its use limit its more widespread use. The objectives of our study were to determine the incidence of AmB-d associated nephrotoxicity, to evaluate clinical and epidemiological characteristics of patients, and to support the notion that conventional amphotericin B remains a valid therapeutic option among hematologic patients with proper patient selection. MATERIALS AND METHODS: A total of 110 patients with hematologic malignancies were admitted to our Hematology Unit between January 2014 and November 2017 who required anti-fungal therapy during intensive systemic chemotherapy. The incidence of AmB-d associated nephrotoxicity, side effect profile, time to nephrotoxicity, and clinical and epidemiological characteristics associated with treatment success were assessed retrospectively. RESULTS: Of the 110 patients receiving AmB-d, 70 (63.6%) were male and 40 (36.4%) were female. The mean age of participants was 44 years. The most common diagnosis was acute myeloid leukemia (n=53, 48.2%), and the most common chemotherapy protocol was 7 + 3 remission-induction (cytarabine 100 mg/m² days 1-7, Idarubicin 12 mg/m² days 1-3; n=24, 21.8%). In 56.4% of the patients, antifungal therapy was given empirically. In 40 patients (36.4%), nephrotoxicity was observed following antifungal treatment, and only four patients had stage 3 renal failure. The mean duration of time to nephrotoxicity from initiation of amphotericin B was four days (min: 2, max: 31). All patients were found to receive at least one additional potential nephrotoxic treatment during the antifungal treatment process.  Conclusion: AmB-d is associated with a significant risk of nephrotoxicity. In most hematological patients, antifungal treatment is initiated empirically, and patients received prolonged courses of treatment. Therefore, it is plausible to initiate such treatment with AmB-d, when one considers the already high treatment costs in this patient group as well as the fact that AmB-d offers similar efficacy to antifungal agents at a lower cost. AmB-d may be recommended as a first-line agent in this patient group with the introduction of newer and more costly antifungal agents when needed, on the basis of the fact that these patients can be closely monitored in a hospital setting, reversible nature of nephrotoxicity upon discontinuation, and rare occurrence of severe renal failure requiring dialysis.

Vancomycin-resistant enterococci infection and predisposing factors for infection and mortality in patients with acute leukaemia and febrile neutropenia.

BACKGROUND: Vancomycin-resistant enterococcus (VRE) is an infectious agent that can increase morbidity and mortality, especially in patients with neutropenia in haematology departments. We analysed VRE infections and mortality rates among VRE colonized patients with acute leukaemia, defined predisposing risk factors for infection and mortality, and investigated the influence of daptomycin or linezolid treatment on mortality. PATIENTS-METHODS: We included 200 VRE colonized adult acute leukaemia patients with febrile neutropenia between January 2010 and January 2016. Data were collected from electronic files. RESULTS: There were 179 patients in the colonized group, and 21 patients in the infected group. Enterococcus faecium (van A) was isolated from all patients. The infection rate was 10.5 %, and the types of infections noted were as follows: bloodstream (n = 14; 66.7 %), skin and soft tissue (n = 3; 14.3 %), urinary (n = 2; 9.5 %), and others (9.5 %). In the multivariate logistic regression analysis, exposure to invasive procedures, coinfection status, and >15 days of VRE positivity were independent risk factors for VRE infections. In hospital mortality rates were 57.1 % in the infected group, and 9.5 % in the colonized group (p < 0.001). Older age, female gender, absolute neutropenia, and coinfection status were statistically significant predictor of survival. CONCLUSION: Vancomycin-resistant enterococcus infections are associated with high morbidity and mortality in haematology patients with neutropenia. Clinicians should be aware of predisposing risk factors for VRE infection to avoid unfavourable outcomes. We believe that larger studies are necessary regarding the influence of treatment with daptomycin and linezolid.

The Outcome of Antifungal Prophylaxis with Posaconazole in Patients with Acute Myeloid Leukemia: A Single-Center Study

Objective: Invasive fungal infections (IFIs) are a significant cause of morbidity and mortality among neutropenic patients undergoing chemotherapy for acute myeloid leukemia (AML) and stem cell transplantation. The aim of this study was to evaluate the real-life impact of posaconazole prophylaxis. Materials and Methods: Eighty-four adult patients were included with AML under remission induction chemotherapy and posaconazole prophylaxis. The 34 patients in the control group did not receive primary antifungal prophylaxis. The period between June 2006 and January 2009, when antifungal prophylaxis was not administered (control group), was retrospectively compared to the period between December 2010 and May 2012 when primary oral posaconazole prophylaxis was administered in similar conditions (posaconazole group) according to the use of antifungal agents for treatment, breakthrough infections, galactomannan performance, and the necessity for performing bronchoalveolar lavage (BAL) procedures. Results: The two groups were compared according to the use of antifungal agents; progression to a different antifungal agent was found in 34/34 patients (100%) in the control group and in 9/84 patients (11%) in the posaconazole group (p<0.001). There were four breakthrough IFIs (4/84, 4.8%) in the posaconazole group and 34 IFIs in the control group (p<0.001). In addition, 15/34 patients (44%) in the control group required BAL compared to 11/84 patients (13%) in the posaconazole group (p<0.001). Posaconazole treatment was discontinued within 7-14 days in 7/84 patients (8.3%) due to poor oral compliance related to mucositis after chemotherapy. Conclusion: Posaconazole appears to be effective and well-tolerated protection against IFIs for AML patients.

Central nervous system infections in the absence of cerebrospinal fluid pleocytosis.

Previous multicenter/multinational studies were evaluated to determine the frequency of the absence of cerebrospinal fluid pleocytosis in patients with central nervous system infections, as well as the clinical impact of this condition. It was found that 18% of neurosyphilis, 7.9% of herpetic meningoencephalitis, 3% of tuberculous meningitis, 1.7% of Brucella meningitis, and 0.2% of pneumococcal meningitis cases did not display cerebrospinal fluid pleocytosis. Most patients were not immunosuppressed. Patients without pleocytosis had a high rate of unfavorable outcomes and thus this condition should not be underestimated.