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Background: Lactate dehydrogenase (LDH) levels predict coronavirus disease 2019 (COVID-19) severity. We investigated LDH isoenzyme levels to identify the tissue responsible for serum LDH elevation in patients with COVID-19. Methods: Hospitalised COVID-19 patients with serum LDH levels exceeding the upper reference limit included. LDH isoenzymes were detected quantitatively on agarose gels. The radiological severity of lung involvement on computed tomography was scored as 0-5 for each lobe (total possible score, 0-25). Disease severity was determined using the World Health Organization (WHO) clinical progression scale. Results: In total, 111 patients (mean age, 59.96 ± 16.14), including 43 females (38.7%), were enrolled. The serum levels of total LDH and all five LDH isoenzymes were significantly higher in the severe group. The levels of all LDH isoenzymes excluding LDH5 positively correlated with the WHO score. LDH3 levels correlated with chest computed tomography findings (r2 = 0.267, p = 0.005). On multivariate analysis, LDH3 was an independent risk factor for the deterioration of COVID-19. Conclusions: LDH3 appears to be an independent risk factor for deterioration in patients with COVID-19. LDH elevation in patients with COVID-19 predominantly resulted from lung, liver and muscle damage.

Background: A rapid and reliable diagnostic test is needed to reduce mortality through early diagnosis of invasive aspergillosis (IA) in patients with hematological malignancies. Objective: To evaluate the efficacy of serum and bronchoalveolar lavage (BAL) Aspergillus galactomannan lateral flow assay (GM-LFA) in IA diagnosis and determine the correlation of GM-LFA with GM enzyme immunoassay (GM-EIA) in patients with hematological malignancies. Methods: In this prospective multicenter study, we used serum and BAL fluid samples from patients with hematological malignancies and suspected IA and performed GM-LFA and GM-EIA. According to the EORTC/MSGERC criteria, patients were grouped as proven (n=6), probable (n=22), possible IA (n=55), or no IA (n=88). The performance of serum GM-LFA at 0.5 optical density index (ODI) and area under the curve (AUC) were calculated. Spearman’s correlation analysis and kappa statistics were performed to determine the agreement between the tests. Results: GM-LFA showed an AUC of 0.832 in proven/probable IA (sensitivity [SEN], specificity [SPE], negative predictive value [NPV], and diagnostic accuracy were 75%, 100%, 92.6%, and 93.9%, respectively, at a 0.5 ODI) versus that in no IA. A moderate positive correlation was noted between the GM-LFA and GM-EIA scores (p=0.01). The observed agreement between the tests at 0.5 ODI was almost perfect (pConclusions: Serum GM-LFA demonstrated high discriminatory power and good diagnostic performance for IA in patients with hematological malignancies.

Item does not contain fulltext BACKGROUND: Rezafungin is a next-generation, once-a-week echinocandin in development for the treatment of candidaemia and invasive candidiasis and for the prevention of invasive fungal disease caused by Candida, Aspergillus, and Pneumocystis spp after blood and marrow transplantation. We aimed to compare the efficacy and safety of intravenous rezafungin versus intravenous caspofungin in patients with candidaemia and invasive candidiasis. METHODS: ReSTORE was a multicentre, double-blind, double-dummy, randomised phase 3 trial done at 66 tertiary care centres in 15 countries. Adults (≥18 years) with systemic signs and mycological confirmation of candidaemia or invasive candidiasis were eligible for inclusion and randomly assigned (1:1) to receive intravenous rezafungin once a week (400 mg in week 1, followed by 200 mg weekly, for a total of two to four doses) or intravenous caspofungin (70 mg loading dose on day 1, followed by 50 mg daily) for no more than 4 weeks. The primary endpoints were global cure (consisting of clinical cure, radiological cure, and mycological eradication) at day 14 for the European Medical Agency (EMA) and 30-day all-cause mortality for the US Food and Drug Administration (FDA), both with a target non-inferiority margin of 20%, assessed in the modified intention-to-treat population (all patients who received one or more doses of study drug and had documented Candida infection based on a culture from blood or another normally sterile site obtained within 96 h before randomisation). Safety was evaluated by the incidence and type of adverse events and deaths in the safety population, defined as all patients who received any amount of study drug. The trial is registered with ClinicalTrials.gov, NCT03667690, and is complete. FINDINGS: Between Oct 12, 2018, and Aug 29, 2021, 222 patients were screened for inclusion, and 199 patients (118 [59%] men; 81 [41%] women; mean age 61 years [SD 15·2]) were randomly assigned (100 [50%] patients to the rezafungin group and 99 [50%] patients to the caspofungin group). 55 (59%) of 93 patients in the rezafungin group and 57 (61%) of 94 patients in the caspofungin group had a global cure at day 14 (weighted treatment difference -1·1% [95% CI -14·9 to 12·7]; EMA primary endpoint). 22 (24%) of 93 patients in the rezafungin group and 20 (21%) of 94 patients in the caspofungin group died or had an unknown survival status at day 30 (treatment difference 2·4% [95% CI -9·7 to 14·4]; FDA primary endpoint). In the safety analysis, 89 (91%) of 98 patients in the rezafungin group and 83 (85%) of 98 patients in the caspofungin group had at least one treatment-emergent adverse event. The most common treatment-emergent adverse events that occurred in at least 5% of patients in either group were pyrexia, hypokalaemia, pneumonia, septic shock, and anaemia. 55 (56%) patients in the rezafungin group and 52 (53%) patients in the caspofungin group had serious adverse events. INTERPRETATION: Our data show that rezafungin was non-inferior to caspofungin for the primary endpoints of day-14 global cure (EMA) and 30-day all-cause mortality (FDA). Efficacy in the initial days of treatment warrants evaluation. There were no concerning trends in treatment-emergent or serious adverse events. These phase 3 results show the efficacy and safety of rezafungin and support its ongoing development. FUNDING: Cidara Therapeutics and Mundipharma.

Background: The prediction of disease severity in COVID-19 is valuable for providing appropriate supportive care earlier and reducing mortality. We aimed to evaluate the impact of baseline cortisol values on disease severity and assess the correlation between the neutrophil to lymphocyte ratio (NLR) and cortisol levels. Methods: In this retrospective study, we compared the prognostic value of baseline the NLR, morning cortisol, ferritin, and C-reactive protein (CRP) levels among patients with severe and nonsevere COVID-19. The relationships were assessed with Spearman’s correlation. Results: Of 167 patients, 63 (37.7%) had severe disease, and their baseline cortisol levels were higher than those in the nonsevere group (18.92 µg/dL vs 13.8 µg/dL, p=0.011). The baseline cortisol level and NLR had area under the curve (AUC) values of 0.62 (95% confidence interval [CI] 0.53-0.71) and 0.70 (CI 95% 0.62-0.78) for the prediction of severe COVID-19, respectively. Severe disease was predicted in patients with a baseline cortisol cutoff ≥ 18.92 µg/dL (552 nmol/L) with a specificity of 75.0%, a sensitivity of 50.79%. The cutoff value for the NLR on day 1 was ≥ 6.2, with a specificity of 93.27% and a sensitivity of 32.79%. Baseline cortisol levels showed a significant weak-moderate positive correlation with the NLR and levels of CRP and ferritin on day 1 (r=0.33, r= 0.29, r= 0.28, respectively, p

Coronavirus disease 2019 (COVID-19) is a worldwide pandemic, causing a global health threat. Up to 15% of the confirmed cases develop severe disease, requiring hospitalization or intensive care unit (ICU) admission. Tocilizumab, an IL-6 receptor antagonist, is a promising treatment of severe pneumonia with acute respiratory distress syndrome (ARDS) or cytokine release syndrome (CRS) in the course of COVID-19. We report a suppurative costochondritis and chest wall abscess in a severe COVID-19 patient treated with tocilizumab.

Background Pre‐existing chronic liver disease is currently considered a poor prognostic factor for coronavirus disease 2019 (COVID‐19). The present study aimed to investigate the association of liver stiffness measurement (LSM) with disease severity and clinical course of COVID‐19. Methods We prospectively recruited consecutive hospitalised adult patients with COVID‐19 in a 3‐month period. Demographic, laboratory, clinical and vibration‐controlled transient elastography (VCTE) features were recorded at entry, and all patients were prospectively followed‐up. Severe liver fibrosis was defined as an LSM value higher than 9.6 kPA. Multivariate logistic regression analysis was performed to reveal factors associated with disease severity and outcomes. Results Out of 98 eligible patients with COVID‐19, 12 (12.2%) had severe liver fibrosis. Patients with severe liver fibrosis had higher baseline disease severity (P = .022), more commonly required oxygen treatment at entry (P = .010), and had intensive‐care unit (ICU) requirements during the 6 (1‐39)‐day median follow‐up time (P = .017). The presence of severe liver fibrosis was independently associated with disease severity (odds ratio (OR): 7.685, 95% confidence interval (CI): 1.435‐41.162, P = .017) and ICU requirement (OR: 46.656, 95% CI: 2.144‐1015.090, P = .014). LSM was correlated with alanine aminotransferase levels (P = .005, r: 0.283), but not with other markers of acute hepatic injury or inflammation. Conclusion Initial VCTE application might help physicians identify patients who are more likely to have severe illness or worse clinical outcomes, in addition to other well‐established clinical and laboratory factors. Further multicentre prospective studies are warranted to validate our results.

Candiduria is commonly seen in hospitalized patients and most of the patients are asymptomatic, but it may be due to cystitis, pyelonephritis, prostatitis, epididymo-orchitis or disseminated candidiasis. Major risk factors are diabetes mellitus, indwelling urinary catheters, use of broad-spectrum antibiotics, urinary obstruction, and admission to intensive care units. Candida urinary tract infections can be caused by hematogenous spread following candidemia, or retrograde route via the urethra. The presence of Candida species in urine in asymptomatic patients does not warrant antifungal therapy except neutropenic patients, very low-birth-weight infants and patients undergoing urologic procedures. Fluconazole is the treatment of choice for symptomatic infections, it achieves high urinary levels. The other azole antifungals and echinocandins do not reach sufficient urine levels. Amphotericin B deoxycholate is the alternative antifungal agent if fluconazole can not be used because of resistance, allergy or failure.

Objective: This study aimed to identify the effect of tocilizumab (TCZ) on clinical outcomes in severe COVID-19 patients. Material and Methods: We included hospitalized COVID-19 patients with an initial WHO scale ≥4. We matched the patients with baseline characteristics by using propensity scores. Then, we selected patients with C-reactive protein levels above 30 and showing an upward trend. We assessed the effect of TCZ in patients on clinical outcomes by using Mann – Whitney U and Chi-square tests. Results: Of 200 patients who had an initial WHO scale ≥ 4, 42 (21%) were given TCZ in addition to standard of care (SOC). Twentyfive patients (50%) needed mechanical ventilation (MV) in the TCZ group, compared with 35 (21%) of 158 patients with SOC (p

Cryptococcus neoformans is generally observed with immunosuppressive conditions. Rarely, it may be seen in immunocompetent individuals and presented with non-specific conditions. We described an immunocompetent case of cryptococcal meningitis presented with multiple cerebral infarcts. Despite the late diagnosis and emergence of hydrocephalus during treatment, the patient was recovered without any sequelae. In immunocompetent patients, the conventional diagnostics tests may be negative because of the low fungal load. If it is available, the Biofire FilmArray meningitis panel has high sensitivity and specificity for diagnosis. (C) 2021 The Authors. Published by Elsevier Ltd.

BackgroundCoronavirus disease 2019 (COVID-19) quickly spread worldwide to become a pandemic. This study aimed to define the predictors of critical illness development within 28 days postadmission.MethodsWe conducted a prospective cohort study including 477 PCR-positive COVID-19 patients admitted to a tertiary care hospital in Istanbul from March 12 to May 12, 2020. The development of critical illness, e.g., invasive mechanical ventilation and/or death, was followed for a period of 28 days postadmission. Demographic characteristics, number of comorbidities, illness severity at admission defined by the WHO scale, vital signs, laboratory findings and period of admission to the hospital were independent variables. Cox proportional hazards analysis was performed, and the C-index was calculated.ResultsThe median (IQR) age of the cohort was 55.0 (44.0-67.0) years, and 50.1% were male. The most common presenting symptoms were cough, dyspnea and fatigue. Overall, 65.2% of the patients had at least one comorbidity. Hydroxychloroquine was given to 99.2% of the patients. Critical illness developed in 45 (9.4%; 95% CI: 7.0%-12.4%) patients. In the multivariable analysis, age (HR: 1.05, pConclusionsAge, comorbidity number, WHO scale, LDH and procalcitonin were independently associated with critical illness development. Mortality from COVID-19 seems to be decreasing as the pandemic advances.summaryWe analyzed 477 confirmed COVID-19 patients for the development of critical illness, e.g., invasive mechanical ventilation and/or death within 28 days postadmission. Age, comorbidity number, WHO scale, LDH and procalcitonin were independently associated with critical illness development.

One of the most problematic issues in hematological malignancies is the diagnosis of invasive fungal diseases. Especially, the difficulty of mycological diagnosis and the necessity of immediate intervention in molds have led to the adoption of "surrogate markers" that do not verify but rather strongly suggest fungal infection. The markers commonly used are galactomannan (GM), beta-glucan, and imaging methods. Although there are numerous studies on these diagnostic approaches, none of these markers serve as a support for the clinician, as is the case in human immunodeficiency virus (HIV) or cytomegalovirus (CMV) infections. This paper has been prepared to explain the diagnostic tests. As molecular tests have not been standardized and are not used routinely in the clinics, they will not be mentioned here.Hematolojik malignitelerin tedavisinde önemli sorunlardan birisi de invazif fungal infeksiyonların tanısıdır. Mikolojik tanıdaki zorluklar ve hızlı müdahele etme gerekliliği, küf mantarlarının tanısında dolaylı işaretleyicilerin geliştirilmesine yol açmıştır. En sık kullanılan tanı testleri galaktomannan, beta-glukan ve moleküler yöntemlerdir. Her ne kadar bu tanı yöntemleri ile ilgili çok sayıda araştırma yapılmakta ise de, hiçbiri HIV ya da CMV’de olduğu gibi doğrudan yarar sağlamamaktadır. Tanı ile ilgili bu yazı klinisyene eldeki araçları kullanma konusunda yol göstermeyi amaçlamaktadır. Moleküler testlere henüz standardize edilmediği ve klinik kullanıma girmediği için bu yazıda değinilmeyecektir.

Objectives: Previously, in an animal study we showed that N-acetylcysteine (NAC) could decrease deoxycholate amphotericin B (DAmB) induced renal tubular apoptosis. In this clinical study, we aimed to evaluate the efficacy of NAC in preventing acute kidney injury (AKI) in febrile neutropenic patients with invasive pulmonary aspergillosis treated with DAmB.Patients and Methods: Thirty-three patients were included in the study. 17 patients were randomly placed into the DAmB group and 16 were randomly placed into the DAmB plus NAC group.Results: The characteristics of patients, durations and cumulative doses of DAmB, concurrent nephrotoxic drugs and basal serum creatinine (SCr) levels of patients were similar. Occurrence of a 1.5 fold or greater increase in the concentration of basal SCr and serum electrolytes were observed prospectively. The overall AKI was found in 13 patients (76.4%) in DAmB group and 6 patients (37.5%) in combination group (P = 0.024). No significant difference was observed in hypokalemia incidence between the groups (87.5 % in combination vs. 94.1 % in DAmB only groups).Conclusion: This clinical pilot study showed that NAC may be a promising anti-oxidant agent to decrease DAmB-induced AKI in febrile neutropenic patients.Keywords: Amphotericin

Summary A ‘trailing’ effect has been commonly observed when azole antifungals are tested against Candida spp. Previous experience with fluconazole indicates that 24-h minimum inhibitory concentration (MIC) values are more compatible endpoints when compared with clinical outcomes. We evaluated the trailing effect of Candida isolates tested with itraconazole in a guinea pig model of systemic candidiasis. Survival and organ burden were only significantly affected by using a higher dose of itraconazole, irrespective of the MIC differences at 24 and 48 h. A fluconazole-resistant strain with susceptible dose-dependent MICs to itraconazole was successfully treated with high-dose itraconazole. Our data suggests that survival and microbiological response depend more on drug dosing than on the trailing phenotype of the isolates.

Infective Endocarditis caused by Streptococcus bovis may usually be associated with gastrointestinal pathologies, particularly colon cancer. S. bovis endocarditis may cause higher rates of neurological complications and more extensive valvular destruction compared to other microorganisms. This case report describes a patient with a recent history of rectal adenocarcinoma diagnosed as S. bovis endocarditis and complicated by intracranial and subarachnoidal hemorrhage after cardiac valve replacement. Because of high rates of neurological complications, these patients should be carefully followed up even after the medical and/or surgical treatment. Key Words: Endocarditis, bacterial, Streptococcus bovis rectal carcinoma, intracranial hemorrhage, subarachnoid hemorrhage, valvular destruction

Hepatobiliary tuberculosis is uncommon even in endemic countries. It is associated with a high mortality and is even diagnosed early in the disease course. Acute liver failure (ALF) caused by tuberculosis bacilli has been reported in only a few reports. All previous cases have been diagnosed by postmortem examination. Time to antituberculosis treatment is very critical. In case of suggestive findings on clinical and radiologic examination, antituberculosis treatment should be initiated immediately. Drug use can be a challenge in patients with ALF. However, as long as the other possible causes of ALF can be excluded and hepatotoxic drugs were avoided during the early course of treatment, such a highly fatal presentation of tuberculosis can be treated safely. Here, we report a case of acute liver failure as a presentation of miliary tuberculosis. He was treated successfully with antituberculosis treatment.

Nineteen cases of suspected Crimean-Congo hemorrhagic fever reported from Turkey., In 2002 and 2003, a total of 19 persons in Turkey had suspected cases of Crimean-Congo hemorrhagic fever (CCHF) or a similar viral infection. Six serum samples were tested; all six were found positive for immunoglobulin M antibodies against CCHF virus. Two of the samples yielded CCHF virus isolates. Genetic analysis of the virus isolates showed them to be closely related to isolates from former Yugoslavia and southwestern Russia. These cases are the first of CCHF reported from Turkey. Eighteen patients handled livestock, and one was a nurse with probable nosocomial infection. The case-fatality rate was 20% among confirmed CCHF case-patients (1 of 5 patients), and the overall case-fatality rate was 11% (2 of 19 patients). In addition to previously reported symptoms and signs, we report hemophagocytosis in 50% of our patients, which is the first report of this clinical phenomenon associated with CCHF.

To determine the prevalence of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae (PE) fecal carriage in patients that undergo transrectal ultrasonography-guided biopsy (TRUSbx) and its relationship with post-biopsy infections.A prospective clinical study in 4 different tertiary hospitals between 2008 and 2010 was conducted. Four hundred men with sterile urine who were to undergo a TRUSbx because of the suspicion of prostate cancer were included and followed for 14 days after biopsy. Rectal swab culture specimens were acquired immediately before the procedure. Demographic data, prophylaxis choice, quinolone or any other antibiotic consumption within the past 2 months, history of prostatitis, repeat biopsy, intensive care unit admission, hospitalization, urethral catheterization, diabetes mellitus (DM), and steroid usage were recorded.ESBL carriage was detected in 19% of patients and quinolone use within the last 2 months; other antibiotic use within the last 2 months and DM were found to be significantly associated (P.05). Symptomatic urinary tract infection (UTI) on the third day after biopsy was seen in 9% of patients and was associated with fluoroquinolone (FQ) consumption before biopsy. Although ESBL-PE carriage was associated with post-biopsy UTI symptoms, it was not found to be associated with post-biopsy symptomatic UTI. Urosepsis was seen in 2 patients (0.5%) after biopsy, and both the patients were ESBL-PE carriers.The presence of ESBL-PE was associated with DM and FQ consumption before biopsy. ESBL-PE carriage was associated with a high rate of post-biopsy UTI symptoms requiring further elucidation; however, it was not associated with microbiologically proven infections. FQ consumption before TRUSbx was also associated with post-biopsy infections.

The in vitro interactions of anidulafungin with itraconazole, voriconazole, and amphotericin B were evaluated by using the checkerboard method. For Aspergillus spp., anidulafungin with amphotericin B showed indifference for 16/26 isolates, while anidulafungin with either azole showed a synergy trend for 18/26 isolates. All drug combinations showed indifference for 7/7 Fusarium sp. isolates.

Background. Inflammation is one of the main contributors to atherosclerosis in haemodialysis (HD) patients. Activation of Toll-like receptors (TLRs) leads to inflammatory response. In this study, we aimed to evaluate the expression of TLRs on monocytes and relate their expression with inflammation in chronic kidney disease (CKD) and HD patients. Methods. Thirty-four age- and gender-matched controls and stage 3-4 CKD patients and thirty-two HD patients were included in each study group. The effect of HD on the expression of Toll-like receptor-2 (TLR-2) and Toll-like receptor-4 (TLR-4) on CD14(+) monocytes was determined at the beginning (baseline), during (120 min) and following (300 min and 24 h) HD and compared with control and stage 3-4 CKD groups. The HD procedure was performed by using low-flux polysulphone dialysers. In addition, serum IL-6 levels were evaluated in both groups at baseline and after a HD session. Results. The percentage of CD14(+) monocytes expressing TLR-2 were similar in all of the study groups, whereas the percentage of CD14(+) monocytes expressing TLR-4 were significantly lower in both stage 3-4 CKD and HD patients at baseline than in controls. The mean fluorescence intensities (MFI) of TLR-2 were significantly lower in controls than in stage 3-4 CKD and HD patients at baseline. The MFI of TLR-4 was similar in all of the groups. The percentage of CD14(+) monocytes expressing TLR-2 did not change during and after HD. The MFI of TLR-2 decreased at 120 min of HD compared with baseline (1837 +/- 672 vs 1650 +/- 578, P < 0.05), and recovered back to baseline values at 300 min and at 24 h post-HD. MFI of TLR-4 increased at 24 h compared with baseline (941 +/- 294 vs 1087 +/- 441, P < 0.05). Serum IL-6 levels correlated with MFI of TLR-2 and TLR-4 in stage 3-4 CKD patients and in HD patients at baseline and after HD in univariate analysis. Stepwise multiple regression analysis revealed that MFI of TLR-2 was an independent determinant of serum IL-6 concentrations in stage 3-4 CKD and in HD patients at baseline, at 300 min and at 24 h post-HD. Conclusions. Our study demonstrates that TLR-2 is associated with the inflammatory response of non-dialysed and dialysed CKD patients.

An 87 -year-old female who was undergoing peritoneal dialysis presented with peritonitis caused by Alcaligenes faecalis and Pantoea agglomerans in consecutive years. With the following report we discuss the importance of these unusual microorganisms in peritoneal dialysis patients.

Concomitant infections, which are common in patients who have received an organ transplant, must be diagnosed and treated early to prevent high mortality rates. We describe a case of concomitant Cytomegalovirus infection and Aspergillus pneumonia in a heart transplant patient who received pulsed steroids as therapy for rejection, and we describe the successful treatment of that coinfection with ganciclovir and voriconazole.

A 'trailing' effect has been commonly observed when azole antifungals are tested against Candida spp. Previous experience with fluconazole indicates that 24-h minimum inhibitory concentration (MIC) values are more compatible endpoints when compared with clinical outcomes. We evaluated the trailing effect of Candida isolates tested with itraconazole in a guinea pig model of systemic candidiasis. Survival and organ burden were only significantly affected by using a higher dose of itraconazole, irrespective of the MIC differences at 24 and 48 h. A fluconazole-resistant strain with susceptible dose-dependent MICs to itraconazole was successfully treated with high-dose itraconazole. Our data suggests that survival and microbiological response depend more on drug dosing than on the trailing phenotype of the isolates.

The reduction of amphotericin B (AmB)-induced renal tubular apoptosis and nephrotoxicity by N -acetylcysteine (NAC) in a murine model was evaluated. Four groups of rats were treated with AmB for 5 days, and each group concomitantly received two doses of 30, 60, or 120 mg of NAC/kg of body weight/day or sterile water for 5 days. Groups that received concomitant NAC at any dose had significantly decreased levels of apoptosis compared to that in animals receiving AmB only (48.8% versus 27.4, 23.6, or 23.5%, respectively; P < 0.001).

The effects of protein binding on the activities of caspofungin, anidulafungin, and micafungin were evaluated against Candida and Aspergillus species. Adding human serum sharply increased the MICs of micafungin and anidulafungin and modestly affected the MIC of caspofungin. The increase in MICs does not appear consistent with the rate of protein binding for the three compounds.

(1 -> 3)-beta-d-glucan is a well known cell wall constituent of fungal isolates that can be detected by assays in vivo and in vitro. Previous studies have shown that different fungal isolates may show different levels of reactivity with an assay for beta glucan. In this study we evaluated the in vitro reactivity of 127 clinical fungal isolates belonging to 40 different genera, with the Glucatell (TM) assay. The majority of the fungal isolates released high levels of beta glucan. Beta glucan test reactivity appears to be species-specific and this may reflect the beta glucan content of the organism.

Sera from 76 immunocompetent and 293 immunocompromised subjects were assayed for anti- Candida antibodies. The sensitivity, specificity, positive predictive value, and negative predictive value for invasive candidiasis were 74%, 75%, 62%, and 84% in the immunocompetent group and 15%, 60%, 1.7%, and 93% in the immunocompromised group, respectively. Syscan3 has high negative predictive value.

In this study, we evaluated the in vitro activity of anidulafungin against selected mold isolates. Anidulafungin showed promising activity against Bipolaris spicifera , Exophiala jeanselmei , Fonsecaea pedrosoi , Madurella mycetomatis , Penicillium marneffei , Phialophora verrucosa , Pseudallescheria boydii , Sporothrix schenckii , and Wangiella dermatitidis.

The Glucatell (1-->3)- beta-D-glucan (BG) detection assay (Associates of Cape Cod) was studied as a diagnostic adjunct for invasive fungal infections (IFIs). On the basis of findings from a preliminary study of 30 candidemic subjects and 30 healthy adults, a serum BG level of >or=60 pg/mL was chosen as the cutoff. Testing was performed with serial serum samples obtained from 283 subjects with acute myeloid leukemia or myelodysplastic syndrome who were receiving antifungal prophylaxis. At least 1 serum sample was positive for BG at a median of 10 days before the clinical diagnosis in 100% of subjects with a proven or probable IFI. IFIs included candidiasis, fusariosis, trichosporonosis, and aspergillosis. Absence of a positive BG finding had a 100% negative predictive value, and the specificity of the test was 90% for a single positive test result and >or=96% for >or=2 sequential positive results. The Glucatell serum BG detection assay is highly sensitive and specific as a diagnostic adjunct for IFI.

Zone diameters for anidulafungin by disk diffusion for 139 isolates of C. parapsilosis were compared with MICs by NCCLS M27-A2 broth microdilution. The comparison was poor unless the disks were prepared by dissolving anidulafungin in 1% dimethyl sulfoxide plus 0.1% Tween 80 and testing on Mueller-Hinton agar flooded with glucose and methylene blue.

A 24-year-old male patient with acute myeloid leukemia (AML), who had been in remission for 18 months following the completion of chemotherapy, presented with fatigue and nasal bleeding. He was found to have pancytopenia, and bone marrow aspiration showed relapsed AML. He was given high-dose sequential chemotherapy consisting of cytosine arabinoside, 500 mg/m per day as a 24-h continuous infusion, idarubicin, 12 mg/m per day on days 1–3, etoposide, 200 mg/m per day as a 24-h continuous infusion on days 8–10, and granulocyte colony-stimulating factor (GCSF), 5 mg/kg per day subcutaneously, starting from day 12 until absolute neutrophil recovery above 1000/mL. The patient became neutropenic, with a count below 100/mL, on the 5th day of chemotherapy. He was pyrexial on the next day, with a temperature of 39 8C, without any localizing symptoms or signs of infection. Blood cultures were taken, and chest X-ray was normal. Empirical antibiotic therapy with piperacillin–tazobactam was commenced, and vancomycin was added 48 h later, when no response was obtained. Examination revealed widespread oral mucositis on the fourth day of the febrile neutropenic episode. Blood cultures, which had been taken every other febrile day, revealed extended-spectrum b-lactamase-producing Escherichia coli on the seventh day of pyrexia, and meropenem and amikacin were substituted for piperacillin–tazobactam. Total parenteral nutrition was also commenced on the same date, as the patient now suffered from severe dysphagia and could not tolerate any oral intake. Fever and dysphagia continued, and an endoscopy was performed, revealing esophageal candidiasis on the 12th day of pyrexia. Fluconazole, 6 mg/kg per day, was commenced intravenously. A non-albicans Candida sp. was grown in both esophageal and blood cultures on the 14th day of pyrexia, and fluconazole was changed to amphotericin B deoxycholate, 0.7 mg/kg per day, due to continuing pyrexia and the possibility of a fluconazole-resistant Candida sp. Surprisingly, two different non-albicans Candida species were identified later, with esophageal cultures revealing C. krusei, whereas blood cultures yielded C. kefyr with a fluconazole MIC of 4 mg/L and an amphotericin B deoxycholate MIC of 0.25 mg/L. Fundoscopic examination was negative for candida retinitis. The patient’s neutrophil count rose above 500/ mL on the 19th day of pyrexia (25th day following chemotherapy). Mucositis and dysphagia gradually resolved with a subsequent increase in the oral intake, and parenteral nutrition was terminated. However, pyrexia reaching 39 8C continued. Amphotericin B deoxycholate was replaced with liposomal amphotericin B, 100 mg, daily due to hypokalemia refractory to intravenous replacement therapy, and meropenem, amikacin and vancomycin treatment was terminated on the 26th day of pyrexia. The patient remained febrile, and liver transaminase levels were found to be elevated. Abdominal CT on the 33rd day of pyrexia demonstrated numerous, prominent hypodense lesions within the spleen, and few lesions in the liver and kidneys, consistent with abscesses. A diagnosis of chronic disseminated candidiasis (CDC) was made. A bone marrow aspirate at this stage confirmed that the patient’s AML was still