Impact of revised EORTC/MSGERC 2020 criteria on diagnosis and prognosis of invasive pulmonary aspergillosis in patients with hematological malignancies undergoing bronchoscopy.

INTRODUCTION: The first consensus definitions for invasive fungal diseases (IFD) were published in 2002. Advances in diagnostic tests and a clear need for improvement in certain areas led to a revision of these definitions in 2008. However, growing data on Aspergillus galactomannan (GM) thresholds and the introduction of new polymerase chain reaction-based diagnostic tests resulted in a further update by EORTC and Mycoses Study Group Education and Research Consortium (MSGERC) in 2020. Compared to the 2008 version, the 2020 EORTC/MSGERC criteria have stricter definitions, especially regarding GM levels, which should lead to improved specificity. Thus, our study aimed to evaluate diagnostic changes, based on GM levels, resulting from these new definitions and ascertain the impact of the new classification on mortality rates. METHOD: Patients hospitalized in a single tertiary care center with hematologic malignancies and undergoing bronchoscopy for suspected IPA between April 2004 and December 2019 were included in this retrospective study. RESULTS: The study population consisted of 327 patients with 31 patients (nine patients with proven IPA and 22 patients with no IPA) excluded from the study. 194 patients were classified as probable IPA cases according to 2008 EORTC/MSG criteria. However, 53 (27.3%) of these patients were re-classified as possible IPA according to 2020 EORTC/MSGERC criteria, due to novel galactomannan cut-off levels. Compared to re-classified possible IPA patients, those remaining in the probable IPA category experienced a higher incidence of septic shock (34.0% vs 16.9%, p=0.02), and required more non-invasive (12.0% vs 0.0%, p=0.004) and invasive (44.6 vs 24.5%, p=0.01) mechanical ventilation. There was a higher in-hospital mortality rate in probable IPA patients than in the re-classified possible IPA group (42.5% vs 22.6%, p=0.01). Patients reassigned to possible IPA had similar underlying diseases, radiological features and prognosis to patients already classified as possible IPA. Independent risk factors for mortality were classification as probable IPA according to 2020 EORTC/MSGERC criteria, lack of remission from hematologic malignancy, and number of nodules in Thorax CT. CONCLUSION: The use of 2020 EORTC/MSGERC criteria resulted in a 27.3% significant reduction in probable IPA diagnoses and created a more homogeneous category of patients with respect to treatment response, prognosis and mortality. Therefore, 2020 EORTC/MSGERC criteria afford more reliable mortality prediction than 2008 EORTC/MSG criteria.

The Effects of O6-methyl Guanine DNA-methyl Transferase Promotor Methylation and CpG1, CpG2, CpG3 and CpG4 Methylation on Treatment Response and their Prognostic Significance in Patients with Glioblastoma.

This retrospective study examined the prognostic significance and treatment effect of promoter methylation of O6- methyl guanine methyl transferase (MGMT) and meth-ylation of CpG 1, CpG2, CpG3 and CpG4 in glioblastoma (GB) patients received postoperative radiotherapy (PORT), with or without adjuvant temozolomide (TMZ). One hundred patients with GB who received PORT with concomitant TMZ plus adjuvant TMZ or PORT alone, were included. The MGMT promoter methylation of CpG1, CpG2, CpG3 and CpG4 islands were examined. Overall, MGMT-methylation emerged as a significant prognostic factor for better overall survival (OS) and progression-free survival (PFS) [odds ratio (OR): 0.609, 95% confidence interval (95% CI): 0.395-0.939, p = 0.02; OR: 0.662,95% CI: 0.430-1019, p = 0.5, respectively]. The methylation of each CpG1, CpG2, CpG3 and CpG4 islands was found to have no significant effects on OS and the methylation of each CpGl, CpG2 and CpG4 islands had no significant effect on PFS (p <0.05 for all). On the other hand, the methylation of CpG3 had a positive prognostic effect on PFS (OR: 2.1, 95% CI: 0.99-4.67, p = 0.04). In the group that only received radiotherapy (RT), CpG1 and CpC3 methylations were found to have a positive prognostic significance in terms of PFS (OR: 266, 95% CI: 1.05-6.75, p -0.03 for CpG1; OR: 2.4, 95% CI: 1.01-5.92, p = 0.04 for CpG3). The MGMT promoter methylation represents an important biomarker for predicting response to therapy. Individual islands, particularly CpG3, deserves further investigation as a prognostic marker. Further studies need to be done with larger sample sizes to clarify the results.

Rapid emergence of colistin resistance and its impact on fatality among healthcare-associated infections.

This article describes the emergence of resistance and predictors of fatality for 1556 cases of healthcare-associated Gram-negative bloodstream infection in 2014 and 2015. The colistin resistance rate in Klebsiella pneumoniae was 16.1%, compared with 6% in 2013. In total, 660 (42.4%) cases were fatal. The highest fatality rate was among patients with Acinetobacter baumannii bacteraemia (58%), followed by Pseudomonas aeruginosa (45%), Klebsiella pneumoniae (41%), Enterobacter cloacae (32%) and Escherichia coli (28%). On multi-variate analysis, the minimum inhibitory concentrations for carbapenems [odds ratio (OR) 1.02, 95% confidence interval (CI) 1.01-1.04; P = 0.002] and colistin (OR 1.1, 95% CI 1.03-1.17; P = 0.001) were found to be significantly associated with fatality.

Healthcare-associated Gram-negative bloodstream infections: antibiotic resistance and predictors of mortality.

This article describes the prevalence of antibiotic resistance and predictors of mortality for healthcare-associated (HA) Gram-negative bloodstream infections (GN-BSI). In total, 831 cases of HA GN-BSI from 17 intensive care units in different centres in Turkey were included; the all-cause mortality rate was 44%. Carbapenem resistance in Klebsiella pneumoniae was 38%, and the colistin resistance rate was 6%. Multi-variate analysis showed that age >70 years [odds ratio (OR) 2, 95% confidence interval (CI) 1.22-3.51], central venous catheter use (OR 2.1, 95% CI 1.09-4.07), ventilator-associated pneumonia (OR 1.9, 95% CI 1.1-3.16), carbapenem resistance (OR 1.8, 95% CI 1.11-2.95) and APACHE II score (OR 1.1, 95% CI 1.07-1.13) were significantly associated with mortality.

Integrase Strand Transfer Inhibitors (INSTIs) Resistance Mutations in HIV-1 Infected Turkish Patients.

OBJECTIVES: Integrase strand transfer inhibitor (INSTI) is a new class of antiretroviral (ARV) drugs designed to block the action of the integrase viral enzyme, which is responsible for insertation of the HIV-1 genome into the host DNA. The aim of this study was to evaluate for the first time INSTI resistance mutations in Turkish patients. METHODS: This study was conducted in Turkey, between April 2013 and April 2015 using 169 HIV-1-infected patients (78 ARV naive patients and 91 ARV-experienced patients). Laboratory and clinical characteristics of ARV naive and ARV-experienced patients were as follows: gender (M/F): 71/7 and 80/11, median age: 38 and 38.4; median CD4(+) T-cell: 236 and 216 cells/mm(3), median HIV-1 RNA: 4.95+E5 and 1.08E+6 copies/ml. Population-based seqeunces of the reverse transcriptase, protease, and integrase domains of the HIV-1 pol gene were used to detect HIV-1 drug resistance mutations. RESULT: INSTI resistance mutations were not found in recently diagnosed HIV-1-infected patients. However, ARV-experienced patients had major resistance mutations associated with raltegravir and elvitegravir; the following results were generated:F121Y, Y143R, Q148R and E157Q (6/91 - 6.6%). CONCLUSIONS: The prevalence of INSTI resistant mutations in ART-experienced patients suggested that resistance testing must be incorporated as an integral part of HIV management with INSTI therapies.

Expression of Glutamate Transporters in Alcohol Withdrawal.

INTRODUCTION: The study aimed to investigate the expression of glutamate transporters during withdrawal in the alcohol-dependent patients. METHOD: The study consisted of 20 male inpatient alcoholics during the withdrawal period and 20 healthy controls. Expressions of glutamate transporters, namely the excitatory amino acid transporter 2 (EAAT2) and EAAT3, in white blood cells were measured with the real-time polymerase chain reaction (RT-PCR) method in early (first day) and late (28(th) day) withdrawal in alcoholic patients and once in the controls. RESULTS: EAAT2 and EAAT3 expressions in the patients during both early and late withdrawal were higher than those of the controls. There was no difference in the EAAT2 and EAAT3 levels of the patients between early and late abstinence. DISCUSSION: The study revealed an upregulation of glutamate transporters EAAT2 and EAAT3 during early and late withdrawal in patients with alcohol withdrawal.

A mucormycosis case treated with a combination of caspofungin and amphotericin B.

Mucormycosis is a rare, invasive and fatal disease that occurs mainly in diabetes mellitus patients with uncontrolled blood glucose levels or in immunocompromised patients. The mortality rate of this disease is as high as 25 to 80%, despite aggressive surgical treatment and antifungal therapy. This high mortality requires alternative treatment approaches. The accepted treatment modality of invasive mucormycosis are amphotericin B lipid formulations. Although echinocandins generally show no activity against Mucorales, it was shown that Rhizopus oryzae expressed the target enzyme for echinocandins, 1,3-beta-glucan synthase. Additionally, there are some experimental studies in a diabetic mouse model and case reports regarding the effects of caspofungin. In this report, we present a rhinocerebral mucormycosis case treated with liposomal amphotericin B and caspofungin. There was regression of the patient's clinical and radiological condition with the addition of caspofungin, but she died due to discontinuation of her treatment and reasons other than mucormycosis.

Partial trisomy 14q due to maternal t(4;14)(p16;q32) in a dysmorphic newborn.

Partial Trisomy 14q is a rare chromosomal disorder that mostly results from a parental translocation. We report here a newborn boy with partial trisomy 14q and dysmorphic features that are compatible with previously reported cases. Conventional cytogenetic analysis revealed an extra chromosomal segment at the end of the short arm of chromosome 4. In order to determine the origin of this chromosome region we used subtelomeric FISH technique. Based on the results of these cytogenetic studies and the physical examination, this dysmorphic case was diagnosed as partial trisomy of 14q and his karyotype determined as 46 XY, der(4)t(4;14)(p16;q32) resulting from a balanced maternal translocation identified as 46,XX, t(4;14)(p16;q32).

Epidemiology of nosocomial candidaemia in a university hospital: a 12-year study.

The incidence of nosocomial candidaemia was evaluated in a retrospective study in a Turkish tertiary-care hospital. Over a 12-year period (1996-2007), a total of 743 episodes of candidaemia occurred in 743 patients, accounting for an average incidence of 1.9 episodes/1000 admissions and 2.9 episodes/10 000 patient-days per year. The annual incidence was almost constant during the study period except for 1996 when it was significantly higher in comparison with other years (P<0.05). The most common species isolated was Candida albicans (45%), followed by C. parapsilosis (26%), C. tropicalis (7%), C. krusei (7%), and C. glabrata (3.5%). A significant increase in C. albicans isolates causing candidaemia linked to a decrease in C. parapsilosis isolates in adult patients and C. krusei isolates in children was found between the two 6-year study periods. This trend reflects improved infection control at Uludag University Hospital. Ninety percent of isolates were susceptible to fluconazole (8 microg/ml) and resistance was found only in C. glabrata and C. parapsilosis isolates. Regular local surveillance of Candida spp. is important in order to develop empirical treatment protocols to reduce the incidence and mortality of candidaemia.

Multiple intracranial abscesses due to Cryptococcus neoformans: an unusual clinical feature in an immunocompetent patient and a short review of reported cases.

We present a case of multiple intracranial abscesses caused by Cryptococcus neoformans in a patient who presented with no symptoms of immunodeficiency.

Mixed gonadal dysgenesis with 45,X/46,X,idic(Y)/46,XY,idic(Y) karyotype.

To present the new karyotype with mixed gonadal dysgenesis, the aetiologic approach and difficulties in genetic counseling in mosaic sex chromosome disorders. We report a fourteen-year-old boy presented with slightly ambigious genitalia. Cytogenetic and fluorescence in situ hybridization investigations were carried out on his peripheral lymphocytes. As a result, three cell lines, 45,X, 46,X,idic(Y)(q11.2) and 46, XY were observed. A markedly higher percentage of Y-containing cells was observed in the blood (68%), which was not considered to be the major reason why the case did not have distinct ambiguous genitalia. We suggest that study of cytogenetic and molecular mosaicism involving sex chromosomes may help to further unravel the mysterious process in mixed gonadal dysgeneic patients.

Nosocomial diarrhea and Clostridium Difficile associated diarrhea in a Turkish University Hospital.

BACKGROUND: Clostridium difficile (C. difficile) is a well-established cause of nosocomial diarrhea. The aim of our study was to define the incidence of nosocomial diarrhea in our hospital and to determine the role of C. difficile. Additionally, the risk factors for nosocomial diarrhea and Clostridium difficile associated diarrhea (CDAD) were investigated. METHODS: We included all patients, 18 years of age or more, who were admitted to the Uludag Teaching Hospital between October 1, 2004 and February 1, 2005, and developed diarrhea at least three days after hospital admission. A case-control study was performed. RESULTS: The total incidence of nosocomial diarrhea was 0.6 per 1,000 hospitalization-days and 5 per 1,000 patients' admissions. Previous use of chemotherapy was found to be an important predisposing factor for nosocomial diarrhea. The incidence of CDAD was 0.26 per 1,000 hospitalization-days and 2.1 per 1,000 admissions, comparable with incidence rates in Europe. CDAD was diagnosed in 43% of patients with nosocomial diarrhea. No severe cases of CDAD were diagnosed. A correlation was found between CDAD and antibiotic use before admission and during admission in univariate analysis. PCR ribotyping revealed four strains of PCR ribotype 002 and 1 strain of ribotype 012 out of 5C. difficile strains available for extensive identification. CONCLUSION: The incidence rates of nosocomial diarrhea and CDAD are not different than the usual incidence rates in Europe. C. difficile was the causative agent in 43% of patients with nosocomial diarrhea.

Risk factors in community-acquired/onset urinary tract infections due to extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae.

We investigated the risk factors for community acquired/onset urinary tract infections due to extended spectrum beta-lactamase (ESBL)-positive Escherichia coli or Klebsiella pneumoniae in 62 patients who were followed-up from August 1, 2003 to September 1, 2006. Sixty patients with community-acquired urinary tract infections caused by ESBL-negative E. coli or K. pneumoniae who were followed-up during the same dates were included as a control group. Age (> or =65 or <65 years old), sex, bladder cancer, benign prostate hypertrophy (BPH), prostate cancer, urolithiasis, urethral catheter, previous urological operation, diabetes mellitus, use of antibiotics during the last 3 months and hospitalization during the last 3 months were investigated as risk factors. The presence of previous urological operation and quinolone or cephalosporin use for any infection during the last 3 months were found to be independent risk factors. Knowing the risk factors for community acquired/onset urinary tract infections caused by ESBL-positive E. coli or K. pneumoniae is of great importance in planning empirical antibiotic therapy.

Aspergillosis osteomyelitis and joint infection in a renal transplant recipient.

Invasive Aspergillosis occurs in almost every human organ, most commonly in the lungs. Bone involvement classically has been considered exceedingly rare for both immunocompromised and immunocompetent hosts, however, there are limited data in transplant recipients. We report an unusual case of osteomyelitis and joint infection of the ankle caused by Aspergillus fumigatus in a renal transplant recipient.

Two cases of cryptococcal meningitis in immunocompromised patients not infected with HIV.

We present the cases of two patients with cryptococcal meningitis who were predisposed to fungal infection because of diabetes mellitus (Case 1) and systemic lupus erythematosus (Case 2). Both patients were tested negative for anti-HIV antibodies.

Bacillus spp. among hospitalized patients with haematological malignancies: clinical features, epidemics and outcomes.

Between April 2000 and May 2005, 350 bacteraemic episodes occurred among patients treated in our haematology unit. Two hundred and twenty-eight of these episodes were caused by Gram-positive pathogens, most commonly coagulase-negative staphylococci and Staphylococcus aureus. One hundred and twenty-two episodes were due to Gram-negative pathogens, with a predominance of Escherichia coli, Acinetobacter baumannii and Pseudomonas aeruginosa. Bacillus bacteraemias constituted 12 of these episodes occurring in 12 patients, and accounted for 3.4% of all bacteraemic episodes. Of the 12 strains evaluated, seven were Bacillus licheniformis, three were Bacillus cereus and two were Bacillus pumilus. Seven episodes presented with bloodstream infection, three with pneumonia, one with severe abdominal pain and deterioration of liver function, and one with a catheter-related bloodstream infection. B. licheniformis was isolated from five patients who had been hospitalized at the same time. This outbreak was related to non-sterile cotton wool used during skin disinfection. B. cereus and B. licheniformis isolates were susceptible to cefepime, carbapenems, aminoglycosides and vancomycin, but B. pumilus isolates were resistant to all antibiotics except for quinolones and vancomycin. Two deaths were observed. In conclusion, Bacillus spp. may cause serious infections, diagnostic and therapeutic dilemmas, and high morbidity and mortality in patients with haematological malignancies. Both B. cereus and B. licheniformis may be among the 'new' Gram-positive pathogens to cause serious infection in patients with neutropenia.

Efficacy of antiseptic-impregnated catheters on catheter colonization and catheter-related bloodstream infections in patients in an intensive care unit.

This study was conducted to evaluate the impact of central venous catheters impregnated with chlorhexidine and silver sulphadiazine on the incidence of colonization and catheter-related bloodstream infection in critically ill patients. One hundred and thirty-three patients requiring central venous catheterization were chosen at random to receive either an antiseptic-impregnated triple-lumen catheter (N=64) or a standard triple-lumen catheter (N=69). The mean (SD) durations of catheterization for the antiseptic and standard catheters were 11.7 (5.8) days (median 10; range 3-29) and 8.9 (4.6) days (median 8.0; range 3-20), respectively (P=0.006). Fourteen (21.9%) of the antiseptic catheters and 14 (20.3%) of the standard catheters had been colonized at the time of removal (P=0.834). Four cases (6.3%) of catheter-related bloodstream infection were associated with antiseptic catheters and one case (1.4%) was associated with a standard catheter (P=0.195). The catheter colonization rates were 18.7/1000 catheter-days for the antiseptic catheter group and 22.6/1000 catheter-days for the standard catheter group (P=0.640). The catheter-related bloodstream infection rates were 5.3/1000 catheter-days for the antiseptic catheter group and 1.6/1000 catheter-days for the standard catheter group (P=0.452). In conclusion, our results indicate that the use of antiseptic-impregnated central venous catheters has no effect on the incidence of either catheter colonization or catheter-related bloodstream infection in critically ill patients.