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.

Emergence of fusarioses in a university hospital in Turkey during a 20-year period.

Fusarium species have started appearing increasingly as the main cause of infections, particularly in immunocompromised patients. In this study, we aimed to present the first epidemiological data from Turkey, analyze fusariosis cases that have been monitored in a university hospital during the past 20 years, identify the responsible Fusarium species, and determine antifungal susceptibilities. A total of 47 cases of fusariosis was included in the study. Fusarium isolates were identified by multilocus sequence typing (MLST). Antifungal susceptibility was tested by the broth microdilution method according to the Clinical and Laboratory Standards Institute (CLSI) methodology. Of the Fusarium infections, 23.4 % were superficial, 44.7 % were locally invasive, and 31.9 % were disseminated. A significant increase was observed over the years. The Fusarium fujikuroi species complex (FFSC) proved to be the most frequent agent group (17 cases; 51.5 %), followed by the Fusarium solani species complex (FSSC) (14 cases; 42.4 %), the Fusarium dimerum species complex (FDSC), and the Fusarium oxysporum species complexes (FOSC) (one case each). Amphotericin B had the highest in vitro activity against all species. Voriconazole and posaconazole showed interspecies variability across and within Fusarium species complexes. In conclusion, our data support the fact that regional differences exist in the distribution of the Fusarium species and that species-specific differences are observed in antifungal susceptibility patterns. The monitoring of local epidemiological data by determining fungal identity and susceptibility are of importance in guiding the clinical follow-up of patients.

Autonomic arterial neuropathy in lower limbs.

AIM: This prospective and controlled study was carried out to show the role of hyperperfusion due to decreased arterial resistance in patients with arterial neuropathy of lower limbs. METHOD: Arterial Duplex color scanning and magnetic resonance imaging (MRI) angiography were made in 54 patients with lower limb venous stasis in which Pulsatility Index (PI) from pedal arteries by using CW Doppler was below cut off value of 5 as a confirmatory evidence of autonomic neuropathy and in 24 healthy subjects. RESULTS: PI was mean 2.79 ranged from 4.87 to 0.82 in patients. It was mean 9.38 between 5.43 and 15.25 in control subjects. PSV was found mean 44.52 cm/sec ranged from 26 to 74 cm/s in patients. It was found between 10 and 23 cm/sec with average 16.08 cm/s in healthy ones. In addition to venous duplex scanning findings, MRI angiography demonstrates arterial contrast enhancement, vascular blush, early venous filling and permanent venous dilatation in 16 patients (group 2) having PI below 3 with severe degrees of hyperperfusion. In this group, PI was mean 1.70 ranged from 2.46 to 0.82 and PSV was mean 61.19 cm/s, between 53 to 74 cm/s. Out of patients, 38 (group 1) had no pathological findings in MRI angiography and had PI>3 and <5. In this group, PI was mean 3.26, ranged from 4.87 to 2.55 and PSV was mean 37.5 cm/s, between 26 to 47 cm/s. CONCLUSION: In this trial, we observed that patients with arterial neuropathy in the leg (groups 1 and 2) had a significant increase in PSV and a decrease in PI values from foot arteries compared with that of the control group (P=0.001). A remarkable difference was found in parameters between patient groups (P=0.001). Finally, it can be said that lower limb hyperperfusion owing to arterial neuropathy in various degrees produce venous stasis and is also responsible for some venous abnormalities.

An investigation of Candida species isolated from blood cultures during 17 years in a university hospital.

Candidemia is the most frequent manifestation observed with invasive candidiasis. The aim of this study was to analyse the trends of candidemia in a large tertiary-care hospital to determine the overall incidence during January 1996-December 2012, as well as to determine the susceptibility of 453 isolates according to the revised Clinical and Laboratory Standards Institute (CLSI) breakpoints. Candidemia episodes in adult and paediatric patients were retrospectively analysed from the laboratory data of Uludag University Healthcare and Research Hospital. The 17-year period studied was divided into three periods (1996-2001, 2002-2007 and 2008-2012) for better comparison, and candidemia incidence was determined by the ratio of total number of patients with candidemia per 1000 patients admitted to the hospital and per 10 000 patient days in these three periods. Redefined CLSI M27-A3 breakpoints were used for interpretation of antifungal susceptibility results. Candidemia incidence was determined as 2.2, 1.7 and 1.5 per 1000 admitted patients during 1996-2001, 2002-2007 and 2008-2012 respectively. A significantly decreased candidemia incidence was obtained in the third period. C. albicans (43.8%) was the most common candidemia agent, followed by C.parapsilosis (26.5%) in all three periods. According to the revised CLSI breakpoints, there was fluconazole resistance in C. albicans, C.parapsilosis, C.tropicalis and C.glabrata species (1.4%, 18.2%, 2.6% and 14.3% respectively). Almost all Candida species were found susceptible to voriconazole except one C.glabrata (7.1%) isolate. Candidemia is an important health problem. Local epidemiological data are determinative in the choice of appropriate antifungal treatment agents.

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.

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.

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.

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.

Aspergillus pneumonia in renal transplant recipients at a medical center in Turkey.

Pulmonary aspergillosis is a devastating disease. Early diagnosis allowing early treatment may improve the prognosis. However, this goal remains difficult to achieve. When the diagnosis is confirmed, it is often already too late. Despite antifungal treatment, the mortality rate is high. Patients with immunosuppression show a high mortality rate. We present five patients of ages ranging between 34 and 43 years who displayed aspergillus pneumonia between 1991 and 2000. All patients received cyclosporine, azathioprine, and prednisone for maintenance immunosuppressive therapy. Their ages ranged from 34 to 43 years with the onset of infection between 1 to 25 months posttransplant. In all cases, the infection was localized to the lungs. Standard methods of fungal culture and identification were used. No coinfections with tuberculosis or other fungi or bacteria were identified. Three cases were successfully treated but two patients showed deterioration despite appropriate therapy and died. Among patients with solid organ transplantation, lung, liver, and renal transplant patients are at the highest risk of developing aspergillus lung infections. A high degree of awareness and efforts for early diagnosis and therapy may improve the poor prognosis.

Dorsal pedal venous oximetry as an outcome index of lower extremity revascularizations.

Dorsal pedal venous blood gas analysis was performed in 24 patients with arterial occlusive disease requiring revascularizations of the lower extremities. After the reconstructive surgical procedure, measurements were repeated. It has been observed that this method is useful before surgery since it proves the severity of tissue hypoxia due to perfusion impairment of the foot. Postoperative measurements have detected the effectiveness of the vascular restorations. The results of the trial showed a mean increase in partial pressure of venous blood oxygen (PVO2) and pH of 30.3% and 13.7% (p<0.05), respectively and a mean decrease in partial pressure of arterial carbon dioxide (PCO2) of 12.9% (p<0.05) between initial and postsurgical measurements in involved legs. In the healthy, unoperated on side, there was no significant (p>0.05) change in response to arterial reconstructions. Symptoms decreased markedly in direct proportion to the increase in dorsal pedal venous PO2 induced by changes in blood flow. This method can be reliably used for assessing the treatment to ensure adequate oxygen delivery to the foot as a result of improved pedal perfusion.

Systemic candidiasis with acute Epstein-Barr virus infection.

Systemic Candida infections are usually encountered as opportunistic infections in a setting of immunologic depression. Sepsis or arthritis due to Candida is not expected in healthy people. Epstein-Barr virus may infect B cells, but does not cause immunosuppression of any clinical significance. As far as we know, invasive non-albicans Candida infection complicating Epstein-Barr virus infection has not been reported in previously healthy children. In this report, two previously healthy children, one with sepsis due to Candida species and the other sepsis and arthritis due to Candida parapsilosis are described. Both patients were male and were aged 2 and 9 y. The diagnosis was confirmed by culture. Both children also had coincidental acute Epstein-Barr virus infection, confirmed by Epstein-Barr virus viral capside antigen-IgM. They were both cured with fluconazole given for 21 days and 48 days, respectively.

Early decortication for postpneumonic empyema in children. Effect on pulmonary perfusion.

Early pulmonary decortication was performed on 66 of 137 children with postpneumonic empyema, while 71 received conventional treatment. The mean age of the 66 patients with decortication was 5.5 years (range 6 months-14 years). The empyema was left-sided in 34 and right-sided in 32. Decortication was performed when lung expansion was not obtained after 10-12 days of intercostal tube drainage, antibiotic therapy (guided by sensitivity tests of pleural fluid) and pleural irrigation. Scintigraphy showed loss of pulmonary perfusion on the side of empyema to be 65% +/- SD 20 (25-98)% before decortication in the 23 tested patients. In ten of them the test was repeated after surgery and showed significant (p < 0.001) diminution of the perfusion defect, from 57 +/- 6.8 (25-84)% to 4 +/- 2.6 (0-8)%. The hospital stay was significantly (p < 0.001) shorter for the surgically treated than for the classically managed patients, viz. 19.5 +/- 4 (13-36) days vs 73.6 +/- 14 (34-110) days. Early decortication thus had beneficial effects on pulmonary perfusion and hospital stay.

Serum tumor necrosis factor levels in acute myocardial infarction and unstable angina pectoris.

Tumor necrosis factor (TNF) enhances leukocyte adherence to vascular endothelium and increases procoagulant activity in the endothelial cells. Thus it may be implicated in the pathogenesis of acute vascular occlusions. To study the role of TNF in the early stages of acute myocardial infarction (MI), the authors measured circulating TNF levels in the sera of patients with acute MI and unstable angina pectoris. Blood samples were obtained within six hours after onset of chest pain and stored at -70 degrees until tested. A sensitive sandwich enzyme-linked immunosorbent assay (ELISA) test was used for TNF measurement. C-reactive protein (CRP) levels were determined semiquantitatively. Immediate complications such as heart failure, arrhythmia, and shock were also noted. Twenty-four patients with electrocardiographically and biochemically confirmed acute MI and 14 patients with unstable angina pectoris were included in the study. TNF levels were serially assessed at the time of admission and at hours 6, 24, 48, 72, and 96 after onset of chest pain in 2 patients with acute MI. Detectable TNF was found in 13 sera of the acute MI group (range; 10-1510 pg/mL) and 4 sera of the angina pectoris group (range; 15-240 pg/mL). There was no correlation between the serum TNF levels and the occurrence of complications and the extent of myocardial damage. CRP response was unrelated to TNF levels. Contrary to previous reports, serial measurement of TNF revealed that peak values were reached within six hours and disappeared after twenty-four hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Correlation between cell-surface hydrophobicity of Candida albicans and adhesion to buccal epithelial cells.

Adhesion of four isolates of Candida albicans to buccal epithelial cells was determined after growth of the yeasts in defined medium containing 50 mM glucose or 500 mM galactose as the carbon source. With each isolate, adhesion of galactose-grown yeasts was significantly higher than that of glucose-grown organisms. Yeast cell-surface hydrophobicity was assessed by two methods, a modified hydrocarbon adhesion assay and a more sensitive polystyrene microsphere assay. All four isolates were significantly more hydrophobic after growth on 500 mM galactose than after growth on 50 mM glucose. Overall, a strong positive correlation between adhesion and surface hydrophobicity was observed (r = 0.965). These results are discussed in relation to the role of yeast-surface hydrophobicity in pathogenesis.