Epidemiology, Clinical Characteristics and Risk Factors for Severity of Chronic Disseminated Candidiasis in Jerusalem, Israel.

Chronic disseminated candidiasis (CDC) occurs mostly in patients with acute hematologic malignancy and its clinical manifestations derive from immune reconstitution following neutrophil recovery. The aim of this study was to describe epidemiological and clinical characteristics of CDC and define risk factors for disease severity. Demographic and clinical data were collected from medical files of patients with CDC hospitalized in two tertiary medical centers in Jerusalem between 2005 and 2020. Associations between different variables and disease severity were evaluated, as well as characterization of Candida species. The study included 35 patients. CDC incidence slightly increased during study years and the average number of involved organs and disease duration was 3 ± 1.26 and 178 ± 123 days, respectively. Candida grew in blood in less than third of cases and the most common isolated pathogen was Candida tropicalis (50%). Histopathological or microbiological workup in patients who underwent an organ biopsy demonstrated Candida in about half of the patients. Nine months after starting antifungals, 43% of the patients still didn't have resolution of organ lesions in imaging modalities. Factors associated with protracted and extensive disease were prolonged fever prior to CDC and absence of candidemia. A C- Reactive Protein (CRP) cutoff level of 7.18 mg/dL was found to predict extensive disease. In conclusion, CDC incidence is increasing and the number of involved organs is higher than previously described. Clinical factors such as fever duration prior to CDC and absence of candidemia can predict severe course of disease and assist in treatment decisions and follow-up planning.

Ibrutinib-associated invasive fungal diseases in patients with chronic lymphocytic leukaemia and non-Hodgkin lymphoma: An observational study.

BACKGROUND: Invasive fungal diseases (IFD) are life-threatening infections most commonly diagnosed in acute leukaemia patients with prolonged neutropenia and are uncommonly diagnosed in patients with lymphoproliferative diseases. OBJECTIVES: Following the initial report of aspergillosis diagnosed shortly after beginning ibrutinib for chronic lymphocytic leukaemia, a survey was developed to seek additional cases of IFD during ibrutinib treatment. METHODS: Local and international physicians and groups were approached for relevant cases. Patients were included if they met the following criteria: diagnosis of chronic lymphocytic leukaemia/non-Hodgkin lymphoma; proven or probable IFD; and ibrutinib treatment on the date IFD were diagnosed. Clinical and laboratory data were captured using REDCap software. RESULT: Thirty-five patients with IFD were reported from 22 centres in eight countries: 26 (74%) had chronic lymphocytic leukaemia. The median duration of ibrutinib treatment before the onset of IFD was 45 days (range 1-540). Aspergillus species were identified in 22 (63%) of the patients and Cryptococcus species in 9 (26%). Pulmonary involvement occurred in 69% of patients, cranial in 60% and disseminated disease in 60%. A definite diagnosis was made in 21 patients (69%), and the mortality rate was 69%. Data from Israel regarding ibrutinib treated patients were used to evaluate a prevalence of 2.4% IFD. CONCLUSIONS: The prevalence of IFD among chronic lymphocytic leukaemia/non-Hodgkin lymphoma patients treated with ibrutinib appears to be higher than expected. These patients often present with unusual clinical features. Mortality from IFD in this study was high, indicating that additional studies are urgently needed to identify patients at risk for ibrutinib-associated IFD.

Candida Prophylaxis and Treatment in Critically Ill Patients after Abdominal Surgery: A Survey of Practice.

Purpose: To survey current intensive care unit (ICU) practice in initiating antifungal therapy for prophylaxis and treatment of suspected candidiasis after abdominal surgery. The goal was to establish the need to prioritize research toward standardized care of such patients. Methods: Online questionnaire survey of clinical practice based on theoretical case scenarios. These were structured with expert input to investigate management of: hemodynamically stable/unstable patient after urgent upper/lower gastrointestinal surgery with/without fungal growth in culture. The link to the survey was sent to all active members of the European Society of Intensive Care Medicine (ESICM). Results: The survey was completed by 101 respondents from 29 countries. Fewer than half (48.5%) stated that in their center, ICU antibiotic and antifungal therapy is managed by a dedicated specialist physician/team that manages all ICU patients. Respondents exhibited a greater tendency toward administering antifungal agents, mainly fluconazole, to hemodynamically unstable patients. One week after surgery for a perforated duodenal ulcer, only half responded they would use antifungal agents when a patient develops septic shock. Most respondents chose to administer antifungal therapy in patients with septic shock if Candida had been identified in any culture. The source of infection, location of surgery, or type of Candida were not viewed as triggers for therapeutic decisions. Conclusion: The current survey demonstrates large variability in antifungal use. Decisions are made irrespective of existing guidelines and seem to be driven by patient hemodynamic condition and identification of any Candida in any culture alone.

Effectiveness of twice a week prophylaxis with atovaquone-proguanil (Malarone®) in long-term travellers to West Africa.

BACKGROUND: Current guidelines recommend daily dosing of atovaquone-proguanil (AP), beginning a day before travel to endemic areas and continuing for 7 days after departure. Adherence of long-term travellers to daily malaria chemoprophylaxis tends to be poor, even when residing in highly endemic malaria regions. Evidence from a volunteer challenging study suggests that non-daily, longer intervals dosing of AP provides effective protection against Plasmodium falciparum This study examines the effectiveness of twice weekly AP prophylaxis in long-term travellers to highly endemic P. falciparum areas in West Africa. METHODS: An observational surveillance study aimed to detect prophylactic failures associated with twice weekly AP, during the years 2013-2014, among long-term expatriates in two sites in West Africa. The expatriates were divided according to the malaria prophylaxis regimen taken: AP twice weekly; mefloquine once weekly and a group refusing to take prophylaxis. Malaria events were recorded for each group. The incidence-density of malaria was calculated by dividing malaria events per number of person-months at risk. RESULTS: Among 122 expatriates to West Africa the malaria rates were: 11.7/1000 person-months in the group with no-prophylaxis (n = 63); 2.06/1000 person-months in the 40 expatriates taking mefloquine (P = 0.006) and no cases of malaria (0/391 person-months, P = 0.01) in the twice weekly AP group (n = 33). CONCLUSIONS: No prophylaxis failures were detected among the group of expatriates taking AP prophylaxis twice weekly compared with 11.7/1000 person-months among the no-prophylaxis group. Twice weekly AP prophylaxis may be an acceptable approach for long-term travellers who are unwilling to adhere to malaria chemoprophylaxis guidelines.

Schistosomiasis in pregnant travelers: a case series.

BACKGROUND: Travel-related acquisition of schistosomiasis in Africa is well established. Data concerning Schistosoma infection in pregnant travelers are lacking and treatment derives from studies in endemic regions. METHODS: This study was a retrospective case-series of pregnant patients who were infected with Schistosoma species. Data regarding exposure history, clinical presentation, diagnosis, treatment, and fetal outcomes were collected and analyzed. Diagnosis of schistosomiasis was based on serology tests and/or ova recovery. RESULTS: Travel-related schistosomiasis during pregnancy was diagnosed in 10 travelers (with 20 pregnancies). Of the 10 women, 4 pregnant travelers with recent exposure were treated during their pregnancy with praziquantel (PZQ). The course and outcome of pregnancy in these patients was uneventful, and treatment had no apparent adverse effects on either the mothers or their babies. Six asymptomatic women were diagnosed years after exposure. During this period, they gave birth to 13 babies. They were never treated with PZQ. Birth weights of their infants were significantly smaller as compared with those of the infants of the women who were treated during their pregnancy (median 2.8 vs 3.5 kg). One baby was born preterm. One patient had three miscarriages. CONCLUSION: This is the first case-series of pregnant travelers with schistosomiasis. Although a small case-series with possible confounders, it suggests that schistosomiasis in pregnant travelers can be treated. A trend of lower birth weights was observed in the infants of the pregnant travelers who were not treated. PZQ therapy during pregnancy was not associated with adverse pregnancy or fetal outcomes in those four cases. Our results emphasize the importance of screening female travelers of childbearing age with a relevant history of freshwater exposure. Further studies are needed to reinforce these recommendations.

[Use of N-acetylcysteine prior to cardiac catheterization to prevent acute renal injury in patients with stage III chronic kidney disease].

BACKGROUND: The role of N-acetylcysteine (NAC) to protect against contrast-induced nephropathy (CN) in patients with pre-existing renal insufficiency remains controversial despite several randomized controlled trials and meta-analyses. The potential reasons of inconsistency may be due to differences in definition, type and dose of contrast medium, imaging procedures, and the frequency of other potential causes of acute renal injury. Renal function before contrast administration is a major determinant of deterioration in function after administration. METHODS: We conducted a retrospective review of patients with Stage III Chronic Kidney Disease (CKD) who underwent cardiac catheterization from January 2000 through January 2004 in our hospital. The incidence of CN was examined in patients pretreated and not pretreated with NAC. RESULTS: From January 2000 to January 2004, 189 patients with Stage III CKD underwent cardiac catheterization. All patients received 0.45% or 0.9% saline hydration prior to catheterization. NAC was given prior to 83 catheterizations and not given prior to 57. Eleven of 57 patients (19.3%) not pretreated with NAC developed acute renal injury (ARI) while 6 of 83 who received NAC (7.2%) developed ARI (p<0.05). Nineteen patients underwent more than one cardiac catheterization, but there was no pattern to their potential for multiple episodes of ARI irrespective of prophylactic NAC administration. CONCLUSION: In our study NAC offered significant protection against ARI in patients with Stage III CKD. No overt risk factor for multiple episodes of ARI was observed, nor was the occurrence of ARI after first cardiac catheterization predictive of ARI after a subsequent catheterization.