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.

[Effect of a computer application on appropriate use and control of broad spectrum antibiotics].

BACKGROUND: Antibiotics are among the greatest contributions of modern medicine. However, since the onset of the antibiotic age, resistance has emerged, threatening the future usability of these drugs. The complexity of antibiotic prescribing and associated expense has led to the development of infectious disease (ID) expert stewardship programs. PURPOSE: To describe an in-house created computer application, in use since 2005 with which all restricted antimicrobials are ordered and approved by ID physicians before being supplied by the pharmacy. RESULTS: In the nine years since the application was adopted by the entire hospital, 173,436 prescriptions for restricted antibiotics have been ordered through the application, of which 52% were for male patients, 8% for children ≤ 20 years, 31% for adults 21-70 years old and 61% for patients > 70. All prescriptions were reviewed by ID physicians; their response included approval (mean 87%, range 82-92%), rejection (7%, 3-12%), or change (6%, 4-18%). The latter two decisions always involved written and/or oral interaction with the prescribing physicians. The result analysis showed that: by clinical diagnoses, the approval rate ranged from 82% (for central line associated infection) to 94% (for tuberculosis); by class of antimicrobial, the approval rate ranged from 71% (IV ciprofloxacin) to 95% (IV amoxicillin-calvulanate). Overall hospital expenditure on antimicrobials, corrected by 100 admissions and 100 admission days, did not change significantly. CONCLUSIONS: During the nine years of its use, the described computer program has significantly contributed to physician awareness of appropriate antibiotic use, provided tools to assist physicians in their choice of antimicrobial treatment, allowed ID supervision with unprecedented scope and depth and has significantly contributed to cost control.

Treatment of giardiasis after nonresponse to nitroimidazole.

During January 2008-October 2013, a total of 12 cases of giardiasis at the Chaim Sheba and Shaare Zedek Medical Centers, Israel, did not respond to nitroimidazole; 83.3% were associated with travel and 33% with immunoglobulin deficiency. Among 110 published cases, the most effective treatment was quinacrine (efficacy 90%-100%), but its availability is limited.

High rate of schistosomiasis in travelers after a brief exposure to the high-altitude Nyinambuga crater lake, Uganda.

Travel-related schistosomiasis is usually associated with prolonged freshwater exposure. Until recently, Uganda's crater lakes were considered schistosomiasis free due to their high-altitude location. We describe an outbreak of acute schistosomiasis after a brief exposure (mean, 22 ± 9.5 minutes) to a high-altitude crater lake.

Morbidity of Returning Travelers Seen in Community Urgent Care Centers throughout Israel.

Information regarding post-travel morbidity is usually reported via dedicated post-travel clinics and mainly relates to travelers returning from low-middle-income countries (LMIC), however, the spectrum of morbidity seen within the community setting is scarcely reported. This prospective observational study among visitors to 17 community Urgent Care Centers (UCC) was designed to evaluate the reasons for post-travel community clinic visits and to compare travelers returning from LMIC to high-income countries (HIC). All visitors within one-month post-travel to all destinations were included. A total of 1580 post-travel visits were analyzed during 25 months. Travelers to LMICs were younger (mean 36.8 years old vs. 41.4 in the HIC group) and stayed longer periods abroad (30.1 ± 41.2 vs. 10.0 ± 10.6 in the HIC group) but more of them had pre-travel vaccines (35.5% vs. 6.6%). Travel-related morbidity was significantly more common in the LMIC group 58.3% (253/434) vs. 34.1% (391/1146) in the HIC group, (p < 0.001). Acute diarrhea was the leading cause of morbidity after visiting LMIC (28.8%) and was significantly more common than in the HIC (6.6%, p < 0.001). Other common morbidities in the LMIC cohort were respiratory (23.3%), cutaneous (15.8%), and injuries (9.9%). In the HIC group, the common morbidities were respiratory (37.3%), and diarrhea composed only 6.6% of the complaints. Our study group represents a less biased sample of travelers to LMIC as well as HIC, therefore, data from the UCC setting and at the specialized travel clinics complete each other in understanding the true extent of morbidity in travelers.

The use of a diversion tube to reduce blood culture contamination: A "real-life" quality improvement intervention study.

BACKGROUND: Blood culture contamination is associated with health care costs and potential patient harm. Diversion of the initial blood specimen reduces blood culture contamination. We report results of the "real-life" clinical implementation of this technique. METHODS: Following an educational campaign, use of a dedicated diversion tube was recommended prior to all blood cultures. Blood culture sets taken from adults using a diversion tube were defined as "diversion sets," those without, "non-diversion" sets. Blood culture contamination and true positive rates were compared for diversion and nondiversion sets and to nondiversion historical controls. A secondary analysis investigated efficacy of diversion by patient age. RESULTS: Out of 20,107 blood culture sets drawn, the diversion group included 12,774 (60.5%) and the nondiversion group 8,333 (39.5%) sets. The historical control group included 32,472 sets. Comparing nondiversion to diversion, contamination decreased by 31% (5.5% [461/8333] to 3.8% [489/12744], P < .0001]. Contamination was also 12% lower in diversion than historical controls [3.8% (489/12744) vs 4.3% (1,396/33,174) P = .02)]. The rate of true bacteremia was similar. In older patients, contamination rate was higher, and the relative reduction associated with diversion decreased (54.3% amongst 20-40-year-olds vs 14.5% amongst >80-year-olds). CONCLUSIONS: Use of a diversion tube in the ED reduced blood culture contamination in this large real life observational study. Efficacy decreased with increasing age, which requires further investigation.

Morbidity among Arab-Israeli and Palestinian Hajj Pilgrims: A Prospective Study.

Thousands of Palestinian and Arab-Israeli pilgrims travel to Mecca each year to complete their pilgrimage. To the best of our knowledge, no previous studies have characterized the infectious and noninfectious morbidity among Arab-Israeli or Palestinian Hajj pilgrims. Thus, we designed and conducted an observational questionnaire-based study to prospectively investigate the occurrence of health problems among these Hajjis who traveled to complete their Pilgrimage during 2019 Hajj season. For the purpose of the study, questionnaires were distributed to Hajj pilgrims at three different time occasions-before travel, inquiring on demographics and medical comorbidities; and 1 and 4 weeks after returning recording any health problems encountered during or after travel. Initial recruitment included 111 Hajjis. The mean age of responders was 49.5 (±9.1) years, with a Male:Female ratio of 1.3:1. The mean travel duration was 18.7 (13-36) days. Altogether, 66.3% of the pilgrims reported at least one health problem during and after the trip, of which 38.6% sought medical attention. Five (4.8%) hajjis were hospitalized, including life-threatening conditions. Cough was the most common complaint (53.8%), and 11.5% also reported fever. Pretravel counseling was associated with reduced outpatient and emergency room visits. We therefore concluded that a high rate of morbidity was reported among this cohort of Hajj pilgrims with a morbidity spectrum similar to pilgrims from other countries. Pretravel consultation with the purpose of educating the pilgrims on the health risks of Hajj may help reduce the morbidity for future Hajj seasons.

National multicenter study of predictors and outcomes of bacteremia upon hospital admission caused by Enterobacteriaceae producing extended-spectrum beta-lactamases.

Extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae are pathogens that may lead to a spectrum of clinical syndromes. We aimed to identify predictors and outcomes of ESBL bacteremia upon hospital admission (UHA) in a nationwide prospective study. Thus, a multicenter prospective study was conducted in 10 Israeli hospitals. Adult patients with bacteremia due to Enterobacteriaceae diagnosed within 72 h of hospitalization were included. Patients with ESBL producers (cases) were compared to those with non-ESBL producers (controls), and a 1:1 ratio was attempted in each center. A case-control study to identify predictors and a cohort study to identify outcomes were conducted. Bivariate and multivariate logistic regressions were used for analyses. Overall, 447 patients with bacteremia due to Enterobacteriaceae were recruited: 205 cases and 242 controls. Independent predictors of ESBL were increased age, multiple comorbid conditions, poor functional status, recent contact with health care settings, invasive procedures, and prior receipt of antimicrobial therapy. In addition, patients presenting with septic shock and/or multiorgan failure were more likely to have ESBL infections. Patients with ESBL producers suffered more frequently from a delay in appropriate antimicrobial therapy (odds ratio [OR], 4.7; P, <0.001) and had a higher mortality rate (OR, 3.5; P, <0.001). After controlling for confounding variables, both ESBL production (OR, 2.3; P, 9.1) and a delay in adequate therapy (OR, 0.05; P, 0.001) were significant predictors for mortality and other adverse outcomes. We conclude that among patients with bacteremia due to Enterobacteriaceae UHA, those with ESBL producers tend to be older and chronically ill and to have a delay in effective therapy and severe adverse outcomes. Efforts should be directed to improving the detection of patients with ESBL bacteremia UHA and to providing immediate appropriate therapy.

The spectrum of bacteria and mechanisms of resistance identified from the casualties treated in the Israeli field hospital after the earthquake in Nepal, 2015: A retrospective analysis.

BACKGROUND: On the April 25, 2015, a 7.8 magnitude earthquake struck Nepal. Soon-after, the Israel Defense Force (IDF) dispatched a tertiary field-hospital to Kathmandu. The field-hospital was equipped with a clinical laboratory with microbiology capabilities. Limited data exists regarding the spectrum of bacteria isolated from earthquake casualties. We aimed to identify the spectrum of bacteria and their mechanisms of resistance in-order to allow preparedness of antibiotic treatment protocols for future disaster scenarios. METHODS: - The field-laboratory phenotypically processed cultures from sterile and non-sterile sites as needed clinically. Later-on, the isolates were brought to Israel for quality control, definite identification and molecular characterization including mechanisms of resistance. RESULTS: A total of 82 clinical pathogens were isolated from 56 patients; 68% of them were Gram negative bacilli. The most common isolates were Enterobacteriaceae (55%) -36% carried bla-NDM and 33% produced Extended-spectrum beta-lactamase (ESBL), mostly blaCTX-M-15. Enterococcus spp were the main Gram positive bacteria isolated (22 isolates), yet, none were vancomycin resistant. The overall level of resistance was 27% MDR and 23% extensively drug resistant (XDR) bacteria. CONCLUSIONS: - Gram negative bacteria were the predominant organism cultured from the casualties, of them 77% were MDR or XDR. NDM was the most common resistance mechanism. The Antibiotic inventory of a field-hospital should be set to cover a wide and unexpected spectrum of bacteria, including resistant organisms. This report adds important information to the scarce reports of bacterial resistance in Nepal.

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.

The effectiveness of empirical anti-parasitic treatment in returning travellers with persistent abdominal symptoms.

BACKGROUND: Persistent abdominal symptoms (PAS) are common among returning-travellers. In the absence of sensitive tests to identify intestinal parasites, gastrointestinal (GI) symptoms often remain a diagnostic challenge. In this study we examined the effectiveness of empirical anti-parasitic treatment in returning-travellers with PAS despite no positive stool-test. METHODS: A retrospective study among returning travellers who approached the clinic between the years 2014 and 2016 with GI complaints without a positive stool-test. The empirical treatment included broad-spectrum anti-parasitic agents-oral Tinidazole and Albendazole. A follow-up questionnaire was performed at least 6 months post-treatment. RESULTS: A total of 102 patients responded the questionnaire-50% women; average age 31.14 (±12.20) years. The average duration of complaints before treatment was 16.52 (±30.06) months. Common GI symptoms included abdominal pain (83.3%) and diarrhoea (78.4%); 67.6% of the patients complained of extreme fatigue. Overall, 69% of the patients reported an improvement in GI symptoms, 37% of them reported full recovery within a few weeks post-treatment. Furthermore, there was an improvement in the energy level and general well-being in 68% and 70% of the patients, respectively. Only 33% of the patients reported minor side effects related to the treatment. CONCLUSIONS: The improvement in GI symptoms, energy level and general well-being shortly after anti-parasitic treatment justifies this empirical approach in returning-travellers with PAS despite negative stool-tests. The association between fatigue and PAS post-travel and the improvement in both as a response to treatment defines fatigue as part of a new syndrome-'Post-travel fatigue and abdominal symptoms'.

Enoxaparin dosage adjustment in patients with severe renal failure: antifactor xa concentrations and safety.

STUDY OBJECTIVE: To evaluate the safety and efficacy, by measuring antifactor Xa levels, of enoxaparin 1 mg/kg subcutaneously once every 24 hours in patients with severe renal failure. DESIGN: Prospective study. SETTING: Emergency, internal medicine, geriatrics, and cardiology departments of a medical center in Israel. PATIENTS: Nineteen patients with stage 4 or 5 chronic kidney disease who required full anticoagulation. INTERVENTION: Patients received enoxaparin 1 mg/kg subcutaneously every 24 hours for 2 or more days, as determined by a treating physician. MEASUREMENTS AND MAIN RESULTS: Data on patients' demographic and clinical characteristics were collected. Blood samples for peak and trough antifactor Xa levels were obtained during the enoxaparin treatment period. Of the 19 study patients, 14 (74%) had peak antifactor Xa levels within the recommended range for full anticoagulation of 0.5-1.0 U/ml after their first enoxaparin dose; no concentration exceeded 1.0 U/ml. The mean peak antifactor Xa level was not significantly different after the first enoxaparin dose compared with the second and third doses. The mean +/- SD trough antifactor Xa level, thought to be an indicator of drug accumulation, was 0.12 +/- 0.12 U/ml; its clinical significance and target range are still unknown. No major bleeding events were noted. CONCLUSION: Enoxaparin 1 mg/kg once every 24 hours in patients with stage 4 or 5 chronic kidney disease who required full anticoagulation was safe, and this dose did not exceed recommended concentrations. The significance of enoxaparin trough levels remains unclear and should be investigated in future studies. Other dosing regimens of enoxaparin for specific patient populations should also be assessed for safety and efficacy.

[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.

Morbidity among the Israeli Defense Force response team during Nepal, post-earthquake mission, 2015.

BACKGROUND: On 25 April 2015, a 7.8-magnitude earthquake struck Nepal. Soon after, the Israel Defense Force (IDF) dispatched a rapid-response team and opened a tertiary field hospital in Kathmandu. There is limited data regarding the spectrum of diseases among rescue teams to disease-stricken areas. The aim of this study was to assess the morbidity among the field-hospital staff during the mission. METHODS: The rescue team was deployed for a 2-week mission in Kathmandu. Pre-travel vaccinations were given prior to departure. The field-hospital was self-equipped including food and drinking water supply with a self-serving kitchen, yet had a shortage of running water. A Public Healthcare and Infectious-Diseases team was present and active during the entire mission. A survey assessing the morbidities and risk-factors throughout the mission was performed at the last day. RESULTS: One hundred thirty-seven (69%) team members completed the questionnaire. Medical complaints were recorded in 87 of them (64%). The most common symptoms were gastrointestinal (GI) (53% of all responders, 84% of the 87 with symptoms). Respiratory symptoms were recorded in 16% and fever in only 8%. There was no significant difference in the rate or spectrum of morbidity between the medical and the non-medical staff. CONCLUSIONS: The Israeli field hospital was a stand-alone facility, yet 53% of its' staff suffered from GI complaints. Prevention of morbidity and specifically of GI complaints upon arrival to a disaster-stricken area in a developing country is difficult. Medical teams in such missions should be acquainted with treating GI complaints.

Cutaneous Myiasis.

Myiasis is defined as the infestation of live vertebrates, either humans or animals, with dipterous larvae. Many organs can be infested by these larvae with cutaneous myiasis being the most common form. Cutaneous myiasis can be divided into three categories: localized furuncular myiasis, migratory myiaisis and wound myiasis, which occurs when fly larvae infest the open wounds of the host. Human myiasis has worldwide distribution, with more species and a heavier burden in tropical and subtropical countries. In recent years with increased travel to the tropics, myiasis has become common in returning travelers from these regions, Furuncular myiasis, mainly Dermatobia homonis becomes the most common form seen among them. Treatment is based on full extraction of the larva and no antibiotic treatment is needed. Understanding the mode of transmission of each type of myiasis may help to prevent the infestation.

Amebic Liver Abscess in Israeli Travelers: A Retrospective Study.

Amebic liver abscess (ALA) is endemic in developing countries. The epidemiology and clinical characteristics of the disease in developing countries are well described. Travelers from nonendemic countries can serve as a model for the natural history of ALA. Currently, the available literature on travelers is limited. This is a retrospective observational study on Israeli travelers diagnosed with ALA. Data regarding travel history, clinical presentation, imaging, and treatment were collected and analyzed. Among 6,867 ill returning Israeli travelers, amebiasis was diagnosed in 53 travelers (0.77%), of whom 14 were with ALA (0.2%). Twelve ALA cases (86%) had an exposure in the Indian subcontinent. The male to female ratio was 1:1, with no significant clinical differences between the sexes. The average lag period between exposure and onset of symptoms was 17.1 months. The lack of male predominance and the prolonged lag period may imply that behavioral factors are pivotal in the development of ALA. Larger case series of travelers are required.