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Listeriosis is rare after hematopoietic stem cell transplantation (HCT). Little is known about listeriosis in this population. In this retrospective international case-control study, we evaluated 41 listeriosis episodes occurring between 2000 and 2021 in HCT recipients (111 transplant centers in 30 countries) and assessed risk factors for listeriosis by comparisons with matched controls. The 41 listeriosis episodes (all due to Listeria monocytogenes [LM]) occurred in 30 allogeneic (allo)-HCT recipients and 11 autologous (auto)-HCT recipients at a median of 6.2 months (interquartile range [IQR], 1.6 to 19.3 months) post-HCT. The estimated incidence was 49.8/100,000 allo-HCT recipients and 13.7/100,000 auto-HCT recipients. The most common manifestations in our cohort were fever (n = 39; 95%), headache (n = 9; 22%), diarrhea, and impaired consciousness (n = 8 each; 20%). Four patients (10%) presented with septic shock, and 19 of 38 (50%) were severely lymphocytopenic. Thirty-seven patients (90%) had LM bacteremia. Eleven patients (27%) had neurolisteriosis, of whom 4 presented with nonspecific signs and 5 had normal brain imaging findings. Cerebrospinal fluid analysis revealed high protein and pleocytosis (mainly neutrophilic). Three-month mortality was 17% overall (n = 7), including 27% (n = 3 of 11) in patients with neurolisteriosis and 13% (n = 4 of 30) in those without neurolisteriosis. In the multivariate analysis comparing cases with 74 controls, non-first HCT (odds ratio [OR], 5.84; 95% confidence interval [CI], 1.10 to 30.82; P = .038); and lymphocytopenia <500 cells/mm 3 (OR, 7.54; 95% CI, 1.50 to 37.83; P = .014) were significantly associated with listeriosis. There were no statistically significant differences in background characteristics, immunosuppression, and cotrimoxazole prophylaxis between cases and controls. HCT recipients are at increased risk for listeriosis compared to the general population. Listeriosis cause severe disease with septic shock and mortality. Neurolisteriosis can present with nonspecific signs and normal imaging. Lymphocytopenia and non-first HCT are associated with an increased risk of listeriosis, and cotrimoxazole was not protective., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Fosmanogepix is a first-in-class antifungal targeting the fungal enzyme Gwt1, with broad-spectrum activity against yeasts and moulds, including multidrug-resistant fungi, formulated for intravenous (IV) and oral administration., Methods: This global, multicenter, non-comparative study evaluated the safety and efficacy of fosmanogepix for first-line treatment of candidaemia in non-neutropenic adults. Participants with candidaemia, defined as a positive blood culture for Candida spp. within 96 h prior to study entry, with ≤2 days of prior systemic antifungals, were eligible. Participants received fosmanogepix for 14 days: 1000 mg IV twice daily on Day 1, followed by maintenance 600 mg IV once daily, and optional switch to 700 mg orally once daily from Day 4. Eligible participants who received at least one dose of fosmanogepix and had confirmed diagnosis of candidaemia (<96 h of treatment start) composed the modified intent-to-treat (mITT) population. Primary efficacy endpoint was treatment success at the end of study treatment (EOST) as determined by the Data Review Committee. Success was defined as clearance of Candida from blood cultures with no additional antifungal treatment and survival at the EOST., Results: Treatment success was 80% (16/20, mITT; EOST) and Day 30 survival was 85% (17/20; 3 deaths unrelated to fosmanogepix). Ten of 21 (48%) were switched to oral fosmanogepix. Fosmanogepix was well tolerated with no treatment-related serious adverse events/discontinuations. Fosmanogepix had potent in vitro activity against baseline isolates of Candida spp. (MICrange: CLSI, 0.002-0.03 mg/L)., Conclusions: Results from this single-arm Phase 2 trial suggest that fosmanogepix may be a safe, well-tolerated, and efficacious treatment for non-neutropenic patients with candidaemia, including those with renal impairment., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

In order to characterize pneumococcal endovascular infection in the post-vaccination era, a retrospective nationwide study based on the Israeli Adult IPD database was conducted. Between 2010 and 2019, 0.6% (23 cases) of IPD cases were of endovascular type, occurring mainly in males (72.3%) with underlying medical conditions (78.2%). Additional pneumococcal source (10 patients) and concomitant infections were not uncommon. Penicillin and ceftriaxone susceptibility rates were 65.2% and 91.3%, respectively; 60.9% of the isolates were not covered by the pneumococcal conjugate vaccine. 21.7% of patients died during hospitalization. In conclusion, pneumococcal endovascular infections still carry significant morbidity and mortality., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Immune reconstitution inflammatory syndrome (IRIS) is increasingly reported in various HIV negative patients with immunosuppression, but the relationship with hematopoietic cell transplantation (HCT) is not well defined. We report a case of IRIS in a patient infected with pulmonary and CNS Nocardiosis following HCT due to primary myelofibrosis., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Advances in treatment for multiple myeloma (MM) patients entail a high risk for opportunistic infections such as invasive pulmonary aspergillosis (IPA)., Objectives: This study was conducted to describe the patient's profile, clinical manifestations, diagnosis and outcome of MM patients with IPA, in our large haemato-oncology centre., Patients/methods: We retrospectively analysed patients with MM who underwent Broncho alveolar lavage for pneumonia at Rambam Hospital during a 13-year period from July 2005 to February 2018. We focused on those with Aspergillus pneumonia., Results: Of the 669 patients with multiple myeloma, mean age 62.6 (±7.6) years, forty-two patients (6.2%) were diagnosed with IPA. Among them, 60% had a probable diagnosis and 40% possible. Clinical presentation was similar for IPA and other pulmonary infections. Compared to those with other pulmonary infections, IPA was more commonly diagnosed in patients with long-standing disease (p = .00012) and among patients receiving 3 or more lines of myeloma therapies (p = .04). Thirty-day mortality rates following diagnostic bronchoscopy did not differ between IPA and non-IPA patients. (p = .85)., Conclusions: Multiple myeloma patients had an increased risk for IPA, most notably in patients with 3 or more lines of anti-myeloma treatment and more advanced disease. This clearly emphasises the vigilance needed for IPA in these patients., (© 2021 Wiley-VCH GmbH.)

Background: Patients with hematological malignancies and allogeneic hematopoietic stem-cell transplant recipients carry a high risk of rare (non-Aspergillus molds and non-Candida yeasts) invasive fungal infections (IFI)., Methods: We retrospectively evaluated and described the patient profile, clinical manifestations, isolated species, treatment and outcome of patients with hematological malignancies diagnosed with these rare IFIs during 15 years in a large single hemato-oncology center., Results: Eighty-seven patients with hematological malignancies treated in our center had at least one positive culture or molecular identification of a rare fungus. Ninety-three isolates were considered the etiological agents of the infection. The most common underlying hematological malignancy was acute myeloid leukemia, 36 patients (41.4%). Eighty patients (91%) received chemotherapy less than 30 days prior to IFI diagnosis. The most frequent site of infection was the respiratory tract: 34 patients (39%) had pulmonary and 19 patients (22%) had a sinusal or nasopharyngeal infections. Disseminated infection, defined as positive blood cultures or parallel infection in multiple organ systems, was documented in 20 patients (23%). The most common fungal species were Fusarium (35%) and Zygomycetes (25%). Coinfection with more than one fungus was noted in 20 patients (23%). Forty-seven of 87 patients (54%) in this study died within 90 days of IFI diagnosis., Conclusions: Rare IFIs in patients with hematological malignancy become increasingly frequent. Early identification with traditional and molecular methods is important in management of these patients.

Invasive pulmonary aspergillosis (IPA) has dire consequences in hemato-oncological patients. We report our experience with performing routine baseline chest computed tomography for early diagnosis of IPA. We found high rates of proven or probable IPA diagnosed on admission among patients with newly diagnosed acute myeloid leukemia., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: This study aimed to evaluate the diagnostic role of PCR detection of Aspergillus DNA in the broncho-alveolar lavage (BAL) fluid in a large cohort of patients suspected to have invasive pulmonary aspergillosis (IPA)., Methods: Consecutive immunocompromised patients who underwent bronchoscopy with BAL sampling and PCR detection of Aspergillus DNA for the diagnosis of pulmonary infiltrates were included in the study. Galactomannan (GM) antigen testing in BAL and serum and BAL fungal culture were also performed. Patients were classified as having IPA (proven/probable/possible) or no-IPA according to the EORTC/MSG diagnostic criteria., Results: During 12 years (2005-2016), 1248 bronchoscopies were performed for 1072 patients. 77% had hematological malignancy, of them 40% had AML and 35.6% underwent HSCT. IPA was diagnosed in 531 patients (42.5%), 7-proven, 280-probable and 244-possible. PCR was positive in 266 cases, of them 213 had IPA, indicating a true positive rate of 80% (213/266) and a false positive rate of 20% (53/266). These results establish the diagnostic performance of PCR to have sensitivity of 40%, specificity of 93%, PPV- 80% and NPV-68%. Of 244 patients with possible IPA, 80 had positive PCR. Including PCR in the diagnostic criteria would move 80 cases from the possible group to the probable one. A combination of positive PCR and/or BAL-GM increases sensitivity to 74%, while positivity of both tests elevates PPV to 99.4%., Conclusions: Inclusion PCR for the detection of Aspergillus-DNA in BAL in the mycological criteria of the EORTC/MSG definitions increases the rate and the certainty of IPA diagnosis., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Treatment options for carbapenem-resistant Enterobacteriaceae (CRE) infections are limited and CRE infections remain associated with high clinical failure and mortality rates, particularly in vulnerable patient populations. A Phase 3, multinational, open-label, randomized controlled trial (TANGO II) was conducted from 2014 to 2017 to evaluate the efficacy/safety of meropenem-vaborbactam monotherapy versus best available therapy (BAT) for CRE., Methods: A total of 77 patients with confirmed/suspected CRE infection (bacteremia, hospital-acquired/ventilator-associated bacterial pneumonia, complicated intra-abdominal infection, complicated urinary tract infection/acute pyelonephritis) were randomized, and 47 with confirmed CRE infection formed the primary analysis population (microbiologic-CRE-modified intent-to-treat, mCRE-MITT). Eligible patients were randomized 2:1 to meropenem-vaborbactam (2 g/2 g over 3 h, q8h for 7-14 days) or BAT (mono/combination therapy with polymyxins, carbapenems, aminoglycosides, tigecycline; or ceftazidime-avibactam alone). Efficacy endpoints included clinical cure, Day-28 all-cause mortality, microbiologic cure, and overall success (clinical cure + microbiologic eradication). Safety endpoints included adverse events (AEs) and laboratory findings., Results: Within the mCRE-MITT population, cure rates were 65.6% (21/32) and 33.3% (5/15) [95% confidence interval (CI) of difference, 3.3% to 61.3%; P = 0.03)] at End of Treatment and 59.4% (19/32) and 26.7% (4/15) (95% CI of difference, 4.6% to 60.8%; P = 0.02) at Test of Cure;.Day-28 all-cause mortality was 15.6% (5/32) and 33.3% (5/15) (95% CI of difference, - 44.7% to 9.3%) for meropenem-vaborbactam versus BAT, respectively. Treatment-related AEs and renal-related AEs were 24.0% (12/50) and 4.0% (2/50) for meropenem-vaborbactam versus 44.0% (11/25) and 24.0% (6/25) for BAT. Exploratory risk-benefit analyses of composite clinical failure or nephrotoxicity favored meropenem-vaborbactam versus BAT (31.3% [10/32] versus 80.0% [12/15]; 95% CI of difference, - 74.6% to - 22.9%; P < 0.001)., Conclusions: Monotherapy with meropenem-vaborbactam for CRE infection was associated with increased clinical cure, decreased mortality, and reduced nephrotoxicity compared with BAT., Clinical Trials Registration: NCT02168946., Funding: The Medicines Company.

Objectives: The risk of cytomegalovirus (CMV) reactivation in multiple myeloma (MM) patients treated with bortezomib-based induction regimens is increased following autologous stem cell transplantation (ASCT). There is paucity of data regarding the risk of CMV infections in MM patients who did not receive bortezomib and ASCT., Methods: We herein report three cases of heavily pretreated MM patients, receiving daratumumab-containing combination regimens, in whom ASCT had been performed long ago and who recently developed severe CMV-related gastrointestinal disease., Results: All the three patients had a prolonged CMV disease course requiring a long-term antiviral treatment. All the patients suffered from CMV colitis. One patient had concurrent CMV duodenitis and another patient had a concurrent CMV retinitis., Conclusion: Novel myeloma treatments prolong patient survival and more patients with profound immunosuppression following multiple lines of therapies are seen in clinical practice. These patients may present with opportunistic infections that were rare in the past. Our findings suggest a possible association between daratumumab therapy (in combination with other immunosuppressive therapies) and severe CMV gastrointestinal disease. A longer follow-up is needed to explore long-term side effects of novel agents like daratumumab in newly diagnosed as well as heavily pretreated MM patients., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Data regarding treatment of rare invasive fungal diseases (IFDs) are scarce. We documented the efficacy and safety of isavuconazole for treatment of uncommonly diagnosed IFDs. VITAL was a single-arm, international, open-label study evaluating the efficacy and safety of isavuconazole (200 mg orally or intravenously every 8 hours for 48 hours, then once daily). The primary outcome was overall response at Day 42; key secondary outcomes were overall responses at Day 84 and end of treatment (EOT), mortality at Days 42 and 84, and safety. This analysis includes patients with IFD caused by rare or unidentified pathogens. Twenty-six patients with IFDs caused by rare moulds (n = 17), non-Candida yeasts (n = 2), or unidentified moulds (n = 7) were enrolled (median treatment duration [range], 114.5 [1-496]) days. Overall treatment success was observed in 11/26 (42.3%), 10/26 (38.5%), and 15/26 (57.7%) patients at Days 42, 84, and EOT, respectively. All-cause mortality rates were 2/26 patients (7.7%) at Day 42 and 4/26 patients (15.4%) at Day 84; another two patients died after Day 84. All patients had ≥1 treatment-emergent adverse event (TEAE); 15 patients (57.7%) had serious TEAEs, and TEAEs led to discontinuation of isavuconazole in four patients (15.4%). Isavuconazole may be efficacious for treatment of a range of rare IFDs., (© 2018 The Authors. Mycoses Published by Blackwell Verlag GmbH.)

The optimal approach to treat invasive fungal disease (IFD) caused by more than one fungal species is unknown. We documented the efficacy and safety of isavuconazole for treatment of IFDs caused by more than one fungal species. VITAL was a single-arm, international, open-label study evaluating the efficacy and safety of isavuconazole (200 mg orally or intravenously every 8 hours for 48 hours, then once daily) for treatment of rare IFDs. The primary outcome was the overall response at Day 42; key secondary outcomes were overall responses at Day 84 and end of treatment (EOT), mortality at Days 42 and 84, and safety. This analysis includes patients with IFD caused by multiple fungal species. Fifteen patients were included in this analysis (including Aspergillus spp., n = 11; without Aspergillus spp., n = 4); median treatment duration was 97 days [range, 6-544] days). Overall treatment success was observed in 2/15 patients (13.3%) at Days 42 and 84, and 2/14 (14.3%) at EOT. All-cause mortality was 2/15 (13.3%) at Day 42 and 4/15 (26.7%) at Day 84. All patients had ≥1 treatment-emergent adverse event (TEAE); 12 patients (80.0%) had serious TEAEs; TEAEs led to discontinuation of isavuconazole in two patients (13.3%). Isavuconazole may be useful to treat some IFDs caused by multiple fungal species., (© 2018 The Authors. Mycoses Published by Blackwell Verlag GmbH.)

Purpose: Available data suggest that respiratory infections are associated with increased morbidity and mortality in patients hospitalized due to acute leukemia and allogeneic stem cell transplantation (allo-SCT). However, the precise incidence, risk factors, and severity of respiratory infection, mainly community-acquired, in patients with lymphoma and multiple myeloma (MM) are not fully determined. The current study aimed to investigate risk factors for respiratory infections and their clinical significance in patients with B cell non-Hodgkin lymphoma (NHL) and multiple myeloma (MM) in the first year of diagnosis., Methods: Data of consecutive patients diagnosed with NHL or MM and treated at the Rambam Hematology Inpatient and Outpatient Units between 01/2011 and 03/2012 were evaluated. Information regarding anticancer treatment, incidence and course of respiratory infections, and infection-related outcomes was analyzed., Results: One hundred and sixty episodes of respiratory infections were recorded in 103 (49%) of 211 (73-MM, 138-NHL) patients; 126 (79%) episodes were community-acquired, 47 (29%) of them required hospitalization. In univariate analysis, age < 60 years, MM diagnosis, and autologous SCT increased the respiratory infection risk (P = 0.058, 0.038, and 0.001, respectively). Ninety episodes (56% of all respiratory episodes) were examined for viral pathogens. Viral infections were documented in 25/90 (28%) episodes, 21 (84%) of them were community-acquired, requiring hospitalization in 5 (24%) cases. Anti-flu vaccination was performed in 119 (56%) patients. Two of the six patients diagnosed with influenza were vaccinated., Conclusions: Respiratory infections, including viral ones, are common in NHL and MM. Most infections are community-acquired and have a favorable outcome. Rapid identification of viral pathogens allows avoiding antibiotic overuse in this patient population.

Introduction: Antibiotic stewardship programs (ASP) are designed to optimize antibiotic use in hospitals. Antibiotic consumption is one of the measures assessing the effects of ASPs., Aims: To evaluate the effect of an ASP on antibiotic consumption in our hospital and compare it to hospitals in Israel and worldwide., Methods: Between October 2012 and March 2013 an ASP was implemented in Rambam Hospital. The program included educational activities, publication of local guidelines for empirical antibiotic treatment, structured infectious diseases consultations, pre-authorization antibiotic restrictions and stop orders. We compared antibacterial antibiotic consumption in defined daily doses (DDD)/100 hospital days (HD) between the periods before (1/2010-3/2013) and after (4/2013-9/2014) implementing the ASP. The study was conducted in the medical departments, hematology, the intensive care unit (ICU) and all pediatric wards., Results: Total antibiotic consumption before implementing the ASP was 96±11.2 DDD/100 HD in medical departments, 186.4±42.8 in the ICU and 185.5±59 in hematology; all values were higher than the worldwide-reported averages for these departments. Following the ASP, total antibiotic consumption decreased by 12% (p=0.008) in the medical departments and by 26% (p=0.002) in hematology, mostly due to reductions in non-restricted antibiotics. No significant changes were observed overall in the ICU and in pediatric wards. There was a significant reduction in consumption of vancomycin and carbapenems in all settings, the latter was reduced to nearly half. Amikacin use quadrupled in the medical departments., Conclusions: Implementation of an ASP lead to a reduction in non-restricted and restricted antibiotic consumption, especially carbapenems.

Background: Campylobacter bacteraemia (CB) is rare and usually occurs in immune-compromised patients. In this study we examined the incidence and epidemiology of CB in one institution over 15.5 years., Methods: The medical records of all the consecutive patients with CB admitted to our hospital from 2000 to 2015 were retrospectively reviewed. Clinical characteristics, microbiologic and outcome data were collected., Results: During the study period, 65 patients with CB were identified. The majority of the patients were middle aged and immune-compromised. Campylobacter jejuni was the most commonly identified species (33/47, 70%). The main underlying conditions were haematological malignancies (43%) and chronic liver disease (14%). Fifty-seven percent of the patients were receiving immunosuppressive therapy at the time of bacteraemia. The most common presenting symptoms were fever (85%), diarrhoea (40%), abdominal pain (40%), and nausea and vomiting (40%). Of the isolates tested, 97% were susceptible to macrolides, and only 35% were susceptible to quinolones. Susceptibility to quinolones decreased over the years. Most patients did not receive adequate empiric antibiotic treatment (81.5%) and about 20% never received directed therapy. Mortality and relapse rates were low (5% each). There was no association between adequate empirical or definitive antibiotic therapy and adverse outcomes., Conclusion: The main predisposing factor for Campylobacter bacteraemia in our cohort was immunosuppression. Prognosis was generally favourable regardless of appropriateness of antibiotic therapy.

Objectives: The identification of the specific pathogen responsible for a respiratory infection in patients with hematological malignancies (HM) would ensure relevant treatment and prevent toxicity associated with anti-infective therapy. This large-scale study aimed to explore the clinical impact of fiberoptic bronchoscopy with bronchoalveolar lavage (FOB-BAL) in conjunction with molecular analysis on the diagnosis and management of respiratory infections in hemato-oncological patients., Methods: All consecutive patients with HM and pulmonary infiltrates, who underwent FOB-BAL between January 2008 and January 2013, were included in the analysis. Clinical characteristics, FOB-BAL results, and treatment adjustments were recorded, and factors predicting a positive BAL were assessed., Results: Four hundred and twenty-five FOB-BAL procedures were analyzed. BAL revealed a specific diagnosis in 219 (51.5%) patients, 208 of them with a pulmonary infection. Infectious etiological agents found were mainly Aspergillus spp (n=142), bacterial species (n=44), and Pneumocystis jirovecii (n=34). Multivariate analysis showed that a lymphoproliferative disease, ≥2 symptoms (dyspnea/cough/hemoptysis/pleuritic pain), and less than 4 days between symptom appearance and FOB-BAL, predicted a positive FOB-BAL result. BAL results prompted a treatment modification in 48% of subjects., Conclusions: FOB-BAL in conjunction with molecular assays is efficient in the rapid detection of life-threatening infections, allowing for adjustment of anti-infective therapy, which may result in better outcomes and reduce treatment-related toxicity., (Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: The frequency and clinical significance of polymicrobial pneumonia in patients with hematological malignancies (HM) are poorly understood. The aim of the present study is to describe the prevalence, risk factors, clinical characteristics, and outcome of patients with HM and polymicrobial pneumonia., Methods: Over a 5 year period, 436 consecutive adult patients with HM and pulmonary infiltrates underwent diagnostic fiberoptic bronchoscopy with bronchoalveolar lavage. For 219 patients an infectious etiology was diagnosed, of them 45 (20.5 %) had polymicrobial etiology. Risk factors, clinical course and outcome of polymicrobial pulmonary infection in patients with HM were established., Results: 45 patients with HM were identified with polymicrobial pulmonary infection, 39 of them with two pathogens, and 6 with three. The most common co-pathogen identified was Aspergillus sp. (87 %). Allogeneic hematopoietic stem cell transplantation (HSCT) and graft versus host disease (GVHD) were predictors of polymicrobial infection. Compared to patients with monomicrobial pneumonia, patients with polymicrobialpulmonary infection had a more severe clinical course with more dyspnea (69 vs. 49 %, P = 0.016), hemoptysis (16 vs. 7 %, P = 0.065) and more required respiratory support (27 vs. 17 %, P = 0.125). In-hospital mortality was significantly higher in patients with polymicrobial pulmonary infection than in patients with monomicrobial pulmonary infection (49 vs. 19 %, P < 0.001)., Conclusions: Polymicrobial pulmonary infection occurs quite frequently in patients with HM, especially in allogeneic HSCT recipients and in patients with GVHD. The clinical course of polymicrobial pulmonary infection is severe and mortality approaches 50 %. The clinician taking care of these patients should always look for additional copathogens in profoundly immunosuppressed patients with pneumonia.

Background: Mucormycosis is an uncommon invasive fungal disease with high mortality and few treatment options. Isavuconazole is a triazole active in vitro and in animal models against moulds of the order Mucorales. We assessed the efficacy and safety of isavuconazole for treatment of mucormycosis and compared its efficacy with amphotericin B in a matched case-control analysis., Methods: In a single-arm open-label trial (VITAL study), adult patients (≥18 years) with invasive fungal disease caused by rare fungi, including mucormycosis, were recruited from 34 centres worldwide. Patients were given isavuconazole 200 mg (as its intravenous or oral water-soluble prodrug, isavuconazonium sulfate) three times daily for six doses, followed by 200 mg/day until invasive fungal disease resolution, failure, or for 180 days or more. The primary endpoint was independent data review committee-determined overall response-ie, complete or partial response (treatment success) or stable or progressive disease (treatment failure)-according to prespecified criteria. Mucormycosis cases treated with isavuconazole as primary treatment were matched with controls from the FungiScope Registry, recruited from 17 centres worldwide, who received primary amphotericin B-based treatment, and were analysed for day-42 all-cause mortality. VITAL is registered with ClinicalTrials.gov, number NCT00634049. FungiScope is registered with ClinicalTrials.gov, number NCT01731353., Findings: Within the VITAL study, from April 22, 2008, to June 21, 2013, 37 patients with mucormycosis received isavuconazole for a median of 84 days (IQR 19-179, range 2-882). By day 42, four patients (11%) had a partial response, 16 (43%) had stable invasive fungal disease, one (3%) had invasive fungal disease progression, three (8%) had missing assessments, and 13 (35%) had died. 35 patients (95%) had adverse events (28 [76%] serious). Day-42 crude all-cause mortality in seven (33%) of 21 primary-treatment isavuconazole cases was similar to 13 (39%) of 33 amphotericin B-treated matched controls (weighted all-cause mortality: 33% vs 41%; p=0·595)., Interpretation: Isavuconazole showed activity against mucormycosis with efficacy similar to amphotericin B. Isavuconazole can be used for treatment of mucormycosis and is well tolerated., Funding: Astellas Pharma Global Development, Basilea Pharmaceutica International., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Isavuconazole is a novel triazole with broad-spectrum antifungal activity. The SECURE trial assessed efficacy and safety of isavuconazole versus voriconazole in patients with invasive mould disease., Methods: This was a phase 3, double-blind, global multicentre, comparative-group study. Patients with suspected invasive mould disease were randomised in a 1:1 ratio using an interactive voice-web response system, stratified by geographical region, allogeneic haemopoietic stem cell transplantation, and active malignant disease at baseline, to receive isavuconazonium sulfate 372 mg (prodrug; equivalent to 200 mg isavuconazole; intravenously three times a day on days 1 and 2, then either intravenously or orally once daily) or voriconazole (6 mg/kg intravenously twice daily on day 1, 4 mg/kg intravenously twice daily on day 2, then intravenously 4 mg/kg twice daily or orally 200 mg twice daily from day 3 onwards). We tested non-inferiority of the primary efficacy endpoint of all-cause mortality from first dose of study drug to day 42 in patients who received at least one dose of the study drug (intention-to-treat [ITT] population) using a 10% non-inferiority margin. Safety was assessed in patients who received the first dose of study drug. This study is registered with ClinicalTrials.gov, number NCT00412893., Findings: 527 adult patients were randomly assigned (258 received study medication per group) between March 7, 2007, and March 28, 2013. All-cause mortality from first dose of study drug to day 42 for the ITT population was 19% with isavuconazole (48 patients) and 20% with voriconazole (52 patients), with an adjusted treatment difference of -1·0% (95% CI -7·8 to 5·7). Because the upper bound of the 95% CI (5·7%) did not exceed 10%, non-inferiority was shown. Most patients (247 [96%] receiving isavuconazole and 255 [98%] receiving voriconazole) had treatment-emergent adverse events (p=0·122); the most common were gastrointestinal disorders (174 [68%] vs 180 [69%]) and infections and infestations (152 [59%] vs 158 [61%]). Proportions of patients with treatment-emergent adverse events by system organ class were similar overall. However, isavuconazole-treated patients had a lower frequency of hepatobiliary disorders (23 [9%] vs 42 [16%]; p=0·016), eye disorders (39 [15%] vs 69 [27%]; p=0·002), and skin or subcutaneous tissue disorders (86 [33%] vs 110 [42%]; p=0·037). Drug-related adverse events were reported in 109 (42%) patients receiving isavuconazole and 155 (60%) receiving voriconazole (p<0·001)., Interpretation: Isavuconazole was non-inferior to voriconazole for the primary treatment of suspected invasive mould disease. Isavuconazole was well tolerated compared with voriconazole, with fewer study-drug-related adverse events. Our results support the use of isavuconazole for the primary treatment of patients with invasive mould disease., Funding: Astellas Pharma Global Development, Basilea Pharmaceutica International., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objectives: Carbapenem-resistant Gram-negative bacteria (CRGNB) pose a clinical challenge. We attempted to estimate the mortality burden of CRGNB among haematological cancer patients., Methods: This was a retrospective cohort study. We included adult patients hospitalized in the haemato-oncological/bone marrow transplantation departments for chemotherapy, between 2008 and 2014, with Gram-negative aerobic bacteraemia. We compared patients with CRGNB and carbapenem-susceptible Gram-negative bacteraemia (CSGNB). The primary outcome was 14 day all-cause mortality. In addition, we assessed 1 year survival. Multivariable logistics regression analysis and adjusted Cox regression analysis were conducted. Analyses were adjusted to the propensity for CRGNB bacteraemia., Results: The cohort included mostly young patients (mean age 50.1 years) with acute leukaemia (264/423, 62.4%) and the median absolute neutrophil count at bacteraemia onset was 0 × 10(9)/L. The unadjusted 14 day mortality rate was higher for patients with CRGNB compared with CSGNB [45.6% (47/103) versus 15% (48/320), respectively (P < 0.001)]. Adjusting to baseline prognostic factors, infection characteristics and the propensity score retained a significant association between CRGNB and 14 day mortality (OR 5.14, 95% CI 2.32-11.38). Including only the first bacteraemic episode per patient, 1 year mortality was 74.7% (68/91) for patients with CRGNB versus 49.8% (119/239) for patients with CSGNB (P < 0.001). Adjusting for risk factors associated with 1 year mortality, the HR for mortality with CRGNB was 1.48 (95% CI 1-2.2). CRGNB bacteraemia was associated with several risk factors for mortality, including inappropriate empirical antibiotic treatment and less effective definitive antibiotics., Conclusions: This study demonstrated a significant adjusted association between CRGNB and mortality up to 1 year among haemato-oncological patients receiving chemotherapy., (© The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: PCV7 was introduced as a universal childhood vaccination in Israel on July 2009 and was gradually replaced by PCV13 from November 2010. We report data on adult invasive pneumococcal disease (IPD), two years post PCV13 implementation., Methods: An ongoing nationwide active surveillance (all 27 laboratories performing blood/CSF cultures nationwide), initiated in 2009, providing all blood/CSF Streptococcus pneumoniae isolated from persons ≥18 years. Capture-recapture method assured reporting of >95% cases. All isolates were serotyped in one central laboratory. Medical history and outcomes were recorded in ∼90%., Results: Of 1809 IPD episodes, S. pneumoniae was isolated from the blood in 95% and most cases had pneumonia. Predisposing comorbidities were present in >70%. During the four study years, overall IPD incidence decreased from 9.2 to 7.2/100,000, incidence of pneumonia and particularly severe pneumonia cases decreased significantly from 6.6 to 4.7/100,000, (p=0.029). Vaccine type (VT7/VT13) serotypes decreased by 70%/57% within 4 years. This was accompanied by a 52% increase in non-VT13 strains. These changes were most apparent in winter. PCV impact was most pronounced in younger adults (39% decrease in overall IPD with only a non-significant increase in non-VT13 cases) while in those >65 years a non-significant decrease in overall IPD was observed with a 64% increase in non-VT13 cases. Non-VT13 serotypes that increased significantly were 12F, 15A 10A and 6C. A continuous reduction in isolates with penicillin MIC>0.06μg/ml was observed (26% to 11%, p<0.001)., Conclusions: Four years after PCV7 and 2.5 years after PCV13 universal implementation in children, incidence of adult IPD caused by VT7 and VT13 decreased in all ages, mainly in younger adults. Despite increase in non-VT13 IPD, overall IPD decreased. Additional follow-up is needed to determine the long-term impact of PCV13., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Varicella zoster virus (VZV) like other alphaherpes viruses stays latent after its primary infection. During its reactivation, it can infect the central nervous system (CNS) causing a variety of clinical presentations. Using polymerase chain reaction (PCR) for detection of VZV DNA in cerebrospinal fluid (CSF), it is now recognized in some series as the most common causative agent of viral CNS infection. We aimed to investigate in our study the correlation between VZV viral load in the CSF and the clinical course of its infection, using quantitative real-time PCR. For this purpose, we examined 56 specimens of consecutive patients with positive CSF for VZV DNA in a qualitative test, with a clinical picture of meningitis or encephalitis collected over 10years in Rambam medical center. We found a significant correlation between VZV viral load and the severity and duration of neurological disease. We believe that using quantitative measurement of VZV DNA in the CSF, could serve as a prognostic marker which would influence treatment decisions., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Carbapenem-resistant Enterobacteriaceae (CRE) are emerging. In attempt to eradicate CRE colonization, we conducted a semirandomized, prospective, controlled trial using oral nonabsorbable antibiotics., Methods: Consecutive hospitalized CRE carriers were studied. Patients whose rectal isolates were gentamicin sensitive but colistin resistant were treated with gentamicin. Patients whose isolates were colistin sensitive but gentamicin resistant were treated with colistin. Patients whose isolates were sensitive to both drugs were randomized to 3 groups of oral antibiotic treatment: gentamicin, colistin, or both. Patients whose isolates were resistant to both drugs, and those who did not consent, were followed for spontaneous eradication., Results: One hundred fifty-two patients were included; 102 were followed for spontaneous eradication for a median duration of 140 days (controls), and 50 received 1 of the 3 drug regimens: gentamicin, 26; colistin, 16; both drugs, 8, followed for a median duration of 33 days. Eradication rates in the 3 treatment groups were 42%, 50%, and 37.5%, respectively, each significantly higher than the 7% spontaneous eradication rate in the control group (P < .001, P < .001, and P = .004, respectively) with no difference between the regimens. No significant adverse effects were observed., Conclusion: Oral antibiotic treatment with nonabsorbable drugs to which CRE is susceptible appears to be an effective and safe for eradication of CRE colonization and, thereby, may reduce patient-to-patient transmission and incidence of clinical infection with this difficult-to-treat organism., (Copyright © 2013 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.)

We report the case of a 28-year-old previously healthy male who presented with a 1-week history of fever, headache, vomiting, and jaundice. Blood cultures were positive for group G streptococci and transesophageal echocardiography demonstrated vegetations on the aortic valve, leading to a definitive diagnosis of infective endocarditis. The combination of fever, splenomegaly, anemia, thrombocytopenia, hypertriglyceridemia, elevated ferritin level, low natural killer (NK) cell activity, and hemophagocytosis in bone marrow aspirate confirmed the diagnosis of hemophagocytic syndrome (hemophagocytic lymphohistiocytosis). Antibiotic treatment and intravenous immunoglobulins were administered and the patient made a full recovery., (Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

We present a case of progressive disseminated histoplasmosis in an immunocompetent traveler. Histoplasmosis was acquired in South America; its manifestations included prolonged fever, splinter hemorrhages, erythema multiforme, arthritis, and mediastinal lymphadenopathy. To the best of our knowledge no splinter hemorrhages had previously been reported in a patient with histoplasmosis., (© 2013 International Society of Travel Medicine.)

Background: Staphylococcus aureus infective endocarditis (IE) is a characteristic community-acquired infection, however most cases are presently occurring in the health care setting. This study investigated the incidence and risk factors for S. aureus IE in patients with nosocomial and health care-associated S. aureus bacteraemia (SAB)., Methods: Consecutive patients with health care-associated and hospital-acquired SAB were prospectively recruited over a 30-month period. Patients were followed up for at least 12 weeks after the initial positive blood culture result. The primary endpoint was the diagnosis of IE., Results: IE occurred in 11 of 303 patients (3.6%). Patient characteristics at diagnosis and that were associated with IE included the number of positive blood cultures obtained during hospitalization (p = 0.003), the duration of bacteraemia (p < 0.001), bacteraemia persisting for > 3 days (odds ratio (OR) 14.5, 95% confidence interval (CI) 4.0-52.8; p < 0.001), performance of echocardiography (OR 1.88, 95% CI 1.69-2.1; p = 0.001), presence of a well known predisposing risk for IE (OR 57.2, 95% CI 13.6-240.5; p < 0.001), a non-fatal McCabe score (OR 2.10, 95% CI 1.4-3.1; p = 0.02), and the duration of fever related to the infection (p = 0.026). On multivariable analysis, the presence of a predisposing risk for IE, prolonged bacteraemia, and non-fatal McCabe score remained significantly associated with IE., Conclusions: In this study the incidence of IE was lower than previously reported. Three clinical characteristics were identified as risk factors for IE among patients with SAB acquired in a health care setting.

Recent exposure to azoles is an important risk factor for infection with fluconazole-resistant Candida spp., but little is known about the role of antibacterial drug exposure in the emergence of drug-resistant Candida. We did a prospective nationwide surveillance study of candidemia in Israel and analyzed the propensity score-adjusted association between antifungal and antibacterial drug exposure and bloodstream infection with C. glabrata and fluconazole-resistant Candida isolates. Four hundred forty-four episodes of candidemia (450 Candida isolates, 69 [15%] C. glabrata isolates, and 38 [8.5%] fluconazole-resistant isolates) from 18 medical centers in Israel were included. C. glabrata bloodstream infection was strongly associated with recent metronidazole exposure (odds ratio [OR], 3.2; P < 0.001). Infection with a fluconazole-resistant isolate was associated with exposure to carbapenems, trimethoprim-sulfamethoxazole, clindamycin, and colistin (odds ratio, 2.8; P = 0.01). The inclusion of antibacterial drug exposure in a multivariable model significantly enhanced the model's predictive accuracy for fluconazole-resistant Candida bloodstream infection. Our findings may be relevant to the selection of empirical antifungal treatment and broaden the scope of antibiotic-associated collateral damage.

Background and Objective: Pneumonia caused by Pneumocystis jirovecii (PCP) in patients without human immunodeficiency virus (HIV) infection is associated with high mortality. The diagnosis of PCP at our institution is based on detection of DNA using a polymerase chain reaction (PCR) assay. The aim of this study was to describe the clinical manifestations, outcomes and factors associated with mortality due to PCP, as diagnosed by PCR, in patients without HIV infection., Methods: Over a 6-year period, all HIV-negative immunocompromised patients suspected of having an opportunistic pulmonary infection underwent diagnostic bronchoscopy. A multigene PCR assay that detects Pneumocystis jirovecii DNA was used for the diagnosis of PCP. Patients were considered to have PCP if they had underlying immunodeficiency, compatible signs and symptoms, abnormal radiological findings, and Pneumocystis jirovecii DNA was detected in a bronchoalveolar lavage fluid sample. Data was collected retrospectively., Results: PCP was diagnosed in 58 patients. The underlying conditions included haematological malignancies (60.3%), solid tumours (17.2%) and immunosuppressive treatment (22.4%). The most common clinical features in patients with PCP were fever (94.6%), dyspnoea (67.2%) and cough (36.2%). The overall in-hospital mortality was 17.2% (10/58). Mortality was associated with co-infections, high lactate dehydrogenase levels, female gender, and higher pneumonia severity index and acute physiology and chronic health evaluation III scores., Conclusions: In this study, the mortality of HIV-negative patients with PCP was low compared with previous reports. We hypothesize that this finding resulted from the increased sensitivity of a PCR-based assay, as compared with traditional methods, for the diagnosis of PCP in HIV-negative patients., (© 2012 The Authors. Respirology © 2012 Asian Pacific Society of Respirology.)

Introduction: Nocardiosis, although very rare, is considered as an important opportunistic infection; however, recent literature is limited. This study describes all cases of nocardial infection treated in the authors' hospital to provide more information about clinical manifestations, species isolated, treatment and outcome of patients with nocardiosis., Methods: A retrospective review of the clinical features and outcome of nocardial infections was conducted during a 15-year period (1996-2010) at Rambam Health Care Campus., Results: The study included 53 patients with nocardial infection, 43 of them had underlying immunodeficiency. The most common clinical form was pulmonary nocardiosis with and without dissemination (60%), followed by skin and soft tissue infection (21%), bacteremia (11%) and pertonitis (5%). Resistance to trimethoprim/sulfamethoxazile was detected in 15% of isolates; to imipenem in 5% and to ciprofloxacin in 65%. Overall mortality was 25% (13/53), mainly observed in patients with pulmonary involvement (37.5%)., Conclusions: Nocardiosis is a rare infection and mainly affects immunocompromised patients. Higher index of suspicion is needed for earlier diagnosis and treatment to improve prognosis.

Herpesvirus 6 (HHV-6) infection is a common complication during immunosuppression. Its significance for multiple myeloma (MM) patients undergoing autologous stem cell transplantation (ASCT) after treatment with novel agents affecting immune system remains undetermined. Data on 62 consecutive MM patients receiving bortezomib-dexamethasone (VD) (n = 41; 66%) or thalidomide-dexamethasone (TD) (n = 21, 34%) induction, together with melphalan 200 mg/m(2) autograft between 01.2005 and 09.2010, were reviewed. HHV-6 reactivation was diagnosed in patients experiencing postengraftment unexplained fever (PEUF) in the presence of any level of HHHV-6 DNA in blood. There were no statistically significant differences in patient characteristics between the groups, excluding dexamethasone dosage, which was significantly higher in patients receiving TD. Eight patients in TD and 18 in VD cohorts underwent viral screening for PEUF. HHV-6 reactivation was diagnosed in 10 patients of the entire series (16%), accounting for 35% of those screened; its incidence was 19.5% (n = 8) in the VD group versus 9.5% (n = 2) in the TD group. All patients recovered without sequelae. In conclusion, HHV-6 reactivation is relatively common after ASCT, accounting for at least a third of PEUF episodes. Further studies are warranted to investigate whether bortezomib has an impact on HHV-6 reactivation development.

Recent studies suggest an increased risk for Pneumocystis jirovecii pneumonia (PJP) in adults receiving short-interval rituximab-CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) therapy for diffuse large cell B cell lymphoma (DLBCL). This retrospective study evaluates precise PJP incidence and the efficacy of anti-PJP prophylaxis in DLBCL. Patients with DLBCL, aged ≥18 years and treated between December 2004 and December 2010, were included. Details of treatment-related respiratory infections, focusing on PJP incidence, risk factors and prophylaxis, were assessed. A total of 132 patients were analyzed; 47 were treated with rituximab-CHOP therapy every 21 days (R-CHOP-21) and 85 were treated every 14 days (R-CHOP-14). The incidence of treatment-related respiratory infections was higher in patients receiving R-CHOP-14. PJP was diagnosed in 5 patients: 4 in the R-CHOP-14 (6.6%) and 1 in the R-CHOP-21 cohort (2.6%), using triplex polymerase chain reaction (PCR) for PJ in bronchoalveolar fluid. None of the patients receiving P.jirovecii prophylaxis (n = 33) developed PJP, compared with 6.6% of those treated with R-CHOP-14 without such prophylaxis. An older age and R-CHOP administered every 14 rather than every 21 days increased the PJP risk. Trimethoprim/sulfamethoxazole prophylaxis is found to be highly efficient in preventing this life-threatening complication and, therefore, should be recommended for patients receiving the R-CHOP-14 regimen., (Copyright © 2011 S. Karger AG, Basel.)

Skin and soft tissue infections (SSTIs) are one of the most common infection syndromes and may be caused by a large number of microorganisms. Some principles of aquatic injuries are different than those of land-based trauma. Wounds sustained in marine environment are exposed to a milieu of bacteria rarely encountered in different settings. These include Vibrio spp., Aeromonas spp., Shewanella spp., Erysipelothrix rhusiopathiae, Mycobacterium marinum, Streptococcus iniae, and other microbes. Failure to recognize and treat these uncommon pathogens in a timely manner may result in significant morbidity or death. These infections are frequently contracted as a result of recreational swimming, fishing injuries, or seafood handling. The spectrum of manifestations is wide, varying from cases of mild cellulitis, to severe life-threatening necrotizing fasciitis requiring radical surgery, to sepsis and death. This review will focus on the epidemiology, clinical manifestations, and treatment of SSTIs caused by the most important marine pathogens.

Introduction: The diagnosis of pneumocystis pneumonia (PCP) in non-human immunodeficiency virus (HIV)-infected immunocompromised patients is notoriously difficult. The recent advent of polymerase chain reaction (PCR)-based detection systems, based on the identification of single fungal genes, has markedly improved diagnostic accuracy in this ominous disease. In an attempt to further improve diagnostic yield, the authors used a PCR-based detection system for Pneumocystis jirovecii, based on targeting 3 distinct genes., Methods: During the 4-year period (January 2005 to January 2009), all consecutive immunocompromised patients suspected of having PCP in the differential diagnosis underwent bronchoscopy with bronchoalveolar lavage sampling for the evaluation of the etiology of pulmonary infiltrates. Bronchoalveolar fluid was tested for the presence of a wide variety of possible etiological microorganisms., Results: In a cohort of 214 immunocompromised patients (of which 198 were non-HIV immunocompromised patients) who underwent bronchoscopy with bronchoalveolar lavage for evaluation of pulmonary infiltrates, PCR correctly diagnosed PCP in 75% (42/56) compared with 14% (8/56) diagnosed by traditional stains, and increased diagnostic yield 5.4-fold., Conclusions: Given the absence of a sensitive gold standard, this study demonstrates the usefulness of a multigene PCR-based detection of Pneumocystis jirovecii DNA for supporting the clinical diagnosis of PCP, with high sensitivity and negative predictive value rates compared with direct stains, especially in non-HIV immunocompromised patients.

Background: Carbapenem resistance among isolates of Klebsiella pneumoniae has been unusual., Objectives: To identify risk factors for infection with carbapenem-resistant K. pneumoniae (CRKP) and to characterize microbiological aspects of isolates associated with these infections., Design: Retrospective case-control study., Setting: A 900-bed tertiary care hospital., Results: From January 2006 through April 2007, K. pneumoniae was isolated from 461 inpatients; 88 had CRKP infection (case patients), whereas 373 had carbapenem-susceptible K. pneumoniae infection (control subjects). The independent risk factors for infection with CRKP were prior fluoroquinolone use (odds ratio [OR], 1.87 [95% confidence interval [CI], 1.07-3.26]; P=.026), previous receipt of a carbapenem drug (OR, 1.83 [95% CI, 1.02-3.27]; P=.042), admission to the intensive care unit (OR, 4.27 [95% CI, 2.49-7.31]; P<.001), and exposure to at least 1 antibiotic drug before isolation of K. pneumoniae (OR, 3.93 [95% CI, 1.15-13.47]; P=.029). All CRKP isolates carried the bla(KPC) gene. Approximately 90% of the tested isolates carried the bla(KPC-2) allele, suggesting patient-to-patient transmission. Almost all CRKP isolates were resistant to all antibiotics, except to colistin (resistance rate, 4.5%), gentamicin (resistance rate, 7%), and tigecycline (resistance rate, 15%)., Conclusions: CRKP should be regarded as an emerging clinical threat. Because these isolates are resistant to virtually all commonly used antibiotics, control of their spread is crucial.

Background Context: Vertebral osteomyelitis and disciitis caused by Aspergillus spp is a rare event. Early diagnosis and early antifungal therapy are critical in improving the prognosis for these patients. The diagnosis of invasive fungal infections is, in many cases, not straightforward and requires invasive procedures so that histological examination and culture can be performed. Furthermore, current traditional microbiological tests (ie, cultures and stains) lack the sensitivity for diagnosis of invasive aspergillosis., Purpose: To present a case of vertebral osteomyelitis caused by Aspergillus spp diagnosed using a novel polymerase chain reaction (PCR) assay., Study Design: Case report., Methods: Aspergillus DNA was detected in DNA extracted from the necrotic bone tissue by using a "panfungal" PCR novel method., Results: Treatment with voriconazole was started based on the diagnosis., Conclusion: Using this novel technique enabled us to diagnose accurately an unusual bone pathogen that requires a unique treatment.

A gram-positive rod with a restriction pattern closely related to the published nucleotide sequence of Mycobacterium mucogenicum was isolated from 6 of 45 units of peripheral blood stem cell products. The source of the contamination was traced to ice cubes used in processing the peripheral blood stem cell products. Substituting reusable ice trays for ice from an ice machine terminated the outbreak.

This is an unusual case report of an elderly patient with spontaneous acute rupture of rotator cuff complicated by large subacromial hematoma. The hematoma fluid was aspirated with significant reduction of pain. The shoulder movements were restored after one month with conservative therapy. The compensatory role of preserved deltoid muscle is considered in the rehabilitation of normal shoulder movement, which may replace aggressive immobilization or surgical procedures in the elderly population. Investigation of hematoma fluid compared with blood 24 hours after the event revealed severe lactic acidosis with low glucose level, preserved red blood cell count and significant decrease of white blood cells. There were normal values of CBC, pH, lactate and glucose in blood. These results showed high susceptibility of leukocytes to anaerobic and acid environment and its dependence on oxygen supplement.

Between March 1997 and January 2002, 18 consecutive patients (18-47 years) with hematological malignancies and previous proven invasive fungal infection underwent stem cell transplantation (SCT) (10 matched sibling allograft, 6 autograft, and 2 haploidentical). All patients had full myeloablative conditioning. The fungal pathogens diagnosed were Aspergillus (14), Fusarium (2), Mucor (1), Exserohilum (1), and Candida (1), involving the lungs (15), sinuses (5), and liver (1). All patients were treated pre- and during transplant with systemic antifungal therapy. Eleven out of 18 (61%) patients survived the transplant. Only 1 of 5 patients who transplanted with an active fungal infection accompanied with active leukemia survived the transplant, compared with 10/13 (84%) survivals in patients who had no clinical and radiological signs of infection or active leukemia (P < 0.025). None of the autografted patients has died, compared with 7/12 allografted patients, of whom 5 underwent transplant with active hematological/active fungal disease. In only 3 patients was the cause of death reactivation of previous fungal infection. Both active fungal infection and active leukemia place patients at a very high risk for procedure-related mortality. Pre-transplant therapy of fungal infection, aiming to achieve a clinically undetectable state of infection, followed by an antifungal treatment during transplant may allow the SCT with no fungal reactivation in selected patients., (Copyright 2003 Wiley-Liss, Inc.)

Invasive pulmonary aspergillosis is the most common fungal pulmonary infection in certain immunocompromised patients. The most commonly affected patients are hematopoietic stem cell transplant recipients and patients with hematological malignancies undergoing intensive chemotherapy. The survival of patients with invasive pulmonary aspergillosis is very poor because of difficulties in early diagnosis and lack of effective treatment options. Research efforts are being made constantly to improve different diagnostic techniques. Early, repeated, high resolution computed tomography of the chest, and sequential nonculture-based monitoring of Aspergillus antigen and DNA can improve earlier diagnosis. New antifungal drugs for treatment and prevention of invasive pulmonary aspergillosis continue to emerge, with better safety, efficacy, and pharmacologic profiles.