Doses Of Liposomal Amphotericin Research Articles

Implementation of single high-dose liposomal amphotericin B based induction therapy for treatment of HIV-associated cryptococcal meningitis in Uganda: a comparative prospective cohort study.

In 2022, the World Health Organization (WHO) recommended a single 10mg/kg dose of liposomal amphotericin B in combination with 14 days of flucytosine and fluconazole (AMBITION-cm regimen) for induction therapy of HIV-associated cryptococcal meningitis, based on the results of the multisite AMBITION-cm trial. We evaluated outcomes after real-world implementation of this novel regimen in Uganda. We enrolled Ugandan adults with cryptococcal meningitis into an observational cohort receiving the AMBITION-cm regimen with therapeutic lumbar punctures in routine care during 2022-2023. We compared 10-week survival and CSF early fungicidal activity with the outcomes observed in the AMBITION-cm clinical trial conducted at the same sites. During 2022-2023, 179 adults were treated with the AMBITION-cm regimen via routine care and compared to the 171 adults randomized to the AMBITION-cm trial interventional arm in Uganda from 2018-2021. No significant difference in 10-week survival occurred between the observational cohort (68.6%; 95%CI 61.6%-76.3%) and AMBITION-cm trial participants in the intervention arm (71.7%; 95%CI 65.2%-78.8%; absolute risk difference = -3.1%; 95%CI -13.1% to 6.9%; p=.61). Early fungicidal activity did not differ (0.42 vs 0.39 log10CFU/mL/day; p=.80) between groups. Among observational cohort participants discharged alive initially and for whom follow up data were available, the incidence of re-hospitalizations due to persistently elevated intracranial pressure was 2.8% (4/144). The AMBITION-cm regimen for cryptococcal meningitis resulted in similar outcomes as observed in the AMBITION-cm clinical trial when implemented in routine care. Intracranial pressure management during hospitalization and awareness after discharge are key components of optimizing outcomes.

Infectious Diseases Physician Management of Cryptococcal Meningitis in North America-Is Single High-Dose Liposomal Amphotericin B Being Used?

Several recent randomized trials have been conducted in resource-limited settings for cryptococcal meningitis that have rapidly innovated international guidelines. The 2010 Infectious Diseases Society of America (IDSA) cryptococcal meningitis guideline has not been updated with recent trials. The 2022 AMBITION-cm trial found that a single 10-mg/kg dose of liposomal amphotericin B plus daily flucytosine and fluconazole for 2 weeks was noninferior to 1 week of amphotericin B deoxycholate with flucytosine. It is unknown whether physicians in high-resource settings are using this regimen or more traditional regimens. We developed an electronic survey in June 2023 to better understand whether physician members of the IDSA Emerging Infections Network (EIN) and Mycoses Study Group Education and Research Consortium (MSG-ERC) had used the AMBITION-cm induction regimen, would use the regimen in hypothetical clinical scenarios, and what perceived barriers to use existed. A total of 242 of 561 (43%) physicians responded to the survey, of whom 205 provided care for persons with cryptococcal meningitis in the last year. Overall, 29 (14%) had used the AMBITION-cm regimen, and 176 (86%) had not. In various hypothetical clinical scenarios, only ∼10% of 209 respondents selected the AMBITION-cm regimen as preferred. Perceived barriers to uptake included the applicability of trials performed in low-resource settings to high-resource settings, that the regimen is not recommended in the 2010 IDSA guidelines, and the applicability to persons without HIV. Most respondents had not used the single-dose liposomal amphotericin B regimen, but the regimen is being used. Further study of this regimen in other patient populations and settings is necessary.

Estimating the proportion of relapse following treatment of Visceral Leishmaniasis: meta-analysis using Infectious Diseases Data Observatory (IDDO) systematic review

Occurrences of relapse after 6-months post-treatment has been reported in recent Visceral Leishmaniasis (VL) efficacy studies. A meta-analysis was carried out to quantify the proportion of relapses observed at and beyond 6-months using the Infectious Diseases Data Observatory (IDDO) systematic review (SR) database. Studies in the IDDO SR database (1983-2021; 160 studies) were eligible for inclusion if follow-up was at least 6-months, relapse was clearly reported, and patients with HIV coinfections were excluded. Meta-analysis of single proportion was undertaken and the estimates were reported with 95% confidence intervals (CI). Overall, 131 studies enrolling 27,687 patients were included; 1193 patients relapsed. In the Indian sub-continent (ISC), relapse estimates at 6-months was 4.5% [95% CI: 2.6%-7.5%; I2=66.2%] following single dose liposomal amphotericin B (L-AmB) and 1.5% [95% CI: 0.7%-3.3%; I2=0%] for L-AmB in a combination therapy. In East Africa (EA), corresponding estimates were 3.8% [95% CI: 1.3%-10.9%; I2=75.8%] following pentavalent antimony (PA), and 13.0% [95% CI: 4.3%-33.6%; I2=0%] for PA+paromomycin. From 21 studies with follow-up longer than 6-months, 0.6% [95% CI: 0.2%-1.8%; I2=0%] of patients relapsed after 6-months and estimated 27.6% [95% CI: 11.2%-53.4%; I2=12%] of relapses would have been missed by a 6-month follow-up. The estimated relapse proportion ranged from 0.5% to 4.5% in ISC and 3.8%-13.0% in EA with the currently recommended drugs. Over one-quarter of relapses would be missed with 6-months follow-up suggesting a longer follow-up may be warranted. Wellcome Trust (ref: 208378/Z/17/Z).

845. Clinical Outcomes in Patients Treated with High vs. Standard Dose Liposomal Amphotericin B for Invasive Mucormycosis

Abstract Background Mucormycosis is a life-threatening invasive fungal infection associated with high mortality. Amphotericin B is first-line therapy; however, the benefit of high doses remains uncertain. The purpose of this study is to describe outcomes in patients treated with high dose versus standard dose liposomal amphotericin B (L-AMB) for mucormycosis. Methods This was a retrospective cohort study of adults ≥ 18 years treated with L-AMB for proven or probable invasive mucormycosis at Massachusetts General Hospital and Brigham & Women’s Hospital from 2016-2022. L-AMB dosing was based on clinician preference. Patients were excluded if L-AMB began > 7 days prior to admission. Patients were categorized per L-AMB dose: standard dose (all doses < 6 mg/kg) and high dose (≥ 6 mg/kg for at least one dose). The primary outcome was 6- and 12-week mortality. Results 67 patients were treated with L-AMB for proven or probable mucormycosis during the study period: 57 with standard dose and 10 with at least 1 high dose of L-AMB. Baseline characteristics are shown in Table-1. More patients in the standard dose group had underlying hematologic malignancy. About one third of patients had underlying diabetes and this was evenly distributed between groups. Table-2 shows infection- and treatment-related details. Proven invasive mucormycosis was diagnosed in 51/57 (89%) and 6/10 (60%) patients in the standard and high dose groups, respectively. The most common site of infection in both groups was skin/bone. Approximately 35/57 (61%) and 8/10 (80%) patients in the standard and high dose groups, respectively, had surgical debridement. Mortality at 6- and 12- weeks and renal toxicity outcomes are shown in Table-3. In the entire cohort at 6- and 12 weeks death occurred in 25/67 (37%) and 33/67 (49%) patients, respectively; no difference in mortality was seen between the standard and high dose groups. There appeared to be no difference in renal outcomes, though more patients in the standard dose group required renal replacement therapy within 6-weeks of diagnosis. Conclusion We observed no difference in 6- and 12-week mortality among patients treated with L-AMB at standard and high doses for invasive mucormycosis. Mortality at 6- and 12-weeks of mucormycosis diagnosis remains high. Disclosures Ramy H. Elshaboury, PharmD, DayZero Diagnostics: Advisor/Consultant|Gilead, Inc: Grant/Research Support|Thermofisher: Grant/Research Support Sophia Koo, MD, SM, Aerium Therapeutics: Advisor/Consultant|GSK: Grant/Research Support|Merck: Grant/Research Support|Scynexis: Grant/Research Support Sarah P. Hammond, MD, F2G: Advisor/Consultant|F2G: Grant/Research Support|GSK: Grant/Research Support|Pfizer: Advisor/Consultant|Scynexis: Grant/Research Support|Seres therapeutics: Advisor/Consultant

Prognostic Association of Liposomal Amphotericin B Doses Above 5 mg/kg/d in Mucormycosis: A Nationwide Epidemiologic and Treatment Analysis in Japan.

Mucormycosis is a potentially fatal fungal infection, and there is limited information on its precise epidemiology and treatment practices, including the optimal dosage of liposomal amphotericin B. A retrospective, multicenter, nationwide analysis of 82 proven and probable cases of mucormycosis was performed. Cases between 2015 and 2022 were collected from 51 hospitals in Japan by hematologists and infectious disease specialists. The study included the epidemiology, treatment details, and association between the dose of liposomal amphotericin B and the outcome. The lungs were the most commonly involved organ (70.7% of cases), and 35.4% of patients had disseminated disease. Rhizopus spp., Cunninghamella spp., and Mucor spp. were the most common organisms. Mortality at 4 weeks was 41.5%. The survivors had a shorter duration of neutropenia (P = .006) and less persistent hyperglycemia (P = .023). The site of infection and species of Mucorales had no detectable effect on survival. Survival did not differ between patients receiving liposomal amphotericin B at 5 mg/kg/d relative to those receiving >5 mg/kg/d (P = .625). Using Cox proportional hazards models and adjusting for confounders, the hazard ratio for the influence of >5 mg/kg/d liposomal amphotericin B on 4-week survival was 0.86 (95% CI, 0.28-2.68; P = .796) compared with 5 mg/kg/d. This study provides important insights into the precise epidemiology and treatment practices of mucormycosis. Treatment with liposomal amphotericin B at doses higher than 5 mg/kg/d did not improve outcomes relative to 5 mg/kg/d.

P284 A rare case of post covid bilateral renal mucormycosis

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PM ObjectiveThe most commonly reported sites of COVID-associated invasive mucormycosis till now have been rhino-cerebral-orbital followed by pulmonary. This is a rare instance where an apparently healthy male, who had recovered completely from COVID-19, presented with fulminant isolated bilateral renal mucormycosis.MethodA 60-year-old male was presented with low-grade fever and increased CRP. He had a known history of diabetes, hypertension, and ischemic heart disease since 2007. On examination, he was tachypneic and afebrile; blood pressure and oxygen saturation were within normal limits.He was also double vaccinated. Also had a history of moderate COVID (Omicron) in January, 2022. His CT score was 18/25. He got admitted for 10 days because of COVID and was treated with oxygen, antibiotics, remdesivir, and steroids.Later on, patient developed fatigue, anorexia, abdominal discomfort, and pain in lower back. Also vomiting and nausea for 3 months. So patient was treated with tablets Zifi CV for 5 days bd followed by; IV meropenem 1 g tds for 5 days followed/by; tablets faropenem 200 md bd for 3 weeks followed by; tablets nitrilofurantoin 100 mg bd.Ultrasonography remains the first line of investigation and can show the enlarged echogenic kidneys with hypoechoic areas of abscesses, perinephric fluid collections, hydronephrosis, and cystitis. Cortical thickness appeared normal with raised cortical echo. An unenhanced computed tomography (CT) of his abdomen and pelvis was performed and suggested of mild changes of acute bilateral pyelonephritis. CT features include diffuse patchy nephrogram, inhomogeneous enhancement with areas of low attenuation, perinephric fluid collections, and no contrast excretion.Fungal culture sensitivity report was done and Candida albicans organism was isolated and it was found to be all drug-sensitive. Later on, a biopsy of the urethra was performed and a biopsy specimen revealed a fungal ball composed of thin septate and branching thick abroad aseptate hyphae. And also, which resembled morphologically mucor. spp and Aspergillus. A bacterial culture and sensitivity report were suggestive of E.coli.The patient underwent surgical interventions, ie, cystoscopy with B/L RGP with B/L DJ stenting done under SA with a calculated risk of diabetes, hypertension, age, nature of illness, and high creatinine.Patient started treatment with sulbacin 1.5gm injection with 100 ml sodium chloride 0.9% 6 hourly. As patient's creatinine is not stable so Liposomal Amphotericin B was not given. Later on, as creatinine stabilized patient he began receiving liposomal amphotericin B at a beginning dosage of 300 mg with 25% dextrose 250 ml over 5 h. Also, posaconazole started with a loading dose of 600 mg, and then, 300 mg OD was given to patient.ResultPatient gradually recovered and a dose of liposomal amphotericin was completed for 4 weeks.ConclusionIn conclusion, this paper describes that COVID-associated mucormycosis is a known entity, however, Renal Mucormycosis is a rare disease. Especially, bilateral involvement with limited drug penetration into a urogenital system of the agents which are active in mucormycosis. Its management involves, team approach of diabetologists, infectious disease physicians, urologists, radiologists, and microbiologists. Treatment of mucormycosis is challenging as anti-fungal penetration in renal tissue is difficult. High index of suspicion should be there to make the diagnosis. Early detection and aggressive management may have a favorable outcome.

Clinical manifestations of exuberant leishmaniasis mucocutaneous: case report

Cutaneous mucosal leishmaniasis (LM) is a chronic infection that affects the upper respiratory tract and/or buccal mucosa and is caused by Leishmania protozoan parasites. A 71-year-old male smoker received dental care at the Stomatology Service of the Hospital Metropolitano Odilon Behrens (HMOB), after various appointments with medical specialists. He presented granulomatous and erythematous lesions on the skin of the nose, on upper lip mucosa, and along the entire soft palate and uvula, as well as the destruction of the nasal septum. Due to the suspicion of leishmaniasis, an incisional biopsy was performed. Histopathological examination was performed; however, polymerase chain reaction (PCR) and immunofluorescence were necessary to confirm the diagnosis of LM. The patient was treated with 27 doses of liposomal amphotericin B 20mg / Sbv / kg / day. Due to the lack of improvement, the patient was again hospitalized, and the medication was repeated adding Fluconazol 150mg, to which the patient showed significant improvement. The present case report shows an infectious lesion that is unusual in dental practice and its approach. The description of the characteristics and management, together with the pathological process, were presented.

Combination Therapy for HIV-Associated Cryptococcal Meningitis-A Success Story.

Cryptococcal meningitis is the leading cause of adult meningitis in patients with HIV, and accounts for 15% of all HIV-related deaths in sub-Saharan Africa. The mainstay of management is effective antifungal therapy, despite a limited arsenal of antifungal drugs, significant progress has been made developing effective treatment strategies by using combination regimens. The introduction of fluconazole as a safe and effective step-down therapy allowed for shorter courses of more fungicidal agents to be given as induction therapy, with higher doses achieving more rapid CSF sterilisation and improved treatment outcomes. The development of early fungicidal activity (EFA), an easily measured surrogate of treatment efficacy, has enabled rapid identification of effective combinations through dose ranging phase II studies, allowing further evaluation of clinical benefit in targeted phase III studies. Recent clinical trials have shown that shorter course induction regimens using one week of amphotericin paired with flucytosine are non-inferior to traditional two-week induction regimens and that the combination of fluconazole and flucytosine offers a viable treatment alternative when amphotericin is unavailable. Access to drugs in many low and middle-income settings remains challenging but is improving, and novel strategies based on single high dose liposomal amphotericin B promise further reduction in treatment complications and toxicities. This review aims to summarise the key findings of the principal clinical trials that have led to the success story of combination therapy thus far.

Isolated Laryngeal Leishmaniasis: A Diagnostic Dilemma.

Isolated laryngeal Leishmaniasis is a rare entity in the Indian subcontinent. We describe a case of a 45year old male with hoarseness and noisy breathing. Patient's initial histological and serological workup was inconclusive. Final biopsy findings (suggestive of Leishmania donovani), positive rK-39 serology and his native place being Bihar (endemic for Leishmaniasis) led us to the diagnosis. He was treated with high dose liposomal Amphotericin B to which he responded well. This case report highlights the importance of remaining aware of rare infectious causes of laryngitis. Timely diagnosis and intervention are crucial.

Treatment of widespread nodular post kala-azar dermal leishmaniasis with extended- dose liposomal amphotericin B in Bangladesh: A series of four cases

Background: Post Kala-azar Dermal Leishmaniasis (PKDL) is a sequela of Visceral Leishmaniasis (VL) and suggested as reservoirs of parasite. Currently, Miltefosine (MF), Amphotericin B Deoxycholate (ABD) and Liposomal Amphotericin B (LAmB) are recommended by World health organization (WHO) as treatment options for PKDL. But single MF or LAmB often causes incomplete cure specially cases with extensive lesion. To overcome this problem here we describe four cases of PKDL who had widespread nodular and macular lesions and were treated with two cycles of LAmB doses with 20 mg/kg body weight divided into 4 equal doses and administered every alternate day. Methods & Materials: Patients admitted to the Surya kanta kala-azar research centre (SKKRC) with extensive nodular or mixed lesion were considered to treat with LAmB. Hospital physician collected patients’ history and performed physical examination. Suspected cases were confirmed by microscopic examination of slit skin smear. At first, LAmB treatment was initiated at the dose of 20 mg/kg into four divided doses every alternate day. Before starting treatment all haematological and biochemical markers were checked. Second cycle was initiated for those who displayed marked improvement but not complete recovery. Finally, a follow up physical and microscopic examination was also done to evaluate the treatment outcome. Results: Of them, two had previous VL history and two had no previous VL history at all. The lesions started from chin with macular type, later distributed to other parts of the body with both macular and nodular type. The lesions were non-itching, touch sensitive and rk 39 strip test was positive. All of them were confirmed through microscopic examination of slit skin smear. Their haematological and biochemical markers were within normal limit. After first cycle, all of them showed initial progress and after second cycle all of them attained complete cure. Fever with shivering was the only documented adverse event during treatment and was managed by paracetamol. Conclusion: The cases highlighted in this report explore the success of utilising extended LAmB dose schedule for treating a patient with widespread lesions.The triumph of this alternate treatment schedule for PKDL needs to be supported with clinical trials that evaluate its efficacy and safety.

Efficacy and Safety of Liposomal Amphotericin B for Visceral Leishmaniasis in Children and Adolescents at a Tertiary Care Center in Bihar, India.

Liposomal amphotericin B is being used increasingly to reduce the burden of kala-azar from the Indian subcontinent. There are studies which have evaluated efficacy and safety of liposomal amphotericin B for visceral leishmaniasis in all age groups. However, the only study that specifically addressed treatment of childhood visceral leishmaniasis did not include all ages or document renal and liver function. We, therefore, felt it was important to reassess the efficacy and safety of single dose liposomal amphotericin B in children and adolescents. A total of 100 parasitologically confirmed visceral leishmaniasis patients aged < 15 years were included in this study. Participants consisted of 65 males and 35 females. All of them had come from the endemic region of Bihar. They were administered one dose intravenous infusion of liposomal amphptericin B at 10 mg/kg body weight. Efficacy was assessed as initial and final cure at 1 and 6 months, respectively, and safety of all participants who were recruited in the study. The initial and final cure rate by per protocol analysis was 100% and 97.9%, respectively. Chills and rigors were the most commonly occurring adverse events (AEs). All the AEs were mild in intensity, and none of the patients experienced any serious AEs. No patients developed nephrotoxicity. Our finding indicates that liposomal amphotericin B at 10 mg/kg body weight is safe and effective in children. Results of our study support the use of single dose liposomal amphotericin B in all age group populations for elimination of kala-azar from the Indian subcontinent.

Amphotericin B concentrations in healthy mallard ducks (Anas platyrhynchos) following a single intratracheal dose of liposomal amphotericin B using an atomizer.

Aspergillosis is a fungal infection that primarily affects the respiratory tract. Amphotericin B has broad antifungal activity and is commonly used to treat aspergillosis, a fungal pneumonia that is a common sequela in oiled waterfowl as well as other birds in wildlife rehabilitation. Pharmacokinetic parameters of nebulized amphotericin B in an avian model have been reported, but those of direct intratracheal delivery have yet to be established. The objective of this study was to evaluate if a single 3mg/kg dose of liposomal amphotericin B delivered intratracheally using a commercial atomizer would achieve plasma and lung tissue concentrations exceeding targeted minimum inhibitory concentrations (MIC) for Aspergillus species in adult mallard ducks (Anas platyrhynchos). Following intratracheal delivery, amphotericin B was present in lung parenchyma at concentrations above the targeted MIC of 1μg/g for up to 9 days post-administration; however, distribution of the drug was uneven, with the majority of the drug concentrated in one lung lobe. Concentrations in the contralateral lung lobe and the kidneys were above the targeted MIC 1 day after administration but declined exponentially with a half-life of approximately 2 days. Plasma concentrations were never above the targeted MIC. Histological examination of the trachea, bronchi, lungs, heart, liver, and kidneys did not reveal any toxic changes. Using a commercial atomizer, intratracheal delivery of amphotericin B at 3mg/kg resulted in lung parenchyma concentrations above 1μg/ml with no discernable systemic effects. Further studies to establish a system of drug delivery to both sides of the pulmonary parenchyma need to be performed, and the efficacy of this treatment for disease prevention remains to be determined.

Combined treatment of miltefosine and paromomycin delays the onset of experimental drug resistance in Leishmania infantum.

BackgroundSince miltefosine monotherapy against visceral leishmaniasis (VL) caused by Leishmania donovani has been discontinued in the Indian subcontinent due to an increase in the number of treatment failures, single dose liposomal amphotericin B is now advocated as a treatment option of choice. Paromomycin-miltefosine combination therapy can be used as substitute first-line treatment in regions without cold-chain potential. Previous laboratory studies in the closely related species Leishmania infantum have demonstrated that paromomycin monotherapy fairly rapidly selects for resistance producing a phenotype with increased fitness. Given the possible clinical implications of these findings for the current field situation, the present study aimed to identify the potential hazards of paromomycin-miltefosine combination therapy.Principal findingsDrug interaction studies using the fixed-ratio isobologram method revealed an indifferent interaction between paromomycin and miltefosine. In hamsters infected with L. infantum, the combination resulted in cumulative efficacy in reducing parasite burdens in the liver, spleen and bone marrow. Selected resistant lines against the single drugs did not display cross-resistance. When the intracellular amastigote stage was repeatedly exposed to the paromomycin-miltefosine combination, either in vitro or in vivo, no significant susceptibility decrease towards either drug was noted.ConclusionsThese results suggest that implementation of paromomycin-miltefosine combination therapy indeed could represent a safe and affordable treatment option for L. donovani VL as miltefosine appears to overrule the anticipated rapid development of PMM resistance.

Aspergillus flavus Disseminated Infection in Paediatric Acute Lymphoblastic Leukaemia: A Case Report

Here we report the case of a disseminated Aspergillus flavus infection in an adolescent affected by acute lymphoblastic leukaemia at the beginning of first-line chemotherapy. Association of surgery and combination antifungal therapy (high dose liposomal amphotericin B and caspofungin) allowed infection improvement. 18-FDG PET-MRI was used for response-to therapy monitoring.

Safety and efficacy of liposomal amphotericin B for treatment of complicated visceral leishmaniasis in patients without HIV, North-West Ethiopia.

BackgroundVisceral leishmaniasis (VL) is a protozoan disease that is invariably fatal if left untreated. The disease is found in 70 countries with incidence of 0.2 – 0.4 million cases. The mainstay of treatment in resource limited countries like Ethiopia is antimonials, while use of liposomal amphotericin B is reserved for treatment of complicated VL cases. The aim of this study was to assess the safety and efficacy of liposomal amphotericin B in HIV negative VL patients diagnosed with complications.MethodsA retrospective chart review was conducted involving records of patients admitted between January 2009 and December 2014. Baseline sociodemographic, clinical, and treatment outcome data were collected. The doses of liposomal amphotericin B and adverse events related to treatment were retrieved. Categorical and continuous variables respectively were analyzed by Chi-square and Mann–Whitney U tests. A p-value of less than 0.05 was considered statistically significant.ResultsA total of 147 patients with severe VL were treated with liposomal amphotericin B in total dose ranges of 20 mg/kg to 35 mg/kg. In the overall treatment outcome analysis, initial cure (30 days after start of treatment) was observed in 128 (87.1 %), treatment failures in 10 (6.8 %), interruptions in 2(1.4 %) and deaths in 7 (4.8 %) patients. Initial cure rate at high dose (24-35 mg/kg total dose) was 96.7 % (59/61) versus 80.2 % (69/86) at lower doses (<24 mg/kg); which was significantly higher (P < 0.01), OR = 4.56: 95 %, Confidence Interval (CI) = 1.17 – 20.78). Ten cases (11.8 %) of treatment failure occurred in the low dose treatment group. The most common adverse events (AEs) were hypokalemia in 39 cases (26.5 %) and infusion related reactions in 16 (10.9 %). The frequency of hypokalemia and infusion related reactions were not significantly different between the low and high dose liposomal amphotericin B.ConclusionIn HIV negative complicated VL patients, high dose of liposomal amphotericin B was found to have high cure rate at the end of treatment. The appropriate dose for better efficacy needs to be determined. Monitoring serum potassium level during treatment with liposomal amphotericin B should be an essential component of the clinical management of VL.

5 Year-old Boy with a Hearth Murmur and Fever

A 5 year old boy was admitted to the emergency ward. Physical examination revealed a heart murmur and fever. During his stay on the emergency ward oxygen saturation progressively worsened. A cardiac ultrasound showed an occlusion of the right pulmonic artery and severe narrowing of the left pulmonic artery. Computed Tomography Angiography (CTA) confirmed the diagnosis. Pathology examination of the retrieved thrombus during emergency thoracotomy revealed a fungus cast from Zygomycete; Rhizopus microsporus. The patient was treated with Posaconazole and high dose of liposomal Amphotericin B. The patient was fully recovered forty-five days after admittance to the emergency ward.

Safety and Efficacy of Low Dose Liposomal Amphotericin B for Prophylaxis of Invasive Fungal Infection in Hematopoietic Stem Cell Transplantation- a Single Center Experience

CD34 /uL Median CD34/ kg Initial Collection Median CD34/ kg Second Collection Median % of Initial Collection Days to ANC >0.5 x10/L Days to Plt >50 x10/L NHL (n1⁄47) 2.1 (1.5-6.2) 1.5 (1.27-1.68) 0.68 (0.27-1.96) 41% (21-114) 11 (10-12) 16 (11->28) MM (n1⁄43) 3.1 (3.1-5.7) 3.01 (1.85-3.77) 1.51 (1.11-3.01) 60% (40-85) 11 (9-12) 14 (13-14) Abstracts / Biol Blood Marrow Transplant 21 (2015) S240eS265 S258

Atypical presentation in adults in the largest community outbreak of leishmaniasis in Europe (Fuenlabrada, Spain)

Since 2009, the largest reported outbreak of leishmaniasis by Leishmania infantum in Europe was reported in Fuenlabrada, Spain. In our hospital, 90 adults with localized leishmanial lymphadenopathy (LLL) or visceral leishmaniasis (VL) were treated during this outbreak; 72% were men, and the mean age was 46.2 years (range 15–95 years). A total of 17 cases (19%) were LLL, an atypical form with isolated lymphadenopathies without other symptoms. All LLL cases occurred in immunocompetent subjects, and only one subject (6%) was a native of sub-Saharan Africa. Diagnosis was performed by fine needle aspiration cytology of the lymphadenopathy. Serology was negative in 38%. LLL outcomes at 6 months were benign, even with doses of liposomal amphotericin B that were often lower (10 mg/kg) than those recommended for VL in Mediterranean areas. A total of 73 subjects (81%) presented with typical VL; 66% of this group were immunocompetent, and 50% of those who were immunocompetent were descendants of natives of sub-Saharan Africa. The rK39 test and polymerase chain reaction were the most useful tests for confirmation of the diagnosis. An initial response to treatment was observed in 99% of cases, and relapses occurred in 14% of cases. Leishmaniasis should be included in the differential diagnosis of isolated lymphadenopathies in endemic areas. LLL could be considered a more benign entity, one different than VL, and less aggressive management should be studied in future investigations.

Successful therapy of progressive rhino-orbital mucormycosis caused by Rhizopus arrhizus with combined and sequential antifungal therapy, surgery and hyperbaric therapy

We present a case of rhino-orbitary mucormycosis which progressed despite liposomal amphotericin and early surgical debridement. Combined echinocandin and high dose liposomal amphotericin, repeated debridement, prolonged therapy with hyperbaric oxygen and continued therapy with posaconazole, along with strict diabetic control, allowed cure without disfigurement.

Vertebral infection with Candida albicans failing caspofungin and fluconazole combination therapy but successfully treated with high dose liposomal amphotericin B and flucytosine

A patient with Candida spondylitis failed two weeks of fluconazole combined with caspofungin, and the infection relapsed despite six weeks of liposomal amphotericin B followed by two months of fluconazole. Six months therapy with high dose liposomal amphotericin B combined with flucytosine effectively cured the patient.