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Background Post–kala-azar dermal leishmaniasis (PKDL) is a dermal complication of visceral leishmaniasis. Oral miltefosine (MF) is the first-line treatment for PKDL patients in South Asia. This study assessed the safety and effectiveness of MF therapy after 12 months of follow-up to explore more precise data. Methods In this observational study, 300 confirmed PKDL patients were enrolled. MF with the usual dose was administered to all patients for 12 weeks and followed up for 1 year. Clinical evolution was recorded systematically by photographs at screening and at 12 weeks, 6 months, and 12 months after treatment onset. Definitive cure consisted of disappearance of skin lesions with a negative PCR at 12 weeks or with >70% of lesions, disappearing or fading at 12-month follow-up. Patients with reappearing clinical features and any positive diagnostics of PKDL during the follow-up were considered as nonresponsive. Results Among 300 patients, 286 (95.3%) completed 12 weeks of treatment. The per-protocol cure rate at 12 months was 97%, but 7 patients relapsed and 51 (17%) were lost to 12-month follow-up, resulting in a final cure rate of only 76%. Eye-related adverse events were noted in 11 (3.7%) patients and resolved in most (72.7%) within 12 months. Unfortunately, 3 patients had persistent partial vision loss. Mild to moderate gastrointestinal side effects were seen in 28% patients. Conclusions Moderate effectiveness of MF was observed in the present study. A significant number of patients developed ocular complications, and thus MF for treatment for PKDL should be suspended and replaced with a safer alternative regimen. [ABSTRACT FROM AUTHOR]

Abstract Background The most appropriate alternative to induction therapy for HIV-associated cryptococcal meningitis (CM) remains unclear when standard treatment is unavailable, inaccessible, intolerable, or ineffective. Methods A prospective, multi-centre cohort study was conducted to analyze the data of 156 HIV-infected patients with CM who were treated with amphotericin B deoxycholate (AmB-D) + flucytosine (5FC), voriconazole (VCZ) + 5FC, or AmB-D + Fluconazole (Flu) as induction regimens. Clinical efficacy, cumulative mortality, and adverse effects were compared among the three treatment groups. Results Fewer deaths occurred by week 4 and week 10 among patients receiving AmB-D + 5FC than among those receiving AmB-D + Flu [4 (5.1%) vs. 8 (16.0%) deaths by week 4; hazard ratio, 1.8; 95% confidence interval [CI], 1.0 to 3.3; p = 0.039; and 8 (10.3%) vs. 14 (28.0%) deaths by week 10; hazard ratio, 1.8; 95% CI, 1.1 to 2.7; p = 0.008, respectively]. AmB-D plus 5FC was found to result in significantly higher rates of cerebrospinal fluid (CSF) culture sterility (57.6% vs. 34% by week 2; 87.9% vs. 70% by week 10; p

Considering the fact that two available and commonly used formulations of amphotericin B could be used instead of each other by mistake. Also, an updated and comprehensive data regarding management of this medication error was not available; the current review was conducted to gather available data among the pediatric population and discuss management and outcome of patients in case such an error occurs. We review all the cases of amphotericin B overdose which reported in PubMed and google scholar so far then discuss an 8-years-old girl diagnosed with Ewing sarcoma who inadvertently received five times more than therapeutic dose of amphotericin B deoxycholate (5mg/kg/day).In total, ten of the cases were exactly matched to our purpose of the study. In our case, fluid and electrolyte management was aggressively undertaken and she was put under cardiac monitoring for 7 days following detection of the medication error. Finally, she was discharged from hospital with stable condition. Reviewed data in this manuscript showed that amphotericin B deoxycholate overdose could cause severe complications and lead to cardio toxicity, electrolyte imbalance and death. Aggressive cardiac, fluid and electrolyte monitoring and management of any problem as soon as they were detected was the pathway followed by the authors of this review and others who faced this medication error. The role of NAC and hydrocortisone in the managing amphotericin B deoxycholate overdose requires further investigation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The most appropriate alternative to induction therapy for HIV-associated cryptococcal meningitis (CM) remains unclear when standard treatment is unavailable, inaccessible, intolerable, or ineffective.Methods: A prospective, multi-centre cohort study was conducted to analyze the data of 156 HIV-infected patients with CM who were treated with amphotericin B deoxycholate (AmB-D) + flucytosine (5FC), voriconazole (VCZ) + 5FC, or AmB-D + Fluconazole (Flu) as induction regimens. Clinical efficacy, cumulative mortality, and adverse effects were compared among the three treatment groups.Results: Fewer deaths occurred by week 4 and week 10 among patients receiving AmB-D + 5FC than among those receiving AmB-D + Flu [4 (5.1%) vs. 8 (16.0%) deaths by week 4; hazard ratio, 1.8; 95% confidence interval [CI], 1.0 to 3.3; p = 0.039; and 8 (10.3%) vs. 14 (28.0%) deaths by week 10; hazard ratio, 1.8; 95% CI, 1.1 to 2.7; p = 0.008, respectively]. AmB-D plus 5FC was found to result in significantly higher rates of cerebrospinal fluid (CSF) culture sterility (57.6% vs. 34% by week 2; 87.9% vs. 70% by week 10; p < 0.05 for both comparisons). However, the differences in CSF culture sterility and mortality between the VCZ + 5FC group and the AmB-D + 5FC group were not statistically significant. VCZ plus 5FC had a significantly advantageous effect on the incidence of new AIDS-defining illness and length of hospital stay, compared with AmB-D plus 5FC. Laboratory adverse events (grade 3 or 4), such as severe anemia, were less frequent with VCZ + 5FC use than with AmB-D combined with 5FC or Flu use.Conclusion: Our results suggest that AmB-D combined with 5FC remains the more efficacious induction regimen compared to AmB-D plus Flu, and that VCZ + 5FC might be a potential alternative when the standard regimen is not readily available, accessible, tolerated, or effective.Clinical Trials: Registration number, ChiCTR1900021195. Registered 1 February 2019, http://www.chictr.org.cn/showproj.aspx?proj=35362 . [ABSTRACT FROM AUTHOR]

Introduction: Current guidelines recommend amphotericin B as the preferred drug for induction therapy; however, amphotericin B is not available in certain settings. Induction therapy with amphotericin B deoxycholate or voriconazole has been shown to be an effective treatment for talaromycosis. However, prospective clinical trials comparing these two antifungal drugs are absent from the literature. Methods: In this open-labeled, multicenter, prospective controlled trial, we enrolled patients at 15 hospitals in China from 2019 to 2020. Participants received induction treatment with either amphotericin B deoxycholate intravenously at a dose of 0.5 to 0.7 mg per kilogram per day or voriconazole at a dose of 6 mg/kg intravenously twice daily for the first day, followed by 4 mg/kg intravenously twice daily for 3 days, and then voriconazole was given either intravenously (4 mg/kg intravenously twice daily) or orally (200 mg twice daily) for the remaining 10 days. The primary outcome was all-cause mortality during 48 weeks after baseline. Secondary outcomes were mortality at week 2 or week 24, clinical resolution of talaromycosis, and fungal clearance at week 2. A propensity score (PS) matching analysis was performed to control confounding factors. Results: We observed no difference in the risk of death at week 2, at week 24, or at week 48 in either the unmatched cohort or the matched cohort. Both in the unmatched and the matched cohorts, logistic regression analysis revealed a significantly lower odds ratio of clinical resolution (OR 0.450, 95% CI 0.291–0.696, p < 0.001; OR 0.443, 95% CI 0.261–0.752, p = 0.003) and fungal clearance (OR 0.514, 95% CI 0.333–0.793, p = 0.003; OR 0.542, 95% CI 0.318–0.923, p = 0.024) in voriconazole users compared to amphotericin B deoxycholate users over the course of 2 weeks. In the induction therapy without ART subgroup patients in the amphotericin B deoxycholate group showed a significantly higher rate of clinical resolution and fungal clearance than those in the voriconazole group (56.1% vs. 30.4%, 95% CI 13.4–36.5, p = 0.000; 63.8% vs. 40.4%, 95% CI 11.1–34.7, p = 0.000), whereas there was no significant difference in clinical resolution and fungal clearance in the induction therapy combined with ART subgroup. Conclusions: Induction therapy using voriconazole had a similar efficacy, in terms of all-cause mortality rate, to induction therapy using amphotericin B deoxycholate in HIV-infected patients with talaromycosis over a 48-week observation period. Amphotericin B deoxycholate contributed to earlier fungal clearance and earlier clinical resolution of symptoms in the induction therapy without ART subgroup, whereas amphotericin B deoxycholate use did not contribute to a significant difference in clinical resolution and fungal clearance in the induction therapy combination with ART subgroup. Trial Registration: ChiCTR1900021195. Registered 1 February 2019, http://www.chictr.org.cn/showproj.aspx?proj=35362. [ABSTRACT FROM AUTHOR]

Objectives: To determine the incidence and frequency of adverse drug reactions (ADRs) to find out factors, if any contributing to the same, while also exploring the use of amphotericin B deoxycholate as a cheaper and safe alternative to liposomal amphotericin B. Materials and Methods: It was a cross-sectional observational study, with a study population of 50 conducted over three months after ethics approval. All adult patients admitted to a tertiary care center, in a metropolitan city of Maharashtra, diagnosed with Rhino-orbito-cerebral mucormycosis, with a history of previous COVID-19 infection and receiving antifungals for the treatment of the same were included in the study. Central Drugs Standard Control Organization (CDSCO) ADR reporting forms were used to collect data. Results: Electrolyte disturbances mainly hypokalemia were the most frequently encountered ADR with both Amphotericin formulations (39/50; 20.31%) followed by pain at the injection site (33/50; 17.19%). Nephrotoxicity occurred slightly more frequently with Amphotericin B Deoxycholate (19/29; 65%), compared to Liposomal Amphotericin B (11/19; 57%), while Posaconazole was mainly associated with gastrointestinal (GI) disturbances and hepatotoxicity. Conclusion: Amphotericin B Deoxycholate was associated most with ADRs, hypokalemia, and pain at the injection site being the most frequent. However, concerning nephrotoxicity, both Amphotericin formulations showed only a modest difference. Posaconazole was associated with the least number of ADRs and had a favorable safety profile. [ABSTRACT FROM AUTHOR]

Introduction: Access to and the cost of induction treatment for cryptococcal meningitis (CM) is rapidly changing. The newly-announced price for flucytosine ($0.75 per 500 mg pill) and possibly lower prices for liposomal amphotericin B (AmB-L) create opportunities to reduce CM treatment costs compared to the current standard treatment in low- and middle-income countries. Methods: We developed an Excel-based cost model to estimate health system treatment costs for CM over a two-week induction phase for multiple treatment combinations, newly feasible with improved access to flucytosine and AmB-L. CM treatment costs include medications, laboratory tests and other hospital-based costs (bed-day costs and healthcare worker time). We report results from applying the model using country-specific information for South Africa, Uganda, Nigeria, and Botswana. Results: A 14-day induction-phase of seven days of inpatient AmB-D with flucytosine, followed by seven days of high-dose fluconazole as an outpatient, will cost health systems less than a 14-day hospital stay with AmB-D and fluconazole. If daily AmB-L replaces AmB-D for those with baseline renal dysfunction, with a cost of $50 or less per 50 mg vial, incremental costs would still be less than the AmB-D with fluconazole regimen. Simple oral combinations (e.g., seven days of flucytosine with fluconazole as an inpatient) are practical when AmB-D is not available, and treatment costs would remain less than the current standard treatment. Conclusions: Improved access to and lower prices for flucytosine and AmB-L create opportunities for improving CM treatment regimens. An induction regimen of flucytosine and AmB-D for seven days is less costly than standard care in the settings studied here. As this regimen has also been shown to be more effective than current standard care, countries should prioritize scaling up flucytosine access. The cost of AmB-L based regimens is highly dependent on the price of AmB-L, which currently remains unclear.

Introduction: Access to and the cost of induction treatment for cryptococcal meningitis (CM) is rapidly changing. The newly-announced price for flucytosine ($0.75 per 500 mg pill) and possibly lower prices for liposomal amphotericin B (AmB-L) create opportunities to reduce CM treatment costs compared to the current standard treatment in low- and middle-income countries. Methods: We developed an Excel-based cost model to estimate health system treatment costs for CM over a two-week induction phase for multiple treatment combinations, newly feasible with improved access to flucytosine and AmB-L. CM treatment costs include medications, laboratory tests and other hospital-based costs (bed-day costs and healthcare worker time). We report results from applying the model using country-specific information for South Africa, Uganda, Nigeria, and Botswana. Results: A 14-day induction-phase of seven days of inpatient AmB-D with flucytosine, followed by seven days of high-dose fluconazole as an outpatient, will cost health systems less than a 14-day hospital stay with AmB-D and fluconazole. If daily AmB-L replaces AmB-D for those with baseline renal dysfunction, with a cost of $50 or less per 50 mg vial, incremental costs would still be less than the AmB-D with fluconazole regimen. Simple oral combinations (e.g., seven days of flucytosine with fluconazole as an inpatient) are practical when AmB-D is not available, and treatment costs would remain less than the current standard treatment. Conclusions: Improved access to, and lower prices for flucytosine and AmB-L create opportunities for improving CM treatment regimens. An induction regimen of flucytosine and AmB-D for seven days is less costly than standard care in the settings studied here. As this regimen has also been shown to be more effective than current standard care, countries should prioritize scaling up flucytosine access. The cost of AmB-L based regimens is highly dependent on the price of AmB-L, which currently remains unclear.

Leishmania (Mundinia) martiniquensis is responsible for visceral leishmaniasis in patients with no known underlying immunodeficiency, and visceral or disseminated cutaneous leishmaniasis in HIV-infected patients. The available anti-Leishmania drugs for treatment have limitations such as high toxicity and variable efficacy. To improve the therapeutic index of anti-Leishmania drugs, the search for a new drug or a new natural compound in combination therapy instead of using monotherapy to reduce drug side effect and have high efficacy is required. In this study, anti-Leishmania activity of 8-hydroxyquinoline (8HQN) and its synergistic effect with amphotericin B (AmB) against L. martiniquensis were evaluated in vitro for the first time. These results showed that 8HQN presented anti-Leishmania activity against L. martiniquensis with IC50 1.60 ± 0.28 and 1.56 ± 0.02 µg/mL for promastigotes and intracellular amastigotes, respectively. The selectivity index (SI) value of 8HQN was 79.84 for promastigotes and 82.40 for intracellular amastigotes, which highlight promising results for the use of 8HQN in the treatment of L. martiniquensis-infected host cells. Interestingly, four combinations of 8HQN and AmB provided synergistic effects for intracellular amastigotes and showed no toxic effects to host cells. These results provided information of using a combination therapy in treating this Leishmania species leads to further development of therapy and can be considered as an alternative treatment for leishmaniasis. [ABSTRACT FROM AUTHOR]

Objective: G-ABCD is a biosimilar product of amphotericin B colloidal dispersion (ABCD). This study was designed to systematically examine the plasma pharmacokinetics (PK) and tissue distribution of G-ABCD in rats, using amphotericin B deoxycholate (DAmB) as a positive control. Methods: Male Sprague-Dawley rats received single dose or 14 doses of G-ABCD (1.0, 2.0 or 5.0 mg/kg) or the conventional micellar formulation DAmB) (1.0 mg/kg) via intravenous injection. Plasma and tissue samples were obtained for analysis of amphotericin B concentration by liquid chromatography-tandem mass spectrometry. Results: After a single-dose administration of 1 mg/kg, G-ABCD resulted in a significantly lower plasma peak drug concentration (Cmax) (1536 vs. 5256 ng/mL) and area under the curve from time 0 to ∞ (AUC0–∞) (3972 vs. 7006 h ng/mL) of non-complexed amphotericin B than DAmB. G-ABCD was associated with quicker distribution but slower elimination of amphotericin B than DAmB. Amphotericin B concentration reached a steady state after seven doses of G-ABCD. After multiple doses of 1 mg/kg, G-ABCD showed a lower peak level and longer half-life of amphotericin B in plasma than DAmB. G-ABCD treatment in rats was associated with relatively higher distribution to liver and spleen, but reduced amphotericin B delivery to kidneys, the major target organ of toxicity. Conclusion: These results suggest that G-ABCD provides a flatter but more lasting plasma level of amphotericin B and lower kidney burden in rats than DAmB.

Background: Limited data exist on the antifungal activity of daily liposomal amphotericin B with flucytosine induction regimens for cryptococcal meningitis, which are recommended in high-income countries. Liposomal amphotericin B monotherapy at 3 mg/kg previously failed to meet non-inferiority criteria compared to amphotericin B deoxycholate in its registrational clinical trial. We aimed to compare the quantitative antifungal activity and mortality between daily amphotericin B deoxycholate and daily liposomal amphotericin among persons with HIV-related cryptococcal meningitis receiving adjunctive flucytosine 100 mg/kg/day., Methods: We analyzed data from three clinical studies involving participants with HIV-associated cryptococcal meningitis receiving either daily liposomal amphotericin B at 3 mg/kg/day with flucytosine (N = 94) or amphotericin B deoxycholate at 0.7-1.0 mg/kg/day with flucytosine (N = 404) as induction therapy. We compared participant baseline characteristics, CSF early fungicidal activity (EFA), and 10-week mortality., Results: We included 498 participants in this analysis, of whom 201 had available EFA data (N = 46 liposomal amphotericin; N = 155 amphotericin deoxycholate). Overall, there is no statistical evidence that the antifungal activity of liposomal amphotericin B (mean EFA = 0.495 log10 CFU/mL/day; 95%CI, 0.355-0.634) differ from amphotericin B deoxycholate (mean EFA = 0.402 log10 CFU/mL; 95%CI, 0.360-0.445) (P = 0.13). Mortality at 10 weeks trended lower for liposomal amphotericin (28.2%) vs amphotericin B deoxycholate (34.6%) but was not statistically different when adjusting for baseline characteristics (adjusted Hazard Ratio = 0.74; 95%CI, 0.44-1.25; P = 0.26)., Conclusions: Daily liposomal amphotericin B induction demonstrated a similar rate of CSF fungal clearance and 10-week mortality as amphotericin B deoxycholate when combined with flucytosine for the treatment of HIV-associated cryptococcal meningitis., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Abstract Objective Based on studies in India (as there was no studies from outside India) amphotericin B deoxycholate has been considered as a backup drug for treatment of visceral leishmaniasis. However, treatment response and adverse effect to anti-leishmanial drugs may vary across different populations and in Bangladesh the effect to amphotericin B deoxycholate for treatment of visceral leishmaniasis is still unknown. Therefore, there is a need to explore cure rate and adverse effects to amphotericin B deoxycholate to justify its use on visceral leishmaniasis patients in Bangladesh. Result Here we report 34 visceral leishmaniasis patients who received treatment with amphotericin B deoxycholate in the Surya Kanta Kala-azar Research Centre from December 2011 to June 2015. The dose of the treatment was 1 mg/kg body weight for 15 days followed up until 12 months after treatment. Response to amphotericin B deoxycholate treatment was excellent as all 34 patients achieved a final cure. Hypokalaemia (47%), shivering (47%), vomiting (35%) and acidity (15%) were most common adverse events. However, we did not observe any serious adverse events. Amphotericin B deoxycholate for relapse visceral leishmaniasis was found to be highly effective and safe. Our study justified to include amphotericin B deoxycholate as a second line drug for visceral leishmaniasis in Bangladesh.

Disseminated talaromycosis caused by Talaromyces marneffei is a life-threatening opportunistic infection. Although amphotericin B deoxycholate (dAmB) remains the first-line induction treatment, voriconazole can also be used. However, no clinical trials have compared dAmB and voriconazole in the administration of talaromycosis. We retrospectively evaluated the efficacy and safety of voriconazole or dAmB as induction therapy for talaromycosis in HIV-infected patients. We enrolled HIV-infected patients with a confirmed Talaromyces marneffei infection who received intravenous dAmB (0.6 to 0.7 mg/kg daily for 2 weeks) or voriconazole (6 mg/kg every 12 h on day 1 and 4 mg/kg every 12 h afterward) as induction therapy, followed by oral itraconazole as consolidation and maintenance therapy. Drug efficacy was evaluated based on response rate. Drug safety was evaluated based on the occurrence of adverse events. In total, 58 patients who received voriconazole and 82 who received dAmB were enrolled from two hospitals. The voriconazole and dAmB treatment groups had similar response rates at the primary and follow-up efficacy evaluations. However, the durations of induction antifungal therapy and hospital stay were shorter for patients in the voriconazole group than in the dAmB group. Few adverse reactions occurred in either the voriconazole or dAmB group. Our retrospective study indicated that voriconazole is an effective and safe induction antifungal drug for HIV-associated disseminated talaromycosis. The duration of induction treatment with voriconazole was shorter, indicating its potential as a better choice in clinical practice. The duration of voriconazole induction therapy is 11 to 13 days. [ABSTRACT FROM AUTHOR]

Treatment for visceral leishmaniasis (VL) is hampered mainly by drug toxicity, their high cost, and parasite resistance. Drug development is a long and pricey process, and therefore, drug repositioning may be an alternative worth pursuing. Cardenolides are used to treat cardiac diseases, especially those obtained from Digitalis species. In the present study, cardenolide digitoxigenin (DIGI) obtained from a methanolic extract of Digitalis lanata leaves was tested for its antileishmanial activity against Leishmania infantum species. Results showed that 50% Leishmania and murine macrophage inhibitory concentrations (IC50 and CC50, respectively) were of 6.9 ± 1.5 and 295.3 ± 14.5 μg/mL, respectively. With amphotericin B (AmpB) deoxycholate, used as a control drug, values of 0.13 ± 0.02 and 0.79 ± 0.12 μg/mL, respectively, were observed. Selectivity index (SI) values were of 42.8 and 6.1 for DIGI and AmpB, respectively. Preliminary studies suggested that the mechanism of action for DIGI is to cause alterations in the mitochondrial membrane potential, to increase the levels of reactive oxygen species and induce accumulation of lipid bodies in the parasites. DIGI was incorporated into Pluronic® F127-based polymeric micelles, and the formula (DIGI/Mic) was used to treat L. infantum–infected mice. Miltefosine was used as a control drug. Results showed that animals treated with either miltefosine, DIGI, or DIGI/Mic presented significant reductions in the parasite load in their spleens, livers, bone marrows, and draining lymph nodes, as well as the development of a specific Th1-type response, when compared with the controls. Results obtained 1 day after treatment were corroborated with data corresponding to 15 days after therapy. Importantly, treatment with DIGI/Mic induced better parasitological and immunological responses when compared with miltefosine- and DIGI-treated mice. In conclusion, DIGI/Mic has the potential to be used as a therapeutic agent to protect against L. infantum infection, and it is therefore worth of consideration in future studies addressing VL treatment. [ABSTRACT FROM AUTHOR]

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Disseminated Acanthamoeba species infection is likely an underrecognized and underdiagnosed opportunistic infection in patients with advanced human immunodeficiency virus (HIV) disease in South Africa. It presents a unique clinical challenge in that the diagnosis can be difficult to establish and management options are limited in low-resource settings. To our knowledge, there is a paucity of literature to date on the successful use of combination treatment options for patients in low-resource settings without access to miltefosine. We present a case describing the clinical improvement of disseminated Acanthamoeba infection in a patient with advanced HIV using a non-miltefosine-based treatment regimen. The case serves to highlight that Acanthamoeba sp. infection should be considered as a differential diagnosis for nodular and ulcerative cutaneous lesions in patients with advanced HIV in South Africa, and that although there are alternative options for combination treatment in countries without access to miltefosine, efforts should be made to advocate for better access to miltefosine for the treatment of acanthamoebiasis in South Africa.

We present a 27-year-old lady with HIV-1 infection who died due to rapidly worsening respiratory failure one day after commencing amphotericin B deoxycholate therapy for cryptococcal meningitis. Chest x-ray appearances were consistent with pneumocystis pneumonia but post mortem examination showed evidence of severe necrotizing cryptococcal pneumonia. Cryptococcal pneumonia is an underrecognized condition and should be considered in the differential of patients with HIV-1 infection and low CD4 count who develop respiratory symptoms.

Introduction: Fungal urinary tract infections predominantly affect the critically ill premature infant and those with urogenital tract abnormalities. Fungal balls are an uncommon complication which require prompt detection and treatment to prevent morbidity and mortality. The evidence on the management of fungus balls in young infants with Candida urinary tract infections is very scarce., Methods: Case reports and review of the literature., Results: We report two immunocompetent young infants with urogenital abnormalities that received local amphotericin B deoxycholate, and systemic therapy, for the treatment and prevention of Candida urinary tract infection-associated fungus balls. We identified 21 similar cases in the literature, with very limited data about drug compounding, optimal dosages, dwell times and length of treatment. Different management strategies are discussed., Conclusions: Amphotericin B deoxycholate local irrigations were safe and effective for the therapeutic management and prophylaxis of Candida fungus balls in young infants, in combination with systemic antifungal therapy., (Copyright © 2023 Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Conventional amphotericin B deoxycholate (AmBd) is the preferred amphotericin B formulation in countries with limited resources despite its nephrotoxicity. Normal saline pre-infusion is a recommended measure to reduce the risk of nephrotoxicity in patients receiving AmBd., Objectives: To examine the effect of different normal saline solution (NSS) pre-infusion doses, and other potential risk factors, on the development of acute kidney injury (AKI) in patients with invasive fungal infection receiving AmBd., Methods: Adult patients with invasive fungal infections who received intravenous AmBd were included in this retrospective study. Doses of the normal saline pre-infusion were adjusted to the body weight (NSS/BW) and the daily dose of amphotericin B (NSS/AmBd). Kaplan-Meier survival analysis was used to estimate 14 d AKI-free survival rates, and the log-rank test was used to compare AKI-free survivals between groups., Results: The present study included 60 patients; 31 patients developed AKI during the AmBd therapy. The overall 14 d AKI-free survival was 48.3%. NSS/AmBd, but not NSS/BW, was associated with AKI-free survival in patients receiving AmBd: the higher the NSS/AmBd, the higher the AKI-free survival. Gender, baseline blood urea nitrogen (BUN), and baseline plasma bicarbonate (Bicarb) also affected AKI-free survival. Female gender, higher BUN, and lower Bicarb were associated with higher AKI-free survival., Conclusions: The present study suggests that low NSS/AmBd, male gender, low BUN, and high Bicarb are risk factors for AmBd-associated AKI. Excluding gender, these risk factors are potentially modifiable and would guide tailoring appropriate preventive measures for AmBd-associated AKI., (© 2023 Mathurot Virojanawat et al., published by Sciendo.)

Leishmania (Mundinia) martiniquensis is a causative agent of visceral leishmaniasis, but in HIV-infected patients both visceral and disseminated cutaneous leishmaniasis are presented. Recurrence of the disease after treatment has been reported in some cases indicating that improved chemotherapy is required. In this study, the susceptibility of L. martiniquensis to Amphotericin B deoxycholate (AmB), allicin, and andrographolide was evaluated and the synergistic effects of allicin or andrographolide combined with AmB against L. martiniquensis intracellular amastigotes in mouse peritoneal exudate macrophages (PEMs) were investigated in vitro for the first time. The results showed that L. martiniquensis was highly susceptible to AmB as expected, but allicin and andrographolide had selectivity index (SI) values greater than 10, indicating promise in both compounds for treatment of host cells infected with L. martiniquensis. Four AmB/allicin combinations presented combination index (CI) values less than 1 (0.58−0.68) for intracellular amastigotes indicating synergistic effects. The combination with the highest dose reduction index (DRI) allowed an approximately four-fold reduction of AmB use in that combination. No synergistic effects were observed in AmB/andrographolide combinations. The data provided in this study leads for further study to develop novel therapeutic agents and improve the treatment outcome for leishmaniasis caused by this Leishmania species.

Continuous administration of amphotericin B deoxycholate over 24 hours (24 h-D-AmB) is better tolerated than rapid infusions. However, toxicity and outcome have not been assessed in a homogenous patient population with acute myeloid leukaemia (AML). We retrospectively analysed renal function and outcome in all adult patients with AML undergoing intensive chemotherapy between 2007 and 2012 at our institution. We compared a patient group with exposure to 24 h-D-AmB to a patient group without exposure to 24 h-D-AmB. One hundred and eighty-one consecutive patients were analysed, 133 (73.5%) received at least 1 dose of 24 h-D-AmB, and 48 (26.5%) did not. Reasons for 24 h-D-AmB initiation were invasive fungal disease (IFD) in 63.5% and empirical treatment for febrile neutropenia in 36.5% of the cases. Most patients with IFD received an oral triazole drug at hospital discharge. Baseline characteristics were well matched. Amphotericin B deoxycholate over 24 hours was given for a median 7 days (interquartile range 3-13). Peak creatinine concentration was higher in the 24 h-D-AmB-group (104.5 vs. 76 μmol/L, P < .001) but normalized within 1 month after therapy (65.5 vs. 65 μmol/L, P = .979). In neither of the 2 groups, end-stage renal disease occurred. There was no difference in 60-day survival (90% vs. 90%) and 2-year survival (58% vs. 58%). Invasive fungal disease partial response or better was observed in 68% of the patients. We conclude that antifungal therapy with continuously infused amphotericin B deoxycholate is safe in patients with AML. An antiinfective strategy based on 24 h-D-AmB in first line followed by an oral triazole compound represents an economically attractive treatment option. [ABSTRACT FROM AUTHOR]

An overview of the literature data concerning the comparison of toxicity, efficacy and cost of amphotericin B lipid complex and liposomal amphotericin B, as well as their comparison with amphotericin B deoxycholate are provided.

Background: Amphotericin B Deoxycholate (ABD) has been the best therapeutic agent for treatment of most systemic fungal infections. However, untoward adverse effects like nephrotoxicity may limit its appropriate therapeutic use. We studied administration of fat emulsion early after infusion of ABD to evaluate its effects on ABD-associated nephrotoxicity.Methods: This study was a randomized clinical trial. Patients with fungal infections admitted in Amir-Alam and Imam-Khomeini University Hospitals, Tehran, Iran, entered the study during 1390- 1391. The patients were randomized to intervention and control groups. In both groups, patients received 1mg/kg/day ABD in dextrose 5%. In intervention arm, the patients additionally received intralipid 10% daily that was started as soon as possible within one hour after infusion of ABD. ABD-associated nephrotoxicity (a minimum 50% increase in baseline serum creatinine to a minimum of 2mg/dl), daily serum creatinine changes during first two weeks of treatment and some other relevant indices of renal function were compared between groups. ABD-related hypokalemia was also compared as an additional target. Results: Thirty one patients entered the study. ABD-associated nephrotoxicity and values of other relevant indices of renal function were not different between intervention and control groups (P>0.05). Daily changes in serum creatinine level within first two weeks of treatment in both groups were not also statistically different (P=0.62). Furthermore, ABD-related hypokalemia was not significantly different between groups (P=0.47).Conclusion: Administration of intralipid 10% early after infusion of ABD in dextrose 5% does not have any effect in decreasing ABD-associated nephrotoxicity. Moreover, it does not have any significant effect on ABD-related hypokalemia.

Objectives Preparation of amphotericin B deoxycholate (AmB-d) in different volumes of 5% dextrose (D5W) was studied to investigate a interesting phenomenon that AmB-d was easy to bring pipe blockage when diluted in 500 ml but not in 50 ml. Methods AmB-d (25 mg/vial) in 50 ml, 250 ml or 500 ml D5W was prepared. Fluids were collected before and after infusion, then were assayed by validated high-performance liquid chromatography ( HPLC) method. Light obscuration assay was used to detect the particles in transfusions. Key findings pH values of different volumes of D5W were all about 3.7, which was lower than the requirement of AmB-d package insert ( pH > 4.2). The number of insoluble particles >10 μm/25 μm in 25 mg/500 ml infusions exceeded China Pharmacopoeia limit. Filters in 25 mg/500 ml infusion set were full of AmB-d after dripping slowly for 6 h, and 331.3 ml solution was left in the bottles and only 11.3% of AmB-d could flow out. Whereas the AmB-d infusion consists of 25 mg/50 ml, 25 mg/250 ml and 50 mg/500 ml could meet with China Pharmacopoeia standards, and they flowed out easily and completely. Conclusions In practice, 25 mg/250 ml and 50 mg/500 ml would be more suitable for clinical use, rather than 25 mg/500 ml. We provided a convenient method for AmB-d preparation. [ABSTRACT FROM AUTHOR]

The effect of tenofovir and amphotericin coadministration on kidney function is poorly characterized. We measured creatinine during induction therapy and at 4 weeks after diagnosis in Ugandans undergoing cryptococcal meningitis therapy and classified as not receiving antiretroviral therapy (ART), receiving nontenofovir ART or receiving tenofovir-based ART. Longitudinal creatinine changes and grade 2-4 creatinine adverse events were evaluated across groups. Creatinine concentrations were similar across ART groups. At 4 weeks after diagnosis, creatinine was 0.25 mg/dL higher than at diagnosis, but similar across groups. Adverse event incidence was also similar across ART groups. Tenofovir and amphotericin coadministration did not increase the risk of kidney dysfunction. [ABSTRACT FROM AUTHOR]