amphotericin-b--deoxycholate-drug-combination and Mucormycosis

Patients with diabetes are known as an important high-risk group for cerebral mucormycosis (CM).. We conducted a structured search using PubMed/MEDLINE to collect both case reports and case series case (ie including at least two patients) onto CM in diabetic patient published between 2000 and March 2020.. Forty-five reports of individual cases and eighteen case series articles were included. India accounted for the largest share of reports with 37.7% and 38.8% of individual cases and case series, respectively. Mortality ranged from 0% to 100% in the case series. The overall mortality in the individual cases was 46.3%, and 64.2% of deaths were reported in patients with ketoacidosis diabetes. Facial swelling (53.3%), headache (44.4%), loss of vision (35.5%) and ophthalmoplegia (35.5%) were the most frequently reported clinical symptoms. In all patients except 4 (91.1%), CM was treated surgically; however, in many cases (42%), despite the use of surgery, death occurred. Amphotericin B deoxycholate (AMB) and lipid-based AMB (LAMB) were used as the first lines of treatment for all patients; however, posaconazole, echinocandins, hyperbaric oxygen therapy (HBOT) and deferasirox were used in combination for a number of patients. Posaconazole has been shown to have positive therapeutic effect; however, posaconazole, LAMB and HBOT are not commonly used in low-income and health-challenged countries.. Cerebral mucormycosis is a rapidly progressive infection in diabetic patients and carries immense morbidity despite early diagnosis and treatment. Low-income countries have had the highest number of reports of the disease in recent years, indicating the need to control diabetes in these countries.

Topics: Amphotericin B; Antifungal Agents; Brain Diseases; Deoxycholic Acid; Diabetes Complications; Diabetes Mellitus; Drug Combinations; Humans; Mucormycosis; Risk Factors; Triazoles

Mucormycosis is a rare, invasive disease associated with high mortality rates, produced by opportunistic pathogens related to the Mucorales order and characterised by a diverse range of clinical forms; acute rhino-orbital-cerebral and pulmonary symptoms are the most reported ones.. To report the experience of mucormycosis observed in a tertiary-care hospital in Mexico for 35 years.. This was a retrospective, descriptive and observational study on mucormycosis at a tertiary-care hospital in Mexico from January 1985 to December 2019. Demographic and clinical data and mycological and histopathological records were selected.. Two hundred fourteen proven cases of mucormycosis for 35 years at a tertiary-care hospital in Mexico were included. Most of the cases were male patients with a median age of 45 years. The two most associated underlying diseases were diabetes mellitus (76.6%) and haematologic malignancy (15.4%). The three primary clinical forms were as follows: rhino-orbito-cerebral (75.9%), cutaneous (8.41%) and pulmonary (7.47%) mucormycosis. The most isolated agents were Rhizopus arrhizus (58.4%) and Lichtheimia corymbifera (12.3%). The overall therapeutic response was 58.5%, and the best response was observed with amphotericin B deoxycholate and surgical debridement.. Mucormycosis is an emerging disease, and its incidence has increased at our hospital over the years. In this study, the rhino-cerebral clinical type was the most frequent in patients with uncontrolled diabetes; the main aetiological agent was R. arrhizus. Early diagnosis, control of the underlying disease and prompt management may increase the survival rate.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Child; Child, Preschool; Deoxycholic Acid; Drug Combinations; Female; Humans; Infant; Infant, Newborn; Male; Medical Records; Mexico; Middle Aged; Mucorales; Mucormycosis; Retrospective Studies; Tertiary Care Centers; Time Factors; Young Adult

Most fungal infections found in wounds are secondary or superadded, and are generally benign in their clinical course in healthy individuals, with the exception of mucormycosis. This is a life-threatening infection caused by fungi of the order Mucorales. Primary cutaneous disease may occur following traumatic implantation of spores, or use of contaminated bandages, or as a complication of extensive burns, diabetic acidosis and other specific immunocompromised conditions. The clinical spectrum is highly non-specific and is often triggered by seemingly innocuous trauma. The superficial vesicles or patchy erythema rapidly degrade to haemorrhagic necrosis and rapidly progressive gangrenous lesion. The problem with diagnosing mucormycosis remains, therefore, that the condition has poor clinical indicators and requires reliance on microscopy and fungal culture. Management starts with a clinical suspicion, taking into account the risk factors and lack of response to first-line agents, as well as an aggressive clinical course. Treatment is multimodal, with medical correction of the risk factors and optimisation of limiting factors, such as diabetes, neutropenia and immunosuppressants. Treatment generally involves radical and repetitive surgical debridement, intravenous amphotericin B with monitoring of the nephrotoxicity, along with adjuvant modalities, such as hyperbaric oxygen therapy, colony stimulating factor, interferons gamma and white blood cell transfusion. Successful courses of therapy typically last 4-6 weeks and require cumulative doses that are equivalent to >2g of amphotericin B deoxycholate.

Topics: Adult; Amphotericin B; Antifungal Agents; Debridement; Deoxycholic Acid; Drug Combinations; Humans; Hyperbaric Oxygenation; Male; Middle Aged; Mucorales; Mucormycosis; Treatment Outcome; Wound Infection; Young Adult

Topics: Amphotericin B; Antifungal Agents; Child; Child, Preschool; Debridement; Deoxycholic Acid; Diabetes Mellitus, Type 1; Drug Combinations; Humans; Mucormycosis; Rhinitis; Sinusitis

Whether isavuconazole, an extended-spectrum triazole, possesses synergistic activity in combination therapy with echinocandins or amphotericin B for the treatment of invasive molds infections has not been studied. Our in vitro combination studies showed that isavuconazole and micafungin are synergistically active against Aspergillus fumigatus, Aspergillus flavus, Aspergillus terreus, and Cunninghamella bertholletiae. These results suggest that isavuconazole, in combination with micafungin, may have a role in the treatment of invasive aspergillosis and warrants further investigation.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus; Cunninghamella; Deoxycholic Acid; Drug Combinations; Drug Interactions; Echinocandins; Lipopeptides; Micafungin; Microbial Sensitivity Tests; Mucormycosis; Nitriles; Pyridines; Triazoles

We present a single-centre, retrospective study (1985-2012) of 22 cases of mucormycosis in children. A total of 158 mucormycosis cases were identified, of which 22 (13.96%) were children. The mean age of the children was 10.3 years (range: 6 months-18 years), and 59% of the infections occurred in males. The rhinocerebral form was the main clinical presentation (77.27%), followed by the primary cutaneous and pulmonary patterns. The major underlying predisposing factors were diabetes mellitus in 68.18% of the patients and haematologic diseases in 27.7% of the patients. The cases were diagnosed by mycological tests, with positive cultures in 95.4% of the patients. Rhizopus arrhizus was the foremost aetiologic agent in 13/22 cases (59.1%). In 21 cultures, the aetiologic agents were identified morphologically and by molecular identification. In 10 cultures, the internal transcribed spacer region of the ribosomal DNA was sequenced. Clinical cure and mycological cure were achieved in 27.3% cases, which were managed with amphotericin B deoxycholate and by treatment of the underlying conditions.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Child; Child, Preschool; Deoxycholic Acid; DNA, Fungal; Drug Combinations; Female; Humans; Infant; Male; Mexico; Mucormycosis; Retrospective Studies; Rhizopus; Sequence Analysis, DNA

Topics: Amphotericin B; Antifungal Agents; Biopsy; Brain Diseases; Deoxycholic Acid; Diabetes Mellitus, Type 2; Drug Combinations; Eye; Eye Diseases; Fatal Outcome; Female; Humans; Kidney Failure, Chronic; Magnetic Resonance Imaging; Middle Aged; Mucormycosis; Multiple Organ Failure; Paranasal Sinuses; Temporal Lobe

Mucormycosis is an opportunistic infection caused by fungi of the order Mucorales. It is characterized by rapid progression and high morbidity and mortality in the absence of early diagnosis and prompt treatment. It was an infrequent disease, but in recent years, its incidence appears to have increased. The aim of this paper is to report the cases of mucormycosis diagnosed from 1982 to 2010 at the Hospital de Clinicas José de San Martín, University of Buenos Aires. We diagnosed 10 cases of mucormycosis; the first three between 1982 and 2004 and the last 7 between 2005 and 2010. The incidence from 1980 to 2004 was 0.13 patient-years and the frequency 0.1/10 000 discharges (95% CI 0.00- 0.3). In the period 2005 to 2010, the incidence was 0.86 patients per year with 1.1/10 000 discharges (95% CI 0.5-2.4). There was a pulmonary mucormycosis case (in a patient treated with corticosteroids) and nine rhinocerebral cases, two in neutropenic and seven in diabetic patients. The diagnosis was made by observation of cenocytic hyphae in 10/10 patients. Mucorales were recovered in 8/9 cultures (5 Rhizopus spp and 3 Mucor spp.). In one case diagnosis of pulmonary mucormycosis was made post-mortem. Nine patients were treated with amphotericin B deoxycholate (in 3 patients supplemented with liposomal amphotericin B) and surgery. Three patients underwent hyperbaric chamber. Seven patients had favorable outcome. In conclusion, mucormycosis is a rare disease, but its incidence has increased over the past five years. A good evolution of the patients is linked to early diagnosis and treatment.

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Argentina; Deoxycholic Acid; Drug Combinations; Eye Infections, Fungal; Female; Humans; Incidence; Lung Diseases, Fungal; Male; Middle Aged; Mucormycosis; Nose Diseases; Paranasal Sinus Diseases

The objective of this study was to investigate the efficacy of liposomal amphotericin B (L-AMB) at a clinical dose (3 mg/kg) against six species (5 genera) of Zygomycetes in a murine lethal infection model, and to compare findings with those for deoxycholate amphotericin B (D-AMB). The correlation between in-vitro activity and in-vivo efficacy of L-AMB was also investigated. Cyclophosphamide-treated mice were inoculated intravenously with conidial suspensions. Four hours or 1 day after inoculation, a single dose of L-AMB or D-AMB was administered intravenously. The number of mice that survived for 14 days was recorded. L-AMB at a dose of at least ≥1 mg/kg significantly prolonged the survival time of infected mice compared with the control group. The ED₅₀ of L-AMB was nearly equivalent to that of D-AMB, except for the treatment initiated on day 1 in the Rhizopus oryzae model. At the maximum tolerated dose (MTD) of each agent, survival percentages with L-AMB (10 mg/kg) were equal to or higher than those with D-AMB (1 mg/kg). The ED₅₀ of L-AMB decreased as the MIC against the infecting strain decreased. In conclusion, L-AMB was effective at a clinical dosage, and at the MTD the efficacy of L-AMB was equal or superior to that of D-AMB in a murine model of disseminated zygomycosis. The in-vivo activity of L-AMB was correlated with its in-vitro activity.

Topics: Amphotericin B; Animals; Antifungal Agents; Deoxycholic Acid; Disease Models, Animal; Drug Combinations; Humans; Male; Mice; Microbial Sensitivity Tests; Mucorales; Mucormycosis; Species Specificity; Survival Rate; Treatment Outcome

Topics: Amphotericin B; Antifungal Agents; Cyanosis; Deoxycholic Acid; Drug Combinations; Fingers; Hand; Humans; Male; Middle Aged; Mucormycosis; Phosphatidylcholines; Phosphatidylglycerols

The efficacies of liposomal amphotericin B (LAmB) and amphotericin B deoxycholate (AmB) were compared in a diabetic murine model of hematogenously disseminated Rhizopus oryzae infection. At 7.5 mg/kg of body weight twice a day (b.i.d.), LAmB significantly improved overall survival compared to the rates of survival in both untreated control mice (P = 0.001) and mice treated with 0.5 mg of AmB per kg b.i.d. (P = 0.047). These data indicate that high-dose LAmB is more effective than AmB in treating murine disseminated zygomycosis.

Topics: Amphotericin B; Animals; Deoxycholic Acid; Diabetes Mellitus, Experimental; Drug Combinations; Humans; Liposomes; Male; Mice; Mice, Inbred BALB C; Mucormycosis; Rhizopus