amphotericin-b and Burns

Mucormycosis is a rare fungal infection with a high mortality rate. It presents with scattered black/necrotic ulcers, white fungal elements, and progression of wounds despite seemingly adequate debridement. Diagnosis is confirmed on wound histology; however, this is often delayed. There is currently no comprehensive review of burn-related mucormycosis within the literature, making this the first article to provide evidence-based treatment guidance. We performed a review of publications from 1946 to the present. There were 151 cases of mucormycosis complicating burns. The mortality rate was 54.5%, and there was a significant increase in mortality with axial body site involvement compared with isolated peripheral involvement. The standard treatment was prompt and radical debridement. Utilization of frozen section to guide debridement aided in clinical decision making. No systemic treatment reached statistical significance; however, amphotericin B trended toward significance. Although there is no strong evidence for topical amphotericin B or hyperbaric oxygen, there may be benefit in some cases. This study recommends early radical debridement in conjunction with the European Confederation of Medical Mycology guidelines of IV liposomal/lipid complex amphotericin B more than 5mg/kg/day, with posaconazole 800 mg daily in divided doses as a salvage or oral step-down.

Topics: Amphotericin B; Antifungal Agents; Burns; Debridement; Humans; Mucormycosis

Trichosporon beigelii is a fungus once thought to cause only superficial infections, but recently has been increasingly identified as an opportunistic systemic pathogen in immunocompromised patients. There have been very limited reports of this organism in the burn patient population. We describe the first report of pharmacological management of invasive T. beigelii with a combination of amphotericin B and high dose fluconazole in a burn patient. Antifungal susceptibility testing of T. beigelii determined a change in minimum inhibitory concentrations (MICs) of amphotericin B and a consistent resistance pattern with the use of flucytosine. This paper will review our experience with T. beigelii fungus in a regional burn treatment center and review the literature on other experiences in the burn population.

Topics: Adult; Amphotericin B; Antifungal Agents; Burns; Catheters, Indwelling; Drug Resistance, Microbial; Fatal Outcome; Female; Fluconazole; Flucytosine; Fungemia; Humans; Immunocompromised Host; Male; Mycoses; Opportunistic Infections; Sputum; Trichosporon; Wound Infection

Deep seated candidosis are the most common invasive fungal infections occurring in various categories of patients including those with cancer, burns as well as patients with AIDS or undergoing organ transplantation. Various clinical entities have to be distinguished with implications for diagnostic procedures as well as for adequate therapy. During the last decade, tremendous progress has been achieved leading to a major reduction of mortality attributable for candidaemia from 80% (in the seventies) to 40% in the nineties, mainly due to early empiric antifungal and better prophylaxis treatment. Other antifungal strategies than conventional amphotericin B are now available and have been shown effective, in particular, new modalities to administer amphotericin B including various lipid formulations, but also new azoles and mainly the triazoles such as fluconazole and itraconazole. Fluconazole has been shown effective as prophylaxis of candidosis including in patients undergoing bone marrow transplantation as well as in treatment of oropharyngeal candidosis and for candidaemia occurring in non-neutropenic patients. More limited data are available on itraconazole so far in particular in patients with documented invasive candidosis, but preliminary reports are encouraging. Oral therapy with systemic efficacy is more easy to recommend and allows ambulatory treatment. Candidosis is not a benign disease and in every single patient with fungemia antifungal treatment is mandatory.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Burns; Candidiasis; Fluconazole; Humans; Incidence; Itraconazole; Neoplasms; Opportunistic Infections; Postoperative Complications; Transplantation

Topics: Amphotericin B; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Burns; Candida albicans; Candidiasis; Catheterization; Central Nervous System Diseases; Diabetes Complications; Diagnosis, Differential; Fluorescent Antibody Technique; Fluorouracil; Hemagglutination Inhibition Tests; Humans; Hydrogen-Ion Concentration; Immunologic Deficiency Syndromes; Immunosuppression Therapy; Lung Diseases, Fungal; Nystatin; Pneumonia, Pneumocystis; Pyelonephritis; Respiratory Hypersensitivity; Sepsis; Serologic Tests

To determine if patients receiving topical amphotericin B in combination with 5% mafenide acetate solution will acquire systemically detectable levels of amphotericin B.. A prospective, observational study of consecutive patients from May 2007 to March 2008 who received 5% mafenide acetate/amphotericin B (2 mcg/ml) solution topically every 4h to their excised and grafted burn wounds for at least 5 days. Serum amphotericin B levels were measured every 5 days during treatment. In addition, the percentage of graft take, occurrence of infection, and potential adverse reactions or toxicities were monitored and recorded.. A total of 27 patients were enrolled, accumulating 420 treatment days and 72 amphotericin B levels. Sixty-nine of the amphotericin B levels were undetectable, while 3 were detectable at non-therapeutic levels (<0.5 mcg/ml). Of the patients with a detectable serum amphotericin B level, only one experienced adverse reactions that could potentially be attributed to amphotericin B. The mean TBSA burned was 32% (SD+/-14%), with a mean TBSA treated with solution of 21% (SD+/-13%). The median duration of treatment was 8 days (range 5-52 days), and the median number of amphotericin B levels drawn per patient was 1 (range 1-19). The median percentage graft take was 95%, and there were no fungal wound infections.. We conclude that 5% mafenide acetate/amphotericin B (2 mcg/ml) solution, applied to excised and grafted burn wounds, does not produce clinically relevant serum levels of amphotericin B. Based on our observations, this topical regimen is safe.

Topics: Administration, Cutaneous; Amphotericin B; Anti-Infective Agents; Anti-Infective Agents, Local; Burns; Drug Administration Schedule; Drug Combinations; Graft Survival; Humans; Mafenide; Postoperative Care; Prospective Studies; Skin Absorption; Surgical Wound Infection

Infection is still one of the leading causes of morbidity and mortality in severely burned patients. Evidence suggests that many of the responsible organisms are endogenous. Systemic antibiotic prophylaxis is not effective, and produces resistant strains of microorganisms. SDD has been postulated to be beneficial for controlling and decreasing infections in critically ill patients. Its efficacy in severely burned patients, however, remains controversial. In order to analyze the efficacy of selective decontamination of the digestive (SDD) tract, to decrease the bacterial colonization of the aerodigestive tract and burn wounds, and the incidence of septic complications in severely burned children, 23 pediatric patients affected of severe burns were prospectively randomized in a double-blinded study. Eleven patients received SDD (Polymyxin E, Tobramycin, and Amphotericin B), and 12 placebo. Demographics, hospital course, microbiology results, complications, infectious episodes, and serum levels of IL-1beta, IL-6, IL-10, and TNF-alpha were compared to determine the efficacy of SDD. Colonization rates to the wound, sputum, nasogastric aspirates, and feces were similar. Pneumonia, sepsis and other complications had similar incidence in both groups. Serum levels of all cytokines studied were also comparable, suggesting a similar inflammatory status in all patients, regardless of the treatment received. Patients in the SDD group, however, had a significantly higher incidence of diarrhea (P=0.003). We can conclude that selective decontamination of the digestive tract with Polymixin E, Tobramycin and Amphotericin B is not effective to decrease bacterial colonization and infectious episodes in severely burned pediatric patients.

Topics: Amphotericin B; Analysis of Variance; Bacteremia; Burns; Child; Cross Infection; Cytokines; Digestive System Diseases; Double-Blind Method; Drug Therapy, Combination; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Humans; Injury Severity Score; Intubation, Gastrointestinal; Linear Models; Male; Polymyxins; Probability; Prospective Studies; Reference Values; Survival Rate; Tobramycin; Treatment Outcome

Sepsis due to candida infection is a major cause of mortality and morbidity on our unit. Over a period of 3 years and 4 months, 29 cases of candida septicaemia, diagnosed by blood cultures, were encountered at the burn unit at Augusta Regional Medical Center. Factors known to predispose to fungal sepsis were present in all cases. All patients had large burns (14-98 per cent total body surface (TBSA) with a mean of 48.3 per cent). All but one patient had at least one central venous line. Respiratory problems requiring ventilator support were present in 24 patients. Sixteen patients had Candida albicans sepsis, two in association with another fungal sepsis. Candida parapsilosis was encountered in nine patients, one in combination with another species. Four patients had Candida tropicalis. Amphotericin B was prescribed therapeutically in 25 patients, in seven together with fluconazole. Two patients received fluconazole only and two received no antifungal therapy. There were eight deaths all attributed to sepsis and all of whom had multiple organ failure. Five of those who died had completed a course of amphotericin B therapy, two were receiving treatment at the time of death, and one patient died before culture data became available. Early and aggressive therapy is advised and amphotericin B appears to be the drug of choice.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Burn Units; Burns; Candidiasis; Child; Fluconazole; Fungemia; Humans; Middle Aged

Cutaneous Fusarium infections carry significant morbidity and mortality in burn-injured patients. Treatment involves surgical source control in combination of systemic and topical therapy. Given drug shortage constraints with conventional amphotericin deoxycholate, we describe the first case of successful treatment with adjunctive topical liposomal amphotericin in a critically ill burn-injured patient.

Topics: Amphotericin B; Antifungal Agents; Burns; Fusarium; Humans; Liposomes

Fusarium species represent an opportunistic fungal pathogen. The data in Mexico about Fusarium infections in humans are scarce. Here, we present a retrospective series of patients with a confirmed diagnosis of fusariosis in eight different hospitals in Mexico from January 2010 to December 2019. The diagnosis of proven fusariosis was made according to the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium (EORT/MSG) criteria. A total of 49 cases were identified in our series. Most patients had burn injuries (49%), and 37% had hematological malignancies. Most patients had fire injuries (40%), followed by electric injuries (8%), febrile neutropenia (10%), and pancytopenia (6%). Patients had skin and soft tissue involvement in 49%, followed by blood culture isolation and biopsies from different sites of the body (lung, sinuses, bone tissue, and eyes). Febrile neutropenia (10%) and fungemia (8%) were the most common clinical syndromes in immunosuppressed patients. Most patients received monotherapy (67%), where voriconazole was used in 30% of the cases, followed by conventional amphotericin B (16%), and lipidic formulations of amphotericin B in 10% (either liposomal amphotericin B or amphotericin B lipid complex). Combination therapy was used in 20% of the cases, and the most common combination therapy was triazole plus any lipidic formulation of amphotericin B (10%). Mortality related to Fusarium infection occurred in 22% of patients. Fusariosis is a serious threat. Burn injuries and hematologic malignancies represent the most common causes of infection in this small series from Mexico.. This study describes the epidemiological characteristics of patients with fusariosis from a multicenter cohort in Mexico. These findings provide information from this invasive fungal disease that threatens different countries in Latin America.

Topics: Amphotericin B; Antifungal Agents; Burns; Febrile Neutropenia; Fusariosis; Fusarium; Hematologic Neoplasms; Humans; Mexico; Retrospective Studies; Voriconazole

The Mucorales fungi-formerly classified as the zygomycetes-are environmentally ubiquitous fungi, but generally rare causes of clinical infections. In the immunocompromised host, however, they can cause invasive, rapidly spreading infections that confer a high risk of morbidity and mortality, often despite surgical and antifungal therapy. Patients with extensive burn injuries are particularly susceptible to skin and soft-tissue infections with these organisms. Here, we present a case of Lichtheimia infection in a patient with extensive full-thickness burns that required significant and repeated surgical debridement successfully treated with isavuconazole and adjunctive topical amphotericin B washes. We also review the available literature on contemporary antifungal treatment for Lichtheimia species and related Mucorales fungi.

Topics: Amphotericin B; Antifungal Agents; Burns; Debridement; Dermatomycoses; Humans; Male; Middle Aged; Mucorales; Mucormycosis; Nitriles; Pyridines; Treatment Outcome; Triazoles

Fungal infections remain a major cause of mortality in the burned population. Mafenide acetate/amphotericin B solution (SMAT) has been used topically for prophylaxis and treatment of these infections. Current manufacturer guidelines only guarantee the stability of mafenide solution and amphotericin B at room temperature. Additionally, the recommended maximum storage time for mafenide solution is 48h, leading to significant financial and material loss when unused solutions are discarded. The purpose of this study was to characterize the chemical stability, structure and bioactivity of SMAT stored at 2°C, 25°C, and 40°C for up to 90 days.. Stability analyses of SMAT solutions containing 2.5% or 5% mafenide plus 2μg/mL amphotericin B were performed using high performance liquid chromatography. Chemical structure was assessed using Fourier-transform infrared spectroscopy. Bioactivity against clinically relevant species was examined.. The chemical structure and stability of mafenide did not change over 90days at all temperatures. Amphotericin B was undetectable in SMAT solutions after two days at high temperatures, which was slowed by refrigerated storage. Against Staphylococcus aureus, SMAT activity began to decrease generally between two and seven days. Against Pseudomonas aeruginosa, activity slowly tapered and was gone by day 90. SMAT retained high bioactivity against Candida albicans for over 40days and was not affected by temperature.. The amphotericin B component of SMAT is degraded within 2days under warm storage. While mafenide was stable over 90 days, the bioactivity of SMAT solution may be lost within 2days as well.

Topics: Administration, Cutaneous; Amphotericin B; Anti-Infective Agents, Local; Burns; Candida albicans; Chromatography, High Pressure Liquid; Drug Stability; Drug Storage; Humans; Mafenide; Pharmaceutical Solutions; Pseudomonas aeruginosa; Skin Diseases, Infectious; Spectroscopy, Fourier Transform Infrared; Staphylococcus aureus; Temperature

Topics: Amphotericin B; Antifungal Agents; Aortic Valve; Burns; Candida tropicalis; Candidemia; Echocardiography; Endocarditis; Heart Valve Prosthesis Implantation; Hospitalization; Humans; Invasive Fungal Infections; Male; Micafungin; Middle Aged; Mitral Valve

Topics: Amphotericin B; Antifungal Agents; Burns; Critical Illness; Diffusion; Humans; Liposomes; Mucormycosis; Muscles; Renal Dialysis; Triazoles

Survivors of combat trauma can have long and challenging recoveries, which may be complicated by infection. Invasive fungal infections are a rare but serious complication with limited treatment options. Currently, aggressive surgical debridement is the standard of care, with antifungal agents used adjunctively with uncertain efficacy. Anecdotal evidence suggests that antifungal agents may be ineffective in the absence of surgical debridement, and studies have yet to correlate antifungal concentrations in plasma and wounds.. Here we report the systemic pharmacokinetics and wound effluent antifungal concentrations of five wounds from two male patients, aged 28 and 30 years old who sustained combat-related blast injuries in southern Afghanistan, with proven or possible invasive fungal infection. Our data demonstrate that while voriconazole sufficiently penetrated the wound resulting in detectable effluent levels, free amphotericin B (unbound to plasma) was not present in wound effluent despite sufficient concentrations in circulating plasma. In addition, considerable between-patient and within-patient variability was observed in antifungal pharmacokinetic parameters.. These data highlight the need for further studies evaluating wound penetration of commonly used antifungals and the role for therapeutic drug monitoring in providing optimal care for critically ill and injured war fighters.

Topics: Adult; Amphotericin B; Amputation, Surgical; Antifungal Agents; Aspergillosis; Blast Injuries; Burns; Critical Illness; Debridement; Drug Monitoring; Fusariosis; Humans; Male; Mucormycosis; Mycoses; Voriconazole; War-Related Injuries; Wounds, Penetrating

Candida spp. infection in the context of burn wounds leads to invasive disease with a 14-70% mortality rate. Unfortunately, current administrations of AmB, an important therapeutic demonstrating minimal resistance, are only available via potentially cytotoxic IV infusions. In order to circumvent these sequelae, we investigated the efficacy of nanoparticle encapsulated AmB (AmB-np) as a topical therapeutic against Candida spp. (drug release equilibrated solubilized AmB [AmB-sol] included as control). Clinical strains demonstrated equal or enhanced killing efficacy with 72.4-91.1% growth reduction by 4 hours. AmB-nps resulted in statistically significant reduction of fungal biofilm metabolic activity ranging from 80% to 95% viability reduction (P<0.001). Using a murine full-thickness burn model, AmB-np exhibited a quicker efficiency in fungal clearance versus AmB-sol by day three, although wound healing rates were similar. These data support the concept that AmB-np can function as a topical antifungal in the setting of a burn wound.. The control of fungal infections with Candida species remains a challenge in the context of burn wounds. A nanoencapsulated topical amphotericin-B compound was studied in a murine model of full thickness burn injury, showing remarkable efficacy in controlling Candida infection. This may become a viable alternative to the potentially toxic intravenous formulations.

Topics: Administration, Topical; Amphotericin B; Animals; Antifungal Agents; Burns; Candida; Humans; Mice; Nanoparticles; Wounds and Injuries

Topics: Aged, 80 and over; Amphotericin B; Antifungal Agents; Burns; Candida; Fatal Outcome; Female; Humans; Infusions, Intravenous; Injury Severity Score; Microbial Sensitivity Tests; Polyenes

Mucormycosis is usually an invasive mycotic disease caused by fungi in the class mucormycetes. Here we report a case of cutaneous mucormycosis due to Lichtheimia ramosa in a 20-year-old female patient with burn injuries. She was admitted to the hospital with accidental flame burns covering 60 % total burn surface area. After 15 days of admission to hospital, the burn wound showed features of fungal infection. Culture showed white cottony growth belonging to the Mucorales order. Morphological identification confirmed it as L. ramosa. She was managed surgically and medically with the help of amphotericin B. Patient survived due to prompt diagnosis and appropriate medical and surgical treatment. Early diagnosis is critical in prevention of morbidity and mortality associated with the disease. Fungal infection in burn wounds can be difficult to diagnose and manage.

Topics: Amphotericin B; Antifungal Agents; Burns; Debridement; Dermatomycoses; Female; Humans; Microbiological Techniques; Mucorales; Mucormycosis; Treatment Outcome; Young Adult

The prevalence of fungemia due to non-albicans Candida species is increasing currently. However, there is no reported case of fungemia due to Candida famata in a burn unit. This retrospective study was aimed to evaluate the clinical and laboratory characteristics and outcomes of seven burn patients with fungemia due to C. famata. The study included a total of 410 burn patients followed-up during January 2003-January 2006. Six of the patients (85.7%) were males and one was female (14.3%), with a mean age of 22.2 years. Mean total body surface area of the burns was 39.2% (24%-64%), flame being the most frequent cause of the burns (n= 4), followed by hot water (n= 2) and electroshock (n= 1). Six of the cases had central venous catheter and in 5 of these catheter-associated bacteremia had developed before the establishment of candidemia. Pseudomonas aeruginosa (n= 5) was the most frequent cause of bacteremia; Escherichia coil being isolated from a patient with urinary tract infection and methicillin-resistant Staphylococcus aureus from a patient with wound infection. All patients had received treatment with systemic antibiotics prior to the development of the C. famata episode. C. famata was detected from the blood cultures of the patients, however, the wound swabs were negative in terms of C. famata growth. The isolates were defined according to their negative germ tube test and their carbohydrate assimilation profile in API 20 C AUX (BioMerieux, France). Since the environmental cultures yielded negative results for C. famata, the infections were thought to be derived from cross contamination. Once a positive blood culture for C. famata was obtained, the catheter was removed, and treatment with liposomal amphotericin-B was implemented. Presence of a central venous catheter and prior antibiotic therapy seem to be the predisposing factors in the development of fungemia due to C. famata. Thus, when fungemia due to C. famata is established, central venous catheter should be removed and amphotericin-B therapy should be implemented promptly.

Topics: Amphotericin B; Antifungal Agents; Burn Units; Burns; Candida; Candidiasis; Catheterization, Central Venous; Female; Fungemia; Humans; Male; Prevalence; Retrospective Studies; Turkey; Young Adult

Since the first human infection by Saksenaea vasiformis in 1976 another 26 cases have been reported. Here is a report of a new case which involved an Ecuadorian adolescent who suffered serious burns after a car accident. It developed as a localized cutaneous infection which was successfully treated with surgical debridement and amphotericin B. This is the second report of this infection from South America and the third involving a burn patient. The previously reported 27 cases are reviewed.

Topics: Adolescent; Amphotericin B; Burns; Dermatomycoses; Humans; Male; Microscopy, Electron, Scanning; Microscopy, Polarization; Mucorales; Mucormycosis

Due to the generation of burn-associated CD8+ CD11b+ TCR gamma/delta+ type 2 T cells (burn-associated type 2 T cells), the susceptibility of thermally injured mice to infection with C. albicans has been shown to be increased by up to 50-fold when compared with normal mice. Glycyrrhizin (GR), an active component of licorice roots, reduced the susceptibility of thermally injured mice to C. albicans infection to levels observed in normal mice. Thermally injured mice inoculated with CD4+ T cells from GR-treated mice were also resistant to C. albicans infection. The following demonstrated that susceptibility to fungal infection was similar in thermally injured mice and normal mice inoculated with T6S cells (a clone of burn-associated type 2 T cells). This susceptibility of T6S mice (normal mice inoculated with T6S cells) was reversible by (i) administration of GR, (ii) inoculation of CD4+ T cells from GR-treated mice, and (iii) injection of a mixture of MoAbs targeted against type 2 cytokines (IL-4 and IL-10). After stimulation with anti-CD3 MoAb, splenic T cells from thermally injured and T6S mice, treated with GR or inoculated with CD4+ T cells from GR-treated mice, did not have type 2 cytokines in culture supernatants. They were present in splenic T cell cultures from thermally injured and T6S mice that were treated with saline or inoculated with naive T cells. These results suggest that GR, by inducing CD4+ T cells which suppress type 2 cytokines produced by burn-associated type 2 T cells, improves the resistance of thermally injured mice to C. albicans. An anti-type 2 T cell action of the CD4+ T cells derived from GR-treated mice was previously described.

Topics: Amphotericin B; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal; Burns; Candida albicans; Candidiasis; CD4-Positive T-Lymphocytes; Cytokines; Glycyrrhizic Acid; Mice; Mice, Inbred BALB C

Mucormycosis is an opportunistic infection occurring in the severely immunocompromised patient. A case of mucormycosis occurring in a patient who sustained an 85 per cent TBSA burn injury is reported. Diagnosis and management is reported in the paper.

Topics: Administration, Oral; Adult; Amphotericin B; Antifungal Agents; Body Surface Area; Burns; Debridement; Drug Therapy, Combination; Female; Flucytosine; Humans; Immunocompromised Host; Injections, Intravenous; Mucormycosis; Opportunistic Infections; Rhizopus; Wound Infection

Mycethemia was diagnosed in 56 burn patients between 1958 and 1992. The overall incidence was 0.39% and the mortality rate was 39.29%. Candida albicans, constituting for 75% of cases, was most common encountered. The incidence was 0.26% and the mortality 72.73% in years before 1985, while that in the years after 1985 were 0.58% and 17.65%, respectively. The differences are of significance (P < 0.01) predisposing. The clinical characteristics were summed up, and the causes, clinical diagnosis and treatment were studied and discussed.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Burns; Candidiasis; Child; Child, Preschool; Female; Fungemia; Humans; Infant; Male; Middle Aged

Cultured skin grafts are destroyed more easily than split-thickness skin grafts by common burn wound organisms, including gram-negative and gram-positive bacteria and fungi. To increase the survival and engraftment of cultured skin grafts, formulations of antimicrobial agents were tested for cytotoxicity to cultured human keratinocytes and fibroblasts and for activity against common organisms from burn wounds. On the basis of previous studies, a base formulation containing neomycin (40 micrograms/ml), polymyxin B (700 U/ml), and mupirocin (40 micrograms/ml) was prepared, to which ciprofloxacin (20 micrograms/ml) or norfloxacin (20 micrograms/ml) and amphotericin B (0.25 microgram/ml) or nystatin (100 U/ml) were added. Toxicity to cultured human cells was determined by the growth response of cell cultures (n = 6) to each drug combination over 4 days. Activity against clinical isolates (n = 40) of Staphylococcus aureus, Pseudomonas aeruginosa, other gram-negative bacteria, and Candida spp. was determined by the wet disc assay. Analysis of variance testing showed no significant differences in the growth of keratinocytes or fibroblasts under control or experimental conditions. Medium without antimicrobial agents was not effective against any of the 40 microbial strains tested. The base formulation was effective against all bacterial strains tested but against none of the fungi, while all experimental formulations were effective against all microbial strains tested. These findings suggest that neomycin, mupirocin, and polymyxin B may be combined with a quinolone and an antimycotic agent to provide broad antimicrobial activity for a formulation for topical use with cultured skin on burns. However, the formulations described here are strictly experimental and are not recommended for clinical use without further evaluation.

Topics: Administration, Topical; Amphotericin B; Burns; Candida; Cells, Cultured; Ciprofloxacin; Culture Techniques; Drug Therapy, Combination; Enterobacteriaceae; Fibroblasts; Humans; Keratinocytes; Microbial Sensitivity Tests; Norfloxacin; Nystatin; Skin; Skin, Artificial; Staphylococcus aureus

Patients with significant degrees of immunocompromise, such as cancer, AIDS and large burns, who have received significant amounts of antibiotics, may develop infections with yeast organisms. Over a 3-year period, all patients with positive fungal blood cultures and most wounds of patients with large burns considered to be a risk of yeast infection were selected and tested for their susceptibility to five antifungal agents, amphotericin B, ketoconazole, miconazole, diflucan, and 5-fluorocytosine. In all, 244 specimens of yeast were tested: 142 Candida albicans, 52 Candida parapsilosis, 26 Candida tropicalis and 13 Trichosporon beigelii. A limited number of other isolates of Candida (12) were also encountered. All Candida organism were sensitive to amphotericin B. There was wide variation in regard to the susceptibility to the other four agents, with C. albicans and C. tropicalis being largely resistant to miconazole and ketoconazole. T. beigelii was recovered in 13 patients. One-half of these organisms was resistant to amphotericin B. Awareness of variations in species and susceptibility are helpful in the selection of appropriate therapeutic antifungal agents.

Topics: Amphotericin B; Antifungal Agents; Burns; Candida; Drug Resistance, Microbial; Fluconazole; Flucytosine; Humans; Ketoconazole; Miconazole; Microbial Sensitivity Tests; Trichosporon; Yeasts

Yeast isolates from burned patients were analyzed retrospectively for a 7-year period (1984-1991). Topical nystatin was used routinely in the burn wound dressing as antifungal therapy beginning in July 1986. Nystatin used was associated with a significant decrease in overall yeast acquisitions in burn wounds; yeasts were isolated from 15.5% of admitted patients before the use of nystatin vs. 10.5% with use of nystatin (odds ratio [OR] = 0.64; 95% confidence interval [CI], 0.48-0.86). New acquisitions of Candida rugosa in burn wounds increased from 0.36% of admissions during the period July 1984 to June 1986 (before nystatin use) to 5.25% in the period July 1986 to June 1991 (during use of nystatin) (OR = 15.3; 95% CI, 4.1-128). The incidence of fungemia decreased from 3.25% of admissions in the pre-nystatin period to 1.43% in the postnystatin period (OR = 0.43; 95% CI, 0.22-0.87). C. rugosa caused none of 18 fungemias in the former period and 15 of 21 in the latter period (P = .002). Susceptibility testing of recent C. rugosa isolates demonstrated resistance to nystatin and moderate susceptibility to amphotericin B and fluconazole. Topical nystatin use was associated with a decrease in fungemias and acquisition of yeasts in burn wounds but with an increase in colonization and fungemias caused by nystatin-resistant, amphotericin B-susceptible C. rugosa.

Topics: Amphotericin B; Burn Units; Burns; Candida; Candidiasis; Case-Control Studies; Cross Infection; Fluconazole; Flucytosine; Humans; Ketoconazole; Microbial Sensitivity Tests; Nystatin; Retrospective Studies

Topics: Adolescent; Adult; Amphotericin B; Burns; Candida albicans; Candidiasis; Child; Child, Preschool; Female; Humans; Male; Middle Aged; Mycoses

A 3-year-old white-skinned female sustained a 44 per cent deep partial and full skin thickness burn due to petrol. She developed an invasive wound infection due to a fungus later identified as Curvularia species, an organism, usually a saprophyte, not previously reported as a cause of invasive burn wound infection. Treatment with surgical excision and Amphotericin B resulted in cure.

Topics: Amphotericin B; Burns; Child, Preschool; Female; Humans; Mitosporic Fungi; Mycoses; Skin Transplantation

Candida sepsis is a very serious complication in severely burned patients. This mainly affects patients whose immune system is weakened by illness and/or by drugs. Often diagnosis is difficult because candida sepsis occurs after an initial infection, but therapy is always difficult. Good fungicidal drugs are available, but their side effects limit their effectivity. Two severely burned patients who were suffering from a gram-negative sepsis confirmed by clinical and laboratory data developed candida sepsis. Conventional therapy failed, and both patients suffered from renal failure with constantly high candida-latex-antigen titre. By means of the liposomal encapsulated amphotericin B, which has the same fungicidal effect as amphotericin B, but without its limiting side effects, both, patients could be saved. The kidneys functioned as normal again, the laboratory findings were normal when the patients were discharged.

Topics: Adult; Amphotericin B; Burns; Candidiasis; Drug Carriers; Humans; Liposomes; Male; Middle Aged; Opportunistic Infections

Topics: Amphotericin B; Burns; Candidiasis; Fluconazole; Humans; Infant; Male

In this study the effect of selective intestinal decontamination of the digestive tract (SDD) on wound colonization was investigated. Ninety-one patients with at least 25 per cent total burned surface area (TBSA) were included in this study. All patients received oral polymyxin. In 63 patients oral co-trimoxazole and amphotericin B were added to the regimen. The addition of co-trimoxazole decreased the incidence of Enterobacteriaceae wound colonization from 71 per cent to 11 per cent (P less than 0.005). Colonization with Proteus was eliminated in patients treated with co-trimoxazole, compared with an incidence of 36 per cent in the group treated with polymyxin alone (P less than 0.001). The addition of amphotericin B decreased yeast colonization of the burn wound from 39 per cent to 10 per cent (P less than 0.005). A close relation was observed between burn wound colonization and colonization of the gastrointestinal tract. No resistant bacterial strains emerged during the period of study. These results suggest that SDD is an effective method for prevention of wound colonization. Further controlled studies are needed to establish the role of SDD in preventing burn wound colonization and wound sepsis.

Topics: Adult; Amphotericin B; Burns; Digestive System; Drug Therapy, Combination; Humans; Middle Aged; Polymyxin B; Proteus; Proteus Infections; Pseudomonas; Pseudomonas Infections; Retrospective Studies; Staphylococcal Infections; Staphylococcus aureus; Trimethoprim, Sulfamethoxazole Drug Combination; Wound Infection

Candidiasis causes serious problems for compromised hosts. Effective treatments for Candida albicans infections are few. To see if immunoglobulin (Ig) therapy could be beneficial, burn-immunocompromised mice were treated intravenously with 2.5 mg of five different IgG preparations 48 h postburn and post-C. albicans challenge. Despite up to fourfold differences in titer (1:1,600 to 1:6,400) to C. albicans, all preparations improved 10-day survival about 30% (P less than 0.0001). Treatment with a low dose of amphotericin B (AmB; 0.09 mg/kg of body weight) intravenously 24 and 48 h after burn and challenge improved survival 9 to 45% (P less than 0.0001). Treatment with a low dose of AmB plus IgG showed the same results as treatment with AmB alone and better results than treatment with IgG alone. Quantitative renal cultures from burned mice treated with AmB plus one IgG preparation, Sandoglobulin, showed that C. albicans counts decreased in sham-treated mice from 7.21 +/- 0.15 log10 CFU/g (mean +/- standard error of the mean) to 5.31 +/- 0.34, which was significantly less than counts with AmB (6.11 +/- 0.35) or Sandoglobulin (6.39 +/- 0.18) treatment alone. We conclude that (i) by using decreases in mortality and in renal fungal load as end points, treatment with IgG preparations alone or with a low dose of AmB alone protected burn-immunocompromised mice from candidiasis; (ii) though AmB plus one IgG preparation significantly decreased renal fungal load, the combination did not significantly decrease mortality beyond that found with AmB alone; and (iii) survival data did not correlate with IgG titers to C. albicans.

Topics: Amphotericin B; Animals; Burns; Candida albicans; Candidiasis; Female; Immunoglobulins, Intravenous; Kidney; Mice

An oral prophylactic antibiotic regimen aiming at suppression of the gram-negative rods and yeasts of the bowel flora was utilised in 48 severely burned patients to prevent burn wound colonisation. Only 17% of the patients had an actual or potential infection. Only one Pseudomonas infection occurred. The effect of this selective gastro-intestinal decontamination is discussed.

Topics: Adult; Amphotericin B; Anti-Infective Agents; Burns; Digestive System; Drug Combinations; Drug Therapy, Combination; Humans; Polymyxins; Sulfamethoxazole; Tobramycin; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Wound Infection

Immunosuppressed burned patients receiving antibiotics for suppression of bacterial infection are ideal hosts for opportunistic fungi. Massive excision of burns with autograft and homograft coverage has radically changed the course of disease. Three hundred ninety-three patients were admitted to the Shriners Burns Institute, of whom 125 patients had fungus cultured during their hospitalization and 42 patients subsequently developed involvement of three or more organs. Twenty-one of the 42 patients developed Candida septicemia requiring amphotericin B or flucytosine therapy. The mean third-degree burn in patients with Candida septicemia was 65% total body surface area compared to three-organ involvement/no clinical sepsis at 38% mean third-degree burn. Patients developing candidemia did so during the first week postburn and 7 days after excision therapy. It is hypothesized that massive burns with immunosuppression are further suppressed by repeated surgical intervention, anesthesia, and perioperative use of broad-spectrum antibiotics, further predisposing these patients to early development of Candida septicemia. With early recognition of burn wound invasion by routine biopsies, wound swabs, and early amphotericin therapy, the mortality has been reduced to 14% compared to 60-90% reported in other series.

Topics: Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Burns; Candidiasis; Child; Flucytosine; Humans; Immune Tolerance; Opportunistic Infections; Retrospective Studies; Wound Infection

A retrospective analysis of Candida sepsis was carried out in 1722 burn patients admitted to this center from 1975 to 1984. Cultures were positive for Candida in 233 (13.5%) of these patients during their hospitalization. Candidemia was present in 70 (4.0%) of the 1722 patients. Of the 70 patients with candidemia, 38 (54%) died. However, only 11 patients (15.7%) died of Candida sepsis or mixed Candida and bacterial sepsis (less than 1% of the total patient population). The remaining 27 patients who had candidemia died of bacterial septicemia or organ system failure. The low incidence of Candida and the low incidence of mortality due to Candida was attributed to a comprehensive program of prevention, detection, and treatment. Early initiation of treatment with amphotericin B was an important aspect of the program.

Topics: Adult; Aged; Amphotericin B; Burn Units; Burns; Candidiasis; Humans; Medical Records; Middle Aged; Retrospective Studies

Burn-wound patients often require potentially ototoxic doses of aminoglycoside drugs in the treatment of gram-negative sepsis. Cochlear hearing impairment may be an unfortunate consequence of this medical therapy. We evaluated auditory sensitivity with the auditory brainstem response (ABR) in a group of 32 children with acute, severe thermal burns ranging in age from 18 months to 17 years. The mean percent of total body surface area burns was 64%. None of the subjects had a known history of hearing deficits or aminoglycoside therapy, and all yielded a normal baseline ABR upon hospital admission. Eight of the subjects (22%) showed either an abnormal ABR, or no response, at 40 dB prior to hospital discharge. The medical treatment for this group of subjects (gentamicin, amikacin, vancomycin, amphotericin B) was compared to that of a second subgroup of 7 subjects without auditory deficit but with a statistically comparable percentage of burns. The mean dosage of vancomycin was higher for the auditory impairment group than for the unimpaired group. Prediction of ototoxicity in the acute burned patient is extremely difficult as there are numerous factors that may influence the risk of cochlear damage. We conclude, however, that the ABR can be applied in early detection of auditory deficit. Follow-up audiometric assessment is advisable since auditory deficits in this population may be delayed or progressive after discontinuance of drug therapy.

Topics: Adolescent; Amikacin; Aminoglycosides; Amphotericin B; Anti-Bacterial Agents; Audiometry, Evoked Response; Brain Stem; Burns; Child; Child, Preschool; Female; Gentamicins; Hearing Disorders; Humans; Infant; Male; Vancomycin

Three patients with Candida parapsilosis septicemia, secondary to large burns, are reported. All patients sustained large burns with inhalation injuries and were treated with various topical antibiotics. All had sepsis with various bacterial organisms and had received treatment with systemic antibiotics prior to the development of the Candida episode. Once a positive blood culture for Candida parapsilosis was obtained, treatment was carried out with amphotericin-B. Sensitivity data indicated that this was the appropriate systemic agent. All patients recovered uneventfully after a 10-day course of amphotericin-B therapy.

Topics: Amphotericin B; Burns; Candida; Candidiasis; Child; Female; Humans; Male; Sepsis

Candida organisms were cultured from 452 of 1,513 hospitalized burned patients during a 6-year study period. Of the 172 patients with colonization of the eschar by this fungus, only 20.7% subsequently developed invasive candidal sepsis. The mortality of untreated Candida burn wound infection was 100%, and with aggressive medical-surgical therapy, 91.6%. Candidemia was present in 52 patients and 76.9% of these died. Candida infection was seen as a preterminal phenomenon, coincident with a generalized collapse of patients' defensive and homeostatic mechanisms. For this reason, mortality was high and the infection rarely responded to treatment. Control of this lethal complication rests with prevention by the judicious use of intravenous broad-spectrum antibiotics and expeditious closure of the burn wound.

Topics: Adult; Amphotericin B; Burns; Candidiasis; Humans; Risk; Wound Infection

Six of 92 patients with invasive mycotic infection of the burn wound survived. These patients demonstrate the value of prompt diagnosis and expdeitious debridement of the infected tissue in successfully managing this dangerous infection.

Topics: Adolescent; Adult; Amphotericin B; Burns; Candidiasis; Child; Child, Preschool; Debridement; Fungi; Humans; Mycoses

Septic thrombosis of central veins is rarely diagnosed during life and nearly always proves fatal. We have recently successfully treated a patient with a 75% body surface burn in whom septic thrombosis of the inferior vena cava developed associated with high-grade candidemia as a complication of parenteral nutrition. Signs of venous thrombosis and candidemia persisted after catheter removal. Prompt and intensive therapy with amphotericin B, monitored by fungicidal assays of serum, resulted in cure. Generous hydration and directed supplementation of sodium bicarbonate permitted us to administer a large total dose of amphotericin over a relatively brief period of time with no nephrototoxic effect whatsoever. Septic central venous thrombosis mandates a pharmacologic approach to therapy similar to that used for infective endocarditis, with the addition of anticoagulation. Should sepsis prove refractory to this program of it pulmonary embolization occurs, operative intervention is indicated despite the high risks involved.

Topics: Adult; Amphotericin B; Burns; Candidiasis; Femoral Vein; Humans; Male; Parenteral Nutrition; Sulfadiazine; Thrombosis; Vena Cava, Inferior

Systemic candidiasis has emerged as a major cause of death in burn patients. An increase both in the incidence of systemic candidiasis and its increase as a cause of death has been observed. Treatment with systemic amphotericin-B prior to 1971 at our institution was rarely successful. This was felt to be in part due to lack of sufficiently early recognition of the infection and to delay in the initiation of appropriate systemic therapy. From 1971 to 1975, fifteen patients have been treated with systemic amphotericin-B with one death. There have been no fatalities from candidiasis since 1972. No serious complications attributed to the use of amphotericin-B were observed. Prompt initiation of therapy with intravenous amphotericin-B is advised for burn patients in whom systemic candidiasis is present.

Topics: Adolescent; Amphotericin B; Burns; Candidiasis; Child; Child, Preschool; Drug Evaluation; Humans; Infant

As a result of progress in the modern treatment of burns, systemic candidosis (CA), in the sense of "surviving mycoses", has become increasingly frequent. The site of entry is not usually the wound, but the intestinal tract, which becomes overgrown by the yeasts as a consequence of the requisite therapy with antibacterial antibiotics in high dosage. Passage of the organism into the circulation occurs by persorption. In view of the bad prognosis of systemic CA, it is essential to recognize its incipient development and counteract by timely prophylactic measures, primarily sterilization of the intestine. In a developed case os systemic CA, the chances of cure improve with rapidity of recognition of the infection and initiation of treatment. Early diagnosis of the infection is achieved by the regular quantitative determination of the organism in the faeces, in urine and blood, as well as in swabs of mucous membranes and the wounds and, above all, by serological examination (movement of titre). The practical problems of the disease are demonstrated and discussed on the basis of 2 cases treated in this department.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Burns; Candidiasis; Flucytosine; Humans; Injections, Intravenous; Male; Middle Aged

Since secondary deep mycoses are frequently seen in internal medicine nowadays, increasing interest has been focused on antimycotic therapy. This report deals with the limited available range of antimycotic substances which can be administered systemically. Since severe adverse effects are often observed with Amphotericin-B, the most effective antifungal agent, the advent of three new systemic antifungal drugs (Clotrimazole, Miconazole, 5-Fluorocytosine) has proven to be a real advance in our therapeutic approach to deep mycoses. To avoid unwanted side-effects, combined therapy with low doses of Amphotericin-B and another antimycotic agent promises to become increasingly important.

Topics: Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Burns; Cardiac Surgical Procedures; Catheterization; Clotrimazole; Flucytosine; Humans; Immunologic Deficiency Syndromes; Immunosuppression Therapy; Miconazole; Mycoses

Topics: Adult; Amphotericin B; Burns; Candida albicans; Candidiasis; Humans; Male; Sepsis

Methods of speciating Candida isolates from clinical specimens are described and the necessity of speciation is emphasized. Differences in susceptibility of C. albicans and C. tropicalis to amphotericin B were observed and the implications of this in relation to treatment with amphotericin B and the development of resistance are discussed.

Topics: Amphotericin B; Burns; Candida; Candida albicans; Culture Media; Drug Resistance, Microbial; Humans; Methods; Microbial Sensitivity Tests

Topics: Amphotericin B; Burns; Dermatomycoses; Humans; Male; Middle Aged; Nystatin

Topics: Adolescent; Amphotericin B; Anti-Bacterial Agents; Burns; Candida; Candidiasis; Catheterization; Child, Preschool; Humans; Sepsis; Wound Infection

Topics: Adolescent; Adult; Amphotericin B; Amputation, Surgical; Aspergillosis; Burns; Child; Child, Preschool; Female; Fungi; Humans; Male; Military Medicine; Mycoses; Retrospective Studies; Wound Infection

Topics: Accidents, Traffic; Adult; Amphotericin B; Antifungal Agents; Burns; Candida; Candidiasis; Chloramphenicol; Gentamicins; Humans; Male; Oxacillin; Penicillins; Pseudomonas Infections; Sepsis; Skin Transplantation; Staphylococcal Infections; Sulfonamides; Wound Infection

Topics: Amphotericin B; Burns; Candidiasis; Child, Preschool; Humans; Male; Sepsis

Topics: Amphotericin B; Anti-Infective Agents, Local; Burns; Candidiasis, Oral; Denture, Complete; Humans; Nystatin; Oral Health

Topics: Adolescent; Amphotericin B; Anti-Bacterial Agents; Burns; Candidiasis; Child; Child, Preschool; Drug Resistance, Microbial; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Sepsis; Wound Infection; Wounds, Gunshot

Topics: Amphotericin B; Aspergillosis; Burns; Child, Preschool; Cortisone; Female; Humans; Male; Wound Infection

Topics: Acute Kidney Injury; Amphotericin B; Bronchopneumonia; Burns; Candida; Candidiasis; Child; Drug Therapy; Erythroblastosis, Fetal; Female; Geriatrics; Heart Failure; Humans; Hyperbilirubinemia; Infant; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature, Diseases; Postgastrectomy Syndromes; Renal Insufficiency; Sepsis; Toxicology; Uterine Cervical Neoplasms; Wounds, Gunshot