Study of systemic fungal infections in autopsy material

A retrospective study of 2526 autopsy cases was done in order to find out the pattern of systemic fungal infections. The autopsy records were reviewed for case histories, gross and histological findings. The histological sections from cases showing evidence of fungalo infections were reviewed. The fungal infections were found in 28 cases. Of these 11 (93.29 percent) were aspergillosis, 8 (28.27 percent) were mucormyosis, 6 (21.43 percent) were monilial infections and 3 (10.71 percent) were monilial infections and 3 (10.71 percent) were cryptococcosis. The incidence of systemic fungal infection was 1.11 percent. The most common type of fungal infection was aspergillosis. The maximum number of fungal infection was seen in the respiratory system. The fungal infections presented as opportunistic infections in all but one case. The metabolic disturbance was the most frequent predisposing condition for systemic fungal infections.     

Efficacy of fluconazole in the treatment of systemic fungal infections

The efficacy of fluconazole in the treatment of systemic fungal infections was evaluated in an open non-comparative trial. A total of 48 patients with proven or suspected fungal infections were enrolled in 40 of whom efficacy was evaluable.Candida albicans accounted for 90 % of the infections.Candida parapsilosis, Candida glabrata, Histoplasma capsulatum andAspergillus fumigatus caused the infection in one case each. Fluconazole was administered at a dosage of 200–400 mg daily for a mean duration of 15 days. Fluconazole treatment was successful in 53 % of the patients. In patients with proven or probableCandida albicans infections a clinical and mycological response was achieved in 62 % and 65 %, respectively. In 11 patients elevation of liver enzymes was considered to be possibly related to fluconazole treatment; modification of treatment was not necessary in any case. Fluconazole was found to be a well tolerated and effective agent for the treatment of systemicCandida albicans infections.     

Risk factors for systemic fungal infections in liver transplant recipients

The risk factors for systemic fungal infections were analysed retrospectively in 186 orthotopic liver transplant procedures performed in 152 patients between June 1985 and January 1993. The total incidence of systemic fungal infections was 16.5 % (25/152). The incidence of disseminated candidiasis, aspergillosis, and combined candidiasis and aspergillosis was 6.5 % (n=10), 7.2 % (n=11) and 2.6 % (n=4), respectively. Mortality associated with systemic fungal infections was 80 % (20 of 25 patients). There were ten cases of disseminated candidiasis, with 4 patients surviving, and 11 cases of invasive aspergillosis, with 1 patient surviving. All patients with combined systemic fungal infection died. To identify perioperative risk factors, 39 variables were used to compare patients with systemic fungal infections versus those without fungal infections. Fourteen variables were significantly associated with systemic fungal infections by univariate analysis. A consecutive logistic regression analysis revealed that the amount of fresh frozen plasma transfused due to poor initial function of the allograft and acute renal failure requiring hemofiltration were independently significant risk factors for systemic fungal infections. There was no statistical correlation between systemic fungal infections and the underlying liver disease, previous long-term corticosteroids and the postoperative immunosuppressive therapy. Risk factors identified in this study should be considered in the postoperative care of the individual liver transplant recipient. In our study a poor initial function of the hepatic allograft substantially increased the risk of systemic fungal infection.     

Treatment of systemic fungal infections: Recent progress and current problems

Systemic mycoses continue to emerge as life-threatening infections. Considerable progress in treating these infections is being achieved through better application of established available antifungal agents (amphotericin B, flucytosine, miconazole and ketoconazole), and through development of promising investigational agents (fluconazole, itraconazole). Systemic fungal infections, however, continue to present major problems, including clinical resistance, microbiological resistance, emergence of new pathogens, and involvement of more immunocompromised patients. The purpose of this paper, therefore, is to review the recent progress and current problems in treatment of systemic fungal infections.     

An autopsy study of systemic fungal infections in patients with hematologic malignancies

The aim of this study was to determine the incidence of fungal infections detected on autopsy in a group of 40 patients with hematologic malignancies treated with intensive chemotherapy or bone marrow transplantation, and to evaluate the risk factors for fungal infections. A control group included 38 patients with nonhematologic diseases and without granulocytopenia but with at least one of the known risk factors for fungal infections. Standard histopathological and microbiological methods were used. A higher incidence of invasive fungal infections was found in patients with hematologic malignancies as compared to the control group (p<0.01). The predominant causes of fungal infections wereCandida albicans andAspergillus spp. The incidence of fungal infections caused byAspergillus was higher (p<0.05) in patients with hematologic malignancies than in the control group. The independent risk factors for fungal infections were fungal colonization, number of antibiotics and duration of antibiotic therapy, duration of fever and skin rash. A higher proportion of fungal infections was diagnosed on autopsy than during the patients' life (p<0.01).     

Comparison of non-culture-based methods for detection of systemic fungal infections, with an emphasis on invasive Candida infections

The accepted limitations associated with classic culture techniques for the diagnosis of invasive fungal infections have lead to the emergence of many non-culture-based methods. With superior sensitivities and quicker turnaround times, non-culture-based methods may aid the diagnosis of invasive fungal infections. In this review of the diagnostic service, we assessed the performances of two antigen detection techniques (enzyme-linked immunosorbent assay [ELISA] and latex agglutination) with a molecular method for the detection of invasive Candida infection and invasive aspergillosis. The specificities for all three assays were high (> or = 97%), although the Candida PCR method had enhanced sensitivity over both ELISA and latex agglutination with values of 95%, 75%, and 25%, respectively. However, calculating significant sensitivity values for the Aspergillus detection methods was not feasible due to a low number of proven/probable cases. Despite enhanced sensitivity, the PCR method failed to detect nucleic acid in a probable case of invasive Candida infection that was detected by ELISA. In conclusion, both PCR and ELISA techniques should be used in unison to aid the detection of invasive fungal infections.     

Microbiology of animal bite wound infections

The microbiology of animal bite wound infections in humans is often polymicrobial, with a broad mixture of aerobic and anaerobic microorganisms. Bacteria recovered from infected bite wounds are most often reflective of the oral flora of the biting animal, which can also be influenced by the microbiome of their ingested prey and other foods. Bacteria may also originate from the victim's own skin or the physical environment at the time of injury. Our review has focused on bite wound infections in humans from dogs, cats, and a variety of other animals such as monkeys, bears, pigs, ferrets, horses, sheep, Tasmanian devils, snakes, Komodo dragons, monitor lizards, iguanas, alligators/crocodiles, rats, guinea pigs, hamsters, prairie dogs, swans, and sharks. The medical literature in this area has been made up mostly of small case series or case reports. Very few studies have been systematic and are often limited to dog or cat bite injuries. Limitations of studies include a lack of established or inconsistent criteria for an infected wound and a failure to utilize optimal techniques in pathogen isolation, especially for anaerobic organisms. There is also a lack of an understanding of the pathogenic significance of all cultured organisms. Gathering information and conducting research in a more systematic and methodical fashion through an organized research network, including zoos, veterinary practices, and rural clinics and hospitals, are needed to better define the microbiology of animal bite wound infections in humans.     

Efficacy and safety of fluconazole in the treatment of systemic fungal infections in pediatric patients

In a non-comparative multicentre trial 51 patients aged 24 days to 17 years received treatment with intravenous or oral fluconazole for suspected systemic fungal infections. Twenty-seven patients had confirmed infections, 26 being confirmed mycologically and 1 histologically. All isolates wereCandida species. Of the 43 clinically assessed patients, 30 were considered cured, 7 improved and 6 experienced failure of therapy. Of 27 patients with confirmed fungal infections, 25 were assessed mycologically and all but one were considered cured. Of the six patients experiencing clinical failure, two had a confirmed infection and only one of these experienced mycological failure. This patient had a primary diagnosis of candidemia with persistence ofCandida albicans andCandida parapsilosis. All 51 patients were evaluable for safety. No treatment-related adverse events required termination of treatment. Treatment-related side effects (diarrhea, vomiting, deafness) were reported by three of 51 patients, three patients had laboratory test abnormalities possibly related to fluconazole treatment, including elevation of liver enzyme levels and of the eosinophil count. Results of this study confirm the efficacy and safety of fluconazole in the treatment of pediatric patients with severe fungal infection.K.W. Brammer, Pfizer Central Research, Sandwich, UK; R. Dopfer, University Children's Hospital, Tübingen, Germany; H.J. Schmitt, University Children's Hospital, Mainz, Germany; H. Gadner, A. Zoubek, St. Anna Kinderspital, Vienna, Austria; A. Robert, H. Rubie, Hôpital Purpan, Toulouse, France; H. Holzel, L.A. Bain, D.J. Macrae, The Hospitals for Sick Children, London, UK; P. Reinert, Centre Hospitalier Intercommunal, Creteil, France; J.P. Vannier, Hôpital Charles Nicolle, Rouen, France; C. Margueritte, Hôpital Saint Charles, Montpellier, France; J.B. Gouyon, Hôpital d'Enfants, Dijon, France; G. Paolucci, Policlinico Sant'Orsola, Bologna, Italy; N. Principi, Ospedale Luigi Sacco, Milan, Italy.     

Vaccines against fungal infections

The state-of-the-art reached in developing protective immunity against fungal infections through vaccination makes a survey of methodologies and results timely. This review describes experimental vaccinations against dermatophytes, pathogenic yeasts, and dimorphic fungi with special attention to the anti-Coccidioides immitis vaccine, which has reached clinical trials, and to the anti-Candida albicans and anti-Histoplasma capsulatum ribosomal vaccines. Also covered are vaccination experiments in compromised hosts aimed at eliciting acquired resistance to opportunistic fungal infections which constitute risk factors for these hosts. Immunization procedures include live, killed, and attenuated organisms, as well as different subcellular fractions such as cytoplasmic extracts, fungal culture filtrates, cell walls, or ribosomal fractions. A variety of experimental animal models and isolated human trials constitute the subjects in these studies. Acquired immunity has been evaluated through assessment of resistance to infection and determination of specific immune responses. It has been demonstrated that fungal vaccines do elicit both humoral and cell-mediated immunity in the immunized host. For some vaccines (e.g., H. capsulatum), a correlation between the induced immunity and protection was observed and the immunity could be adoptively transferred. In view of the potential of vaccines against fungal infections, a perspective on their applicability, significance, and value for human use is discussed.     

Dimorphic fungal osteoarticular infections

The objective of this investigation was to review the clinical manifestations, management, and outcome of osteoarticular infections caused by dimorphic fungi. We exhaustively reviewed reports of bone and joint infections caused by dimorphic fungi published between 1970 and 2012. Underlying conditions, microbiological features, histological characteristics, clinical manifestations, antifungal therapy, and outcome were analyzed in 222 evaluable cases. Among 222 proven cases (median age 41 years [interquartile range (IQR) 26–57]), 73 % had no predisposing condition. Histopathology performed in 128 (57 %) cases and culture in 170 confirmed diagnosis in 63 % and 98 % of the cases, respectively. Diagnosis was obtained from an extra-osteoarticular site in 16 cases. The median diagnostic time was 175 days (IQR 60–365). Sporothrix schenckii was the most frequent pathogen (n?=?84), followed by Coccidioides immitis (n?=?47), Blastomyces dermatitidis (n?=?44), Histoplasma capsulatum (n?=?18), Paracoccidioides brasiliensis (n?=?16), and Penicillium marneffei (n?=?13). Arthritis occurred in 87 (58 %) cases and osteomyelitis in 64 (42 %), including 19 vertebral osteomyelitis. Dissemination was reported in 123 (55 %) cases. Systemic antifungal agents were used in 216 (97 %) patients and in combination with surgery in 129 (60 %). Following the Infectious Diseases Society of America (IDSA) guidelines, a successful initial medical strategy was observed in 97/116 (84 %) evaluable cases. The overall mortality was 6 %, and was highest for P. marneffei (38.5 %). This study demonstrates that dimorphic osteoarticular infections have distinctive clinical presentations, occur predominantly in apparently immunocompetent patients, develop often during disseminated disease, and may require surgical intervention.     

Medical history and progress in infectious diseases, especially systemic fungal infections in Japan.

This paper reports on medical history from the end of the Edo period to the present and development of studies on infectious diseases, especially medical mycology including systemic fungal diseases. With the inflow of Dutch studies at the end of the Edo period and the adoption of European, mainly German, medicine in the Meiji Restoration, Japanese medical studies gradually developed. However, evolution in the medical field as well as other scientific fields was prevented during the 2nd World War. After the War, there was marked progress in scientific fields and medical research made strong advances. In the past 20 years, basic fungal studies and clinical fungal diseases, especially clinical analysis, clinical diagnosis and treatment of systemic fungal infections have progressed. The level in this field is now equivalent to or higher than that in European countries. Further development is necessary, however, to relieve patients suffering from systemic fungal infections. Members of the Japanese Association of Medical Mycology must be leaders among international medical mycologists.     

Controversial points in the treatment of patients with haematologic malignancies complicated with systemic fungal infections]

Prophylaxis and treatments for fungal infections differ with the infection type. However, the eradication of risk factors for outbreak of fungal infections, and the usage of appropriate antifungal agents are universally important to prevent these infections. For infections due to intrinsic fungi such as Candida spp., risk factors such as changes in normal flora by aggressive and prolonged broad-spectrum antibiotics therapy should not be permitted to emerge. On the other hand, infections due to extrinsic fungi such as Cryptococcus neoformans and Aspergillus spp. can be prevented by eradication of the colonized fungi using antifungal prophylaxis and the use of air-cleaning machines to combat colonization of patients and contamination in the hospital environment. The most important risk factor of fungal infections in patients suffering from haematologic malignancies is leukopenia. In these cases, it is crucial to reduce the duration of neutropenia and enhance the anti-microbial function using granulocyte-macrophage-colony stimulating factor. When a patient is complicated with a fungal infection, appropriate antifungal agents must be used at appropriate dosages for the appropriate period. However, there are still very few satisfactory antifungals with minimal adverse effects and good potential efficacy for systemic fungal infections. Therefore, combination therapy with amphotericin B and azole antifungals is necessary for patients with severe fungal infections. In patients complicated with fungal infections, the underlying disease is often resistant to aggressive antifungal therapy. Control of this underlying disease is thus a most important therapeutic factor.     

Systemic fungal infections in neonates

Advances in neonatal management have led to considerable improvement in newborn survival. However, early (<72 hours) and late (>72 hours) onset systemic infections, both bacterial and fungal, remain a devastating complication and an important cause of morbidity and mortality in these babies. Most neonatal fungal infections are due to Candida species, particularly Candida albicans. The sources of candidiasis in NICU are often endogenous following colonization of the babies with fungi. About 10% of these babies get colonized in first week of life and up to 64% babies get colonized by 4 weeks of hospital stay. Disseminated candidiasis presents like bacterial sepsis and can involve multiple organs such as the kidneys, brain, eye, liver, spleen, bone, joints, meninges and heart. Confirming the diagnosis by laboratory tests is difficult and a high index of suspicion is required. The diagnosis of fungemia can be made definitely only by recovering the organism from blood or other sterile bodily fluid. Amphotericin B continues to be the mainstay of therapy for systemic fungal infections but its use is limited by the risks of nephrotoxicity and hypokalemia. Newer formulations of amphotericin B, namely the liposomal and the lipid complex forms, have recently become available and have been reported to have lesser toxicity. More recently Indian liposomal Amphotericin B derived from neutral lipids (L-Amp-LRC-1) has shown good response with less toxicity. A clinical trial with this preparation has shown to be safe and efficacious in neonatal fungal infections. Compared to other liposomal preparations, L-Amp-LRC-1 is effective at lower dose and is less expensive drug for the treatment of neonatal candidiasis.     

Serious fungal infections in Peru

Epidemiological data about mycotic diseases are limited in Peru and estimation of the fungal burden has not been previously attempted. Data were obtained from the Peruvian National Institute of Statistics and Informatics, UNAIDS and from the Ministry of Health’s publications. We also searched the bibliography for Peruvian data on mycotic diseases, asthma, COPD, cancer and transplants. Incidence or prevalence for each fungal disease were estimated in specific populations at risk. The Peruvian population for 2015 was 31,151,543. In 2014, the estimated number of HIV/AIDS and pulmonary tuberculosis cases was 88,625, 38,581 of them not on ART, and 22,027, respectively. A total of 581,174 cases of fungal diseases were estimated, representing approximately 1.9% of the Peruvian population. This figure includes 498,606, 17,361 and 4,431 vulvovaginal, oral and esophageal candidiasis, respectively, 1,557 candidemia cases, 3,593 CPA, 1,621 invasive aspergillosis, 22,453 allergic bronchopulmonary aspergilllosis, 29,638 severe asthma with fungal sensitization, and 1,447 Pneumocystis pneumonia. This first attempt to assess the fungal burden in Peru needs to be refined. We believe the figure obtained is an underestimation, because of under diagnosis, non-mandatory reporting and lack of a surveillance system and of good data about the size of populations at risk.