Fungal prophylaxis in neonates: a review article.

Fungemia is a serious problem within neonatal intensive care units around the world. Premature infants are at high risk for this complication, which is often fatal. Prophylaxis for invasive fungal infection has been practiced worldwide in different settings and with various patient groups. Both oral and intravenous drugs have been used with some success. In the population of preterm infants, oral nystatin, intravenous fluconazole, and intravenous amphotericin B have all been cited as possible drugs for prophylactic use. Intravenous fluconazole has emerged as the best choice for chemoprophylaxis in premature infants.

[Current indications for voriconazole in onco-hematological patients]. / Infección micótica plantar e interdigital en pacientes con onicomicosis.

Invasive fungal infections (IFI) are the main cause of infectious death in cancer patients, especially in hematological malignancies and hematopoietic transplant recipients. Current epidemiology is characterized by a predominance of IFI caused by molds, mainly aspergillosis, along with a emergence of hard-to-treat fungi such are Zygomicetes, Fusarium and Scedosporium. Voriconazole is a broad spectrum antifungal agent with oral and intravenous formulations, approved by the EMEA for the treatment of invasive aspergillosis, candidemia in non-neutropenic patients, IFI caused by fluconazole-resistant species of Candida as well as Scedosporium and Fusarium infections. However, its use in clinical practice is broader, as empirical antifungal treatment and as secondary prophylaxis. It should be kept in mind the possibility of breakthrough IFI, particularly zygomycosis, in patients treated with voriconazole for long periods.

[Zygomycosis after hematogeneic stem cell transplantation--a current problem?]. / Zygomykosen nach Blutstammzelltransplantation--ein aktuelles Problem?

Zygomycoses are rare but often lethal mold infections predominantly affecting immunocompromised patients. Over the last years, several tertiary-care cancer centers reported an increase in the incidence of zygomycete infections in allogeneic blood stem cell transplant recipients. These observations are based on a small number of patients and should be considered in the context of a decades-long increase of mold infection rates. Diagnostic obstacles, including the difficult discrimination from the tenfold more frequent aspergilloses, may confound the reported incidences of zygomycete infections. These may be due to changes in frequency, severity and management of graft-versus-host disease promoting filamentous fungal infections, including zygomycoses. Hospitals applying long-term voriconazole prophylaxis in high-risk patients report a significant decrease in aspergillosis rates since the drug became available in 2001. The observation of increased frequencies of zygomycete infections during this period of time is not based on prospective evaluations. Therefore, the causes of these findings remain a matter of debate. Current multicenter trials on antifungal prophylaxis in high-risk patients promise to generate reliable data on the protective effect of antifungals active against molds, and the incidence of zygomycete infections in a controlled setting.

Invasive zygomycosis in hematopoietic stem cell transplant recipients receiving voriconazole prophylaxis.

We report 4 cases of invasive zygomycosis in hematopoietic stem cell transplant recipients, all occurring after May 2003, when voriconazole began to be used as antifungal prophylaxis. No cases of zygomycosis had been detected in this population in the 3 years prior to May 2003. All 4 patients were receiving immunosuppressive therapy for presumed graft-versus-host disease. Profoundly immunosuppressed patients receiving voriconazole prophylaxis remain at risk for less-common pathogens that are intrinsically resistant to this agent.

[Specific antifungal treatment in patients with neutropenia and fever: current status of the fungicidal activity of caspofungin]. / Tratamiento antifungico especifico en pacientes con neutropenia y fiebre: estado actual de la actividad fungicida de la caspofungina.

Candidiasis and aspergillosis are the most frequent mycosis in patients with febrile neutropenia. Other infections caused by emergent yeast-like organisms, such as hyalohyphomycosis, Fusarium disease and scedosporiosis, phaeohyphomycosis (caused by pigmented mycelia) and zygomycosis are becoming more frequent. The management of documented fungal infections should consider several aspects, such as clinical patterns, the patient's clinical condition, the species involved, in vitro sensitivity and the suitable treatment duration, apart from the selection of the drug and suggested regimen. Though new drugs have been developed, the therapeutic armory is still very limited. Combined treatments are promising, but their use is not yet standardized.

Zygomycosis in solid organ transplant recipients: a prospective, matched case-control study to assess risks for disease and outcome.

BACKGROUND: Clinical characteristics, risks, and outcomes in solid organ transplant (SOT) recipients with zygomycosis in the era of modern immunosuppressive and newer antifungal agent use have not been defined. METHODS: In a matched case-controlled study, SOT recipients with zygomycosis were prospectively studied. The primary outcome measure was success (complete or partial response) at 90 days. RESULTS: Renal failure (odds ratio [OR], 3.17; P = .010), diabetes mellitus (OR, 8.11; P < .001), and prior voriconazole and/or caspofungin use (OR, 4.41; P = .033) were associated with a higher risk of zygomycosis, whereas tacrolimus (OR, 0.23; P = .002) was associated with a lower risk of zygomycosis. Liver transplant recipients were more likely to have disseminated disease (OR, 5.48; P = .021) and developed zygomycosis earlier after transplantation than did other SOT recipients (median, 0.8 vs 5.7 months; P < .001). Overall the treatment success rate was 60%. Renal failure (OR, 11.3; P = .023) and disseminated disease (OR, 14.6; P = .027) were independently predictive of treatment failure, whereas surgical resection was associated with treatment success (OR, 33.3; P = .003). The success rate with liposomal amphotericin B was 4-fold higher even when controlling for the aforementioned variables. CONCLUSIONS: The risks identified for zygomycosis and for disseminated disease, including those that were previously unrecognized, have implications for further elucidating the biologic basis and for optimizing outcomes in SOT recipients with zygomycosis.

Zygomycosis--current epidemiological aspects.

Zygomycoses are very rare invasive fungal infections (IFI). They primarily occur in the immunocompromised patients and are associated with a high mortality. During the last years, a rising incidence of zygomycosis in patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT) has been reported, which is probably a part of the trend in the incidence of mould infections that has been going on for decades. Difficulty in diagnosis, especially concerning the differentiation of zygomycosis from the far more common aspergillosis, additionally hampers a reliable assessment of the incidence of zygomycosis. In patients undergoing allogeneic HSCT, changes in the frequency, severity and management of Graft-versus-Host-Disease (GvHD) also favour mould infections, among them zygomycosis. In centres employing voriconazole for prophylaxis of IFI since its approval for treatment in 2001, incidence of aspergillosis has markedly dropped. The assumption that the frequency of zygomycosis has increased since the introduction of voriconazole is not found in prospective trials and therefore needs verification, especially when considering the long ongoing trends in fungal incidence. Currently recruiting multicentre trials on primary prophylaxis of IFI will have to show the preventive effectiveness of antifungals with mould activity and the incidence of zygomycosis under prospectively controlled conditions.

Breakthrough Candida krusei fungemia during fluconazole prophylaxis followed by breakthrough zygomycosis during caspofungin therapy in a patient with severe aplastic anemia who underwent stem cell transplantation.

We report a case of breakthrough invasive zygomycosis in a stem cell transplant recipient who was receiving caspofungin for treatment of a breakthrough Candida krusei fungemia that occurred during fluconazole prophylaxis. Also, patients receiving the echinocandin caspofungin remain at risk for pathogens, such as zygomycetes, that are intrinsically resistant to this agent.