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Invasive Fungal Infections (invasive + fungal_infections)
Selected AbstractsImmunotherapy for Invasive Fungal Infections in Transplant Patients: Back to the Future?AMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2010Hans H. Hirsch For kidney transplant patients with life-threatening disseminated fungal infections and failure of modern antifungal therapies, exogenous interferon-gamma might represent an adjunct salvage therapy, but the risk-benefit ratio is not yet established. See Article by Armstrong-James et al on page 1796. [source] Exogenous Interferon-, Immunotherapy for Invasive Fungal Infections in Kidney Transplant PatientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2010D. Armstrong-James The incidence of invasive fungal infections (IFIs) in nonneutropenic solid organ transplant patients is increasing. We report our clinical experience with the use of interferon-, (IFN-,) immunotherapy in seven renal transplant patients who developed life threatening, disseminated IFIs refractory to conventional antifungal drug therapy. The infections were all microbiologically and histologically proven. The rapid cure of these disseminated infections with exogenous IFN-, injections was not associated with impaired kidney allograft function despite the use of liposomal amphotericin B in all cases. No clinical toxicity from the IFN-, immunotherapy was seen and no IFI relapsed during long-term follow-up. Our experience is both uncontrolled and in patients with unpredictable fungal infection-related outcomes. However, compared to standard approaches, the accelerated cure of life threatening, disseminated IFIs with 6 weeks of combination antifungal drug therapy and IFN-, immunotherapy saved lives, retained allograft function and led to substantial cost savings in this small patient group. [source] Invasive fungal infections in patients with acute myeloid leukemia and in those submitted to allogeneic hemopoietic stem cell transplant: who is at highest risk?EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2008Morena Caira No abstract is available for this article. [source] Antifungal Prophylaxis with Voriconazole or Itraconazole in Lung Transplant Recipients: Hepatotoxicity and EffectivenessAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2009J. Cadena Invasive fungal infections (IFI) are common after lung transplantation and there are limited data for the use of antifungal prophylaxis in these patients. Our aim was to compare the safety and describe the effectiveness of universal prophylaxis with two azole regimens in lung transplant recipients. This is a retrospective study in lung transplant recipients from July 2003 to July 2006 who received antifungal prophylaxis with itraconazole or voriconazole plus inhaled amphotericin B to compare the incidence of hepatotoxicity. Secondary outcomes include describing the incidence of IFI, clinical outcomes after IFI and mortality. Sixty-seven consecutive lung transplants received antifungal prophylaxis, 32 itraconazole and 35 voriconazole and inhaled amphotericin B. There were no significant differences between groups in the acute physiology and chronic health evaluation (APACHE) score at the time of transplantation, demographic characteristics, comorbidities and concomitant use of hepatotoxic medications. Hepatotoxicity occurred in 12 patients receiving voriconazole and inhaled amphotericin B and in no patients receiving itraconazole (p < 0.001). There was no significant difference between groups with regard to the percentage of transplants with IFI, but one case of zygomycosis occurred in a transplant treated with voriconazole. Voriconazole prophylaxis after lung transplantation was associated with a higher incidence of hepatotoxicity and similar clinical effectiveness when compared to itraconazole. [source] Prospective screening by a panfungal polymerase chain reaction assay in patients at risk for fungal infections: implications for the management of febrile neutropeniaBRITISH JOURNAL OF HAEMATOLOGY, Issue 2 2000Holger Hebart Invasive fungal infections are a major cause of mortality in neutropenic cancer patients. To determine whether a polymerase chain reaction (PCR)-based assay enabled the identification of patients at risk for invasive fungal infections, a prospective monitoring once per week was performed during 92 neutropenic episodes in patients receiving chemotherapy for acute leukaemia or high-dose therapy followed by allogeneic or autologous stem cell transplantation, with the investigators blinded to clinical and microbiological data. PCR positivity was documented in 34 out of 92 risk episodes. All patients developing proven invasive fungal infection were found PCR positive, and PCR was found to be the earliest indicator of invasive fungal infection preceding clinical evidence by a mean of 5·75 d (range 0,14 d). In febrile neutropenic patients without a prior history of invasive fungal infection, a sensitivity of 100% and a specificity of 73% of the PCR assay for the development of proven or probable invasive fungal infection was documented. In conclusion, panfungal PCR performed prospectively once a week enabled the identification of patients at high risk for invasive fungal infections. [source] Recent Approaches to Antifungal Therapy for Invasive MycosesCHEMMEDCHEM, Issue 3 2009Bijoy Abstract Antimycotic agents: Diverse classes of antimycotic drugs have been developed over the past decades with the goal of improving selectivity and efficacy. This review discusses both conventional and novel targets for antifungal agents and the possibility of vaccination in the treatment of invasive fungal infections. Invasive fungal infections with primary and opportunistic mycoses have become increasingly common in recent years and pose a major diagnostic and therapeutic challenge. They represent a major area of concern in today's medical fraternity. The occurrence of invasive fungal diseases, particularly in AIDS and other immunocompromised patients, is life-threatening and increases the economic burden. Apart from the previously known polyenes and imidazole-based azoles, newly discovered triazoles and echinocandins are more effective in terms of specificity, yet some immunosuppressed hosts are difficult to treat. The main reasons for this include antifungal resistance, toxicity, lack of rapid and microbe-specific diagnoses, poor penetration of drugs into sanctuary sites, and lack of oral or intravenous preparations. In addition to combination antifungal therapy, other novel antimycotic treatments such as calcineurin signaling pathway blockers and vaccines have recently emerged. This review briefly summarizes recent developments in the pharmacotherapeutic treatment of invasive fungal infections. [source] Invasive fungal infections in paediatric patientsCLINICAL MICROBIOLOGY AND INFECTION, Issue 9 2010E. Roilides No abstract is available for this article. [source] Epidemiology of invasive fungal infections in neonates and childrenCLINICAL MICROBIOLOGY AND INFECTION, Issue 9 2010W. J. Steinbach Clin Microbiol Infect 2010; 16: 1321,1327 Abstract Invasive fungal infections are major causes of morbidity and mortality in neonates and in both immunocompromised and immunocompetent children. Although these infections have been well characterized in adults, the incidence and analysis of risk factors, diagnostic tools, treatments and outcomes have not been well described for large cohorts of paediatric or neonatal patients. Paediatric exclusion has limited our knowledge of the epidemiology and pathophysiology of paediatric fungal disease, and has also resulted in a paucity of data regarding the safety and efficacy of paediatric antifungal therapy. Previous paediatric cooperative models in other disciplines have successfully advanced our understanding and treatments of childhood diseases, but in the past there has not been a similar organization for paediatric invasive fungal infections. Although there are numerous other reviews outlining the differences in paediatric antifungal dosing pharmacokinetics, there are only smaller epidemiological reports depicting the exact distribution and outcomes of paediatric invasive fungal infections treated with these antifungals. This review will highlight some of the available epidemiological data on paediatric invasive fungal infections. [source] Invasive fungal infections: past achievements and challenges aheadCLINICAL MICROBIOLOGY AND INFECTION, Issue 7 2009M. C. Arendrup No abstract is available for this article. [source] Antifungal immunity and adjuvant cytokine immune enhancement in cancer patients with invasive fungal infectionsCLINICAL MICROBIOLOGY AND INFECTION, Issue 1 2007A. Safdar Abstract Invasive fungal infections are common in severely immunosuppressed patients with cancer and in recipients of haematopoietic transplants. Response to antifungal therapy alone is often inadequate. Pro-inflammatory cytokines are critical for promoting innate and adaptive cellular antifungal immune responses. Recombinant cytokines, including granulocyte,macrophage-colony stimulating factor and interferon-,, have been studied as adjuvant therapies for severely immunosuppressed cancer patients with difficult-to-treat invasive mycoses. The limited clinical experience to date shows a possible benefit of these cytokines, and further controlled clinical trials are needed to validate their routine use in cancer patients and stem-cell transplant recipients with invasive fungal infections who are likely to have a poor response to antifungal drug therapy. [source] Invasive fungal infections in the immunocompromised host: recent advances in diagnosis, treatment and preventionCLINICAL MICROBIOLOGY AND INFECTION, Issue 2006Emilio Bouza No abstract is available for this article. [source] Infectious complications after kidney transplantation: current epidemiology and associated risk factorsCLINICAL TRANSPLANTATION, Issue 4 2006George J Alangaden Abstract:, Background:, The impact of newer immunosuppressive and antimicrobial prophylactic agents on the pattern of infectious complications following kidney transplantation has not been well studied. Methods:, This is an observational study in 127 adult recipients transplanted from 2001 to 2004. Patients received thymoglobulin (ATG) (50%) or basiliximab (50%) for induction and were maintained on mycophenolate mofetil, either tacrolimus (73%) or sirolimus (SRL) (27%), and prednisone (79%). Antimicrobial prophylaxis included perioperative cefazolin, trimethoprim/sulfamethaxazole for six months, valganciclovir for three months and nystatin for two months. Regression models were used to examine the association of various factors with infections. Results:, We observed 127 infections in 65 patients, consisting of urinary tract infection (UTI) (47%), viral infections (17%), pneumonia (8%) and surgical wound infections (7%). UTI was the most common infection in all post-transplant periods. Enterococcus spp. (33%) and Escherichia coli (21%) were the most prevalent uropathogens. Of six patients with cytomegalovirus infection, none had tissue-invasive disease. There were no cases of pneumocystis pneumonia or BK nephropathy. Six patients developed fungal infections. Two deaths due to disseminated Rhizopus and Candida albicans accounted for a 1.5% infection-related mortality. Retransplantation and ureteral stents were independently associated with UTI (OR = 4.5 and 2.9, p = 0.06 and 0.03, respectively), as were ATG and SRL with bacterial infections (OR = 3.3 and 2.5, p = 0.009 and 0.047, respectively). Conclusion:, This study suggests that the use of newer immunosuppressive agents in recent years is associated with some changes in the epidemiology of post-transplant infections. Enterococci have become the predominant uropathogen. Invasive fungal infections, although rare, are often fatal. [source] Current diagnostic approaches to invasive candidiasis in critical care settingsMYCOSES, Issue 5 2010Javier Pemán Summary For the specialist, the management of invasive candidiasis infections, from diagnosis to selection of the therapeutic protocol, is often a challenge. Although early diagnosis and treatment are associated with a better prognosis, apart from cases with positive blood cultures or fluid/tissue biopsy, diagnosis is neither sensitive nor specific, relying on many different factors, clinical and laboratory findings but there is certainly a need for the specific markers in this disease. Recently, new serodiagnostic assays as Candida albicans germ-tube antibodies or (1,3)-,- d -glucan detection and molecular techniques for the detection of fungal-specific DNA have been developed with controversial results in critical care setting. One of the main features in diagnosis is the evaluation of risk factor for infection, which will identify patients in need of preemptive or empirical treatment. Clinical scores were built from those risk factors. For these reasons, an approach to the new diagnosis tools in the clinical mycology laboratory and an analysis of the new prediction rules and its application situations has been made. Currently, the combination of prediction rules and non-culture microbiological tools could be the clue for improving the diagnosis and prognosis of invasive fungal infections in critically ill patients. [source] In vitro susceptibility testing in fungi: a global perspective on a variety of methodsMYCOSES, Issue 1 2010Cornelia Lass-Flörl Summary Candida and Aspergillus species are the most common causes of invasive fungal infections in immunocompromised patients. The introduction of new antifungal agents and recent reports of resistance emerging during treatment have highlighted the need for in vitro susceptibility testing. For some drugs, there is a supporting in vitro,in vivo correlation available from studies of clinical efficacy. Both intrinsic and emergent antifungal drug resistance are encountered. Various testing procedures have been proposed, including macrodilution and microdilution, agar diffusion, disk diffusion and Etest. Early recognition of infections caused by pathogens that are resistant to one or more antifungals is highly warranted to optimise treatment and patient outcome. [source] Treatment of invasive candidiasis with echinocandinsMYCOSES, Issue 6 2009Andreas Glöckner Summary Blood stream infections by Candida spp. represent the majority of invasive fungal infections in intensive care patients. The high crude mortality of invasive candidiasis remained essentially unchanged during the last two decades despite new treatment options that became available. The echinocandins, the latest class of antifungals introduced since 2001, exhibit potent activity against clinically relevant fungi including most Candida spp. In several randomised multicentre phase III trials, anidulafungin, caspofungin and micafungin showed convincing efficacy when compared with standard treatment regimens. In all trials, echinocandins were at least non-inferior to standard treatments. Anidulafungin was shown to be superior to fluconazole. Echinocandins have a favourable tolerability profile and exhibit a minimal potential for drug interactions since their pharmacokinetics is independent of renal and , largely , hepatic function. As a result of these properties, echinocandins are appropriate drugs of choice for invasive candidiasis in intensive care where many patients experience organ failure and receive multiple drugs with complex interactions. [source] Is there a need for autopsies in the management of fungal disease?MYCOSES, Issue 4 2008Manfred Knoke Summary The autopsy rates in Germany became low like in other European, American and Asian countries. Main reasons for this development are the lack of acceptance of autopsy in the society as well as in the medical profession, the introduction of a requirement for consent, unclear legal position, the public health system, pressure of costs and a change in the field of activity in pathology with much more diagnostics of surgical and biopsy material. The autopsy is missing with respect to the reliability of causes of death and morbidity statistics and other epidemiological studies. Published data indicate that up to 20,30% of patients who die in hospitals have important diseases/lesions that remain undetected before death but that are found at autopsy. For infectious diseases, the data are similar. Therefore, a higher incidence of invasive fungal infections was found. Some rare fungal disorders are diagnosed by autopsy. Only exact death statistics makes specific health care possible and is cost saving in a public health system in the long term. Autopsy remains an important tool for quality control in medical diagnostic and therapeutic activity. It is also essential for fundamental medical education and further training. [source] Pharmacological properties and clinical efficacy of a recently licensed systemic antifungal, caspofunginMYCOSES, Issue 4 2005Georg Maschmeyer Summary Caspofungin, a semisynthetic derivative of the pneumocandin B0, is the first licensed compound of a new class of antifungal agents, the echinocandins. It attacks the fungal cell by selective inhibition of the beta-(1,3)- d -glucan synthase, which is not present in mammalian cells. In vitro studies have indicated a potent fungicidal effect on Candida species, and in vivo studies in immunocompromised animals with invasive candidiasis demonstrated a favourable outcome. In randomized clinical trials in patients with oropharyngeal/oesophageal and invasive candidiasis, caspofungin was at least as effective as amphotericin B deoxycholate, yet showed a significantly superior safety profile. Of patients with invasive aspergillosis refractory to or intolerant of other antifungal agents, 45% showed a partial or complete response to caspofungin given as a salvage treatment. Also, it demonstrated comparable clinical efficacy but superior tolerability in the empirical antifungal therapy in neutropenic patients compared with liposomal amphothericin B. Caspofungin has an excellent tolerability and a low potential for drug interactions. Thus, caspofungin represents an interesting and clinically valuable new antifungal drug that broadens the available therapeutic armamentarium for the treatment of invasive fungal infections. [source] An overview of the antifungal properties of allicin and its breakdown products , the possibility of a safe and effective antifungal prophylacticMYCOSES, Issue 2 2005Stephen R Davis Summary Reports about the safe and successful intravenous (i.v.) use of garlic derivatives in China against invasive fungal infections have been made, but little has been done to seriously investigate the in vivo use of these derivatives in the West. Laboratories have demonstrated impressive in vitro MICs using allitridium, one of these derivatives, against a range of medically important fungi. In addition, it has been demonstrated that allitridium shows in vitro synergy with amphotericin B, one of the main i.v. antifungal agents. Some of the breakdown products of allicin, the main parent antifungal compound in garlic, have been investigated for their general antimicrobial, anticancer and anticholesterol properties, and it appears that there is a common mode of action that underlies these activities. It appears that these small molecules have the ability to cross cell membranes and combine with sulfur-containing molecular groups in amino acids and proteins, thus interfering with cell metabolism. It has been suggested that the reason human cells are not poisoned by allicin derivatives is that they contain glutathione, a sulfur-containing amino acid that combines with the allicin derivative, thus preventing cell damage. In addition to their biochemical mechanism, these derivatives appear to stimulate cellular immunity, an important ability lacking in conventional antifungal chemotherapy. These derivatives appear to be safe, cheap, wide-spectrum and immunostimulatory, as well as possibly synergistic with conventional antifungal therapy, making them ideal candidates for investigation into their use as prophylactic antifungal agents. [source] Chronic granulomatous disease presenting with disseminated intracranial aspergillosisPEDIATRIC BLOOD & CANCER, Issue 1 2006Abdul Alsultan MD Abstract We describe an 8-year-old boy who presented with multiple unresectable aspergillus brain abscesses as the initial presentation of X-linked chronic granulomatous disease (CGD). He failed initial therapy with amphotericin B, but was subsequently salvaged with voriconazole. CGD should be considered in the differential diagnosis for all children presenting with invasive fungal infections, particularly, those involving the central nervous system (CNS). Whereas, optimal pharmacologic therapy is still unknown for CNS aspergillosis, voriconazole may have an advantage due to its ability to cross the blood brain barrier and excellent oral absorption and bioavailability. © 2005 Wiley-Liss, Inc. [source] Exogenous Interferon-, Immunotherapy for Invasive Fungal Infections in Kidney Transplant PatientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2010D. Armstrong-James The incidence of invasive fungal infections (IFIs) in nonneutropenic solid organ transplant patients is increasing. We report our clinical experience with the use of interferon-, (IFN-,) immunotherapy in seven renal transplant patients who developed life threatening, disseminated IFIs refractory to conventional antifungal drug therapy. The infections were all microbiologically and histologically proven. The rapid cure of these disseminated infections with exogenous IFN-, injections was not associated with impaired kidney allograft function despite the use of liposomal amphotericin B in all cases. No clinical toxicity from the IFN-, immunotherapy was seen and no IFI relapsed during long-term follow-up. Our experience is both uncontrolled and in patients with unpredictable fungal infection-related outcomes. However, compared to standard approaches, the accelerated cure of life threatening, disseminated IFIs with 6 weeks of combination antifungal drug therapy and IFN-, immunotherapy saved lives, retained allograft function and led to substantial cost savings in this small patient group. [source] Prospective screening by a panfungal polymerase chain reaction assay in patients at risk for fungal infections: implications for the management of febrile neutropeniaBRITISH JOURNAL OF HAEMATOLOGY, Issue 2 2000Holger Hebart Invasive fungal infections are a major cause of mortality in neutropenic cancer patients. To determine whether a polymerase chain reaction (PCR)-based assay enabled the identification of patients at risk for invasive fungal infections, a prospective monitoring once per week was performed during 92 neutropenic episodes in patients receiving chemotherapy for acute leukaemia or high-dose therapy followed by allogeneic or autologous stem cell transplantation, with the investigators blinded to clinical and microbiological data. PCR positivity was documented in 34 out of 92 risk episodes. All patients developing proven invasive fungal infection were found PCR positive, and PCR was found to be the earliest indicator of invasive fungal infection preceding clinical evidence by a mean of 5·75 d (range 0,14 d). In febrile neutropenic patients without a prior history of invasive fungal infection, a sensitivity of 100% and a specificity of 73% of the PCR assay for the development of proven or probable invasive fungal infection was documented. In conclusion, panfungal PCR performed prospectively once a week enabled the identification of patients at high risk for invasive fungal infections. [source] Amphotericin B lipid complex as prophylaxis of invasive fungal infections in patients with acute myelogenous leukemia and myelodysplastic syndrome undergoing induction chemotherapyCANCER, Issue 3 2004Gloria N. Mattiuzzi M.D. Abstract BACKGROUND The optimal antifungal prophylactic regimen for patients with acute myelogenous leukemia (AML) or high-risk myelodysplastic syndrome (MDS) undergoing induction chemotherapy has yet to be identified. A prospective historical control study evaluated the efficacy and safety of amphotericin B lipid complex (ABLC) in this patient population. METHODS Newly diagnosed patients with AML or high-risk MDS who were undergoing induction chemotherapy received prophylactic ABLC 2.5 mg/kg intravenously 3 times weekly. This treatment group was compared with a historical control group that had similar baseline characteristics and received prophylactic liposomal amphotericin B (L-AmB) 3 mg/kg 3 times weekly. The primary endpoint was the incidence of documented or suspected fungal infections during and up to 4 weeks after cessation of prophylaxis. Reported adverse events were used to assess tolerability. RESULTS The overall efficacy of antifungal prophylaxis was similar in patients who received ABLC and patients who received L-AmB (P = 0.95). Among 131 ABLC-treated patients and 70 L-AmB-treated patients who ere assessed for efficacy and safety, 49% of patients in each group completed therapy without developing a documented or suspected fungal infection. Documented fungal infections occurred in 5% of ABLC-treated patients and in 4% of L-AmB-treated patients. Alternative antifungal strategies were required because of persistent fever or pneumonia of unknown pathogen in 28% and 32% of ABLC-treated and L-AmB-treated patients, respectively. Grade 3 and 4 adverse events, therapy discontinuations due to adverse events, and survival rates also were similar between treatment groups. CONCLUSIONS ABLC and L-AmB appeared to have similar efficacy and were tolerated well as antifungal prophylaxis in patients with AML and high-risk MDS who were undergoing induction chemotherapy. Cancer 2004. © 2003 American Cancer Society. [source] Liposomal amphotericin B versus the combination of fluconazole and itraconazole as prophylaxis for invasive fungal infections during inductionCANCER, Issue 2 2003Chemotherapy for patients with acute myelogenous leukemia, myelodysplastic syndrome Abstract BACKGROUND Fungal infections are a major cause of morbidity and mortality in patients undergoing induction chemotherapy for acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). The authors evaluated the efficacy and toxicity of liposomal amphotericin B (L-AmB) compared with a combination of fluconazole plus itraconazole (F+I) as prophylaxis in this setting. METHODS Patients with newly diagnosed AML or high-risk MDS who were undergoing initial induction chemotherapy were randomized to receive either F+I (fluconazole 200 mg orally every 12 hours plus itraconazole tablets 200 mg orally every 12 hours) or L-AmB (3 mg/kg intravenously 3 times per week) in this prospective, open-label study. RESULTS Seventy-two L-AmB-treated patients and 67 F+I-treated patients were enrolled in the study. Of these, 47% of patients completed antifungal prophylaxis without a change in therapy for proven or suspected fungal infection. Three patients in each arm developed a proven fungal infection. Twenty-three percent of the L-AmB-treated patients and 24% of the F+I-treated patients were changed to alternative antifungal therapy because of persistent fever (P value not significant). Nine percent of the L-AmB-treated patients developed pneumonia of unknown etiology compared with 16% of the F+I-treated patients (P value not significant). Increases in serum creatinine levels to > 2 mg/dL (20% for the L-AmB arm vs. 6% for the F+I arm; P = 0.012) and increases in serum bilirubin levels to > 2 mg/dL (43% vs. 22%, respectively; P = 0.021) were more common with L-AmB. Infusion-related reactions were noted in five L-AmB-treated patients. Responses to chemotherapy and induction mortality rates were similar for the two arms. CONCLUSIONS L-AmB and F+I appear similar in their efficacy as antifungal prophylaxis during induction chemotherapy for patients with AML and MDS. L-AmB was associated with higher rates of increased serum bilirubin and creatinine levels. Cancer 2003;97:450,6. © 2003 American Cancer Society. DOI 10.1002/cncr.11094 [source] Recent Approaches to Antifungal Therapy for Invasive MycosesCHEMMEDCHEM, Issue 3 2009Bijoy Abstract Antimycotic agents: Diverse classes of antimycotic drugs have been developed over the past decades with the goal of improving selectivity and efficacy. This review discusses both conventional and novel targets for antifungal agents and the possibility of vaccination in the treatment of invasive fungal infections. Invasive fungal infections with primary and opportunistic mycoses have become increasingly common in recent years and pose a major diagnostic and therapeutic challenge. They represent a major area of concern in today's medical fraternity. The occurrence of invasive fungal diseases, particularly in AIDS and other immunocompromised patients, is life-threatening and increases the economic burden. Apart from the previously known polyenes and imidazole-based azoles, newly discovered triazoles and echinocandins are more effective in terms of specificity, yet some immunosuppressed hosts are difficult to treat. The main reasons for this include antifungal resistance, toxicity, lack of rapid and microbe-specific diagnoses, poor penetration of drugs into sanctuary sites, and lack of oral or intravenous preparations. In addition to combination antifungal therapy, other novel antimycotic treatments such as calcineurin signaling pathway blockers and vaccines have recently emerged. This review briefly summarizes recent developments in the pharmacotherapeutic treatment of invasive fungal infections. [source] Epidemiology of invasive fungal infections in neonates and childrenCLINICAL MICROBIOLOGY AND INFECTION, Issue 9 2010W. J. Steinbach Clin Microbiol Infect 2010; 16: 1321,1327 Abstract Invasive fungal infections are major causes of morbidity and mortality in neonates and in both immunocompromised and immunocompetent children. Although these infections have been well characterized in adults, the incidence and analysis of risk factors, diagnostic tools, treatments and outcomes have not been well described for large cohorts of paediatric or neonatal patients. Paediatric exclusion has limited our knowledge of the epidemiology and pathophysiology of paediatric fungal disease, and has also resulted in a paucity of data regarding the safety and efficacy of paediatric antifungal therapy. Previous paediatric cooperative models in other disciplines have successfully advanced our understanding and treatments of childhood diseases, but in the past there has not been a similar organization for paediatric invasive fungal infections. Although there are numerous other reviews outlining the differences in paediatric antifungal dosing pharmacokinetics, there are only smaller epidemiological reports depicting the exact distribution and outcomes of paediatric invasive fungal infections treated with these antifungals. This review will highlight some of the available epidemiological data on paediatric invasive fungal infections. [source] Antifungal pharmacokinetics and pharmacodynamics: bridging from the bench to bedsideCLINICAL MICROBIOLOGY AND INFECTION, Issue 7 2009W. W. Hope Abstract This review considers a way in which experimental data can be used to identify safe and effective antifungal regimens for humans. The process begins with experimental models of invasive fungal infections that enable definition of optimal dosages and schedules of antifungal drug administration to be defined. These preclinical models also enable the identification of drug exposure targets that are associated with therapeutic outcomes of interest. Human pharmacokinetic variability results in a considerable range of drug exposures following the use of fixed antifungal drug regimens. This variability can be quantified using population pharmacokinetic modeling techniques. Monte Carlo simulation can then be used to simulate pharmacokinetic variability and thereby estimate the proportion of patients with a therapeutic outcome of interest. Effective and safe regimens can thus be studied appropriately in clinical settings. This approach can, and should, be used to optimize antifungal therapy for a large number of clinical scenarios. [source] Antifungal immunity and adjuvant cytokine immune enhancement in cancer patients with invasive fungal infectionsCLINICAL MICROBIOLOGY AND INFECTION, Issue 1 2007A. Safdar Abstract Invasive fungal infections are common in severely immunosuppressed patients with cancer and in recipients of haematopoietic transplants. Response to antifungal therapy alone is often inadequate. Pro-inflammatory cytokines are critical for promoting innate and adaptive cellular antifungal immune responses. Recombinant cytokines, including granulocyte,macrophage-colony stimulating factor and interferon-,, have been studied as adjuvant therapies for severely immunosuppressed cancer patients with difficult-to-treat invasive mycoses. The limited clinical experience to date shows a possible benefit of these cytokines, and further controlled clinical trials are needed to validate their routine use in cancer patients and stem-cell transplant recipients with invasive fungal infections who are likely to have a poor response to antifungal drug therapy. [source] Itraconazole vs. fluconazole for antifungal prophylaxis in allogeneic stem-cell transplant patientsCLINICAL MICROBIOLOGY AND INFECTION, Issue 2006D. J. Winston Abstract Results from randomised, controlled trials and routine clinical experience indicate that itraconazole can be more effective than fluconazole for prevention of invasive fungal infections in allogeneic stem-cell transplant patients. The effective and safe use of prophylactic itraconazole requires an appreciation of the drug's pharmacokinetics, the optimal dosing regimen, and potential drug interactions. Because of the erratic bioavailability of oral itraconazole capsules, only the intravenous (200 mg once-daily) and oral cyclodextrin solution (200 mg twice-daily) formulations of the drug should be used. Prophylaxis should be started after the completion of pre-transplant chemotherapy in order to avoid interactions with chemotherapeutic agents. Patients unable to tolerate oral itraconazole should be given intravenous itraconazole to maintain effective prophylaxis. Post-transplant interactions between itraconazole and immunosuppressive agents or other drugs are generally not problematic, can be easily managed, and need not limit the use of itraconazole. If these guidelines are followed, Aspergillus and other invasive fungal infections can be safely prevented in allogeneic stem-cell transplant patients. 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