Systemic Fungal Infections In Patients Research Articles

Conventional Amphotericin B Associated Nephrotoxicity in Patients With Hematologic Malignancies.

Introduction: Amphotericin B (AmB-d) is one of the most effective therapeutic options against frequently life-threatening systemic fungal infections in patients with hematologic malignancies. However, significant adverse effects including nephrotoxicity associated with its use limit its more widespread use. The objectives of our study were to determine the incidence of AmB-d associated nephrotoxicity, to evaluate clinical and epidemiological characteristics of patients, and to support the notion that conventional amphotericin B remains a valid therapeutic option among hematologic patients with proper patient selection.Materials and methods: A total of 110 patients with hematologic malignancies were admitted to our Hematology Unit between January 2014 and November 2017 who required anti-fungal therapy during intensive systemic chemotherapy. The incidence of AmB-d associated nephrotoxicity, side effect profile, time to nephrotoxicity, and clinical and epidemiological characteristics associated with treatment success were assessed retrospectively.Results: Of the 110 patients receiving AmB-d, 70 (63.6%) were male and 40 (36.4%) were female. The mean age of participants was 44 years. The most common diagnosis was acute myeloid leukemia (n=53, 48.2%), and the most common chemotherapy protocol was 7 + 3 remission-induction (cytarabine 100 mg/m² days 1-7, Idarubicin 12 mg/m² days 1-3; n=24, 21.8%). In 56.4% of the patients, antifungal therapy was given empirically. In 40 patients (36.4%), nephrotoxicity was observed following antifungal treatment, and only four patients had stage 3 renal failure. The mean duration of time to nephrotoxicity from initiation of amphotericin B was four days (min: 2, max: 31). All patients were found to receive at least one additional potential nephrotoxic treatment during the antifungal treatment process. Conclusion: AmB-d is associated with a significant risk of nephrotoxicity. In most hematological patients, antifungal treatment is initiated empirically, and patients received prolonged courses of treatment. Therefore, it is plausible to initiate such treatment with AmB-d, when one considers the already high treatment costs in this patient group as well as the fact that AmB-d offers similar efficacy to antifungal agents at a lower cost. AmB-d may be recommended as a first-line agent in this patient group with the introduction of newer and more costly antifungal agents when needed, on the basis of the fact that these patients can be closely monitored in a hospital setting, reversible nature of nephrotoxicity upon discontinuation, and rare occurrence of severe renal failure requiring dialysis.

A comparative evaluation of three methods for the rapid diagnosis of cryptococcal meningitis (CM) among HIV-infected patients in Northern Malawi

Cryptococcal meningitis (CM) is the most common systemic fungal infection in patients with HIV infection. Rapid diagnosis and timely initiation of antifungal therapy are key to reducing mortality rate associated with CM. This study aims to evaluate the ability of four different diagnostic tests (Gram stain, India ink, and two types of commercial lateral flow assay [LFA]) to identify CM-positive patients and to compare the sensitivity and specificity of these tests. This was a prospective cross-sectional study on diagnostic tests accuracy conducted in Northern Malawi. The target population was HIV-infected adult patients presenting with features of meningitis. Four types of diagnostic tests were conducted: India ink, Gram stain, and two types of commercial lateral flow assay (LFA) (Immy, Inc., OK, USA and Dynamiker Biotechnology (Tianjin) Co., Ltd), Singapore). Culture was conducted as the reference standard. A total of 265 samples were collected. The rate of positive CM detection ranged from 6.4% (using India ink) to 14.3% (using LFA). India ink exhibited the lowest sensitivity of 54.8% (95% confidence interval [CI]: 36.0%-72.7%), followed by Gram stain (61.3%; 95% CI: 42.2%-78.2%). The Dynamiker LFA exhibited the highest sensitivity of 100.0% (95% CI: 90.0%-100.0%) but a lower specificity (97.0%; 93.9%-98.8%) compared to the Immy LFA (98.3%; 95% CI: 95.7%-99.5%). LFA diagnostic methods have the potential to double the detection rate of CM-positive patients in resource-limited countries such as Malawi. As such, LFAs should be considered to become the main diagnostic tests used for CM diagnostics in these countries. Our data indicate that LFAs may be the best method for diagnosing CM and exhibits the highest diagnostic accuracy as it has shown that it outperforms cell culture, the current gold standard.

Management of Systemic Fungal Infection in Patients with Hematological Disorders

Management of Systemic Fungal Infection in Patients with Hematological Disorders

Systemic Fungal Infections in Patients with human inmunodeficiency virus

Histoplasmosis is a systemic infection caused by the dimorphic fungus Histoplasma capsulatum. In immunocompromised patients, primary pulmonary infection can spread to the skin and meninges. Clinical manifestations appear in patients with a CD4+ lymphocyte count of less than 150 cells/μL.Coccidioidomycosis is a systemic mycosis caused by Coccidioides immitis and Coccidioides posadasii. It can present as diffuse pulmonary disease or as a disseminated form primarily affecting the central nervous system, the bones, and the skin.Cryptococcosis is caused by Cryptococcus neoformans (var. neoformans and var. grubii) and Cryptococcus gattii, which are members of the Cryptococcus species complex and have 5 serotypes: A, B, C, D, and AD. It is a common opportunistic infection in patients with human immunodeficiency virus (HIV)/AIDS, even those receiving antiretroviral therapy.Histopathologic examination and culture of samples from any suspicious lesions are essential for the correct diagnosis of systemic fungal infections in patients with HIV/AIDS.

Voriconazole and its clinical potential in the prophylaxis of systemic fungal infection in patients with hematologic malignancies: a perspective review.

Invasive fungal infections (IFIs) have become high prevalence in patients with hematologic malignancies. Drug-based strategies for IFIs include various approaches such as prophylactic, empiric, preemptive, and directed treatment. Prophylaxis is an attractive strategy in high-risk patients, given the lack of reliable diagnostics and the high mortality rate associated with IFIs. Prophylaxis includes the use of antifungal drugs in all patients at risk. An ideal antifungal compound for prophylaxis should have a potent and broad activity, be available both orally and intravenously, and have a low toxicity profile. Voriconazole fulfills all these criteria. The clinical efficacy of voriconazole against the majority of fungal pathogens makes it potentially very useful for the prevention of IFIs in patients with hematologic malignancies. Voriconazole appears to be very effective for the primary and secondary prevention of IFIs in these patients and recipients of allogeneic hematopoietic stem-cell transplantation. Randomized controlled trials evaluating voriconazole as primary antifungal prophylaxis in patients with neutropenia treated for a variety of hematologic malignancies have been performed, confirming its value as a prophylactic agent. Voriconazole is generally safe and well tolerated; however, its use is also associated with a number of concerns. In most patients with hematologic malignancies there is the potential for pharmacokinetic drug-drug interactions given that voriconazole is metabolized through the P450 cytochrome system.

Micosis sistémicas en pacientes con virus de la inmunodeficiencia humana/sida

Histoplasmosis is a systemic infection caused by the dimorphic fungus Histoplasma capsulatum. In immunocompromised patients, primary pulmonary infection can spread to the skin and meninges. Clinical manifestations appear in patients with a CD4+ lymphocyte count of less than 150 cells/μL.Coccidioidomycosis is a systemic mycosis caused by Coccidioides immitis and Coccidioides posadasii. It can present as diffuse pulmonary disease or as a disseminated form primarily affecting the central nervous system, the bones, and the skin.Cryptococcosis is caused by Cryptococcus neoformans (var. neoformans and var. grubii) and Cryptococcus gattii, which are members of the Cryptococcus species complex and have 5 serotypes: A, B, C, D, and AD. It is a common opportunistic infection in patients with human immunodeficiency virus (HIV)/AIDS, even those receiving antiretroviral therapy.Histopathologic examination and culture of samples from any suspicious lesions are essential for the correct diagnosis of systemic fungal infections in patients with HIV/AIDS.

Langerhans cell histiocytosis mimicking molluscum contagiosum

To the Editor: Several cutaneous infections are known to mimic molluscum contagiosum. 1 Cohen P.R. Grossman M.E. Recognizing skin lesions of systemic fungal infections in patients with AIDS. Am Fam Physician. 1994; 49: 1627-1634 PubMed Google Scholar We report our experience of a child with Langerhans cell histiocytosis (LCH) who presented with molluscum-like lesions.

The impact of systemic fungal infection in patients with perforated oesophagus.

INTRODUCTIONPerforated oesophagus is a surgical emergency with significant morbidity and mortality. Systemic fungal infection represents a poor response to the magnitude of the insult, which adds significantly to the risk of morbidity and mortality in these patients. We reviewed our experience with this group of patients over a six-year period in a tertiary referral centre.METHODSA retrospective clinical review was conducted of patients who were admitted following a ruptured oesophagus over a period of six years (January 2002 – January 2008).RESULTSWe had 27 admissions (18 men and 9 women) following an isolated perforated oesophagus to our unit. The median patient age was 65 years (range: 22–87 years). The majority (n=24,89%) presented with spontaneous perforations (Boerhaave’s syndrome) and three (11%) were iatrogenic. Fungal organisms, predominantly Candida albicans, were positively cultured in pleural or blood samples in 16 (59%) of the 27 patients. Fourteen patients grew yeasts within the first seven days while two showed a delayed growth after ten days. Overall mortality was 5 out of 27 patients (19%). There was no mortality among the group that did not grow yeasts in their blood/pleural fluid while mortality was 31% (5/16) in the group with systemic fungal infection (p<0.001). A positive fungal culture was also associated with increase ventilation time, intensive care unit stay and inpatient hospital stay but not an increased rate of complications.CONCLUSIONSSystemic fungal infection in patients with a ruptured oesophagus affects a significant proportion of these patients and carries a poor prognosis despite advanced critical care interventions. It may represent a general marker of poor host response to a major insult but can add to mortality and morbidity. It is worth considering adding antifungal therapy empirically at an early stage to antimicrobials in patients with an established diagnosis of a perforated oesophagus.

Invasive fungal infection of the central nervous system in a patient with acute myeloid leukaemia.

Although the new intensive chemotherapeutic programs introduced recently into hematooncological therapies have led to a higher number of recoveries, persistent neutropenia favours the spread of severe infections, frequently fungal infections. Systemic fungal infections in patients treated for proliferative diseases of the hematopoietic system are characterised by a severe, progressing course and high morbidity. We present a case report that demonstrates the diagnostic problem of lesions in the central nervous system which developed following the fourth block of chemotherapy in an eight-year-old boy treated for acute myeloid leukaemia. The risk factors, high values of the inflammatory parameters and imaging results enabled us to diagnose a fungal infection of the central nervous system. A fast improvement in the clinical condition of the patient after the applied antifungal therapy and the regression of lesions in the central nervous system shown in the imaging studies confirmed our final diagnosis.

The Prophylactic Effect of Itraconazole Capsules and Fluconazole Capsules for Systemic Fungal Infections in Patients with Acute Myeloid Leukemia and Myelodysplastic Syndromes: A Japanese Multicenter Randomized, Controlled Study

We performed a randomized, controlled study comparing the prophylactic effects of capsule forms of fluconazole (n = 110) and itraconazole (n = 108) in patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) during and after chemotherapy. There were 4 cases with possible systemic fungal infection in the itraconazole group, and there were 8 possible and 3 probable cases in the fluconazole group. Adverse events did not significantly differ in the 2 groups. In patients with MDS or in the remission-induction phase of chemotherapy, the numbers of cases with probable or possible infections were lower in the itraconazole group than in the fluconazole group, whereas no difference was seen in patients with AML or in the consolidation phase of therapy. In patients with neutrophil counts of >0.1 x 10(9)/L lasting for more than 4 weeks, the frequency of infection in the fluconazole group (5 of 9 patients) was significantly higher than in the itraconazole group (0 of 7 patients; P = .03). Our results suggest that both drugs were well tolerated in patients with AML or MDS who received chemotherapy and that the efficacy of itraconazole for prophylaxis against systemic fungal disease is not inferior to that of fluconazole.

Efficacy and Safety of Micafungin, an Echinocandin Antifungal Agent on Systemic Fungal Infections in Patients with Hematological Disorders.

Background and Purpose: Severe infections in patients (pts) with hematological disorders (HD) are mostly the result of a compromised immune system by the underlying disease itself including neutropenia aggravated by chemotherapy and conditioning treatment for hematopoietic stem cell transplantation (HSCT). Systemic fungal infections (SFIs) particularly are often encountered in this field associated with morbidity and mortality. It is deemed crucial to initiate an early introduction of antifungal therapy by using criteria for an early diagnosis. Micafungin (MCFG) that was launched in Japan in 2002 and approved in another 3 countries is shown to be safe and efficacious for SFIs. Since there are few clinical reports on the effects of MCFG in a large number of patients, a multicenter study (87 institutions) was initiated to see its efficacy and safety.Methods: The study was conducted from Apr. 03 to Mar. 05 on pts diagnosed with HD, who met any of the following criteria: ptswho are found to have a causative fungus identified by mycological or pathological testing (proven),with a SFI defined by clinical symptoms/findings and serological testing or diagnostic imaging (probable/possible), orwith a suspected SFI identified by unexplained persistent fever (an axillary temperature higher than 37.5 °C) and clinical symptoms/findings (refractory to antibacterial treatment).Efficacy was evaluated by the degree of improvement in clinical symptoms/findings, mycological findings, imaging study findings such as chest X-ray or CT, and fungal serological tests. The overall effects were rated as either “effective” or “ineffective”, based on an algorithm combining these indices.Results: A total of 277 pts were registered to the central office and 276 were evaluable for safety assessment. Eighty-one pts were not evaluable for efficacy due to a violation of entry criteria, etc. Thus 196 pts were assessed for clinical efficacy by the steering committee (118 males and 78 females, the mean age: 56.8). There were 62 pts with HSCT and 134 with chemotherapy in whom 67 had acute leukemia. The mean dosage and duration of MCFG were 170.8mg per day and 21.8days, respectively. Overall clinical effects were achieved in 134 out of 196 pts (68.4%). Clinical response was seen in 72.6% (45/62) for those with HSCT and 66.4% (89/134) for those of chemotherapy and particularly 68.7% (46/67) of the pts with chemotherapy for acute leukemia, respectively. The success rates were 87.5% (7/8) for pts with proven SFIs like candidemia, 44.7% (17/38) for probable SFIs, 62.9% (39/62) for possible SFIs, and 80.7% (71/88) for those who failed to respond to antibacterial treatment. The success rate for 13 pts with persistent fever on antibacterials and neutrophil counts below 500/μL before and after MCFG treatment was 69.2%. The incidence of adverse events related to MCFG was 30.1% (83/276), and the most common one was elevation of liver transaminase levels.Conclusions: MCFG demonstrated excellent clinical efficacy and safety when used to treat possible to proven SFIs in pts with HD, indicating its usefulness as a novel therapeutic drug for both empirical and targeted therapy for deep-seeded fungal infection.

Optimal prophylactic dosage and disposition of micafungin in living donor liver recipients

Micafungin, a new candin antifungal drug, has a good safety profile and a significant therapeutic effect against Candida and Aspergillus. Little is known, however, about the optimal prophylactic dosage and the disposition of micafungin in liver transplant recipients, or about the effect of continuous venovenous hemodialysis (CVVH) on the pharmacokinetics of micafungin. Six living donor liver transplant patients were enrolled in this study. The mean C(max) and C(min) (trough) values of micafungin in plasma were 6.31 +/- 1.08 and 1.65 +/- 0.54 microg/mL, respectively. The mean elimination half-life (t(1/2)) and mean area under the curve up to 12 h post-dosing (AUC 0-12 h) were 13.63 +/- 2.77 h and 50.04 +/- 6.48 microg.h/mL, respectively. The concentrations of micafungin at the inlet and outlet of the dialyzer were very similar. The mean (+/-SD) ratio of micafungin concentrations at the inlet and outlet of the dialyzer (coutlet/cinlet) and the clearance of micafungin were 0.96 +/- 0.04 and 0.054 +/- 0.04 mL/min/kg, respectively. The amount in the ultrafiltrate was 1.0 mg. Micafungin effectively prevents systemic fungal infection in patients who have undergone liver transplantation. No significant differences were observed in the disposition of micafungin in recipients, and the therapeutic drug level can be achieved by administration of micafungin at a dosage of 40-50 mg/d. The CVVH had little effect on micafungin kinetics, and no dose adjustment or modification of dosing interval was needed during CVVH.

Mucosal and systemic fungal infections in patients with AIDS: prophylaxis and treatment.

In countries where highly active antiretroviral therapy (HAART) is widely available, a decrease in the incidence of fungal infections has been observed in the last 5 years compared with countries that cannot afford this treatment. Even refractory fungal infections may be controlled when HAART is given to patients, and end-stage AIDS infections, such as aspergillosis, are now only infrequently seen. In contrast, fungal infections in certain regions, such as penicilliosis in Southeast Asia or cryptococcosis in Sub-Saharan Africa, are a growing problem. Antifungal therapy for documented infections has not changed very much during recent years; however, new drugs such as caspofungin and voriconazole may be more effective in the treatment of opportunistic fungal infections, in particular, those involving resistant organisms. Secondary antifungal prophylaxis for many opportunistic pathogens can now be temporarily or even permanently discontinued in many HIV-positive patients who have a marked improvement in immune function parameters, such as CD4(+) cell counts, after initiation of HAART. The link between effective virustatic control of HIV infection and a decreasing incidence of fungal infections has been recognised; and so, despite the availability of very effective new antifungal drugs, the cornerstone of treatment and prevention of opportunistic fungal infections in patients with HIV infection is effective antiretroviral therapy including protease inhibitors.

Candidiasis sistémica y tratamiento con infliximab

The use of infliximab in patients with luminal or fistulizing Crohn's disease refractory to medical treatment (steroids and immunomodulatory drugs) is increasingly widespread. Although the incidence of serious infections in patients undergoing infliximab treatment is not higher than that of controls, systemic fungal infections in patients treated with this antibody have been anecdotally described. We report a case of systemic candidiasis in a patient with refractory Crohn's disease who was treated with infliximab associated with corticosteroids and azathioprine and discuss the role that infliximab could have played in the development of this complication.

The Direct Cost and Incidence of Systemic Fungal Infections

Objectives In this study we determined the incidence and direct inpatient and outpatient costs of systemic fungal infections (candidiasis, aspergillosis, cryptococcosis, histoplasmosis) in 1998. Methods Using primarily the National Hospital Discharge Survey (NHDS) for incidence and the Maryland Hospital Discharge Data Set (MDHDDS) for costs, we surveyed four systemic fungal infections in patients who also had HIV/AIDS, neoplasia, transplant, and all other concomitant diagnoses. Using a case-control method, we compared the cases with controls (those without fungal infections with the same underlying comorbidity) to obtain the incremental hospitalization costs. We used the Student's t-test to determine significance of incremental hospital costs. We modeled outpatient costs on the basis of discharge status to calculate the total annual cost for systemic fungal infections in 1998. Results For 1998, the projected average incidence was 306 per million US population, with candidiasis accounting for 75% of cases. The estimated total direct cost was $2.6 billion and the average per-patient attributable cost was $31,200. The most commonly reported comorbid diagnoses with fungal infections (HIV/AIDS, neoplasms, transplants) accounted for only 45% of all infections. Conclusion The cost burden is high for systemic fungal infections. Additional attention should be given to the 55% with fungal disease and other comorbid diagnoses.

Clinical experience with itraconazole in systemic fungal infections.

The broad spectrum antifungal itraconazole is an effective and well tolerated agent for the prophylaxis and treatment of systemic fungal infections. The recent development of an itraconazole oral solution and an intravenous itraconazole solution has increased the options for the use of this drug and increased the oral bioavailability in a variety of at-risk patients. Reliable absorption of the itraconazole oral solution has been demonstrated in patients with HIV infection, neutropenic patients with haematological malignancy, bone marrow transplant recipients and neutropenic children. In clinical trials, itraconazole oral solution (5 mg/kg/day) was more effective at preventing systemic fungal infection in patients with haematological malignancy than placebo, fluconazole suspension (100 mg/day) or oral amphotericin-B (2 g/kg/day) and was highly effective at preventing fungal infections in liver transplant recipients. There were no unexpected adverse events with the itraconazole oral solution in any of these trials. In addition, intravenous itraconazole solution is at least as effective as intravenous amphotericin-B in the empirical treatment of neutropenic patients with systemic fungal infections, and drug-related adverse events are more frequent in patients treated with amphotericin-B. A large proportion of patients with confirmed aspergillosis also respond to treatment with intravenous itraconazole followed by oral itraconazole. The new formulations of itraconazole are therefore effective agents for prophylaxis and treatment of most systemic fungal infections in patients with haematological malignancy.

Systemic Fungal Infections in Patients with Hematologic Malignancies: Indications and Limitations of the Antifungal Armamentarium

The rates of fungal infections have increased substantially in Europe as well as in North America. Most frequently Aspergillus spp. and Candida spp. are isolated. Despite the recent introduction of new azoles and lipid-based formulations of amphotericin B, there are relatively few randomized, controlled studies on the use of antifungal drugs in patients with hematological malignancies and invasive fungal infections. Conventional amphotericin B is considered the gold standard for the treatment of invasive fungal infections; however, adverse events limit conventional amphotericin B treatment. The newer azoles, fluconazole and itraconazole, are well tolerated; however, fluconazole has no activity against Aspergillus spp. An additional serious problem is the emerging resistance of nonalbicans Candida spp. to fluconazole. In this situation, lipid formulations of amphotericin B seem to be attractive, since the use of these drugs has been shown to be safe and effective. Considerably higher medical costs limit broader application of lipid formulations of amphotericin B. Because of the rapidly increasing incidence of serious fungal infections, we have reviewed current strategies and the role of newer antifungal drugs for the treatment of deep-organ infections.

Treatment of systemic fungal infections in patients with hematologic malignancies.

Treatment of systemic fungal infections in patients with hematologic malignancies.

Fluconazole in the prophylaxis of fungal infection after bone marrow transplantation

An open, non-comparative study was conducted to investigate the efficacy and safety of fluconazole in the prophylaxis of superficial or systemic fungal infections in patients having received bone marrow transplantation (BMT). The study population consisted of a total of 53 patients, including 10 children between the ages of 3 and 14 years who were scheduled for BMT. Fluconazole prophylaxis was initiated at 200 mg day-1 in adults and 100 mg day-1 in children. It was started at a mean of 7 days before treatment and continued for up to 112 days in the paediatric patients and 393 days in the adult patients. Apart from the baseline examination and the final evaluation, the patients were evaluated mycologically and serologically for the presence of fungal infections on a weekly basis, if feasible. Proven fungal infection, oesophageal candidosis or oropharyngeal candidosis was not found in any of the patients under study during the fluconazole prophylaxis. Thirteen of the adult patients developed unexplained fevers and had their treatment supplemented by antibiotic therapy and treatment with amphotericin B. In all 10 children, the prophylactic treatment proved successful. Adverse events were seen in 15 patients. In one case only, the event was judged to be causally related or possibly causally related to the study drug. Hence, fluconazole proves to be an effective and well-tolerated agent in the prophylaxis of fungal infections in recipients of bone marrow transplants.

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 were Candida albicans and Aspergillus spp. The incidence of fungal infections caused by Aspergillus 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).