Emerging fungal pathogens, drug resistance and the role of lipid formulations of amphotericin b in the treatment of fungal infections in cancer patients: A review

n/

A European Organization for Research and Treatment of Cancer-International Antimicrobial Therapy Group Study of Secondary Infections in Febrile, Neutropenic Patients with Cancer

Background. Neutropenic patients with cancer may develop several episodes of fever and infection during chemotherapy-induced myeloaplasia. Methods. To identify risk factors for secondary infectious episodes among patients who responded to initial antibiotic therapy, we retrospectively analyzed 2 consecutive, prospective, randomized clinical trials performed by the International Antimicrobial Therapy Group of the European Organization for Research and Treatment of Cancer during 1991-1994. Results. Of 1720 patients with their first episode of febrile neutropenia, 836 responded to the initial antibiotic regimen and were therefore suitable for our analysis. A secondary infection was observed in 129 (15%) of 836 patients that occurred at a median of 10 days (range, 1-28 days) after the onset of the primary febrile episode. Factors at both baseline and day 4 were analyzed. Age of >16 years (odds ratio [OR], 3.46; P < .001), acute leukemia in first induction (OR, 3.17; P < .001), presence of intravenous line (OR, 1.88; P = .04), severe neutropenia (defined as an absolute granulocyte count of <100 cells/mm3) on day 4 (OR, 2.72; P < .001), and type of documentation of the primary episode (i.e., microbiologically documented cause or unexplained fever; OR, 2.56; P = .001) were found to be risk factors for secondary infection. The risk of death was higher among patients who developed a secondary infectious episode than among those who did not (5.4% vs. 1.4%; P < .01). Conclusions. The clinical parameters described above may help to identify neutropenic patients at risk of developing secondary infectio

Invasive Candidiasis in Non-Hematological Patients

Candida is one of the most frequent pathogens isolated in bloodstream infections, and is associated with significant morbidity and mortality. In addition to haematological patients, there are several other populations with a substantial risk of developing invasive candidiasis (IC). These include patients undergoing prolonged hospitalisation with the use of broad-spectrum antibiotics, those fitted with intravascular catheters, admitted to both adult and neonate intensive care units (ICU) or gastrointestinal surgery wards and subjects with solid tumours undergoing cytotoxic chemotherapy. As a general rule, every immunocompromised patient might be at risk of Candida infection, including, for example, diabetic patients

Prophylaxis and treatment of invasive fungal infections in hematological patients

The evidence from the literature strongly support antifungal prophylaxis in high risk haematological patients, such as patients with AML during remission induction chemotherapy and alloHSCT patients. Current antifungal prophylaxis guidelines for high risk patients recommend azoles (fluconazole, posaconazole, voriconazole) and echinocandins (micafungin) with the strongest level of evidence. In terms of treatment, the choice between empiric therapy (or fever driven) and pre-emptive therapy (or diagnostic driven) is still debated. Not a single therapeutic strategy is appropriate in every patients, in particular empirical antifungal therapy may be recommended in patients at very high risk, while a pre-emptive approach may be advised for those at standard risk. In order to exploit the synergistic and/or additive effect of two antifungal drugs it's possible to combine two agents that work with different mechanisms of action (e.g. echinocandins + azoles or polyenes). Once the treatment has been initiated we should consider the therapeutic drug monitoring (TDM) of the drugs, especially when the pharmacokinetic variability is high and the dose-concentration effect relationships is not predictable (e.g. for itraconazole, voriconazole and posaconazole)

Whole body bone scintigraphy in tenofovir-related osteomalacia: a case report

<p>Abstract</p> <p>Introduction</p> <p>Tenofovir disoproxil fumarate (Viread^®) is the only nucleotide reverse transcriptase inhibitor currently approved for the treatment of HIV. It is frequently prescribed not only for its efficacy but also for its decreased side effect profile compared with other nucleotide analogs. In addition, it is now increasingly recognized as a cause of acquired Fanconi's syndrome in individuals with HIV.</p> <p>Case presentation</p> <p>We describe a 48-year-old woman infected with HIV, with chronic renal insufficiency, who developed Fanconi's syndrome after inclusion of tenofovir disoproxil fumarate in her antiretroviral therapy. A whole body bone scintigraphy was performed, revealing an abnormal distribution of radiotracer uptake, with characteristic changes compatible with osteomalacia. All symptoms disappeared after tenofovir discontinuation and mineral supplementation. No other explanation for the sudden and complete resolution of the bone disease was found.</p> <p>Conclusion</p> <p>The case highlights the role of whole body bone scintigraphy in the diagnosis of tenofovir-related osteomalacia.</p

Randomised, multicentre trial of micafungin vs. an institutional standard regimen for salvage treatment of invasive aspergillosis.

Invasive aspergillosis remains associated with significant morbidity and mortality, necessitating new options for salvage therapy. The objective of this study was to evaluate the efficacy and safety of micafungin as salvage monotherapy in patients with invasive aspergillosis. Patients with proven or probable invasive aspergillosis, who were refractory or intolerant to previous systemic antifungal therapy, were randomised 2 : 1 to receive 300 mg day 121 intravenous micafungin monotherapy or an intravenous control monotherapy [lipid amphotericin B (5 mg kg 121 day 121), voriconazole (8 mg kg 121 day 121) or caspofungin (50 mg day 121)] for 3\u201312 weeks. Patients underwent final assessment 12 weeks after treatment start. Seventeen patients with invasive aspergillosis (proven, n = 2; probable, n = 14; not recorded, n = 1) participated in the study (micafungin arm, n = 12; control arm, n = 5). Three patients each in the micafungin (25.0%; 95% CI: 5.5\u201357.2) and control arm (60.0%; 95% CI: 14.7\u201394.7) had successful therapy at end of treatment as assessed by an Independent Data Review Board. Eleven patients died; six due to invasive aspergillosis. No deaths were considered related to study treatment. During this study it became increasingly common to use combination treatment for salvage therapy. Consequently, enrolment was low and the study was discontinued early. No clear trends in efficacy and safety can be concluded

Successful recovery of associated interstitial nephritis and focal segmental glomerulosclerosis in patients with HCV and HIV treated with sofosbuvir and daclatasvir and revision of literature

In this report, we describe the coexistence of two rare and debated complications of hepatitis C virus (HCV) infection: interstitial nephritis, with associated focal glomerulosclerosis, and autoimmune hepatitis, in a 55-year-old HIV/HCV-coinfected woman. The patient was treated for the immune-mediated manifestations with mycophenolate mofetil, which she continued for 9&nbsp;years, as symptoms relapsed at every attempt to discontinue immunosuppression. The patient finally cleared HCV infection thanks to new direct-acting agents and could discontinue immunosuppressive therapy maintaining stable conditions and laboratory parameters after 24-weeks follow-up

Cost-effectiveness analysis of initial HIV treatment under Italian guidelines

INTRODUCTION: Since the mid-1990s, highly active antiretroviral therapy (HAART) has modified the clinical course of human immunodeficiency virus (HIV) infection, reducing the rate of disease progression, the incidence of opportunistic infections, and mortality. The authors of this paper performed an economic analysis to estimate the cost-effectiveness of the HAART regimens in Italy for managing HIV-infected patients according to national guidelines. PATIENTS AND METHODS: The incremental cost-effectiveness analysis was carried out by means of a Markov model, which through a decision-analytic approach, made it possible to compare the studied antiretroviral regimens. The population considered in the model consisted of adult subjects with HIV who received antiretroviral HAART treatment for the first time. The population considered in the analysis reflects the patients' characteristics according to one of the regional surveillance systems HIV/AIDS infection report currently operating in Italy. The analysis was carried out from the point of view of the Italian health care system. The considered outcome measures were quality-adjusted life years (QALYs) and direct health costs calculated for the year 2010. Both the outcomes (QALYs) and the costs were discounted by 3.5%. The time horizon adopted in the model was 10 years. RESULTS: The model shows, in terms of cost per gained QALY, single tablet regimen (STR) appeared to be the most cost-effective therapeutic choice (22,017), followed by tenofovir (TDF) + lamivudine + efavirenz (EFV) (24,526), and TDF/emtricitabine (FTC) + nevirapine (26,416), and TDF + FTC + EFV (26,558); the remaining strategies have an incremental cost-effectiveness ratio (ICER) value varying from 28,000 to 41,000 per QALY. The sensitivity analysis on the main variables confirmed the validity of the base case scenario. CONCLUSION: STR is the most cost-effective treatment strategy, compared with the other therapeutic regimens recommended by the Italian guidelines. All the ICER values of the various regimens considered by the Italian guidelines were lower than the threshold value of 50,000 commonly accepted at the international level. The model developed represents a tool for policy makers and health care professionals to make short- and long-term cost projections and thus evaluate their impact on the available budgets for HIV patients