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

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clinical and diagnostic pathways in pediatric fungal infections

Generally speaking, in pediatrics the patients mostly affected by fungal infections are hematological patients, followed by those with solid tumors, and transplant recipients. Candida infections generally occur just after birth, whereas Aspergillus infections are age-related, and increase their incidence with age. However, among infections, the incidence of bacteremias are still greater than that of mycoses. In pediatrics, in Italy the immunocompromised patients – thus particularly susceptible to fungal infections – are mainly those with severe combined immunodeficiency, chronic mucocutaneous candidiasis, and chronic granulomatous disease. Particular Aspergillus or Scedosporium infections should be considered in peculiar kinds of patients, such as those affected by cystic fibrosis. Finally, different kinds of fungi should be considered in those who come from or spend a lot time in specific areas, such as South America (e.g. coccidioidomycoses, for which differential diagnosis is with tuberculosis)

Antifungal agents in non-neonatologic pediatrics

The spectrum of action of antifungal agents helps driving the choice of the treatment, basing on the activity against the fungus of interest. Pharmacokinetics should also be taken into account, considering the time-dependent and the concentration-dependent drugs. Triazoles belong to the first group, while amphotericin B and echinocandins belong to the second one. The effectiveness of time-dependent drugs hangs on the time spent above the Minimal Inhibitory Concentration (MIC), whereas that of concentration-dependent drugs is related to the peak of concentration achieved. Thetissue penetration is another important factor that should be taken into account while prescribing an antifungal agent. Interactions with other drugs, above all with those used to treat underlying pathologies, should also be considered. Fungicidal drugs are generally preferred to fungistatic agents, therefore echinocandins and amphotericin B are more prescribed than azoles. Combination therapies are not recommended

appropriate use of antifungal agents

As knowledge increases faster and faster, authorizations for drug use often don't report the most recent evidence. In addition, trials on pediatric populations are rare: as a consequence, a lot of drugs in pediatrics are prescribed out of their indications. This is called off-label use, if the drug isn't approved for the treatment of a specific disease, or unauthorized use, if, for example, a dose isn't written in the summary of product characteristics. These uses aren't illegal, but physicians should take some steps in order to protect their liability: for example, the hospital should write documents based on shared scientific evidence, where the reasons supporting a choice are explained. Informed consent should be obtained, after an exhaustive explanation, from the parents. There is also the exceptional use, i.e. the use in desperate cases, where no other treatments are possible, but, for example, a study in an animal model has resulted in good outcomes. Even in this case, similar measures should be taken by the physician

Guidelines for the management of bacterial and fungal infections during chemotherapy for pediatric acute leukemia or solid tumors: what is available in 2010?

Febrile episodes and infections represent important complications during antineoplastic chemotherapy for pediatric neoplastic diseases. In the last years many international association published guidelines for the management of these complications in adults, but no document of this type was prepared for children. One of the major causes of this situation is probably the very low number of pediatric clinical trials with adequate power and design. The paper summarizes guidelines provided for the management of infectious complications in adults with cancer by different international and will comment on how much they may be translated in the management of pediatric patients

mortality related to neonatal and pediatric fungal infections

Thanks to the recent advances in the treatment of neonatal fungal infections, the burden of mortality has been decreasing. However a widely accepted definition is yet to be found, since different thresholds of survival are used in the published trials, and therefore mortality is assumed as occurring 7, 20, 30, or 90 days after treatment, according to the different studies. Regardless of the uncertainty of the definitions, it is more important to know if the patient died with the fungal infection or because of the fungal infection. The new antifungal drugs currently available for neonatal patients were able to increase the survival rates: the attention should, therefore, be focused on the long-term seque­lae, which, on the contrary, still affect a big amount of patients. In particular, neurobehavioral and neurosensorial disorders become often evident with age

Colonization by Escherichia coli strains with increased minimal inhibitory concentration for cefiderocol: When resistance anticipates drug use.

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β-Glucan Antigenemia Assay for the Diagnosis of Invasive Fungal Infections in Patients With Hematological Malignancies: A Systematic Review and Meta-Analysis of Cohort Studies From the Third European Conference on Infections in Leukemia (ECIL-3)

This Third European Conference on Infections in Leukemia meta-analysis of high-quality hemato-oncological cohort studies shows that 2 consecutive positive 1,3-β-D-glucan assays have high specificity and both positive and negative predictive values but low sensitivity for diagnosis of invasive fungal infectio

Etanercept as Treatment of Steroid-Refractory Acute Graft-versus-Host Disease in Pediatric Patients

ABSTRACT Corticosteroids are the standard of care for first-line treatment of patients who develop grade II-IV of acute graft-versus-host disease (aGVHD), but the optimal second-line treatment has not yet been determined. We prospectively evaluated the use of the anti-TNFα monoclonal antibody etanercept (ET) as second-line treatment in children with steroid-refractory (SR) aGVHD. Twenty-five children with either malignant or nonmalignant diseases experiencing grade II-IV SR aGVHD received ET as second-line treatment. ET was administered after a median of 14days (range, 5 to 135 days) from the onset of aGVHD. Seventeen out of 25 patients (68%) developed a complete response (CR) or partial response (PR) to ET. The overall response rate (CR plus PR) was 78% in patients with cutaneous SR aGVHD, 78% in those with gastrointestinal aGVHD, and 57% in those with hepatic aGVHD. On day +100 after the start of ET, 52% of the children were in CR, 16% were in PR, and the remaining 32% failed to respond. Overall survival was 76.5% in responders and 16.7% in nonresponders (P = .004). Transplantation-related mortality at 5years was 34.1% (95% confidence interval, 18.6% to 57.1%). In our experience, ET has proven to be effective as second-line treatment in children with SR aGVHD

ESCMID-ECMM guideline : diagnosis and management of invasive aspergillosis in neonates and children

ACKNOWLEDGEMENT Prof Warris is supported by the Wellcome Trust Strategic Award (grant 097377) and the MRC Centre for Medical Mycology (grant MR/N006364/1) at the University of Aberdeen. FUNDING European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and the European Confederation of Medical Mycology (ECMM)Peer reviewedPostprintPostprin