Although therapeutic first-line approaches have been established in severely immunosuppressed patients with a high risk of invasive fungal infections, treatment modalities for cases with unsatisfactory outcome have not been well defined, especially for the pediatric age gap. Therapy with coadministration of two or three antifungals has been applied by clinicians in difficult-to-treat infections, which still have no support from randomized, controlled clinical trials. The most prevailing reason for a combination regimen is to broaden the antimycotic spectrum, which may even result in antagonistic interaction. The experience and recommendations of combinational antifungal therapy for cryptococcal infections, systemic candidiasis, invasive aspergillosis and other rare mold infections have been presented in this review, giving some information on mechanism of action and principles in combined use of mycotic anti-infectives. Most experience of combination therapy approaches are in adult patients; but in fact, there is no conclusive data documenting definite benefits of this approach, either in adults or children.

Ventilator-associated pneumonia is a serious hospital-acquired infection, with 20-70% crude mortality and 10-40% estimated attributable mortality. Insufficient antibiotic concentrations at the infection site when these drugs are given intravenously may lead to poor outcomes, particularly when difficult-to-treat pathogens are responsible; for example, Pseudomonas aeruginosa, extended spectrum beta lactamase-producing Gram-negative bacilli, Acinetobacter spp. and/or methicillin-resistant Staphylococcus aureus. Direct drug delivery to the infection site via aerosolization combined with intravenous administration achieves concentrations exceeding MICs of the pathogens, even those with impaired susceptibility. Experimental and recent clinical results demonstrated our markedly improved ability to deliver aerosolized antibiotics to the lung with new-generation devices, for example, vibrating-mesh nebulizers. Convincing clinical data from a large randomized trial are still lacking to support the routine administration of aerosolized antibiotics to treat ventilator-associated pneumonia, even though some small-randomized trials' observations are encouraging.

Methicillin-resistant Staphylococcus aureus (MRSA) is well known as one of the most frequent etiological agents of healthcare-associated infections. The epidemiology of MRSA is evolving with emergence of community-associated MRSA, the clonal spread of some successful clones, their spillover into healthcare settings and acquisition of antibacterial drug resistances. Neonatal intensive care unit (NICU) patients are at an especially high risk of acquiring colonization and infection by MRSA. Epidemiology of MRSA in NICU can be very complex because outbreaks can overlap endemic circulation and make it difficult to trace transmission routes. Moreover, increasing prevalence of community-associated MRSA can jeopardize epidemiological investigation, screening and effectiveness of control policies. Surveillance, prevention and control strategies and clinical management have been widely studied and are still the subject of scientific debate. More data are needed to determine the most cost-effective approach to MRSA control in NICU in light of the local epidemiology.

Hepatitis delta virus (HDV) is a defective RNA virus that depends on hepatitis B virus (HBV) for its lifecycle. Treatment of chronic HDV infection is difficult as it does not have an enzymatic function as a target, such as polymerases and proteases of HBV and hepatitis C virus. Recently, it has been suggested that farnesyl transferase could be an enzymatic target. Currently, interferon is the only agent against HDV infection. Virological response has risen to 20-47% with pegylated interferon. Monotherapy of nucleos(t)ide analogs are ineffective against the HDV infection, but adefovir and pegylated interferon combination therapy have had some advantages for reduction of HBV surface antigen (HBsAg) levels. Recent studies suggest that measuring HBsAg levels during treatment could be more meaningful than HDV RNA negativity to predict virological response. Prenylation inhibitors that can affect the interactions between the large HDV antigen and HBsAg in the HDV virion are expected treatments for HDV infection. More studies are needed to understand the molecular mechanisms of HDV to manage the disease.

West Nile virus (WNV), the causative agent of West Nile fever and West Nile neuroinvasive disease in humans, has become endemic in many countries in all continents. Concerns on long-term mobility from WNV have arisen from recent studies that reported chronic kidney disease in patients who recovered from WNV infection, supported by data from animal models that showed prolonged excretion of the virus with urine. The purpose of this review is to summarize and discuss the results of studies in the literature that investigated WNV infection of the kidney in humans and in animal models and WNV excretion with urine, the potential damage to the kidney caused by WNV infection, the risk of WNV disease in kidney transplant recipients, the significance of detecting WNV in urine and its use in the diagnosis of WNV infection, and kidney involvement by other mosquito-borne flaviviruses.

Evaluation of: Mohan GS, Li W, Ye L, Compans RW, Yang C. Antigenic subversion: a novel mechanism of host immune evasion by Ebola virus. PLoS Pathog. 8(12), e1003065 (2012). Ebola viruses encode two glycoproteins (GPs): a membrane-associated GP that is present in the viral membrane and mediates viral attachment and entry into host cells; and a secreted, nonstructural glycoprotein (sGP) that is identical to GP over approximately 90% of its length. A recent study by Mohan and colleagues attributes a novel immune evasion mechanism dubbed 'antigenic subversion' to sGP. Using DNA immunization in mice, the authors demonstrate that sGP elicits antibodies that crossreact with GP, but these antibodies are non-neutralizing. Coimmunization with sGP plus GP or sequential immunizations with GP and sGP direct the host antibody response toward non-neutralizing epitopes. Therefore, the production of sGP may prevent effective neutralization of the virus during Ebola virus infection, and may reduce the effectiveness of vaccines that rely upon neutralizing antibody responses.

Chronic HBV and HCV are progressive diseases leading to cirrhosis and liver transplantation. Persistent viral eradication or suppression can positively affect the natural course of the infection, by preventing disease progression. Since its introduction more than 30 years ago, IFN-α has represented the foundation of HBV and, lately, anti-HCV treatment. Pegylation of the IFN-α molecule (PegIFN-α2a) has provided improvements in both efficacy and administration schedule, thus becoming part of the standard-of-care regimen for HCV and HBV therapy in the last 10 years. Currently, treatment of finite duration with PegIFN-α2a may achieve a sustained virological response off-treatment and HBsAg seroconversion. PegIFN-α2a will most likely remain the backbone of HCV treatment for the next few years, despite the availability of direct-acting antivirals that are expected to improve cure rates. However, many efforts are concentrated on developing new compounds, with the goal of administrating all oral regimens and eliminating PegIFN from anti-HCV treatment.