Infectious Disorders - Drug Targets - Volume 16, Issue 1, 2016

Background: Epstein Barr Virus (EBV) is a common gamma herpes virus with a high prevalence in adults worldwide. Infection is mostly latent in affected individuals. EBV has been linked mostly with lymphoid malignancies but its association with epithelial and other non-lymphoid malignancies has also been described. Methods: Using MEDLINE, the terms “Epstein Barr Virus AND Malignancy”; “EBV mechanisms”; EBV treatment AND outcomes”; and “EBV prevention” were combined to find articles pertinent to this review. The search was limited to more recent publications between January 1, 2000 and August 1, 2015. Results: In this review, we describe current knowledge about the pathogenesis of EBV-related malignancies and evaluate their therapeutic options and outcomes. Current and prospective novel preventive options are also critically reviewed. Conclusions: EBV infection is a very common viral infection worldwide and has been implicated in various malignancies including lymphomas, gastric cancer, and nasopharangeal cancer. Patients with EBV positive PTLD and NK/T-cell lymphoma tend to have a better prognosis than EBV negative patients. On the other hand, patients with EBV positive HL or DLBCL tend to have a poorer prognosis especially in elderly patients. Further research is needed to better understand if EBV status is a true prognostic indicator in most malignancies. Treatment approaches remain similar for EBV positive and EBV negative malignancies while the use of novel agents remain under investigation. EBV vaccination trials are underway and these remain a potentially effective strategy to prevent EBV-related malignancies and the associated sequela.

Prosthetic joint infections (PJI) in orthopedic related devices (ORD) are major issues following replacement of joints. It results in serious morbidity and mortality and is expensive to treat and manage. The pathogenesis of these infections is related to the presence of biofilm on the metallic and plastic surfaces of the devices. This biofilm results in poor penetration of antibiotics resulting in persistence and difficulty in eradication of the infection despite appropriate antibiotics. This paper summarizes the present data of biofilm as it relates to PJI/ORD.

Causative agents of infectious disease that are multidrug resistant bacterial pathogens represent a serious public health concern due to the increasingly difficult nature of achieving efficacious clinical treatments. Of the various acquired and intrinsic antimicrobial agent resistance determinants, integral-membrane multidrug efflux pumps of the major facilitator superfamily constitute a major mechanism of bacterial resistance. The major facilitator superfamily (MFS) encompasses thousands of known related secondary active and passive solute transporters, including multidrug efflux pumps, from bacteria to humans. This review article addresses recent developments involving the targeting by various modulators of bacterial multidrug efflux pumps from the major facilitator superfamily. It is currently of tremendous interest to modulate bacterial multidrug efflux pumps in order to eventually restore the clinical efficacy of therapeutic agents against recalcitrant bacterial infections. Such MFS multidrug efflux pumps are good targets for modulation.

Background: Animals’ venomous secretions or peptides obtained from those secretions are used in the development of new therapeutic agents. The aims of this study were to investigate antimicrobial and antiviral activity of four different venoms obtained from the frog named Bufo arenarum and the snakes Crotalus atrox, Causus rhombeatus and Naja melanoleuca. Methods: Antimicrobial activities of the venoms tested against 9 bacteria, 1 yeast, 1 fungal species and 2 viral species based on micro-well dilution assay and antiviral assay. Results: Four different venoms were examined to evaluate the antimicrobial and antiviral activity against 9 bacteria, 1 yeast and 1 fungal and 2 viral species. None of the venoms exhibited anticandidal or antifungal activity. However, all of the four venoms tested were found to have both antibacterial and antiviral activities. Conclusion: This is the first study demonstrating that venoms of Crotalus atrox and Bufo arenarum have antibacterial activities against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, Bacillus subtilis, Aeromonas hydrophila, Aeromonas spp. Antiviral activities of 4 venoms against Poliovirus and Adenovirus were also investigated for the first time.

Background: Infection ‘is a common complication in children with hematological malignancies’ during febrile neutropenia. ‘Objective: The aim of this study was to’ evaluate common bacterial and fungal pathogens in children with hematological malignancies during febrile neutropenia in single center Egyptian study. ‘Patients and Methods: This study was carried out on 90’ children with hematological malignancies during febrile neutropenia including 54 with ALL, 27 with AML and 9 with NHL with their ages ranging from 2.5- 13 years and mean age value of 5.5 ± 3.5. Complete blood count, BM aspiration, and blood and throat cultures were done for all patients. Results: Positive bacterial growth was found in 54 cultures (30%) including 42 blood cultures and 12 throat cultures with significantly higher Gram negative bacterial growth. Staphylococcus aurous and Pseudomonas aeruginosa were the most common Gram positive and negative organisms respectively. Cefepime was the most effective antibiotic against isolated bacterial growth where 80% of Gram negative bacterial growth was sensitive to it, 20% showed intermediate response and no Gram negative Cefepime resistance was recorded. On the other hand, 62.5% of Gram positive organisms was sensitive to it, 25% showed intermediate response and Gram positive Cefepime resistance was found in 12.5%. Ampicillin sulbactam ‘was the most effective antibiotic against Gram positive’ organisms with 100% sensitivity. Positive fungal growth was found in 36 cultures (20%) including 30 throat cultures and 6 blood cultures and all fungal isolates were candida. Amphotericin was active against 100% of fungal isolates, while resistance to Fluconazole and Voriconazole was found in 25% and 33.33% respectively. Conclusions: ‘Gram negative is still more common than gram positive’ infections and fungal infection is also a common cause of fever in patients with hematological malignancies during neutropenia and must be taken in consideration in every case of febrile neutropenia.

Background: Over the last two decades, Candida blood stream infections (BSIs) have been increasingly reported from various parts of the world. Recent studies on invasive candidiasis have documented the emergence of non albicans Candida (NAC) species as major pathogens. Candida spp. belonging to NAC group often demonstrate intrinsic or acquired or both resistance to fluconazole which is the most readily available and prescribed cost effective antifungal agent. Echinocandins are recent addition to antifungal armamentarium and are now increasingly used as first line drugs for treatment and management of candidemia. Objective: The aim of this study was to determine echinocandin susceptibility profile of fluconazole resistant Candida Spp. isolated from BSIs. Results: Predominance of NAC spp was noted. C. glabrata followed by C. krusei and C. parapsilosis demonstrated high resistance to fluconazole. Echinocandins demonstrated good activity against all Candida spp. Conclusion: As species distribution of Candida isolates varies greatly by country and by different health care setups within the country, species identification and antifungal susceptibility results are often useful to guide the selection of empiric treatment and design of local therapeutic guidelines. On the basis of antifungal susceptibility profile of the isolates, caspofungin can be suggested as a useful antifungal drug for the treatment of candidemia due to fluconazole resistant species.

Infections are one of the major complications after allogeneic stem cell transplantation (allo-SCT). Disseminated infections with human adenoviruses species A, B or C are associated with a lethality of 24 to 36 %. Fatal outcome is usually observed with high viral loads in blood (median peak HAdV DNAemia 108 copies/mL). Here we report two adult patients with disseminated infection with human adenovirus C2 after allo-SCT. Interestingly, both patients developed bacterial septicaemia following the disseminated HAdV infection. Despite lower peak adenoviral loads in blood (<106 copies/mL) than usually reported for fatal cases of HAdV infection and broad spectrum antimicrobial therapy both patients experienced a rapidly fatal outcome. These cases shared the following similarities: disseminated adenovirus infection, adenovirus pneumonia, neurological symptoms and bacterial septicaemia. This suggests that in patients undergoing allo-SCT, viral bacterial co-infections worsen the clinical outcomes.