Emerging novel and antimicrobial-resistant respiratory tract infections: new drug development and therapeutic options.

The emergence and spread of antimicrobial-resistant bacterial, viral, and fungal pathogens for which diminishing treatment options are available is of major global concern. New viral respiratory tract infections with epidemic potential, such as severe acute respiratory syndrome, swine-origin influenza A H1N1, and Middle East respiratory syndrome coronavirus infection, require development of new antiviral agents. The substantial rise in the global numbers of patients with respiratory tract infections caused by pan-antibiotic-resistant Gram-positive and Gram-negative bacteria, multidrug-resistant Mycobacterium tuberculosis, and multiazole-resistant fungi has focused attention on investments into development of new drugs and treatment regimens. Successful treatment outcomes for patients with respiratory tract infections across all health-care settings will necessitate rapid, precise diagnosis and more effective and pathogen-specific therapies. This Series paper describes the development and use of new antimicrobial agents and immune-based and host-directed therapies for a range of conventional and emerging viral, bacterial, and fungal causes of respiratory tract infections.

Effects of dietary supplementation with conjugated linoleic acid on experimental human rhinovirus infection and illness.

BACKGROUND: Because studies suggest that the dietary supplement conjugated linoleic acid (CLA) has immunomodulatory activities that might benefit common colds, we performed two studies of CLA effects in experimental human rhinovirus (HRV) infection. METHODS: The first study explored whether CLA supplementation (Safflorin; Loders Croklaan, BV, Wormerveer, the Netherlands) altered the virological or clinical course of experimental HRV infection, and the second explored whether CLA affected the frequency and severity of HRV cold-associated sore throat and cough. The trials were randomized, double-blinded and placebo-controlled. In total, 50 healthy volunteers aged 18-45 years and susceptible to HRV type-39 (serum neutralizing antibody titre < or = 1:2) participated in study 1 and 80 similar volunteers susceptible to Hank's HRV participated in study 2. Participants ingested CLA 2 g/day or placebo for 4 weeks before and 4 days following intranasal HRV inoculation. The primary endpoint for study 1 was the frequency of colds and for study 2 was the symptom severity scores for sore throat and cough. RESULTS: In study 1, 10/24 (42%) placebo compared with 7/21 (33%) CLA participants developed colds (P = 0.53). CLA was associated with significant reductions in mean scores for cough (0 CLA versus 0.9 placebo) and sore throat (0.8 CLA versus 2.9 placebo). In study 2, clinical colds developed in 19/33 (58%) placebo and 27/43 (63%) CLA participants. Symptom scores for cough (0.9 CLA versus 1.0 placebo) and sore throat (2.6 CLA versus 3.2 placebo) were not significantly different. Similarly no differences in nasal viral titres or serological responses were found. CONCLUSIONS: CLA dietary supplementation had no consistent effects on the virological or clinical course of experimental HRV colds. A larger study would be required to detect more subtle effects of CLA on HRV cold-associated symptoms.