Flu Season and Trehalose

Most of us who are practicing medicine know that we are in a very active flu season. This was brought home to me when last week trying to admit a patient to the hospital from the office. She was a bone marrow transplant patient who had severe diarrhea and dehydration probably secondary to C. difficile. Hospital admissions said the patient had to be sent to the Emergency Room because the hospital was full due to the flu epidemic.

Nationwide there has been a dramatic increase in the number of hospitalizations due to influenza over the past week from 13.7 to 22.7 per 100,000 (1). Influenza A(H3N2) has been the most common form of influenza reported this season. These viruses are often linked to more severe illness, especially in children and people age 65 years and older. Fortunately, the CDC also says that the flu cases may be peaking. However, at least 11 to 13 more weeks remain in the influenza season and strains other than A(H3N2) will undoubtedly show up.

Clinicians are reminded that in addition to the flu vaccine for prevention, to begin neuraminidase inhibitor antivirals early. Patients at high risk for complications (elderly, children, pregnant women, patients with chronic diseases such as diabetes, heart disease and asthma) should have treatment begun before laboratory confirmation (2).

Many clinicians have noted an increase in the incidence and severity of C. difficile infection over the past 15 years. Because the infection occurs after high dose antibiotics or antibiotics prescribed over a long period of time, it was assumed that this was the cause of the rising rates of infection. However, an alternative explanation was offered by an article appearing last week in Nature (3). The authors showed that two epidemic ribotypes of C. difficile (RT027 and RT078) have acquired unique mechanisms to metabolize low concentrations of the disaccharide trehalose increasing virulence. Trehalose is a sugar widely distributed in nature and used mostly a stabilizing agent in processed foods and products (including influenza vaccine). It was introduced about the same time as the upsurge in C. difficile infection began in the early 2000's.

Richard A. Robbins, MD

Editor, SWJPCC

References

1. Brooks M. US influenza activity widespread and intense, may be peaking. Medscape. January 12, 2018. Available at: https://www.medscape.com/viewarticle/891265?nlid=120062_3901&src=wnl_newsalrt_180112_MSCPEDIT&uac=9273DT&impID=1533392&faf=1 (accessed 1/14/18). 
2. Campbell A. 2016-2017 influenza antiviral recommendations. Medscape. January 9, 2017. Available at: https://www.medscape.com/viewarticle/873988?src=par_cdc_stm_mscpedt&faf=1 (accessed 1/14/18).
3. Collins J, Robinson C, Danhof H, et al. Dietary trehalose enhances virulence of epidemic Clostridium difficile. Nature. 2018 Jan 3. [CrossRef] [PubMed]

Cite as: Robbins RA. Flu season and trehalose. Southwest J Pulm Crit Care. 2018;16(1):44-5. doi: https://doi.org/10.13175/swjpcc011-18 PDF 

Combination Influenza Therapy with Clarithromycin-Naproxen-Oseltamivir Superior to Oseltamivir Alone

As we enter the influenza season, Ivan et al. (1) are reporting in Chest that oseltamivir-clarithromycin-naproxen combination for treatment of serious influenza results in reduced mortality, less frequent ICU admission, and shorter hospital-stay compared to oseltamivir alone. From February to April 2015, the authors conducted a prospective open-label randomized-controlled trial. Adult patients hospitalized for A(H3N2) influenza were randomly assigned to a 2-day combination of clarithromycin 500mg, naproxen 200mg and oseltamivir 75mg twice daily, followed by 3 days of oseltamivir; or oseltamivir 75mg twice daily for 5 days as control (1:1). Among the 217 influenza A(H3N2) patients enrolled, 107 were randomly assigned to the combination treatment. Ten patients succumbed during the 30-day follow-up. The combination treatment was associated with lower 30-day mortality (p=0.01), less frequent ICU/HDU admission (p<0.001), and shorter hospital-stay (p<0.0001). Multivariate analysis showed that combination treatment was the only independent factor associated with lower 30-day mortality (p=0.04). The authors advised further study on the antiviral and immunomodulatory effects of this combination treatment, but those caring for severely ill patients with influenza might wish to consider combination therapy since all these drugs are available.

Richard A. Robbins, MD

Editor, SWJPCC

Reference

1. Hung IF, To KK, Chan JF, et al. Efficacy of clarithromycin-naproxen-oseltamivir combination in the treatment of patients hospitalized for influenza A(H3N2) infection: an open-label, randomized controlled, phase 2b/3 trial. Chest. 2016 Nov 21. [Epub ahead of print] [CrossRef] [PubMed]

Cite as: Robbins RA. Combination influenza therapy with clarithromycin-naproxen-oseltamivir superior to oseltamivir alone. Southwest J Pulm Crit Care. 2016;13(6):302. doi: https://doi.org/10.13175/swjpcc136-16 PDF