Of course they get oseltamivir—but our author has been adding azithromycin for his high-risk patients since the 2015-16 season. He explains why.
The Unthinkable. Despite my conscientious treatment of influenza patients in 2015-16, several ended up with pneumonia and I observed the connection between post-influenza LRTIs and morbidity/mortality. I consulted the literature for guidance but found none. So, yes, I did the unthinkable and prescribed an antibiotic along with osetamivir for my high-risk patients.
1. Troeger CE, Blacker BF, Khalil IA, et al for the GBD 2017 Influenza Collaborators. Mortality, morbidity, and hospitalisations due to influenza lower respiratory tract infections, 2017: an analysis for the Global Burden of Disease Study 2017. Lancet Respir Med. 2019;7:69-89.
2. Malosh, R. et al. The risk of lower respiratory tract infection following influenza virus infection: A systematic and narrative review. Vaccine. 2018; 36:141-147.
Anathema. I know this approach greatly disturbs the ID community—but, by adding azithromycin in select patients I have have avoided having another with influenza and a LRTI. To maintain my scientific integrity, however, I performed a literature search targeting this question: “Will automatically prescribing azithromycin with oseltamivir protect my patients from LTRIs?”
Do Not Pass "Go." I found one randomized trial in the literature.3 The group randomized to oseltamivir/azithromycin recovered sooner and no subjects developed a LRTI. Not much evidence to go on. One other paper4 suggested a similar trend in hospitalized patients. Not the outpatient study I was seeking.
3. Kakeya, H, Seki M, Izumikawa K, et al. Efficacy of combination therapy with oseltamivir phosphate and azithromycin for influenza: a multicenter, open-label, randomized study. PLoS ONE. 2014;9:e91293.
4. Lee, N, Wong, CH, Chan, M, et al. Anti-inflammatory effects of adjunctive macrolide treatment in adults hospitalized with influenza: A randomized controlled trial. Antiviral Res. 2017;144:48-56.
Of Mice, Not Men. In vitro results are mixed and apply even less: adding antibiotics to antivirals helps the expansion of myeloid-derived suppressor cells5 or it enhances airway IgA in mice.6 But alas, a conflicting study showed no survival benefit in mice with influenza A (H1N1) treated with combination therapy vs controls.7 Hours of reading the literature lead nowhere.
5. Namkoong, H. Clarithromycin expands CD11b+Gr-1+ cells via the STAT3/Bv8 axis to ameliorate lethal endotoxic shock and post-influenza bacterial pneumonia. PLoS Pathog 14(4):e1006955.
6. Oral clarithromycin enhances airway immunoglobulin A (IgA) immunity through induction of IgA class switching recombination and B-cell-activating factor of the tumor necrosis factor family molecule on mucosal dendritic cells in mice infected with influenza A virus. J of Virology 2012; 86(20): 10924-10934.
7. Fage, C. The combination of oseltamivir with azithromycin does not show additional benefits over oseltamivir monotherapy in mice infected with influenza A(H1N1)pdm2009 virus. J Med Virol. 2017 Dec; 89(12):2239-2243.
Empiric Evidence Rules Here. What is a clinician to do? What we always do—rely on our clinical judgement and common sense. I will continue adding azithromycin to oseltamivir in my high-risk flu patients. And, of course, I do understand the concepts of drug resistance and economic impact. However the critical question I ask is, “Will this patient need hospitalization if he/she develops a LRTI?” If the answer is yes, I add the azithromycin.
Pre-season Prep. I try to get ahead of the season by promoting influenza and pneumococcal vaccines early. The former can reduce virility and shorten symptom duration. Pneumococcal vaccination is important because about one-third of patients hospitalized with CAP have a coinfection with Streptococcus pneumoniae.8
Reference: Clin Infect Dis. 2010;50:202-209.
Disaster Insurance. There is very little guidance on managing LRTIs in the presence of flu-a dangerous combination. So when that very sick patient presents to us, our clinical acumen and years of experience are the best guides. The simple guidelines I use have kept my practice free of LRTIs in my influenza patients. I offer them for your consideration in this year’s influenza season.