Influenza and MRSA Pneumonia: More Than an 'Achoo' to the Flu

Paul G. Auwaerter, MD


March 05, 2018

This is Paul Auwaerter with Medscape Infectious Diseases, speaking from the Johns Hopkins School of Medicine. I've just finished a few weeks in the hospital on the infectious diseases consultation service. With the busy H3N2 influenza this winter, I'm sure many of you have also seen a number of serious hospitalizations and deaths from this infection.

Two cases of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia in patients who ended up on ventilators in the intensive care unit prompted some questions on our team. For example, why do S aureus and MRSA in particular seem to have such a predilection for causing secondary bacterial pneumonia?[1] How do you best treat this? And the third question would be, what kind of prevention strategies work?

With respect to the genesis, murine and primate models information has suggested that influenza as a viral infection may prompt the immune system to produce certain interferons that might have a negative impact on chemokines and other factors related to neutrophil recruitment and function.[2,3] This may be one aspect.

Two years ago, a study by Reddinger and colleagues[4] was quite interesting. They took a different hypothesis. They thought, in the setting of a severe influenza infection with very high fevers, cortisol and stress responses, and perhaps even hypoperfusion, that these factors may disrupt the biofilm in the nasal passages. About one third of people harbor S aureus in the nostrils, and dispersal from the biofilm in this setting may lead to aspiration of S aureus into the lungs, which might be more susceptible to infection. It's an interesting hypothesis that has been backed up at least in their studies, and it raises the question of whether antipyretics may have some benefit in this avenue.

The second question—how do you best treat MRSA pneumonia?—has been debated a long while, with vancomycin and linezolid being the leading candidates. A number of meta-analyses have not suggested any difference between these two drugs, although vancomycin, in many of these studies, has been underdosed.[5] A study in 2012 by Wunderink and colleagues[6] comparing head-to-head linezolid and vancomycin found that linezolid was the winner, with a 58% versus 47% clinical benefit in favor of linezolid, with superior microbiological eradication. However, at the 60-day mark, there was no difference in all-cause mortality.

The Infectious Diseases Society of America/American Thoracic Society recommendations for hospital-acquired and ventilator-associated pneumonia[7] (which are slightly different from postinfluenza MRSA pneumonia) both say that they have no preference among those drugs. Many times, we take individual patient factors into account; for example, a concern for nephrotoxicity or perhaps cytopenia might cause one to favor vancomycin over linezolid.

The last area is prevention. With this ferocious influenza season, it has become obvious that we need to do better with prevention. Specifically, influenza vaccines need to be reformulated every year, and this year, it was estimated that the flu vaccine effectiveness was only in the mid-30% range, although it was perhaps better among pediatric populations.

Many people, including both adults and children, don't get immunized. There seems to be a genuine need, that I view as quite urgent, that more effort be given to developing a universal influenza vaccine—one that might be more durable and would cover most strains. This not only would lead to less influenza, hospitalizations, and deaths, but also would have a huge economic impact from less absenteeism from work or school, as well as the benefits to individual health.

I was honored to be asked by Senator Edward Markey from Massachusetts to speak about legislation that he introduced last week asking for a $1 billion investment in science and development for production of a universal influenza vaccine. It is certainly right to push this along at a faster pace than has been allocated by our current agencies.

Thanks very much for listening.


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