Maryn McKenna

Journalist and Author

NEJM: Antibiotics for pneumonia in H1N1

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The New England Journal of Medicine has been running an open-access blog on H1N1 flu, and they’ve put up a post on when to give antibiotics to prevent secondary bacterial pneumonia, including MRSA pneumonia, in flu patients.

There’s a table of key clinical points to consider, and these important points are made:

For the child or adult admitted to a hospital intensive care unit in respiratory distress, we believe that empirical initial therapy with broad-spectrum antibiotics to include coverage for MRSA, as well as Streptococcus pneumoniae and other common respiratory pathogens, is appropriate.
For the previously healthy child or adult with influenza who requires admission to a community hospital and has features that suggest a secondary pneumonia (Table 1), we would recommend empirical treatment with a drug such as intravenous second- or third-generation cephalosporin, after an effort has been made to prove the association with influenza and to get adequate lower respiratory tract specimens for Gram’s stain and bacterial culture.
If the Gram’s stain suggests the presence of staphylococci or if there is a rapidly progressive or necrotizing pneumonia, an additional antimicrobial agent to cover MRSA is appropriate. …
We do not believe that initial coverage for MRSA is indicated in all patients who are thought to have secondary bacterial pneumonia.

So, to recap:

  • Development of apparent pneumonia in the presence of flu should be met with antibiotics that will treat drug-sensitive bacteria, along with a test to show which bacteria are causing the illness.
  • If staph is present (or the pneumonia appears very serious), then the antibiotics should be upped to one that can control MRSA.
  • But if the pneumonia is serious enough to send a patient straight to the ICU, then drugs that can quell MRSA should be started right away.

For anyone concerned about pneumonia in the aftermath of H1N1, this is worth bookmarking.

CDC warns of deaths from H1N1 flu + bacterial infections

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Over at CIDRAP, my colleague Lisa Schnirring writes tonight about the CDC’s concern over increasing numbers of deaths from bacterial pneumonia in people who have come down with H1N1 flu.

We’ve talked about this before here. Our concern of course has been MRSA, and there is good evidence that there have been fatal MRSA infections in flu victims. But the primary culprit now is not MRSA but pneumococcus (S. pneumoniae):

Anne Schuchat, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases, told reporters at a press briefing that the CDC is seeing an increasing number of invasive pneumococcal disease cases around the country, but the numbers were particularly high in Denver at a time when pandemic H1N1 activity was peaking in the area.
Over the past 5 years the Denver area averaged 20 pneumococcal disease cases in October, but this year the area recorded 58, and most were in adults between the ages of 20 and 59, many of whom had underlying medical conditions.
Health officials expect to see more pneumococcal disease when seasonal flu circulates, but the infections typically strike people who are older than 65. In past pandemics secondary bacterial pneumonia infections, particularly those involving Streptococcus pneumoniae, frequently contributed to illnesses and deaths.

This is particularly troubling and sad because we have good vaccines for pneumococcus, one for adults and a different one for children. Only, people are not taking them: Uptake is only about 25% in high-risk groups and much lower in the general population, despite urgings from CDC and other health advisory boards.

Perhaps it’s not surprising that people have not heeded advice to get the pneumococcus vaccine as a protection against flu’s worst effects, given that uptake of the flu vaccine itself has been so low. But if you or someone you love is in a high-risk group, it would be a really good idea to rethink that.

More evidence of MRSA involvement in H1N1 flu

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When the H1N1 pandemic started at the end of last April, few of the case-patients seemed to have any secondary bacterial infections. This was unusual: In the 3 20th-c pandemics, the only ones for which there are good records, bacterial pneumonias seem to have accounted for a high percentage of illness and death. But H1N1 was unusual in a number of ways, and so health authorities wrote down the lack of bacterial infections as one more quirk of this novel strain.

Comes now the CDC to say that while that may have been the case in the spring, it is not now. In a conference call conducted Monday for doctors, which I covered for CIDRAP, the agency said that out of 77 deaths for which it had excellent autopsy data (a small subset of the deaths so far), 22, or 29%, had some bacterial co-involvement. Among the 22, the leading bacterium was S. pneumoniae (or Pneumococcus), but S. aureus was the second leading cause, with 7 cases, and 5 of those cases were MRSA.

(There is not yet anything online from that call to link to. A transcript is promised, and the CDC reps conducting the call said the data will be out soon in the MMWR. I’ll update when possible.)

In fact, there is an emerging literature on the role of bacterial infections in illness and deaths in this flu, and an emerging consensus that bacterial infections are playing a bigger and more serious role than was thought at first. At the ICAAC meeting two weeks ago (more on that soon), KK Johnson et al of the Women’s and Children’s Hospital of Buffalo, N.Y., along with researchers from two other institutions, described two severe and ultimately fatal infections with H1N1 complicated by community-strain MRSA. The victims were children, a 9-year-old girl and a 15-year-old boy, who arrived at the emergency room several days after being seen for mild flu symptoms. Both children died of necrotizing pneumonia, one 11 days after being hospitalized and one 3 days. Cite (no link available): K.K. Johnson, H. Faden, P. Joshi, J. F. Fasanello, L. J. Hernan, B.P.Fuhrman, R.C.Welliver, J.K. Sharp and J. J. Schentag, “Two Fatal Pediatric Cases of Pandemic H1N1/09 Influenza Complicated by Community-Acquired Methicillin-Resistant Staphylococcus aureus (CA-MRSA),” poster G1-1558a.

Finally, there is one recent paper that is online, and it describes MRSA necrotizing pneumonia plus flu in an adult, not a child. It comes from Hong Kong, from a group that were the first to describe SARS pneumonia and thus have a lot of experience in surfing the early wave sof a pandemic. In this new paper in the Journal of Infection, they describe the death from necrotizing pneumonia of a healthy 42-year-old man who was in the hospital only 48 hours. They believe this is the first H1N1+MRSA death to be recorded in the medical literature, and so they use the opportunity to issue a warning to doctors: If a flu patient arrives with what appears to be secondary pneumonia, drugs that can treat MRSA must be prescribed, or the infection will flourish unchecked and death will result. The cite is: Cheng VCC, et al., Fatal co-infection with swine origin influenza virus A/H1N1 and community-acquired methicillin-resistant Staphylococcus aureus, J Infect (2009), doi:10.1016/j.jinf.2009.08.021.

We’ve been talking since the beginning of this pandemic, and before that, about the unique hazards of MRSA + flu coinfection. (Archive of posts here.) It’s important ot understand that the bacterial pneumonias now being recorded are not only due to MRSA; Pneumococcus is playing a role as well. That is important because, unlike MRSA, we have vaccines against Pneumococcus; in the United States, one vaccine is approved for children and a second related one for adults. With no MRSA vaccine anywhere, and no H1N1 vaccine yet, it is worth considering whether to take a pneumococcal vaccine for additional protection as this pandemic unfolds.

A parent’s plea and confusion

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I want to highlight a comment that was left on Labor Day by a woman named Valorie in Arkansas (thank you for reading, Valorie). She said:

I am just now learning about all of this and am very concerned about my 12 year old daughter. We were only 10 days into the school year, and she came down with the flu about a week ago. The rate at which it spread within her school as well as to me (her mother) and 2younger siblings was astonishing! We were all running high fevers within 24 hours of the onset of her first noticeable symptoms. Her junior high (which has approximately 500 students) had between 130 and 140 students absent last week due to flu like symptoms. However, the school is saying this is not H1N1 because it is too early in the season to be the actual flu. (This is absurd in my opinion.) Now, on our oldest daughter’s 5th day into the illness she has developed an MRSA infection from a small boil on her tummy. Within a day, it has swollen from a golf ball size to larger than a baseball in size. She now has 2 places of infection and is running a fever of about 101.7 on her 6th, almost 7th day of illness. Her doctor has placed her on a high powered antibiotic, but she is feeling so ill that I am scared to death for her, especially reading about the complications from having both the flu and MRSA. Do you think the oral antibiotics should take care of it, or do you think we need to have her admitted for IV antibiotics. I’ve just been surprised at how long this illness has lasted and how ill she still seems to be. No one seems to want to talk about the flu, much less any other possible complications in order to keep everyone else from panicking. I just want to get my daughter well and keep her safe. Any advice? Thanks so much for your time.

I wanted to highlight Valorie’s comment for a couple of reasons.

First, because it captures the way in which H1N1 has been ripping through schools in most places where school has returned to session. Schools in the Southeast tend to go back before the Northeast or the West; in Atlanta, where I used to live and where schools reopen long before Labor Day, H1N1 has gone through schools like a hot knife. Second, it shows how little the education about flu being pushed out by the CDC (and by others including my colleagues at CIDRAP) has penetrated: There has been H1N1 flu all over the place this summer, and it’s precisely because it is “too early in the season” that we know it is H1N1 and not the seasonal flu.

But what is most concerning and touching is Valorie’s confusion over which drugs her daughter should be taking, and whether her daughter’s physician is giving enough attention to her illness. Despite years of clinical experience, figuring out which drugs to give for MRSA is not easy. That’s first because many of them are old and now generic-only drugs for which clinical trials (in the context of this disease) were never done; and second because community MRSA’s resistance profile keeps changing as it picks up additional resistance factors.

The CDC dealt with this problem of what drugs to give in a meeting held in 2004 and a report issued in 2006. The report, going drug by drug, is here (caution, it’s 24 pages) and a flow chart summarizing the findings is here. Either is useful to have and to take to doctors if you feel uncomfortable about what is being prescribed or about a patient’s lack of progress.

Valorie, I hope your daughter does better. Keep us posted.

Child deaths from flu + MRSA: CDC confirmation

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Hello again, constant readers. It’s been an exciting few weeks at Casa Superbug. I’ll spare you the details — most of them are both grueling and trivial — but out of the murk, here is a piece of excellent news: SUPERBUG has been edited, revised and sent back to the publisher, who has sent it into production. Yes, it’s actually beginning to become a book. There are many more steps to go, but it it is finally, really on its way.

Meanwhile, there is a ton of MRSA news to catch up on, which I will roll out over the next week or so. First: For those of you who don’t read the CDC’s weekly bulletin (called the MMWR, for Morbidity and Mortality Weekly Report. It’s the best-read magazine you’ve never heard of. It’s free. Go already), there was an important and disturbing report last Friday, reporting the case details of children who have died from H1N1 flu.

As of August 8, the CDC said, 477 people had died in the US from H1N1, and 36 of them were children and teenagers. Out of those 36:

  • 7 were younger than 5
  • 24 had at least one high-risk medical condition, many of them neurological (developmental delay, cerebral palsy) or pulmonary; 12, or one-third, did not
  • 23 had some pathologic analysis done during their illness or after their deaths
  • 10 had bacterial co-infections
  • of those 10, 5 had staph infections
  • 3 of the staph infections were MRSA.

Let’s bring the first and last terms of that equation together: 36 children; 3 known MRSA infections. Though it could be an underestimate (because 13 children had no pathology done), that is a non-trivial 8%.

The report splits the data on the child deaths a number of different ways, and reveals details that are important to note. Six of the bacterial infections (four staph) were in children older than 5 who did not have any underlying conditions; they were healthy, normal kids before developing flu. Of the 7 kids younger than 5, 2 had a bacterial infection; again, neither child had a high-risk condition.

How worrisome are these numbers? It’s hard to say with precision, but they are certainly not good news. The CDC has only been counting child deaths from flu for a few years, and the totals they have come up with are very variable: 153 in 2003-04, 47 in 2004-05, 46 in 2005-06 and 73 in 2006-07. But, important point: Those deaths were during the regular flu season, which goes from roughly October to March. These new deaths occurred between late April and early August, when there is not supposed to be any flu. What this will mean for this fall and winter, when H1N1 will still be around, and may co-circulate with seasonal flu, no one yet can say.

For our purposes, the most important point is that lethal MRSA co-infections are now confirmed to be happening in the setting of H1N1 flu. And, as the CDC paper notes, these infections happened in children who would not have been expected to have a tough course, because they had no underlying high-risk conditions:

This report also highlights the prominence of laboratory-confirmed bacterial coinfections, which were identified in 10 (43%) of the 23 children who had culture or pathology results reported. All six children who were aged ≥5 years, did not have a high-risk medical condition, and had culture or pathology results reported had an invasive bacterial coinfection, suggesting that bacterial infection, in combination with 2009 pandemic influenza A (H1N1) virus infection, can result in severe disease in children who might be otherwise healthy. Clinicians should be aware of the potential for severe bacterial coinfections among children diagnosed with influenza and treat accordingly.

Obviously those of us who are concerned about MRSA and the potential for MRSA pneumonia alongside flu have been worried about this (long archive of posts here). If there is any good news in the sad saga of these deaths, it is that the CDC has confirmed that MRSA pneumonia in H1N1 flu is a real and dangerous possibility.

So if you are concerned about this, first, bookmark the MMWR report, because it will be something to show to a physician if necessary. And second, keep in mind the potential for pneumonia if you have a young child who contracts H1N1. I am not suggesting being alarmist; if H1N1 circulates widely, doctors and ERs will be overwhelmed, and we should try not to add to their case load unless really necessary.

But on the other hand, if a child has chest pain or breathing difficulty, don’t hold back. There are online tools such as this one by Children’s Healthcare of Atlanta that can help a worried parent assess whether and when a child with flu should be taken to the ER. If you click through its steps, you’ll see that breathing difficulties and the possibility of pneumonia are things that it takes seriously, and so should we.

Another death from H1N1 flu + MRSA

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Thanks to a commenter who alerted me to this sad story: A teenager in Austin died of a combination of H1N1 flu and MRSA pneumonia. Constant readers will know that we have been watching for this for a while; MRSA pneumonia is a known and dangerous complication of any flu infection.

For stories for CIDRAP and the Annals of Emergency Medicine, I’ve been talking to ER physicians about their expectations for the fall, when the regular flu season begins and H1N1 is expected to intensify. (A friend’s school already has cases circulating.) It’s fair to say that emergency departments are unsettled about the possibility of severe complications from this flu.

H1N1 and MRSA – first disclosed case

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Readers, once again there’s a lot of MRSA-related news piling up, and I’ll try to roll some of it out over the next few days. But first, today we have to deal with an event that many of us have been anticipating, though not with any pleasure: the first known report of a MRSA death secondary to H1N1 “swine” flu infection.

We’ve talked about this possibility for weeks, because bacterial pneumonia, especially due to MRSA, is a known and frequently deadly follow-on to flu infection. (Archive of posts here.) With swine flu so common, CDC has said several times that they have been looking for post-flu bacterial pneumonia, but had not seen it. And commenters to this blog have relayed rumors — or, to be more precise, stories with no names attached — of flu patients so ill with MRSA that they have to be put on an ECMO, what we used to call a “heart-lung machine,” and sometimes do not come off.

Today, however, the Buffalo News carries the story of a New York State teen’s death from MRSA pneumonia as a sequela of flu:

Matthew Davis was a healthy Buffalo teenager who participated in sports before complaining of headaches June 13.
Within a few days, the 15-year-old student at Harvey Austin School 97 on Sycamore Street arrived seriously ill at Women & Children’s Hospital and then died Saturday, making him the first known fatality in Erie County caused by swine flu, officially known as novel H1N1 influenza.
… By the time Matthew entered the hospital, he was seriously ill with the flu, as well as co-infected with a type of bacteria known as methicillin-resistant staphylococcus aureus, or MRSA, according to health officials. (Byline Henry L. Davis)

Under normal circumstances — as in, during the past flu season — the public health advice has been to protect against MRSA pneumonia by getting a flu shot, which by preventing flu prevents the microtrauma to the lungs that allows MRSA and other bacteria to gain a foothold. In this case, though, with no H1N1 vaccine available, ir’s not clear what protective actions could have been taken.

Still, it’s terribly sad.

H1N1 flu and swine surveillance – more relevance for MRSA

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Constant readers, you probably know that yesterday the World Health Organization declared the first flu pandemic in 41 years. I want to point out for you a side issue in the H1N1 story that has great relevance for MRSA, especially ST398.

As described in this article I wrote last night for CIDRAP, three medical journal articles have now pointed out that the virus, or its major components, could have been recognized in swine months to years ago. We missed it, though, because there is so little regular surveillance in pigs for diseases of potential importance to humans. As the authors of the most recent article, in Nature, said yesterday: “Despite widespread influenza surveillance in humans, the lack of systematic swine surveillance allowed for the undetected persistence and evolution of this potentially pandemic strain for many years.”

This is important for our purposes because we know that we are in the same situation with MRSA ST398: The strain was first spotted in France, and has been a particular research project in the Netherlands, but has been found pretty much wherever researchers have looked for it, throughout the European Union, in Canada, and most recently in the United States. All told, though, the scientists concerned with it are still a small community; there is no broad surveillance looking for this bug.

And that’s a problem, for MRSA, for influenza, and for any number of other potentially zonotic diseases: We cannot anticipate the movement of pathogens from animals to humans if we don’t know what’s in the animals to start with. That’s the argument behind the “One Health” movement, which has been arguing for several years now for including veterinary concerns in human health planning. (The human health side would probably say that the animal health side just wants more money. This is also true, which does not make it unimportant.)

To understand the need to look at animal health in order to forecast threats to human health, you can’t do better than the map I’ve inserted above (because Blogger, annoyingly, won’t let me put it below). It has appeared in various forms in various publications for about 10 years but originates I think from the IOM’s Emerging and Reemerging Diseases report in the early 90s. (This iteration comes from the One Health Initiative website.) It depicts the movement of new diseases from animals to humans over about 30 years. It’s up-to-date through SARS and through the 2003-05 movement of H5N1 avian flu around the world. I’m sure H1N1 will be added soon. How many of those outbreaks could we have shortcircuited if we had been warned of their threat in good time?

Quick update: Yes on bacterial pneumonia and new flu.

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Constant readers, I thought you;d like to know that there are a few more indications that secondary bacterial pneumonia (as discussed in this post the other day) does seem to be playing a role in the severe cases of the new flu.

That’s according to this account of the WHO’s technical briefing from Wednesday, along with this item (there are three entries, go to the bottom one) from the excellent disease-alert list ProMED.

More soon.