Maryn McKenna

Journalist and Author

Once again, flu and bacterial co-infection

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With the H1N1 pandemic trending down, it may seem that the question of how much bacterial co-infection affects the outcome of flu is less important than it was. But though the pandemic is subsiding — for ever, for this season, or just until a third wave, who can say — researchers are just now getting enough good data to be able to make solid observations about what happened during the past 10 months.

Case in point: Writing in the journal Public Library of Science (PLoS) ONE, a team of researchers from Australia has pinpointed the incidence of MRSA co-infection during flu in two hospitals in Perth last summer, which was the Australian winter and the height of their flu season. Of 252 patients admitted for H1N1 infection, 3 were identified during treatment as having MRSA pneumonia. They survived, but two other patients who died were found to have MRSA pneumonia during post-mortem exams.

There were 3 female and 2 males, aged between 34 and 79 years… Two patients lived at the same long-term care facility, whilst the other patients lived independently in the community. Four of the 5 patients had conditions that may have increased their risk of pneumonia, including quadriplegia (two patients) asthma (one patient), cirrhosis (one patient) and diabetes mellitus (one patient). Two of the 5 cases (patients 3 and 4) had known MRSA infection/colonization prior to the onset of their illness (with the same cMRSA clone that subsequently caused their co-infection).

 There are some interesting points embedded here. First, incidence: In the Australian patients, MRSA pneumonia was much more common. The Perth researchers found 5 MRSA cases out of 252 flu patients. When the CDC analyzed the occurrence of MRSA pneumonia in flu last summer, it found only 1 case out of 272. Second, treatment: None of the 5 patients got antibiotics that would have affected MRSA — even though two of them were already known to be MRSA carriers. The possibility of MRSA pneumonia subsequent to flu seems not to have occurred to the health professionals taking care of them.

And third, the pathogen: The 5 Australian cases were caused by 3 community MRSA strains that are common in Australia — but only one of the 3 made PVL, the toxin that has so frequently been associated with MRSA pneumonia. That is interesting, and troubling at the same time. At this point, the association of PVL and necrotizing pneumonia has become practically taken for granted; and yet here are two strains that did not make PVL and yet caused severe and fatal pneumonia. It may be an indication that the inflammation that flu causes in the lung can open the door to more severe damage even when PVL is not present; it’s certainly an indication that the absence of PVL does not signal a mild or not-dangerous strain.

The cite is: Murray RJ, Robinson JO, White JN, et al. 2010 Community-Acquired Pneumonia Due to Pandemic A(H1N1)2009 Influenzavirus and Methicillin Resistant Staphylococcus aureus Co-Infection. PLoS ONE 5(1): e8705. doi:10.1371/journal.pone.0008705.
Simultaneously, a new paper in the American Journal of Pathology seeks to clarify how often and in what circumstances bacterial superinfection becomes a risk during flu. Using a range of mice — both healthy ones, and “knockout” mice bred to be without particular immune-system components — researchers from San Diego confirmed that infections with flu and with Haemophilus influenzae can be lethal when the flu infection precedes the bacterial one. That was true even for infections that, if experienced separately, would not have been lethal; it was the synergy of the two infections, flu first followed by the bacterial infection, that caused the high mortality rate. The results may not be directly applicable to human medicine (Do you all know the old flu-research saying, “Mice lie and ferrets mislead?”), but they are an important indicator both of the seriousness of bacterial infection after flu, and also of the potential vulnerability of even healthy beings to that one-two punch.
The cite is: Lee LN, Dias P, Han D, et al.: A mouse model of lethal synergism between influenza virus and Haemophilus influenzae. Am J Pathol 176: 800-811.

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.

It’s World Pneumonia Day

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Readers, we talk all the time here about the unexpected and deadly attack of MRSA pneumonia, both on its own and as a sequela of influenza infection. But we should acknowledge that MRSA pneumonia is part of an epidemic of pneumonia, an under-appreciated disease of severe lung inflammation that takes the lives of 2 million children each year around the world.

Today, Nov. 2, has been declared World Pneumonia Day by an enormous coalition of global health organizations that includes UNICEF and Save the Children. (Mis amigos Latinos sabrán que está hoy también Dia de los Muertos. Fitting, no?) From their press release: “Pneumonia takes the lives of more children under 5 than measles, malaria and AIDS combined. The disease takes the life of one child every 15 seconds, and accounts for 20% of all deaths of children under 5 worldwide.“

World Pneumonia Day is being marked by events around the globe (here’s a clickable map) and by the release of a World Health Organization report, the Global Action Plan for Prevention and Control of Pneumonia. The plan has three main goals, aimed at the recourse-poor countries where most pneumonia deaths occur:

  • promote breastfeeding to ensure children’s nutrition and good immune status
  • protect immunity by guaranteeing the distribution in the developing world of the pneumonia vaccines we take for granted in the industrialized world, against Haemophilus influenzae and Strep pneumoniae (pneumococcus)
  • treat children when they need it by making sure that there is adequate, local primary care and — important for our purposes especially — also making sure that antibiotics are used appropriately, but not overused.

The international organization GAVI (formerly known as the Global Alliance for Vaccines and Immunization, now going just by its acronym) has announced plans to immunize 130 million children worldwide against pneumonia and other diseases by 2015.

I want to underline that pneumonia is of interest to us for several reasons: not just because we are concerned for MRSA pneumonia, but also because we are in the midst of the H1N1 pandemic, and as we have talked about before, bacterial infections appear to be playing a role in a significant percentage of the deaths. There is no MRSA vaccine, but there are Hib and pneumo vaccines, which might have prevented some of those deaths. So increasing the administration of pneumonia vaccines could affect the course of this pandemic right now, as well as the fates of children all over the world who have not contracted this flu but will be in danger of bacterial pneumonia in the future.

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.

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.

Catching up on some reading: health care reform, food bugs, vaccine, MRSA+flu

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Folks, while I was caught in travel hell, some excellent stories and blogposts were released. Here’s a quick round-up of recommendations for a rainy weekend:

  • At Roll Call (covers Congress like a blanket), Ramanan Laxminarayan, PhD MPH, of the rational-use-of-antibiotics project Extending the Cure and infection-control physician Ed Septimus, MD make a strong argument for including control of hospital infections in health care reform. Hard to argue against when you realize that HAIs cost the United States more than $33 billion each year.
  • At Meat Wagon, a blog of the online magazine Grist, the always-excellent Tom Philpott digs into the ongoing outbreak of antibiotic-resistant Salmonella in hamburger meat. Key quote: “Outbreaks of [antibiotic-resistant foodborne illnesses] are really ecological markers — feedback that our way of producing meat is deeply unsustainable and really quite dangerous.”
  • The Associated Press reports that the long-in-development staph vaccine made by Nabi Pharmaceuticals may have received a second life: It’s been purchased by international pharma giant GlaxoSmithKline in a $46-million deal.
  • And finally and sadly, the Sacramento Bee reports that a California nurse who died of H1N1/swine flu also had MRSA pneumonia. Karen Ann Hays, 51, died despite being extremely healthy: she was a triathlete, skydiver and marathon runner. No one yet has been able to say whether she caught the flu — or MRSA — at work (though her partner believes that to be true), but her death has fueled disquiet among members of the California Nurses Association, who are protesting a lack of protective equipment for nurses.

For those of us concerned about MRSA pneumonia — and we have been talking here since the start of the H1N1 pandemic about the danger of MRSA co-infection — that last item about Hays’ very sad death should underline a vital point. Public health authorities have been stressing that H1N1 is most deadly when the infected person has a pre-existing condition: pregnancy, heart disease, obesity, diabetes, cystic fibrosis. It is possible that MRSA infection is also a pre-existing condition that will put anyone infected with flu at risk of deadly complications.

If you have had MRSA, even a minor skin infection — and especially if you have experienced recurrent infections — you should probably discuss with your personal physician whether you should take the H1N1 vaccine when or if it becomes available. It could be the step that prevents a minor case of flu from tipping over into something much more serious.

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.