MRSA involvement in H1N1 flu: UPDATE

The CDC's MMWR report on their analysis of bacterial co-infections in H1N1 flu deaths has been placed online here.

And there are two excellent analyses of it by the marvelous blogs Effect Measure and Mike the Mad Biologist.

Guest Q&A: Jeanine Thomas and World MRSA Day

I want to introduce you all to a MRSA campaigner, Jeanine Thomas of Chicago. Jeanine — whose story will be told in SUPERBUG — is the founder of World MRSA Day, a worldwide event of activism and grieving that will take place Friday, Oct. 2. There will be simultaneous observances in the UK, and a candlelight vigil in Salt Lake City that evening.

Tomorrow, Oct. 1, Jeanine will be at Loyola University in Chicago to lead a press conference, commemoration for MRSA victims, and award ceremony for notable MRSA campaigners, and to urge those harmed by MRSA to observe October as MRSA Awareness Month.

In advance of the observances, I asked Jeanine to talk to SUPERBUG about her experience and her activism.

Tell us about your personal experience with MRSA.
I was infected with MRSA after ankle surgery in 2000. I came back to the ER — my incisions were black and oozing a large amount of pus and I was in teribble pain — and was admitted. Three days later my culture came back positive for MRSA. I was not put on the right antibiotic; the infection went into my bloodstream and bone marrow and I went into septic shock and multiple organ failure in the middle of the night. The night nurses were able to pull me back and save me. I had seven more surgeries to save my leg from amputation, spent a month in the hospital, and then was confined to bed on a cocktail of antibiotics for 5 more months. I also contracted C. difficile. I now have a destroyed ankle joint and a severely compromised immune system.

You started a MRSA patients' group. Tell us about the group and why you did that.
I started MRSA Survivors Network in 2003 to give support, raise awareness and educate others. There was so little out there about this disease. I never wanted anyone else to go through what I had.

You used your experience with MRSA to help pass patients-rights legislation in Illinois. Please talk a little about the bill.
In 2003, I helped push the "Hospital Report Card Act" that then-state senator Obama introduced, to have infection rates reported. As the consumer representative on the state board for the HRCA, I saw that state health officials and doctors did not even want to have MRSA reported as a disease. So I decided I must take action and in 2006 we introduced the "MRSA Screening and Reporting Act." It passed in 2007, the first in the country, and mandated that all ICU and other at-risk patients be screened for MRSA and infection rates reported. Since then, the Illinois Hospital Association has reported that inpatient infection rates have dropped, but they see many more CA-MRSA cases because of the screening.

How and why did you come up with the idea for World MRSA Day?
In January of 2009 I was thinking of ways to raise awareness and the idea of launching World MRSA Day and a MRSA Awareness Month popped into my head. There are awareness days for every other diisease and as MRSA is pandemic, we need global awareness. I did not know how successful I could be the first year during a recession, but the response was surprising, and I was able to launch the campaigns.

Tell us what you hope will change in the aftermath of having had this worldwide event.
I hope that awareness of MRSA as an epidemic in the US and a pandemic sweeping the globe will be revealed, and that action from the World Health Organization, Department of Health and Human Services, the CDC, governments and health departments will happen. I want all of them to declare MRSA an epidemic. This should have happened years ago, but let's move forward now. Their inaction has caused this disease to proliferate. I also want the public to be aware of MRSA as we are all in this together and every single person on this planet is at risk. Prevention is key to saving lives.

More evidence of MRSA involvement in H1N1 flu

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.

New news on MRSA and animals

Constant readers, I've been behind the Great Firewall of China for two weeks, unable to post. (Apparently Blogger is not always unavailable there, but access has tightened up in advance of the National Day celebrations on Oct. 1.) I left with a file of things to post in my spare time — and so now we're way behind, with lots to catch up on.

Latest news first, though. A few days ago, an intriguing conference was held in London: Methicillin-resistant Staphylococci in Animals: Veterinary and Public Health Implications. It was co-sponsored by the American Society for Microbiology and the European Society of Clinical Microbiology and Infectious Diseases, and it was the first conference ever convened to examine the behavior in animals of MRSA and other staph species, including our old friend, ST398.

I have the abstracts (which have not otherwise been published), and wow, there was a ton of news.

Here's the biggest: An investigation by a team at University of Iowa (the same group that first identified ST398 in pigs and pig farmers in the United States) found significant amounts of MRSA in pigs and in human workers on 4 out of 7 conventional farms, but no MRSA on 6 organic farms. MRSA was present — as a colonizing organism, not causing illness — in 23% of the 168 pigs sampled on the conventional farms, and 58% of 45 humans who worked on those farms. "These results suggest a significant number of U.S. swine may be colonized with MRSA, adding to the concern about domestic animal species as a reservoir of this bacterium," the abstract says. "Furthermore, occupational exposure to these colonized pigs may spread the bacteria from the farm to the community via a high number of colonized swine workers." (Author: Abby L. Harper, MPH, University of Iowa)

A partial list of the other findings announced:

• MRSA ST398, which emerged as an animal and human pathogen in the Netherlands, is now causing human colonization and illnesses in other countries. Denmark, which like the Netherlands has a very low background rate of MRSA, has detected 109 cases since 2003, 35 of them with actual infections. Two of the infections were very serious: one pneumonia in a newborn baby, and one septic arthritis in an adult that led to sepsis and multi-organ failure. (J. Larsen, National Centre for Antimicrobials and Infection Control, Denmark)
• Meanwhile, the Netherlands — which conducts routine screening for MRSA carriage on hospital admission — has seen its annual count of MRSA detections rise from 16 per year between 2002 ad 2006 to 148 per year between 2006 and 2008, with 81% of the current cases due to ST398. (M. Wulf, PAMM Laboratory, the Netherlands) UPDATE: Coilin Nunan of the Soil Association in the UK corrects me (thanks, Coilin!): This study covers only the southeastern pig-farming areas, or about 40% of the MRSA cases in the country.
  
• MRSA ST398 spreads from infected to uninfected pigs during transport to slaughterhouses and while being held at slaughterhouses. (E. M. Broens, Wageningen University, the Netherlands)
• More than 15% of slaughterhouse workers who handle live pigs — but none of those who handled pig carcasses after slaughter — were carrying MRSA 398, and 25% of environmental samples such as dust taken from different parts of slaughterhouses were carrying the organism as well. (B. A. van Cleef, RIVM [National Institute for Public Health and the Environment], the Netherlands)
• Along with the pig-origin ST398, recognized human strains of MRSA can also colonize pigs, according to a study on one Norwegian farm, but human strains are less successful at persisting in pigs and tend to die out after months. (M. Sunde, National Veterinary Institute, Norway)
• Animal-origin MRSA is rising in China, the world's largest producer of pork, but the problematic strain there is ST9, not ST398. That MRSA strain was found on 5 out of 9 farms in Sichuan province in mainland China, and in 33.5% of 260 pigs slaughtered in Hong Kong, where more than 90% of pork comes from the mainland. (J. A. Wagenaar, Central Veterinary Institute, the Netherlands; and M. V. Boost, Hong Kong Polytechnic University)
• And an intriguing finding for those concerned about humane slaughter methods: Broiler chickens were significantly more likely to carry MRSA, and transmit it to slaughterhouse workers, if they were killed by the traditional method of electrical shock followed by throat-slitting, and less likely to carry or transmit the bug if they were killed by carbon dioxide asphyxiation, which has been held out as a more humane method of killing. (M. N. Mulders, RIVM [National Institute for Public Health and the Environment], the Netherlands)

UPDATE: I'm still a bit jet-lagged and forgot to mention that, of course, we have a long archive of coverage of ST398 and other strains in animals. Find them here.

A parent's plea and confusion

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

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.