Vancomycin-resistant S. aureus (VRSA) update

The time intervals between introduction of penicillin and the emergence of penicillin-resistant S. aureus, and between the introduction of methicillin and the emergence of MRSA, were very short (3-5 years), and were followed by rapid emergence and spread of the resistant strains. For unclear reasons, the same hasn’t been true for VRSA. Vancomycin was introduced in the 1950s, and use of the drug increased almost exponentially during the advance of MRSA as a hospital pathogen in the 1980s. Yet it wasn’t until 2002 that the first VRSA infection was reported. As soon as it was recognized that plasmid-mediated transfer of the vanA gene to MRSA was responsible, many considered the rapid spread of VRSA to be inevitable. 

Interestingly, this spread hasn’t yet happened—appearance of VRSA strains has remained rare and sporadic, with only 13 confirmed cases in the US since the first report, barely one per year. Furthermore, person-to-person spread hasn’t been demonstrated to be a problem. The first 12 cases were all in the similar genetic background (clonal complex 5, most of which were t002, the most common healthcare-associated MRSA spa type). Furthermore, vancomycin pressure seemed a prerequisite, suggesting that a high fitness cost is associated with maintaining vanA in S. aureus.

In this context, two recent publications should raise new concern about the potential for further emergence of VRSA. As documented in a CDC report of the 13th VRSA case in the US, and in last week’s NEJM report of a VRSA case from Brazil, VRSA has now emerged in the genetic background of community-associated MRSA strains (USA1100 and USA300). USA300 (clonal complex 8) has been particularly successful at rapidly spreading and replacing other MRSA lineages, so stable carriage of vanA in a USA300 background would be a major public health problem.

The above image of the pBRZ01 plasmid harboring vancomycin resistance genes and found in the Brazilian bloodstream infection case is from the NEJM report.

Who are you gonna call….

…when active surveillance cultures reveal MRSA colonization to be rampant in your doll collection?

Contact Precautions Barbie!

h/t to @FoxyContinRN and to Neil Fishman for passing the link along.

Urine Trouble

You may heard about the teenager in Portland, Oregon who urinated in a water reservoir last week. The act wasn't really newsworthy, but the response sure was. Officials in Portland decided to drain the reservoir, which holds 38 million gallons of water. Could there be any reason from an infectious diseases standpoint that this would be necessary?

Let's assume that the young man had to pee really badly. That would probably amount to a 500 mL void. Converting gallons to liters, the reservoir holds 144 million liters of water. So the urine was diluted by a factor of 288 million. That's not even a drop in a bucket! Moreover, given that urinary tract infections in young men are exceedingly rare, the overwhelming odds are that his urine was sterile. But playing devil's advocate, even if he had the most raging UTI known to man, chlorine coupled with the enormous dilution factor would negate any risk. And most urinary pathogens would cause no harm even if ingested.

But a smart person might ask what could happen if the teenager had previously travelled to Africa and was infected with Schistosoma haematobium, the parasite that causes urinary tract schistosomiasis and produces eggs that are found in the urine of infected persons. Well, fortunately, the Bulinus snails required for the life cycle of S. haematobium are not found in the United States.

Lastly, I'm not a wildlife biologist but it would seem to me that nonhuman mammals, birds and reptiles probably use water reservoirs for their bathrooms far more commonly than humans, and we aren't draining reservoirs for that.

Let's hope the Portland standard doesn't become the rule. If so, we'll probably have to drain every swimming pool in the United States.

Photo: Mount Tabor Reservoir in Portland. AP Photo/The Oregonian, Benjamin Brink

1955 - Dawn of the Antibiotic Era and Lessons for the Future

It's easy to fall into despair when pondering the decades long rise of antibiotic-resistant bacterial pathogens and the simultaneous decline in funding for antibacterial discovery, surveillance systems and infection prevention. But this wasn't always the case.  Back before 1969 when it may or may not have been said that "It is time to close the book on infectious diseases, and declare the war against pestilence won," clinicians appreciated antibiotics and even understood the idea of antimicrobial stewardship.

A case in point is this 1955 article in JAMA by GE Burch titled "Cardiology for General Practitioners." After pointing out that the first therapy mentioned by Dr. Burch was antibiotics, I would like to call your attention to a few of his thoughts:

"The most important single therapeutic development in the field of cardiology has been the advent of antibiotics. These drugs have not only made it possible to convert almost all fatal diseases, such as bacterial endocarditis and endarteritis, to almost nonfatal ones but have played an important role in control of infections in all cardiovascular disease states. Until the introduction of these drugs, the physician was often able to manage satisfactorily the cardiac disturbances, such as congestive failure, only to have the patient die of bronchopneumonia or urinary tract infection. The fear of secondary infection as a threat to life was constantly present, and the more chronic or prolonged the illness and the older or more debilitated the patient, the greater was the chance for infection. Once it developed, the physician was virtually helpless, despite the many therapeutic rituals used. Most physicians well remember the preantibiotic era."

and the homage to stewardship:
"It is not necessary, or even advisable, however, to administer those of the so-called broad spectrum type to all patients with cardiovascular disease, without regard for the specific problem."

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After reading Dr. Burch's review I'm convinced that our current situation has several potentially modifiable causes: (1) a lack of understanding of how critical effective antimicrobials are to the practice of modern medicine, (2) a failure to include clinical judgment when selecting antimicrobials and finally (3) a pre-antibiotic era that has been completely lost to history. Addressing all of these will be required if we are to avert a post-antibiotic future.

Keep the beard, Eli!

There's a new paper in the Journal of Hospital Infection that takes a look at the bacterial ecology of facial hair. In this study, 408 male healthcare workers had two areas of their face cultured. About half of the men had facial hair and the other half did not. Interestingly, the men with facial hair were significantly less likely to have skin colonization with S. aureus (lip: 34% vs 45%; cheek 41% vs 52%). When the facial skin was scratched with a sterile swab there was no difference in bacterial shedding between the two groups.

These findings are consistent with what we know about S. aureus. Colonization rates are higher in persons with chronic breaks in the skin (e.g., patients with eczema, dialysis patients, diabetic patients who require insulin injections, and IV drug users). Shaving causes micro- (and sometimes macro-) abrasions and lacerations. And cosmetic body shaving has clearly been associated with MRSA infections.

Based on this study, I would grow a beard, if only I could. Mine is too mangy. It would scare my patients. But for $8500, I could get a facial hair transplant, which is now all the rage in New York. Maybe there's hope...

Sometimes, what we suffer from is bigger than we think

There was a time when the makers of Tamiflu (oseltamivir) ran ads with the tagline "sometimes, what we suffer from is bigger than we think" urging folks to see their doctor for viral URIs and get treatment for the influenza.  Now, however, I think the tagline is perfect for describing the predicament clinicians, public health officials and governments are in when trying to decide what to do with neuraminidase inhibitors (oseltamivir and zanamivir) for influenza prevention and treatment. You see, what they all suffered from when trying to decide what to recommend was a missing data problem, specifically unpublished clinical trial data held back by the pharmaceutical companies (Roche and GlaxoSmithKline). This "missing data" problem was bigger, much bigger, than initially appreciated.

Today, the Cochrane Review updated the "Neuraminidase inhibitors for preventing and treating influenza in healthy adultsand children" based on full internal reports of 46 clinical trails. The key findings are that neuraminidase inhibitors reduced the duration of symptoms by 1/2-day in adults, with data uncertain in children and that there was no evidence of a reduction in hospitalisations or serious influenza complications including pneumonia in adults or children. Side-effects, such as nausea, vomiting, psychiatric events etc, were significantly more common in the oseltamivir treated groups. In prophylaxis trials, both agents reduced the risk of symptomatic influenza in individuals and in households.

Some quotes from key individuals involved with the release of this report:

Dr. David Tovey, Editor-in-Chief, Cochrane: “Initially thought to reduce hospitalisations and serious complications from influenza, the review highlights that Tamiflu is not proven to do this, and it also seems to lead to harmful effects that were not fully reported in the original publications."

Dr. Tom Jefferson and co-authors of the review: “We urge people not to trust in published trials alone or on comment from conflicted health decision makers, but to view the information for themselves.”

Dr. Fiona Godlee, BMJ Editor: “We need the commitment of organisations and drug companies to make all data available, even if it means going back 20 years. Otherwise we risk another knee-jerk reaction to a potential pandemic. And can we really afford it?”

Dr. Harlan Krumholz, Yale Professor, wrote an accompanying editorial in the BMJ. In addition to describing the surprising need for more studies 15 years after the drugs were approved and listing the current and outdated public health guidelines he emphasized that "from a health system perspective, the enormous expenditures do not appear to have commensurate benefit."

UPDATE: CDC Says Stay the Course; Main reason appears to be that observational data were not included in Cochrane analysis. Of course, it is unethical to do an RCT in a pandemic, so much of the data required for decision making around pandemic preparedness wouldn't be from RCTs.

Additional References:
1) Heneghan et al. Zanamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments BMJ 2014

2) Jefferson et al. Oseltamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments. BMJ 2014

It just makes sense....