Tuesday, April 22, 2014

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.

Monday, April 21, 2014

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

Friday, April 18, 2014

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."

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.

Saturday, April 12, 2014

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...

Thursday, April 10, 2014

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....

Monday, April 7, 2014

If you weren't at SHEA, here's what you missed...

Jon Otter, who blogs at Micro Blog, summarizes last week's Society for Healthcare Epidemiology of America meeting here. I'll just add that the topics were interesting, the speakers were excellent, and it was a fun gathering. Next year: Orlando, May 14-17.

Candida CAUTI: An oxymoron

While I was attending the SHEA Meeting last week, a list-serve that I follow had some disturbing comments regarding how some hospitals are addressing CAUTIs that are due to Candida spp. I'll address those comments a little later, but first want to address the concept of Candida CAUTI.

To meet the NHSN definition of CAUTI, a patient could have fever + 100,000 CFU/mL of Candida in the urine, or fever + 10 WBCs/mL + 1,000 CFU/mL of Candida. While this definition is appropriate for bacteria, it really isn't for Candida. There's an excellent paper (free full text here) by Carol Kauffman, one of the world's experts on fungal infections, that clearly outlines why capturing "Candida CAUTI" is inappropriate. Here are a few excerpts from that paper:
Candiduria is often observed in hospitalized patients. Candiduria is neither a symptom nor a sign, and it is clearly not a disease. The finding of yeast (almost always Candida species) in the urine could mean that the patient has pyelonephritis or cystitis. It also could mean that hematogenous seeding of the kidney cortex has occurred in the course of disseminated candidiasis. Finally, and most likely, the presence of candiduria may reflect only colonization of the bladder, perineum, or indwelling urinary catheter. The vast majority of patients with candiduria have no symptoms suggesting the presence of urinary tract infection (UTI); culture of the urine is done because of unexplained fever, elevated WBC count, or less cogent reasons, such as cloudy or smelly urine.
The diagnosis of bacterial UTIs relies on the findings of pyuria and bacteriuria, usually at a certain minimum number of colony-forming units, in a patient with appropriate symptoms. Guidelines exist for establishing the diagnosis of a bacterial UTI, and the existence of excellent diagnostic tests allows appropriate treatment to be evaluated and become standard practice. However, the diagnosis of a UTI due to Candida species is much more difficult. No studies have unequivocally established the importance of pyuria or quantitative urine cultures for UTI due to Candida.
The overwhelming body of evidence points to the fact that the presence of candiduria as an isolated observation generally does not portend subsequent invasive disease. This finding should make it less imperative to use antifungal agents to treat patients who have candiduria.
I took a look at my hospital's CAUTI data for 2013 and found that 41% of CAUTIs in our ICUs were due to Candida. In our medical ICU, 94% of CAUTIs were associated with Candida. The absurdity here is that we are expending enormous amounts of energy trying to prevent an infection that really isn't an infection. But even worse, as pointed out in list-serve comments, some hospitals are now changing urinary catheters before obtaining cultures. If you were a patient, would you want your catheter changed every time a urine culture is obtained?  Other hospitals are empirically treating catheterized patients with fluconazole to prevent candiduria. This will only result in non-albicans colonization and fluconazole resistance.

This could be easily fixed by simply removing Candida from the case definition. It's time to stop punishing hospitals and driving inappropriate treatment. Wake up, CDC!

Wednesday, April 2, 2014

Riding the epidemic curve to glory, Gram-negative edition

Dan has discussed "riding the epidemic curve to glory" before. This is the phenomenom that occurs when a bundle of interventions is started just as an outbreak is entering the “downhill” part of the epidemic curve. Thus, the outbreak would have ended on its own, even without intervention, yet the hospital epidemiologist and their recommended interventions are incorrectly given credit for the success. This effect has only minor importance when looking at a single hospital outbreak. In that situation, it doesn't really matter why the outbreak ended, but it's sure nice that it did.  However, what if the hospital epidemiologist published a paper outlining the successful control of the outbreak? What if others published similar uncontrolled quasi-experimental studies describing how they controlled other outbreaks? Then it might be a problem, no? I think it could be a major problem since we really need to know that interventions work before we recommend them - we can't always rely on the luck of riding the epidemic curve.

This phenomenon is particularly concerning for me when it comes to control of MDR-gram negative infections. A little more background: Back in 2008 we published a paper in ICHE showing that Gram-negative infections were much more common in the summer (vs. winter). In fact, there were 28% more P. aeruginosa, 46% more E. cloacae, 12% more E. coli and 21% more A. baumannii clinical cultures in summer months. We validated these findings in 132 US hospitals and again found that Gram-negative organisms were more frequent in summer months ranging from 12.2% higher rates for E. coli to 51.8% higher for Acinetobacter spp.

Below I've pasted a figure plotting 8-years of monthly aggregate P. aeruginosa from our ICHE study. What if we waited to start interventions to control our peak in summertime pseudomonal infections until September (Intervention B)? I could then ride the epi curve to glory each fall as I reduced infections by 28%. I could then publish my findings and would be asked to write SHEA guidelines recommending what you should do. On the other hand, what if I tried to get ahead of things every spring and start intervening in May (Intervention A)? What if pseudomonal infections went up 5% over the next three months? In that case, I would be told my interventions didn't work, I wouldn't publish my findings and you'd certainly never let me write a SHEA guideline.

With that long background, I'm excited to report that our findings of summer season and higher temperature associated increases in Gram-negative pathogens have been validated in a recent PLoS One paper by Frank Schwab and colleagues.  In a cohort of patients from 73 ICUs in 41 German hospitals covering years 2001-2012, they examined the monthly incidence of 103,000 Gram-positive isolates (S. aureus, Coagulase negative staphylococci (CoNS), E. faecalis and faecium, S. pneumoniae) and 87,000 Gram-negative isolates (E. coli, P. aeruginosa, K. pneumoniae, E. cloacae, S. maltophilia, S. marcescens, Citrobacter spp., A. baumannii) and their relationship to the ambient temperature in the month isolated and also in the prior month.

They found that 11 of the 13 pathogens had a significant temperature association. Only E. faecalis and S. marcescens were not effected by temperature. All remaining Gram-negative pathogens (and CoNS) were positively associated with temperature, and the strongest correlation was with temperature in the prior month. Thus, higher temperatures = higher incidence of Gram-negative pathogens. The magnitude of the effect was similar to what we reported earlier. For example, we reported a 46% increase of E. cloacae in summer vs. winter while they reported a 43% increase. They also found that S. aureus, E. faecium and S. pneumoniae were more frequent when temperatures were colder.

So, as you are reading an outbreak investigation or listening to SHEA2014 talks this week in Denver, ask yourself "did the authors consider seasonal or temperature variation in their analysis?" And if the answer is no, tread carefully. The authors may have ridden the epidemic curve to glory, but you might not be so lucky if you follow their recommendations.