When prevention success stagnates? Treat the patient!

Prevention is paramount – I do believe this, and I know that is so much of what healthcare epidemiologist strive for; however we often become very myopic and focus exclusively on “modifiable risk factors.” It is refreshing to read a nicely done epidemiologic study to illustrate what an impact the infectious disease community can have by improving the way we approach patient treatment. When reading the recent article in JAMA IM by Michihiko Goto and colleagues I was expecting a nice ecologic study showing an impressionistic picture of how improved treatment processes correlate with improved MRSA bacteremia mortality - but our VA colleagues working with big data have painted more of a realistic 

Le Déjeuner sur l’herbe Painting 

by Édouard Manet, 

1863 Musée d’Orsay, Paris

Google Arts & Culture

than an impressionistic picture. Using the VA database, capturing deaths occurring during both the inpatient stay and the post-discharge period, they quantify improved survival at the patient level is driven by improved processes of care for S. aureus bloodstream infection (Association of Evidence-Based Care Processes With Mortality in Staphylococcus aureus Bacteremia at Veterans Health Administration Hospitals, 2003-2014 JAMA IM).

I have been pushing for transitioning efforts to prevent S. aureus (more specifically MRSA) bacteremia to the post-discharge setting, worried that the recent reductions observed among hospital-onset MRSA BSI are not being realized in the post-acute care setting. We’re getting stuck; in fact we have been stuck for a while at preventing community-associated MRSA BSI (See figure). 

Goto and colleagues provide some clarity to preventing deaths related to MRSA BSI (and S. aureus BSI overall) even during periods of prevention stagnation such as we may be in currently. Of note, the incidences of healthcare-associated and hospital-onset MRSA BSI decreased in VHA hospitals between 2003 and 2014, whereas the incidence of CA bacteremia was stable. This is identical to trends illustrated nationally using CDC's EIP data, suggesting the VA analysis may be reflective of what is going on nationally.

Goto utilized the national Veterans Health Administration (VHA) health care system to first determine how to best risk adjust mortality; and then determine the independent effect of each of three pillars of guideline directed processes of care for managing S. aureus bacteremia (SAB): (1) appropriate antibiotic therapy, (2) echocardiography, and (3) consultation with ID specialists. They report lower risk-adjusted mortality among patients with SAB when they received (1), (2), or (3), and there was a nice dose-response relationship between the number of care processes and mortality. They estimate “57.3% of the decrease in risk-adjusted mortality among patients with SAB between 2003 and 2014 could be attributed to increased use of these evidence-based care processes.”

Their paper also sheds some light on the importance of capturing post-discharge data when quantifying mortality related to processes or infections related to the hospital setting!. Risk-adjusted mortality decreased from 23.5% in 2003 to 18.2% in 2014, regardless of MRSA, MSSA, and place of acquisition (Figure).

From Supplemental Figures, Goto et. al.

I was caught by the discrepancy between these mortality rates and the mortality reported by the CDCs Emerging Infections Program invasive MRSA Surveillance, reported around 12%. The latter is limited to in-hospital or 30 day mortality, whichever comes first. Recent data at IDWeek by one Emerging Infection Program site identified another 30% of deaths among patients with MRSA BSI occurred post-discharge. The Goto paper captures these deaths, making their conclusions more realistic. In addition, their risk adjustment for mortality included over 13 comorbidities, timing of infection, and susceptibility. They did an outstanding job of trying to evaluate the relative importance of each care process while accounting for changes/absence/presence of these underlying predictors of mortality (both inpatient and post-discharge). They even did a sensitivity analysis to account for early deaths, before these care processes could occur. Furthermore, the impact of receiving the care processes was similar regardless if the SAB was hospital-onset or community-onset!

The bottom line – following evidence base care processes does save lives. Their analysis support their conclusion that “there is a need for continued implementation of quality improvement initiatives to increase the adoption of these evidence-based care processes for patients with SAB.” Let’s be bold and call these what they are: performance measures! Here we have a potential metric (proportion of SAB receiving said care process), that are closely linked to improved survival, and can be captured electronically in an objective manner (at least in the VA!) improving the reliability of these metrics across facilities. I was glad to find through a google search that IDSA recently (December 2016) urged CMS to move in this direction -- although the details of the status of this proposed measure (#407) are not clear to me.

While we anticipate novel therapeutics for MRSA BSI including immunotherapy adjuvants or vaccines to become available in the not to distant future; quality improvement efforts in the evidence-based processes of care for SAB now will likely improve our patient’s outcome. I hope we can turn our attention here soon -- and have hospitals rewarded for doing so.

Guest Post: The National Hand Hygiene Initiative in Australia

This is a guest post by Nicholas Graves, Professor of Health Economics at Institute of Biomedical and Health Innovation, School of Public Health, Queensland University of Technology Queensland Health, Australia. Nick is currently the Academic Director for The Australian Centre for Health Services Innovation (AusHSI) and the Academic Director for the Centre of Research Excellence in Reducing Healthcare Associated Infections (CRE-RHAI), Queensland University of Technology / Institute of Health and Biomedical Innovation.

Between 2009 and 2012 Hand Hygiene Australia implemented an initiative to improve hand hygiene compliance in all Australian hospitals. Federal and state governments provided the funding and there was political support for this high profile patient safety program. My research group at QUT obtained funding of almost $1M in 2012 to evaluate whether it was cost-effective and here are the results just published in PLoS ONE.

We found the annual maintenance costs to be $2.9M per year. This investment of scarce resources prevented 67 cases of S. aureus bloodstream infection and 96 years of life were gained. The cost per one life year gained was $29,700. Hand Hygiene Australia have indicated the program is today likely to be less costly, due to a 50% reduction in their own running costs and that compliance auditors now spend 50% less time on their tasks. Testing these scenarios in our cost-effectiveness model suggest the cost per one life year gained falls to $25,094 and then $18,960.

The only outcome measure for which reliable data were available was S. aureus bloodstream infection. Because SAB is very expensive to treat and has large mortality risk it is a good outcome measure to demonstrate cost-effectiveness. We did evaluate other infection outcomes in a separate paper and found a statistically significant reduction in 11/23 rates, no change for 9/23 and increases for 3/23. Whether we underestimated the health benefits of the initiative by only including SAB outcomes is uncertain.

This was a challenging and difficult study, but that made it interesting. Now that the project has finished, what do I think?

Estimating the value for money of infection prevention programmes is important. Particularly in today's climate where health funding is tight, and there are multiple competing demands on scarce resources. If this Hand Hygiene initiative displaced other infection prevention programmes that deliver larger health benefits for the same or less money, then has been an opportunity cost measurable in health benefits lost.

Rolling out a national program of this complexity requires massive energy. Hand Hygiene Australia did a remarkable job achieving improvements in hand hygiene compliance. They were successful by being single minded and building momentum for the initiative. They did not let obstacles get in the way. Hand Hygiene Australia achieved the task they set themselves.

The timing of our evaluation was wrong. If it were done during a pilot phase then the results might have been useful to change the national initiative. Presenting the study and results after the programme had gained momentum and had political support reduced the usefulness of the findings. 

Doing this project has been interesting and I learned a lot, and I hope the papers and talks I have given are valuable for others interested in estimating the cost-effectiveness of infection prevention programs.

This blog presents my views alone.

ECCMID 2015 - "Best Of" Infection Control Literature (Part 1)

Every year it seems that one of us at the University of Iowa is roped into giving one of these "Best of Infection Control" talks at an annual conference. This year it seems that almost all of us have been asked and for some inexplicable reason, we all said yes! I was the lucky one to kick off the 2015 season with this talk I gave last week at ECCMID in Copenhagen. I covered S. aureus, MRSA, VRE, VRSA, surgical site infections and hand hygiene. I look forward to Mike's talk at SHEA. Loren Herwaldt's talk at ICPIC and Dan's talk at IDWeek. On Iowa.

Close Proximity Interaction and S. aureus Spread in Long-Term Care

There is little doubt that S. aureus is transmitted between patients via contaminated hands, white coats or fomites carried by healthcare workers. Fortunately, that doesn't curb the enthusiasm of scientists seeking to understand the mechanisms of transmission in clinical settings. A case in point is a recent study in PLOS Computational Biology by Thomas Obadia and colleagues that tracked healthcare worker (HCW) and patient close proximity interactions (CPI) via small wireless sensors and correlated the interactions to incident S. aureus colonization.

The study was conducted in a 200-bed LTCF in France and utilized data collected from 329 patients and 261 HCWs over a 4-month period. Using weekly nasal swabs from all patients and HCW, they spa-typed and determined the resistance profiles to antibiotics of each detected S. aureus. Isolates were considered identical if they shared the same spa type and resistance profile. Incident cases were only considered in patients since HCWs could have been transiently colonized and missed by the weekly swab interval. Each incident case was evaluated to confirm that at least one time-consistent CPI in the prior three weeks with the same strain was possible. The 3-week interval was chosen since all but 4 cases could be linked to another patient with the same strain during that time period.

Without going into all of the statistical modeling methods, major findings include:

(1) When limiting the analysis to the 201 patients not already colonized on admission, 73 acquired S. aureus. The one-month acquisition rate was 33%.

(2) Time to acquisition among new admissions did not change based on the number of colonized neighbors in the preceding week using either raw number of CPIs nor cumulative duration of CPIs.

(3) There were 237 incident cases throughout the 4 months in 111 patients. Only 173 had candidate transmitters. The analysis was limited to 153 because sensors failed to record a CPI in the prior week in 20 cases.

(4) A CPI path existed for 149 of 153 episodes. As seen in the example figure above, P1 (patient) and H1 (HCW) were two-hops away from the incident case. P2 was three-hops away. In the same figure, distance between a transmitter and an incident case (black) was shorter than random simulations predicted (white). Additionally, a direct contact between candidate transmitter and incident case (i.e one hop away) occurred in 48% of cases vs. 30% expected by random chance. These findings supported that CPI predicts S. aureus incident colonization.

(5) HCWs spent about 20% of their shifts in direct contact with patients (110 minutes over 8 hours) and had CPIs with 15 unique individuals during their day (9 were patients, 6 other HCW) with 3.7 hours spent in contact with others. 36.3% of HCW were colonized with S. aureus.

(6) Interestingly, patients had CPIs with 12 unique individuals each day (half were other patients). Overall, patients spent half of their day (12.2 hours) in contact with another person.

A few thoughts. Studying social interactions and transmission in long-term care settings using these methods is quite brilliant. Given that LTCF cohorts are more stable with longer lengths of stay, it is easier to catch acquisition events through repeated screening. It is also important to note the huge amount of contact that LTCF residents have directly with each other - around 10 hours/day. This sort of social interaction among residents is not seen in acute care hospitals and goes a long way to explain why infection control in LTCF is so critical (and so extremely difficult). Given the richness of the CPI data, including frequency and duration of contacts, new mathematical models using these parameters could provide more accurate estimates of S. aureus transmission and effectiveness of candidate control strategies.

One issue that I think the authors might want to address in future studies is the use of spa typing to link transmission events. It is true that they also used susceptibility data, but it is my understanding (from one of Dan's earlier posts) that the discriminatory power of spa typing may be suboptimal. I hope Dan will provide his thoughts on this in the comments.

Additional reference: NPR Shots blog by Scott Hensley with comments from David Hartley on this study. 

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...

Staphylococcus aureus: Here, there and everywhere

To spend any time on our infectious diseases consult service is to be knee-deep in invasive, difficult-to-treat S. aureus disease. Most S. aureus (including MRSA) disease is caused by a strain previously colonizing the host, and given that up to a third of the human population carries S. aureus it is easy to understand why the disease is so common. Exposure to healthcare is a major risk factor for invasive S. aureus disease, simply because so many healthcare interventions (surgery, device use, antibiotic exposure) provide opportunities for the organism to invade. 

Nonetheless, the conventional wisdom still holds that a large proportion of healthcare-associated S. aureus disease results from patient-to-patient transmission events—the corollary being that prevention of S. aureus disease should focus primarily on preventing transmission (including active detection and isolation). However, a careful assessment may demonstrate that interventions solely designed to interrupt transmission are responsible for only a small portion of disease reduction in observational studies (for an example, see my previous post on the VA MRSA directive). This is important, as it should focus our attention on preventing disease among those at risk for colonization (everyone), via such horizontal measures as device-associated infection prevention bundles, chlorhexidine bathing, and suppression/eradication of the carrier state during high-risk intervals. 

A study by UK investigators published in Clinical Infectious Diseases provides further evidence that patient-to-patient S. aureus transmission is a relatively uncommon event, even as an explanation for S. aureus “acquisition” events in the ICU. Using whole genome sequencing (WGS), the investigators found that only 7 of 37 ICU patients who “newly acquired” S. aureus were colonized with strains that were closely related to other patients who had an overlapping ICU stay. There are several limitations to the work, most of which are outlined by the authors in their discussion and by the excellent accompanying editorial by David and Daum. The limitation most concerning to me is the assumption that a single nares + perineum culture plated directly to solid agar media (chromogenic agar and Columbia CNA) is a sensitive method for detection of S. aureus carriers. It isn’t. Failure to perform a throat culture or to use broth enrichment probably reduced sensitivity by 30-50% (explaining their overall carriage rate of only 16.7%, when most published studies demonstrate S. aureus colonization rates of closer to 30%). We recently performed a study wherein we cultured 500 pregnant women at 5 body sites—the table below is taken from our presentation at the Decennial meeting in 2010 in Atlanta. The bottom line? Using only nares and perineal cultures directly plated to solid agar media would have missed more than half of our S. aureus carriers. Achieving 90% sensitivity (using a positive culture at any of the five body sites as the gold standard) required sampling both the nares and the throat and using overnight broth enrichment.

So what about all those “acquirers” carrying isolates that didn’t match other ICU patients? In addition to implicating other potential reservoirs (personnel, visitors, etc.), I’d wager that some were prior carriers who were newly detected due to sampling issues, increase in CFU associated with healthcare exposure, etc. Intermittent detection of S. aureus carriage is well described, and would be magnified using the microbiological techniques in this study.

Finally, while I agree with the authors that WGS is the new gold standard for assessing genetic relatedness, the use of spa typing as the “conventional method” comparator is too easy. As we found in our recently published study, roughly half of all MRSA isolated from epidemiologically unrelated clinical infections in 43 US hospitals were from a single spa type! (How’s that for discriminatory power?) If you’re going to write off the conventional methods, at least use a method with better discrimination, such as PFGE!

What's happening with Staphylococcus aureus?

Antimicrobial resistance surveillance systems are critically important for guiding empiric antibiotics, antimicrobial stewardship programs and hopefully therapeutic and prevention research efforts. While it is true that surveillance always seems to show things are getting worse, it's the speed with which things change that is also important. With that in mind there are two recent reports from a national surveillance study that provide important data in regards to the magnitude and trends of resistance and molecular epidemiology among S. aureus and MRSA clinical isolates. (COI alert: both were authored or co-author by Dan)

Both studies used a sample of 4,131 clinical specimens submitted as 100 consecutive isolates from 43 US Centers during the last half of 2011. The first study published in AAC reported MIC distributions of all isolates stratified by MRSA and MSSA. 51% were MRSA. Over 95% of both MRSA and MSSA isolates remained susceptible to ceftaroline, tigecycline, daptomycin, linezolid, vancomycin, tetracycline and TMP-SMX. Thus, both from an empiric and definitive therapy standpoint, we have many treatment options available. Of the 2,093 MRSA isolates, 60 (2.9%) were hVISA positive via either one or both available screening tests and 25 (1.2%) were confirmed as hVISA. This is three times higher than in 2009 when only 0.4% were hVISA. The paper nicely provides details concerning the sensitivity and specificity of the screening tests for those interested.

The authors also reported a significant increase in high-level mupirocin resistance from 2.2% in 2009 to 3.2% in 2011 when all isolates were analyzed and from 2.8% to 4.0% when restricted to MRSA. The authors correctly state that recent trials highlighting the efficacy of universal mupirocin decolonization will only lead to greater selective pressure for these strains and increase their prevalence. This needs to be watched carefully.

In this month's ICHE, the authors published an analysis highlighting the molecular epidemiology of the MRSA stains using the same cohort. 30% were hospital-onset by the 48-hour rule and 64% were PVL positive. USA300 dominated in all strata (source, age, census region) except from lower respiratory tract isolates and in patients greater than 65yo. Of the 173 spa types identified, 51% were t008 and 18% were t002. 48% of all MRSA strains were the composite type (USA300/t008/SCCmec IV). See the figure below comparing it to the next most prevalent composite type (USA100/t002/II), which was found in 11% of isolates. I encourage you to read the entirety of this paper, as the authors discuss the possibility that MDR-clones of USA300 could emerge since it's now firmly established in the healthcare environment. Hopefully Dan will chime in with some comments. My take-away: USA300 = MRSA and MRSA = USA300, at least for now.

Staphylococcus aureus continues to evolve: MRSA without mec edition

I just returned from a wonderful MRSA conference this past week where I enjoyed learning about how European countries are handling antimicrobial use in livestock and the emergence of potential human pathogens like livestock-associated MRSA. Perhaps I will post further thoughts on the conference later in the week.  However, I just saw this new report in JAC on a novel resistance mechanism in S. aureus, so first things first.

It is known that hyper beta-lactamase producing strains of S. aureus exist and that some strains have chromosomal mutations and resultant modified penicillin binding proteins. These strains can have phenotypic methicillin resistance while lacking the mecA (or mec C) gene. Thus, they can evade detection by genotypic methods and the underlying mechanisms can be missed by phenotypic methods, as Dan nicely described here.

There is now a report by Xiaoliang Ba and colleagues that describes four clinical S. aureus isolates that were found to be MRSA but lacked mec A or mec C. The strains were from clinical wound infections and deposited in the Scottish MRSA Reference Lab. They belonged to sequence types 1, 15 (two isolates) and 8. Three strains were resistant to oxacillin, cefoxitin and PCN by ETest and disc diffusion and the fourth isolate was at the oxacillin Etest breakpoint, while three were beta-lactamase producers. Whole genome sequencing confirmed that none contained a mec-like sequence and that beta-lactamase production was not mediating the resistance. Interestingly they found similar single amino acid substitutions across sequence types in PBP1, PBP2 and PBP3 suggesting independent evolution of the same trait (homoplasy).

The authors acknowledge that their targeted search of the genomes could have missed other possible mechanisms of resistance in these isolates. I would add that this was in four isolates out of an unreported denominator, so we don't know the magnitude of the clinical impact yet. What we can say is that our surveillance techniques had better keep up with S. aureus. Unfortunately, it seems to be just as good at evolving away from our prevention methods as it does our antibiotics.

Obligatory S. aureus image courtesy of wikipedia

Addendum: For further insight, scroll down to read Dan's comment on this study

Are "PSSA" coming back?

On the way to Lac St. Francois a couple weeks ago, we drove near St. Albans, Vermont, the location of the hospital outbreak mystery described in one of Mike’s recent posts (you may remember, the “case of the circumstantial evidence of a complicated conspiracy of hospital personnel using laboratory control strains to intentionally infect patients in order to ruin a doctor who claimed to have uncovered an illegal kickback scheme involving radiology services…”, yeah, that’s the one!).

In expert testimony from this case, the statement is made that penicillin-susceptible Staphylococcus aureus (PSSA) are extremely rare (“less than 2% of all S. aureus isolates”). This widely-held assumption (that PSSA are basically “extinct”) is incorrect, and in some centers there appears to have been a substantial increase in PSSA over the past few years. See this report from John Crane that 15% of all S. aureus from ICU patients in Buffalo, NY, are now PSSA, and this report from IDWeek 2012 that PSSA accounted for 20% of all MSSA (and 13% of all S. aureus) from positive blood cultures in the Kaiser Permanente system (regional reference laboratory in LA). We plan to examine this issue as well in the next round of our nationwide S. aureus resistance surveillance.

The perception that PSSA no longer exist persists in part because many labs don’t test or report the drug (to detect inducible beta-lactamases, labs have to perform a beta-lactamase test on any S. aureus that tests susceptible, before reporting it).

Why is this important? It is another indication of how complex is the epidemiology of S. aureus, demonstrating that emergence and virulence are not necessarily tied to resistance, and that the “loss” of a drug may not be the end of the story—and also, of course, as a reminder that the drug of choice for PSSA is…..penicillin.

Another Staph aureus vaccine failure

The April 3rd JAMA contains the results of a wonderfully designed and executed study by Fowler and colleagues assessing the benefits of a novel (V710) vaccine targeting S. aureus infection in cardiothoracic surgery. The study was negative (i.e. the vaccine didn't work) and highlights how little we know in 2013 about how humoral immunity works for this important human commensal. But first the study and results...

Among 8031 patients entered into the study, the vaccine was given between 14 and 60 days pre-op to 3981 randomly-selected patients prior to surgery while 3982 received saline placebo. The study was powered to detect a 20% reduction in S. aureus bacteremia or deep surgical site infection through 90-days post-op. Secondary outcomes were any invasive S. aureus infection. Three interim analyses were planned but the data monitoring committee terminated the study after the second interim analysis. Thus, only around ~5100 patients completed the full study with 90-day endpoints. Of note, 67% were male, 24% had diabetes, 18% were S. aureus colonized and 2% were MRSA colonized. Randomization appears excellent.

As I suggested, the results are sobering. The primary outcome (deep SSI or bacteremia) occurred in 2.6% of vaccinated patients and 3.2% of controls, p=0.58. There were more adverse events at 14 days in the vaccinated group (31% vs 22% ) and a greater incidence of multiorgan failure. Depressingly, there was far higher mortality secondary to S. aureus infection in the vaccinated group, 23 vs 4.2 per 100 person-years. The overall comparison between vaccinated and unvaccinated for S. aureus related outcomes is striking and humbling. I've pasted Table 4 from the study below, for your review (click on it to enlarge).

The authors of the study point out that their study isn't the first to find worse outcomes in a vaccinated group and also that MRSA infections were more common in the vaccinated arm of the trial. But I don't buy their suggestion that MRSA was a significant contributor to the poorer S. aureus related outcomes in the vaccinated group. There just wasn't enough MRSA disparity between the vaccinated and control groups. I wonder if part of the answer to higher mortality in the vaccinated group could be explained by this old paper by Heiman Wertheim and colleagues that I discussed several years ago. Wertheim report significantly lower mortality among S. aureus carriers vs. non-carriers. Could the vaccine be upsetting the delicate protective effect of pre-existing S. aureus colonization?

There is an excellent accompanying editorial by Preeti Malani and I urge you to read it. She does a wonderful job putting this study in historical context and pointing a path forward for HAI prevention research. The money quote from her editorial is: "Ultimately, the results of the study by Fowler et al say more about the need to rigorously study infection prevention in general than about S aureus per se." I couldn't agree more.

Image source: Vance Fowler, MD MHS from Duke

Extranasal MRSA Colonization

Medical decision makers LOVE a good systematic review.  This is especially true if that review synthesizes the literature surrounding a key parameter input for their decision models. Sometimes these studies can even have clinical importance beyond informing decision-analytic models, which is the case here.

In the February 2013 ICHE, James McKinnell and colleagues completed a systematic review that estimated the incremental benefits of testing for MRSA colonization at extra-nasal sites. They combed 4,381 abstracts and 735 articles to find 23 high-quality studies comparing any-site (extranasal+nasal) screening to nasal screening for MRSA. The specifics are outlined in Table 2 below, while the overall message is that an additional one-third of patients will be detected if extranasal sites are screened. What this means as far as changing practice and the cost-effectiveness of adding extranasal sites to screening algorithms will have to wait for those future pesky decision-analytic models. Stay tuned!

Reference: Quantifying the Impact of Extranasal Testing of Body Sites for Methicillin-Resistant Staphylococcus Aureus Colonization at the Time of Hospital or Intensive Care Unit Admission James A. McKinnell, MD; Susan S. Huang, MD, MPH; Samantha J. Eells, MPH; Eric Cui, BS; Loren G. Miller, MD, MPH Infection Control and Hospital Epidemiology , Vol. 34, No. 2 (February 2013), pp. 161-170

My thoughts exactly...

Source: http://xkcd.com/1147/

The depredations of the Staphylococcus

From: Public Health Image Library

“Among the more chastening chapters in the annals of microbiological research is the story of our apparently dismal failure to control the depredations of the staphylococcus.”

The above quote, by Canadian microbiologist Claude Dolman, remains as true today as when he wrote it in 1955. Each time I attend on our busy ID consult service, I’m astonished again at how very nasty, and how very common, is S. aureus. Earlier this week we saw a patient with a confusing clinical presentation (confusing to me, anyway). At the end of the day, as we were going back over plausible etiologies for his symptoms, I said, “it’ll probably end up being just another presentation of invasive S. aureus disease”. As I was saying those words, his admission blood cultures were turning positive for….yes, S. aureus (in this case, methicillin-susceptible S. aureus). At any given time, I’d say about half the patients on our consult service have invasive S. aureus disease (evenly divided between community-acquired and “community-onset healthcare-associated”).

If you type “aureus” into the IDWeek online program planner, you’ll get 170 matches. That’s a lot of learnin’ you could do about S. aureus epidemiology, diagnosis, treatment and prevention! So if you haven’t yet signed up, please join us next month in San Diego.

The mystery of the Staphylococcus in retreat

Evidence keeps accumulating that Staphylococcus aureus disease, for whatever reason(s), is declining in incidence. The latest massive study to illustrate this trend is courtesy of the U.S. Military Health System and is published this week in JAMA. Using their integrated electronic medical record, military epidemiologists demonstrate that both community- and hospital-onset S. aureus bloodstream infections (MRSA and MSSA) declined in incidence between 2005-2010, and that the proportion of S. aureus skin/soft tissue infections due to MRSA declined beginning in 2007. While it might not be generalizable, the Military Health System is very large, encompassing active duty military, retirees, reservists and their families, and this study included over 56 million person-years of observation.

One strength of this study is that it shows not only healthcare-associated but also community S. aureus disease to be declining, a decline that is difficult to attribute to hospital-focused interventions. The reports now from NHSN, the Active Bacterial Core Surveillance program, the United Kingdom, the EARSS system, and now the military all speak to our ignorance of the complex interplay between S. aureus and its human reservoir. Successive long cycles of waxing and waning epidemic spread have been, and will be, the rule. 

For a nice example, check out this study from Oxfordshire hospitals demonstrating how their MRSA incidence began to drop well in advance of intensified infection control interventions, and how this drop coincided with the rise and fall of two competing strain types.

Image from Planet Science

S. aureus decolonization: Review of the benefits

In the December 2011 Lancet ID, Andrew Simor from the University of Toronto reviewed articles listed in PubMed from 1989-2010 assessing the benefits of S. aureus decolonization. There were no surprising results. In fact, most of the conclusions were hedged.  For example he says that "some data support the use of decolonisation in surgical patients colonised with S aureus, particularly in those undergoing cardiothoracic procedures" and  "patients undergoing chronic haemodialysis or peritoneal dialysis might benefit from decolonisation, although repeated courses of treatment are needed, and the effects are modest." The hedging is not a criticism of the author, but rather due to the lack of funding for proper infection prevention studies.  What is surprising is that this is a single-author paper.  Any systematic review should be completed by more than one author, in my opinion. Another limitation is the lack of summary odds ratios. However, this is a very good literature review and a wonderful resource.

Source:  Simor AE, Lancet ID December 2011

Another nail in vanco's coffin

Photo: Old-Pictures.com

Eli's group, with Marin Schweizer as first author, has just published a retrospective cohort study in BMC Infectious Diseases (full text here) that addresses an important and relatively common clinical question: should we treat methicillin-susceptible Staph aureus bloodstream infections with vancomycin? Most infectious diseases experts agree that cefazolin or nafcillin are better for MSSA because these drugs provide better bactericidal activity than vancomycin. Nonetheless, vancomycin's pharmacokinetics usually allows for more convenient dosing. As more patients are being treated at home with IV antibiotics, drugs that require every four hour dosing (e.g., nafcillin) are much more difficult to use unless the patient is willing to use a small programmable pump that must be carried at all times. Vanco may be even more attractive in patients with renal failure since dosing becomes very infrequent. On the other hand, I am finding it harder to maintain therapeutic trough levels with vancomycin. In young patients with high creatinine clearances, I sometimes find that even every 8 hour dosing results in trough levels that are too low. Supratherapeutic troughs occur when renal dysfunction develops, which is not uncommon in acutely ill hospitalized patients. And it seems that as we push the levels higher we are seeing more renal dysfunction. So vancomycin drives me a little crazy.

But what did Eli find? In his cohort of 267 patients with MSSA bacteremia, those that were treated with cefazolin or nafcillin (including those who also received vancomycin) were nearly 80% less likely to die than those who received only vancomycin for the duration of their treatment. What about the common clinical scenario where vancomycin is started empirically then changed to cefazolin or nafcillin once MSSA has been identified? Those that were switched from vancomycin were 69% less likely to die than those who continued on vanco. Bottom line:  think twice before using vancomycin solely on the basis of convenience.

Papers you should read, September 2011

We know. Postings have been light these past few weeks. Hey, we are getting ready for ICAAC and IDSA. So cut us some slack, already...(joking)

OK, in a matter of full disclosure, I have conflicts of interest with both of these papers, so following our standard practice of not critiquing papers where we have conflicts, I will leave the interpretation of each paper to you, our dear readers.

Click to enlarge: Frequency of non-prescription use of antimicrobials in the general population

Dan Morgan, who was our invited contributor on Veterans Day, has published a review of world-wide, non-prescription antimicrobial use in this months Lancet ID.  The review included 117 articles including 35 community surveys published between 1970 and 2009. I've pasted a summary figure above.

Co-blogger Dan has a paper coming out in ICHE (ahead of print) surveying IDSA's EIN Network of ID clinicians on their pre-op screening and decolonization practices for S. aureus. The survey included 488 respondents, who had knowledge of their hospital's pre-op screening. Overall, 60% screened for S. aureus with 47% screening for MRSA only and 13% for all S. aureus. Less than 20% screened extranasally. Screening method was led by PCR (36%) followed by standard culture (30%) and chromogenic agar (27%). Additionally, 52% decolonized with 31% decolonizing MRSA carriers, 8% decolonizing S. aureus carriers and 15% decolonized irrespective of colonization status. To find out more, you need to read the paper!

Is a graduation handshake a risk factor for bacterial pathogens?

University of Maryland dean, Dr. E. Albert Reece,
shakes hands during a graduation

In all likelihood, many of us have just suffered through enjoyed sitting through a recent preschool, high school, college or medical school graduation. The astute readers of this blog probably noticed the alcohol hand rub dispensers on stage for use by the graduates prior to shaking their dean's hand. You also noticed how few graduates actually used the dispensers.  Maybe they were nervous or rushed or were already wearing gloves to go with their graduation gowns...cool contact precautions.

So, should a dean worry about catching bad bugs from their students?  According to a new study published in the Journal of School Nursing, there is very little risk of acquiring a bacterial pathogen during a brief hand shake. In the study, cultures were collected from school officials' hands before and immediately following graduation. From a sample of 5,209 hands, Staphylococcus aureus was separately detected on one pregraduation right hand, one postgraduation right hand (different strain), and one postgraduation left hand, while nonpathogenic bacteria were found on 93% of the hands. They estimate the acquisition risk as 0.019 pathogens acquired per handshake. Of course, the study didn't test for viral transmission, which to me is a bigger worry.

Bishai D et al. Journal of School Nursing, May 11, 2011

New York Times LA Times May 23, 2011 (Dr. Reece from U. Maryland School of Medicine is quoted in this article)

Would you like Staph with that steak?

Photo: Friend of the Farmer

A new study in Clinical Infectious Diseases cultured meats from grocery stores in 5 US cities. Much of it was found to contaminated with Staph. aureus (77% of turkey samples, 42% of pork, 41% of chicken, and 37% of ground beef samples). Moreover, 52% of the isolates were multidrug resistant.

I am now beginning a campaign to have laws passed in all 50 states which will mandate that all human carnivores be immediately placed in contact precautions.

S. aureus vaccine breakthrough?

Researchers at the University of Rochester have just announced a potential breakthrough in S. aureus (MRSA) vaccine methods.  Edward Schwarz and John Varrone presented their new findings at the Orthopaedic Research Society annual meeting in Long Beach, Calif this past week.

Their work targets the S. aureus glucosaminidase (Gmd) protein, which is thought to act as a zipper by opening the bacterial cell wall during cell division. Importantly they discovered four anti-Gmd monoclonal antibodies that prevented growth in cell culture. They also demonstrated that mice treated with anti-Gmd antibody were half as likely to develop infection. Phase I human trials are planned for 2012.

References:
URMC Press Release

RSC Article

h/t Mark Vander Weg