Category: Infectious Disease

The Rat Around Your Neck

Physicians as plague carriers – but, rather than rats, as in the Middle Ages, suppose it may be our stethoscopes.

In this observational study out of Ethiopia, 176 stethoscopes belonging to healthcare workers and students in a hospital were swabbed and cultured.  Naturally, the authors were able to grow bacteria off 86% of these, half of which were pathologic strains such as S. aureus, Klebsiella, Citrobacter, Proteus, and P. aeruginosa.  The swabs taken from the ICU harbored the greatest percentage of isolates for pathogenic strains.  Most strains demonstrated some level of antibiotic resistance, such as 27% of S. aureus which proved methicillin-resistant.

Colonization, which has previously been demonstrated on the white coats of physicians, is not proof of transmission – but it is not unreasonable to suspect this may yet occur.  However, only 3% of respondents in this study regularly disinfected their stethoscope after each patient.  Even the mildest improvement in hygiene would likely go a long way towards reducing the theoretical risks.

“Bacterial contamination, bacterial profile and antimicrobial susceptibility pattern of isolates from stethoscopes at Jimma University Specialized Hospital”
http://www.ann-clinmicrob.com/content/12/1/39

Intermediate Lactate Values, Lowering the Bar for Cryptic Shock

A guest post by Rory Spiegel (@CaptainBasilEM) who blogs on nihilism and the art of doing nothing at emnerd.com.

Serum lactate has been the darling of Emergency Medicine/Critical Care since Manny Rivers first introduced EGDT to the Emergency Department. Since then we have used it as a screening tool, a means to guide therapy and even to prognosticate outcomes. Despite our universal acceptance of its utility, very little high quality data has been published on its diagnostic properties. I reviewed this evidence in more depth in a past post and will limit this to the question, “Can serum lactate identify a group of patients who are in cryptic shock, despite clinically appearing well?” The Surviving Sepsis Campaign recommends using a lactate level of 4 mmol/L as the threshold for identifying cryptic shock, but lactate has a continuous curvilinear association with mortality and a 4 mmol/L threshold seems like an arbitrary cutoff.

In an attempt to answer this question Puskarich et al conducted a systematic review, published in the Journal of Critical Care, examining the ability of intermediate lactate values (2.0-3.9 mmol/L) to predict cryptic shock and death. Eight studies were included in this review. A total of 11,062 patients with intermediate lactate levels were examined. The authors appropriately decided that given the heterogeneity of these datasets, a formal meta-analysis was not appropriate. Instead they settled for descriptive statistics of each individual trial. In summary they found patients with intermediate lactate values who were normotensive had a 30 day mortality rate of 14.9% (mortality in individual trials ranged from 3.2-16.4%). Obviously the patients with intermediate lactate levels that were concurrently hypotensive fared far worse (30 day mortalities of 35-37%).

This review fails to define the clinical utility of the association between elevated lactate levels and risk of death.  In the few studies included in this review which published diagnostic test characteristics, lactate performed surprisingly poorly. Howell et al found lactate had an AOC of 0.71 for predicting 30 day mortality. Shapiro et al reported a similar AOC of 0.67. In fact in the Shapiro study when a cutoff of 2.5 mmol/L was used as screening tool for cryptic shock, it had a sensitivity of 59% and a specificity of 71%. Even a threshold of 4 mmol/L though very specific (92%) had a sensitivity of 36%, a far lower sensitivity than one would be traditionally accepted for a screening test.

More importantly, this data does not allow us to determine how a lactate threshold of 2.5 mmol/L  performs in the true cryptic shock patient. This is the patient who has end organ hypoperfusion without any clinically obvious signs. In most of the patients with elevated lactates, they appear clinically ill and thus the lactate is only confirming what we already know, that this patient needs aggressive intervention. If lactate is to prove useful as a true screening tool (at whatever threshold), it should be able to identify the patient clandestinely experiencing septic shock before any obvious signs of of end-organ damage (AMS, hypotension, AKI) become apparent. Unfortunately we have little data supporting its use in this manner. Even the secondary analysis of the Jones trial, finding similar mortalities between hypotensive patients and normotensive patients with elevated lactate (above 4mmol/L), fails to impress. Although the cryptic shock patients were not hypotensive in the strictest sense, they were by no means physiologically normal. On the contrary they were older, more tachycardic, with faster respiratory rates, and experienced significantly more intra-abdominal infections (30% vs 16%) than their hypotensive counterparts. And though they were not hypotensive (<90 mmHg), their blood pressures were not necessarily normal. The median blood pressure in the cryptic shock group was 108mmHG with an IQR of 92-126. To put it simply, these patients were sick. They did not require a lactate level to identify them as in need of aggressive therapy. There was nothing cryptic about them….

“Prognosis of Emergency Department Patients with Suspected Infection and Intermediate Lactate Levels: A Systematic Review”
http://www.jccjournal.org/article/S0883-9441(14)00002-1/abstract

Can We Escape Antibiotics in Sore Throat?

Yes.  And no.

It is well-established complications of acute sore throat are incredibly rare.  The likelihood of a patient developing the most concerning of suppurative complications – a peritonsillar abscess or “quinsy” – is less than a fraction of a percent.  Rheumatic fever is virtually eliminated in the United States.  Yet, as we see from this British cohort, over half of patients visiting primary care received a prescription for antibiotics.

This is study reports on a combination of several, prospectively gathered cohorts presenting with acute sore throat to British primary care practices.  Comprising 14,610 adults, only 5,243 escaped the physicians office without an antibiotic prescription, while the remainder received immediate or delayed antibiotics.  Suppurative complications across all cohorts – peritonsillar abscess, sinusitis, otitis media, and cellulitis – ranged from 0.1% to 0.6%.

Unfortunately, this is not a randomized trial – the patients who were given antibiotics by their physician had much more severe initial clinical presentations.  This means, unfortunately, there is no information in this data set describing the actual protective effect of antibiotics without making statistical contortions.  The main value, however, is in describing the futility of clinical judgement for selecting patients for antibiotics.  Of all the various clinical features recorded prospectively for each patient, only severe ear pain and severely inflamed tonsils were significant predictors of suppurative complications – with ORs of 3.02 and 1.92, respectively.  However, these still constituted hundreds of patients with symptoms who otherwise did not progress.  High scores on the Centor and FeverPAIN criteria were similarly, minimally predictive.

In the end, it is ultimately apparent antibiotics confer some protective effect.  The absolute benefit, however, will represent just a handful of patients out of thousands.  The authors sum it up just as nicely as I might:

“Since a policy of liberal antibiotic prescription for sore throat to prevent complications is highly unlikely to be cost effective, and clinicians cannot rely on clinical targeting to predict most complications, clinicians will need to rely on strategies such as safety netting or delayed prescription in managing the low risk of suppurative complications.”

“Predictors of suppurative complications for acute sore throat in primary care: prospective clinical cohort study”
http://www.bmj.com/content/347/bmj.f6867 (open access)

Stop Using the Antibiotic Sledgehammer

There’s an interesting cultural phenomenon regarding inpatient treatment of respiratory illnesses – a sense that monitoring and close evaluation for treatment failure isn’t enough, and we must immediately deploy the nuclear option when the admission decision is made.  This includes nonsense use of intravenous administration when oral is equivalent and unnecessary use of broad-spectrum agents.

This comparative-effectiveness study evaluated the necessity of broad-spectrum agents versus narrow-spectrum antibiotics for the treatment of pediatric community-acquired pneumonia.  492 CAP admissions from four children’s hospitals in 2010 were retrospectively reviewed for outcomes, stratified by antibiotic choice.  Narrow-spectrum antibiotic choices were penicillin-like agents +/- macrolide, while broad-spectrum included cephalosporins or fluoroquinolones.

In their propensity-matched cohort, with the acknowledged limitations of unmeasured baseline characteristics, there were no useful differences in outcomes.  Most trends favored narrow-spectrum antibiotics, but these are at best statistical noise, and at worst reflect underlying unmatched treatment-episode confounders.

Current consensus-based recommendations are for initial treatment with narrow-spectrum agents – follow them.  I’d also note 51% of the population received blood cultures – 2.8% of which were positive.  I’m sure these were also entirely a waste of money.

“Comparative Effectiveness of Empiric Antibiotics for Community-Acquired Pneumonia”
http://www.ncbi.nlm.nih.gov/pubmed/24324001

No, You *Still* Don’t Need Antibiotics For That URI

A guest post by Justin Mazzillo, a community doc in New Hampshire.

Perhaps you’ve seen a case or two this year – a child brought to the emergency department for a cold lasting more than a day. Little Johnny’s parents dragged him in to see you at three in the morning, in hopes of obtaining the instant cure of antibiotics. 
These authors out of Washington and the United Kingdom conducted a systematic review to determine the duration of symptoms of earache, sore throat, cough and common cold in children less than 18 years of age. They included only trial arms that used no treatment, symptomatic treatment or placebo. Their findings include:
·      Symptoms of earache resolved by day three in 50% of patients and day seven to eight in 90%.  
·      Sore throat resolved in two to seven days.
·      General cough resolved by day 10 in 50% and day 25 in 90%. Symptoms of croup were gone in 80% by day two.
·      Bronchiolitis symptoms were gone in 50% by day 13 and estimated to be gone in 90% of patients by day 21.
·      Lastly, it took 10 days for 50% of symptoms of the common cold to resolve and 15 days for 90% to be symptom free.
The authors found this data to differ significantly from estimates by the UK National Institute for Health and Care Excellence and the US Centers for Disease Control. This information may go a long way in preventing parents from convincing doctors to put little Johnny on a myriad of antibiotics while his virus runs its course.
“Duration of symptoms of respiratory tract infections in children: systematic review”

http://www.bmj.com/content/347/bmj.f7027

Remember: Tamiflu is Still Junk

It’s that season of the year again, and with the fatalities from the H1N1 strain returning to the news folks are clamoring for Tamiflu (oseltamivir).

And, there’s still no evidence it has any protective effect at reducing complications from seasonal influenza.  In these two studies, a systematic review and a meta-analysis, some small reductions in symptom duration in mild illness were outweighed by drug adverse events such as nausea, vomiting, and diarrhea.  There is no evidence of any decrease in severe complications of influenza.

Unfortunately, the heterogeneity of trials, irregularities in baseline characteristics, and incomplete peer review all impair knowledge translation of this relatively expensive outpatient medication.  You’re all hopefully aware of the BMJ’s ongoing open data campaign regarding Tamiflu.  The last update from July seemed to indicate independent access to higher-quality trial data had finally been achieved.  If there is a durable, beneficial effect attributable to osletamivir, perhaps we will soon know.  Given the lack of transparency to date, I’m not optimistic.

“The value of neuraminidase inhibitors for the prevention and treatment of seasonal influenza: a systematic review of systematic reviews.”
http://www.ncbi.nlm.nih.gov/pubmed/23565231

“Effectiveness of oseltamivir in adults: a meta-analysis of published and unpublished clinical trials.”
http://www.ncbi.nlm.nih.gov/pubmed/22997224

Sepsis, NHAMCS, and Non-Truths

“… our results provide a worrisome view of the quality of care of septic patients in U.S. EDs.”

Crikey.

This is serious business.  Tell me more.

“Our data suggest that many emergency department patients (31%) with sepsis do not receive antibiotics until they arrive on the inpatient unit.”

This is somewhat concerning data.  Of course, some patients can have sepsis from viremia, and would not warrant antibiotics – but, I think most admitted patients with SIRS and a suspected infectious source ought to receive treatment.

But, unfortunately, for this study, the question is less the quality of ED care, and more the quality of the data source.  The National Hospital Ambulatory Medical Care Survey is a lovely data set, whose quality is only increasing as coding and structured data become more prevalent – but a retrospective analysis of these data is not appropriate substrate to make sweeping generalizations regarding the care in the Emergency Department.

From the ~400 Emergency Departments providing yearly data to NHAMCS, 0.32% of patients met their definition of sepsis.  That meant these data reflect a sample of 1,141 patients, and the admitted limitation of “studies relying on NHAMCS data are vulnerable to errors of omission in data collection.”  These authors lack information regarding previously administered antibiotics from transferred patients, and admit some patients – those spending <1 hour in the ED – may simply have left the ED before antibiotic administration could be completed.

Quite simply, it’s (mostly) garbage in and (mostly) garbage out.

The authors also attempt an assessment of antibiotic appropriateness from this retrospective chart abstraction.  It is so egregiously flawed it doesn’t even warrant comment.

“Sepsis Visits and Antibiotic Utilization in U.S. Emergency Departments”
http://www.ncbi.nlm.nih.gov/pubmed/24201179

Total Fever Illiteracy

If you weren’t already aware, the American Academy of Pediatrics recently published a policy statement concerning the use of antipyretics to reduce temperature in a febrile child.

Don’t do it.

The available evidence is treatment of fever may ultimately attenuate the body’s natural immune defenses, while parents inadvertently place their children at risk by using inappropriate dosages.  The only goal of antipyretic use is to improve overall patient comfort.

And, as this study shows, we have a long, long way to go in educating our patients.

This is a survey of 100 patients – 54 from a private clinic and 46 from a county clinic – and, within the bounds of the small sample, there is essentially no difference in the perception of fever.  Nearly 75% failed to correctly identify the temperature range constituting fever (>38°C).  93% thought high fever results in brain damage.  89% would give antipyretics to a comfortable child with temperature >38°C, and 86% would go ahead and schedule a clinic visit.  Equally surprising (or not), 59% would dose a comfortable child with temperature 37.4-37.8°C with antipyretics, and 38% would schedule a clinic visit.

Given the volume of ambulatory visits for fever – both in the Emergency Department and community Pediatrics – it would seem continued education regarding “fever phobia” has the potential for significant cost savings.

Brain damage, by the way, is not usually a concern until 42°C.

“Fever Literacy and Fever Phobia”
http://www.ncbi.nlm.nih.gov/pubmed/23349363

Stepping Up to Choosing Wisely

ACEP recently published their own “Choosing Wisely” campaign contribution – a list of five changes to Emergency Medicine practice that ought be encouraged in the interests of increasing cost-effective care.  While most would agree the ACEP version is reasonable, I think many clinicians hoped for something a little more earth-shattering.

Something like the Pediatric Hospital Medicine list for Choosing Wisely.

These authors specifically looked at the top 10 inpatient diagnoses in terms of volume and aggregate costs, and specifically evaluated components of treatment as candidates for recommendations.  And, even speaking as someone who makes an effort to minimize testing – I find these recommendations take an impressive step in terms of aggressive reduction in resource utilization.

The highlights:
Do not order chest radiographs in children with asthma or bronchiolitis.
Do not use bronchodilators in children with bronchiolitis.
Do not use systemic corticosteroids in children under 2 years of age with a lower respiratory tract infection.

How often do you get radiographs in patients with respiratory disease – that get discharged?  How about admitted?  The authors estimate 60% of admitted patients receive radiographs, with fewer than 2% affecting clinical management.

Or, routine bronchodilator therapy – which, frankly, is ordered for a lot of children simply due to a sense we ought to do something.  Both beta-agonist and racemic epinephrine fall under this recommendation, as they’ve not been shown to confer any reliable, clinically meaningful, patient-oriented outcome in bronchiolitis.

Finally – corticosteroids.  Young children, even with albuterol-responsive wheezing, showed no benefit when corticosteroids were added.  These are not harmless interventions, particularly for growing infants, and seems to pre-dispose some folks to subsequent readmission.

With pediatric respiratory season on the horizon, I challenge all of you to use this document as a tool share with colleagues and consultants to decrease unnecessary testing and therapy.

“Choosing Wisely in Pediatric Hospital Medicine: Five Opportunities for Improved Healthcare Value”
http://www.ncbi.nlm.nih.gov/pubmed/23955837

It’s Silly Season on Flu

We still don’t know whether neuraminidase inhibitors (e.g., oseltamivir [Tamiflu]) are helpful.  Roche has prevented access to trial data until just this year, and the results of independent review are still pending.  However, that has not stopped plenty of smart, well-meaning folks from taking their claims at face-value and using NAIs to treat influenza.

This is a retrospective registry review of 3 years of children admitted to California ICUs with a laboratory-confirmed diagnosis of influenza.  850 children were identified in the registry, and 784 children had clinical information available for analysis.  Of these, 653 received NAIs and 38 (6%) died.  Of the remaining 131 untreated patients, 11 (8%) died.  Using a multivariate model adjusting for univariate predictors of death, NAI therapy was associated with decreased mortality (OR = 0.36, 95% CI 0.16-0.84).

But, while registry reporting was mandatory for deaths due to influenza, it was only optional for ICU hospitalization – leading to an unknown selection bias in their study cohort.  There were also 23 deaths reported prior to hospitalization for whom no data is available.  Most patients in the study treated with NAIs were H1N1, while the small remainder comes from the post-pandemic period with a mix of H1N1, other influenza As, and influenza B – and therefore may not be generalizable to a non-pandemic influenza season.  A standardized abstraction form was used, but the complete baseline demographics collected are not included in the article; most patients included had significant respiratory comorbidities, and these chronically ill children were far more likely to die regardless of treatment.  In summary, with a small sample size, likely missing data from abstraction, and selection bias underlying their cohort, the multivariate analysis upon which they based their final conclusion is junk.

In contrast to the editor’s summary “What this study adds”, which concludes special emphasis on treatment with NAIs may improve survival, I would revise it to say: “No additional practice-changing evidence”.

Now, I can’t say I’m opposed to treatment of hospitalized influenza patients with NAIs – least of all, those in the ICU.  While outpatient therapy with NAIs for influenza is almost certainly a waste of money, in severe disease, the cost relative to the entire expenditure shrinks rapidly – the threshold for cost-effectiveness is met even if one patient out of a hundred has a one day reduction in ICU length-of-stay.  But, it’s inappropriate to over-sell the meaning in this data to suggest any certainty NAIs are helpful.

“Neuraminidase Inhibitors for Critically Ill Children With Influenza”
http://www.ncbi.nlm.nih.gov/pubmed/24276847