Mythbusting

Shocker! Parents may prefer PO to IV treatement.

FOR MENINGITIS!

One dogma that particularly sticks in my craw is that IV antibiotics are somehow mythically better than their PO counterparts. This is one that clinicians continue to perpetuate despite quite a bit of evidence to the contrary, and sometimes under the guise that “its what the patients want.”

Well, this paper from Brown University in Rhode Island (home of Del’s Lemonade and the Awful Awful) have sought to dispel.

For 3 months, the authors surveyed 102 consecutive parents of children who were not undergoing evaluation for potential Lyme disease and who were being seen in a pediatric ED. The reason for choosing Lyme disease as their hypothetical case is that the great state of Rhode Island is an are endemic to Lyme disease, and children with Lyme meningitis are often treated with intravenous ceftriaxone although oral doxycycline may be effective.

The parents were surveyed after observing a 9 minute video describing a hypothetical Lyme meningitis treatment trial (PO doxy vs IV ceftriaxone), and 84 of 102 parents (82%) would consent to their child participating (!). Even more impressive was that 37% of parents would accept 2 additional days of symptoms with oral meds even if intravenous treatment hastened symptom resolution (44% would accept one additional day symptoms). When told that there was likely equivalence, 47% would prefer doxycycline treatment, 24% thought it would be equivalent, and 29% still preferred IV treatments – with no differences in likelihood of choice based on age, ethnicity, education or knowledge of lyme disease. There was a weak correlation between perceived efficacy and tx preference, while there was a moderate correlation between perceived safety and treatment preference.

Basically, explain that about a third of patients have issues with IV antibiotics or PICCs (more diarrhea, allergic reactions, more DVTs, etc – not to mention bigger bills from VNS services, inpatient stays, etc), and you’ve got ~70% chance that the parents would be ok with outpatient treatment.

Understandably, as the authors put it, “the hypothetical nature of this study may overestimate the proportion of parents who would consent in an actual trial” – but it provides great food for thought to at least consider having the conversation with parents on your next shift when you as the clinician are on the fence of stay or go.

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GI, Improving Outcomes, Mythbusting

The Better Poop Route.

This is a study comparing PO vs colonoscopy inserted fecal microbiota transplant for cdiff with the primary outcome the proportion of patients without a recurrence 12 weeks after stool transplantation.

 

Survey says- it doesnt matter how you do it, but both have their ups and downs.

 

While PO meds were significantly less costly, it was significantly less pleasant (44% vs 66% rated it “not at all unpleasant”) – understandably so as patients took FORTY capsules- under direct observation no less- which were made from a singular 80-100g donation. Colonoscopy implantation was performed with placement of 360cc of “fecal slurry in the cecum” – and was significantly more expensive ($874 vs $308). Colonoscopy patients had a 12.5% rate of minor adverse events vs 5.4% of the PO group (mostly nausea/vomiting or abdominal discomfort).

Further fun facts, participants most frequently characterized fecal transplants as “innovative treatment” (63% of patients), a “natural remedy” (41%), and “unpleasant, gross, or disgusting” (30%); which is surprisingly realistic to how providers feel about this same treatment.

Its nice to see the lower cost, less invasive treatment work equally well (both clocked in at about 95% rates of non-recurrence at 12 weeks), but geez, 40 tablets of poop seems a bit more like a lost dare than a medical necessity.

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Improving Outcomes, Improving Throughput

POCUS guided Flexor Tenosynovitis

It feels good to be back! Now, fresh off the inaugural AAPA18 iScan ultrasound event, its only right that my next post is on two of my favorite things- POCUS and infectious disease.

This is a review of 73 patients presenting to an emergency hand clinic (!) over the course of 3.25 years with a pyogenic flexor tenosynovitis.  Yep, a whole 22 patients a year… at an emergency hand clinic.

All patients underwent a resident and attending surgeon eval as well as labs including CRP and films. 16 confirmed pyogenic flexor tenosynovitis patients were excluded (these were the slam dunk obvious ones)- while the remaining 57 underwent POCUS while pending labs. POCUS was done by either a resident with 2 years experience in MSK sono, an attending surgeon with sono training, or senior radiologist.  Suffice to say, that this isnt exactly us work-a-day EM providers.

Of the remaining 57 patients, there were 29 were ultrasound negative (non-thickened tendon sheath without hyperemia and no peritendonous effusion); all were given PO antibiotics and discharged with every other day follow up until symptom resolution; only one required OR intervention.

Of the 27 patients with positive ultrasound findings- 17 of these had either a positive OR culture or significant purulence seen at the time of OR washout.  While this results in a decreased PPV of 63%, and a decreased specificity of 74% – I maintain POCUS is actually much better; keep in mind these numbers do not include the 16 slam dunks on clinical exam.  It doesnt take into account the rapid sterilization after a single dose of antibiotics seen in CSF and ascites; nor the 30% negative OR-culture rate seen in other pyogenic flexor tenosynovitis studies.  Nor does it take into account that POCUS approaches MRI for sensitivity and specificity in prior studies.

Ultimately, it would be fantastic (and likely better medicine!) if, stateside, we could adopt an ultrasound first strategy (especially with a 97% NPV and 94% sensitivity!).  If POCUS negative, patients could get expedited follow up and oral antibiotics.  This is pretty much exactly what this group has done.  Presumably with this strategy, a small fraction of these more ugly “slam dunk” tenosynovitis cases may not require the OR (the group did not comment on positive OR-culture rates), and the patients in the middle ground could get expedited follow up or overnight observation and serial sonography.  It should be noted that “delayed” diagnoses which resulted in poor outcomes were >10 days out from the initiation of symptoms (!); so a day or two may not make much of a difference.  This study comes with the usual caveats- there are few MSK ultrasound courses in the USA (I contacted the Jefferson MSK fellowship, no dice for hand sonography!), different equipment than our usual sonosite machines, more training.  But that certainly does not mean we can not have something to aspire to.

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Mythbusting

Delayed endocarditis diagnosis? The patient can have as many diseases as they please.

This is exploratory look at patients diagnosed with endocarditis at admission versus those with a delayed diagnosis. Granted, this is not a US study, and over a 9 year period at a single center, but does provide an interesting look at how we manage these patients….

They looked at those with an admitting diagnosis of endocarditis that eventually went on to have this as a final diagnosis as well (54 patients), and compared them to patients with a non-endocarditis initial diagnosis to those who eventually had a final diagnosis of endocarditis (64 patients).

Even in the two slam-dunk groups- the IVDA & those with valve replacements, the diagnosis was delayed in the 38% of the time for those with a history of IVDA. For those with a valve replacement there were also significant delays with native valves delayed 63% of time, vs prosthetics delayed 24% of time…. Are we really bad at diagnosing this? Let’s peel back this onion.

Cases were placed into 3 categories: (1) complications of endocarditis, but not immediately recognized as endocarditis – 70% of cases (2) infectious disease unrelated to endocarditis (14% of cases) – ie, hepatitis (3) inconsistent non-infectious disease (16% of cases).

Of those in the “complications” category, only 10% were unlikely to be dosed with antibiotics – they were admitted for “stroke” or CHF/ pulmonary edema. This is clearly understandable. Do we need STAT echos for the pulmonary edema patient? Or for the stroke? STAT echo’s right away for all of these patients – or perhaps routinely ordering them on all CHF / stroke patients may prove more costly and harmful than its worth.

The author’s make the argument that there is significant mortality involved with an initial missed diagnosis in their cohort- 75% vs 25% (!!!). I’m not certain these represent a complete whiff on the part of the treating clinicians. Rather, I would argue that these patients had their complications recognized and treated appropriately (ie, the pneumonia and UTI’s got antibiotics initially), and that these patients were likely sicker to begin with and that is why they had all the additional complications and higher mortality.

While perhaps a heightened awareness of valve replacement patients, and/or awareness of the disease process may help, but sadly, when you are looking for a needle in the haystack, having a 100% sensitive and specific diagnostic algorithm is unreasonable. When can certainly do better, but how much better without causing harms to the rest of the department remains debatable.

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Mythbusting

Do Prehospital Antibiotics Matter?

In short, probably not, but still not completely disproven.

This randomised controlled open-label trial looked at giving 2 grams of IV ceftriaxone to patients that met SIRS criteria (save for WBC- testing unavailable to EMS) with suspected infectious illness. Patients were randomly assigned (1:1) to the intervention group or usual care group using block-randomisation with blocks of 4. This study took place across ten large regional ambulance services serving 34 secondary and tertiary care hospitals in the Netherlands over a 2 year period. They screened 3228 patients of which 2698 were eligible (pregnancy, beta-lactam or ceftriaxone allergy, suspected prosthetic joint infection, among others); 1150 in the usual care arm (IV fluids, supplemental oxygen prn), and 1548 in the intervention group (2g ceftriaxone plus usual care). 13 patients in each arm were excluded from final analysis or excluded due to withdrawn consent or being lost to follow up. The primary outcome was all-cause mortality at 28 days.

So, while they screened over 3,000 patients over 2 years (a massive undertaking!), unfortunately, only 37 (3.3%) patients in usual care and 66 (4.3%) patients in the early antibiotics group had septic shock. Perhaps you could make an argument that the intervention group was slightly sicker with 22% vs 17% having 2 or more qSOFA criteria. Despite a median time to antibiotics of 70 minutes in the ED (thus, probably close to 90+minutes faster in the intervention cohort), and with 14% having antibiotics >3hrs from presentation and 14% having none at all (suspected viral syndrome) – there was 8% mortality in both arms at 28 days and 12% at 90 days in both arms. No difference.

When you look at mortality for septic shock it was 27% (10/37) in the prehospital antibiotic cohort vs 28.8% (19/66). Again, not statistically significant. While prehospital antibiotics might make a difference in a larger cohort, its probably going to be very hard to ever do that study – this was a 2 year study looking at over 3,000 patients and they were barely able to accumulate over 100 septic shock patients.

While an American might argue “they only gave ceftriaxone, you need a real drug like Pip-tazo and vancomycin!” – slow down. The authors acknowledge that ceftriaxone may not have been appropriate because it was “a big gun” that they could all agree on and most patients were rapidly narrowed to receive, most commonly, amoxicillin–clavulanic acid with ciprofloxacin and ceftriaxone the second and third most common antibiotics given. They did not have culture reports back at time of publication, but having low mortality, and 9% of each cohort were not given antibiotics from the ED due to suspected viral illness makes me suspect that they do not have nearly the resistance problem (or concerns) that the Americans do, likely do to appropriate stewardship. Likewise, while one may be concerned about missed diagnosis due to premature closure, there was a miss rate of 1.4% in the intervention group vs 1.7% in the usual care group, also not statistically significant.

In the end, the authors provide a sensical view of the current state of prehospital antibiotics, “Studies showing that early antibiotic treatment is beneficial for reducing mortality found this positive association mainly in patients with more severe illness and a (time to antibiotic) of more than 5–6 hours… However, we currently do not advise antibiotic administration in the ambulance to patients with suspected sepsis.“

While it is certainly plausible that prehospital antibiotics may be beneficial for those with septic shock, it is a near certainty that, at least in the USA, sepsis hysteria would further ensue and the inertia of giving everyone a dose of broad spectrum antibiotics will likely occur – not to mention our continued fixation with iatrogenic salt-water drowning. The cost to the system – including other patients in the department – of responding to these prehospital alerts for those not in shock will likely be the hidden cost infrequently published or discussed by administrations.

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Improving Outcomes, Improving Throughput, Radiology

Parting the SEA with the almighty H&P (& rapid MRI).

Necessity is the mother of invention, and sometimes, necessity comes in the form of hospital administration after a bad outcome. The authors of this paper, essentially developed a rapid MRI protocol for suspected spinal epidural abscess after “several cases of SEA associated with delayed diagnoses and poor outcomes prompted the chairs of the departments of emergency medicine, neurosciences, medicine, and radiology, and members of the Division of Healthcare Quality, to develop a multidisciplinary, clinical decision support tool and imaging protocol with the goal of facilitating early recognition of SEA.”

Wow. Talk about moving mountains. If you’re department is anything like mine, it takes hours to agree on where we’re getting take out from; I cant imagine adding in 4 entire departments into the lunch-ordering mix, let alone all agree on a protocol.

They took a relatively simple approach – if you have new or worsening back/neck pain AND a history of spinal abscess or current/recent (6 months) bacteremia, straight to MRI. I think the recent bacteremia often gets lost in the work up, so I appreciate that they put this front and center. If there is no recent spinal infection or recent/current bacteremia, They looked at risk factors- and I’ll make this simple and break it into 2 categories: people putting things where they dont belong (IVDA, vascular catheters, spinal procedures/injections) and the recurrently ill: ED visit or antimicrobial treatment within 30 days or an infectious process elsewhere. If yes, head to MRI.

I’m torn a bit on this- while I want to applaud the authors for not dwelling on a variety of risk factors that only a small portion of the population has – alcoholism, HIV, severe COPD, the undomiciled, HepC, oncology patients, transplant patients, etc; to say that this group is pretty much captured in the recent ED visit category probably misses a fair amount of patients on the first go-round. And here is the problem of trying to find a needle in the haystack – its hard to increase sensitivity and specificity without causing a delay at some other portion of the food chain – every stat MRI for so many additional back pain patients pushes out another patient and potentially extends at least 1 other patients length of stay.

However.

Despite an increase from 56 MRI’s in the 7 months pre-intervention to 147 in the 7 months post-intervention, yield for a positive MRI (defined solely as SEA and not vertebral osteomyelitis or infectious discitis), went from 16.1% to 17.7%.

On first glance, that’s not a lot of improvement in yield, but they screened 3 times as many patients without losing yield! This is rather impressive. However, they tripled their ED MRI rate, and, even though they drastically cut turn around times from 8.6 hours to 4.4 hours from time of MRI order to radiology report, thats still well over 4 hours for patients with back pain in a highly optimized system. And while yes, they missed fewer SEAs, they probably still have a good percentage that they missed on first visit – the various forms of immunocompromised – the severe COPDer on repeated steroid prescriptions, the HepC patient, the elderly – these are likely missed on the first go round.

I think this is a great step towards creating a policy towards SEA workup. It needs some refinement, but is the best I’ve seen yet. It poses some issues for smaller facilities that do not have 24/7 MRI capabilities, as well as for consultants (neurology essentially becoming a house officer for ID and neurosurgery), and poses a big time crunch for the ED (again, neurology took control of these cases once the decision to MRI was performed, which the hospitalists must be thankful for!). In the end, there is no such thing as zero miss, but Baystate, with this study, demonstrates that, at least for one day, the H&P is not dead.

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Critical Care, Mythbusting

Even Pharma is getting in on Vanco-PipTazo AKI

This was an entertaining 9 page meta-analysis espousing the therapeutic harm of vancomycin and pip-tazo in the form of acute kidney injury.  With a conflict of interest page that reads like a pharmaceutical mutual fund (The Medicines Company, Cubist, Pfizer, Merck, Forest/Allergan, Melinta), it’s no wonder that they infer increased mortality due to AKI, yet conveniently COMPLETELY ignore that the same papers they reference show no mortality difference – and if anything a trend towards mortality benefit for vanco-PipTazo.  Likewise, with dialysis rates <2%, the induced kidney injury is less likely to cause harm than a suboptimal drug that wont kill your bug.

They also fail to mention cefepime neurotoxicity.

There are other ways to go about this. Like, say, reviewing the damn cultures.

But in the end, since The Medicines Company and Melinta have new broad spectrum antibiotics on the market or on the way, it probably behooves them to run a slight smear campaign on current treatment regimens. Therefore, forgive me for considering the possibility that the authors intentions may not be pure.

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