Improving Outcomes, Mythbusting, Neurology

Early vs late meningitis diagnosis: capturing the needle in the haystack

Needle in the haystack, infectious pathway, take 6.

This is a retrospective study looking at early vs late diagnosis of bacterial meningitis from three hospitals in Denmark (one looking at data from 1998-2014; the other two from 2003-2014). To be eligible, patients had to be >15 years of age, and, obviously, had to be hospitalized with a clinical presentation consistent with possible community acquired meningitis (any combination of headache, neck stiffness, fever, altered mental status, petechiae) with no alternative diagnoses made during or after admission. Furthermore, all patients also had to have a proven bacterial etiology by either: positive CSF culture, positive blood culture and CSF with >10 wbcs, bacteria seen on CSF gram stain, or bacteria in CSF by PCR or antigen analysis.

So what is early and what is late diagnosis? They define “early diagnosis” as being recognized in the ED (1.3 hours to antibiotics median), and “late diagnosis” as, well, not diagnosed in the ED (ie, diagnosed on the wards- 13 hours to antibiotics median). Over roughly 15 years, they saw 358 cases of bacterial meningitis, (~8 cases per year per institute – seems a bit high? They do not mention total number of annual ED visits), with 32% being classified as diagnosed “late.” … so, probably 2-3 cases a year of “late” diagnosis – a true needle in the haystack.

Why the late diagnosis? They tended to be older (65 years of age vs 56), less likely presenting with headache (58% vs 82%), less likely with neck stiffness (36% vs 78%), less likely with fever (59% vs 78%), with the classic triage of AMS, fever, and neck stiffness was only present 20% of the time in the late diagnosis group vs 50% in the early diagnosis…. So, it wasn’t an easy catch.

Why does this matter?  Welp, with early antibiotics having a positive effect on mortality (18% vs 36%) as well as unfavourable outcome (which they do not actually define, 37% vs 66%, in favor of early antibiotics).  This is a HUGE difference in mortality and unfavourable outcomes if you do not catch it early!  … Then again, do we do more harm by giving 1-2g of ceftriaxone to everyone who is a bit altered?  Would the risk of cdiff then outweigh the 2-3 annual misses? I’m not so sure.  What about the recurrent headaches and repeat visits for post-LP headaches?

If you really want to tease out the data a bit, 53% of late diagnosis patients vs 26% or earlier diagnosis patients had a head CT before the LP. 72% of “late diagnosis” patients tentatively had a non-infectious etiology- so let’s explore some of the tentative diagnoses:

loss of consciousness (19 patients)

stroke (12 patients)

intracranial / subarachnoid hemorrhage (7 patients)

impaired mental status (6 patients)

headache (5 patients)

back pain (5 patients)

seizures (5 patients)

loss of vision (2 patients)

(among others)

 

What I’m seeing here is a a trend towards a neurologic issue (a CT scan, a diagnosis of syncope / seizures, AMS, etc) – which may indicate that the thought of meningitis (or even endocarditis) may not have been entertained. Cant make the diagnosis if you dont think about it. In a similar vein, this diagnosis is rare and runs across a spectrum – on one end, the febrile, meningeal and altered, on the other, the vaguely unwell.  And that, surprisingly, even a 12 hour delay to antibiotics can wreck havoc on the patient.

The take home points?  Be vigilant, entertain the spectrum of disease for meningitis, but remember that every decision you make has consequences, including the decision to, and not to, perform an LP, not to mention the decision to indiscriminately give antibiotics for those “altered”.  Choose wisely, and remember there is no such thing as zero risk.

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Improving Outcomes, Mythbusting, Radiology, Radiology

Spinal Abscess: The Baystate Review

This is a review of all spinal abscesses at Baystate (total 162), from 2005 – 2015.  They compare 88 randomly selected controls whom had similar ICD-codes less the spinal abscess plus an MRI that was negative for acute infectious process. 

Interesting take home points, much of which is consistent with prior (albeit scant) literature:

-73% of patients are over age 50.

-more likely to have their second visit (50.6% vs 29.6% of controls) – though this 50.6% of patients with a second visit is surprisingly low for me – no word on how many were sent home from the ED, and had an MRI as an outpatient that were not included in this calculation.; or maybe we’re getting better at finding the needle in the haystack?  Or maybe we’re MRI’ing everyone?

-Many received antibiotics within the month: (35.2% vs 6.8% of controls) – this signifies a huge red flag for me.  If a patient revisits the ED and recently had pyelo (or anything infectious really), and now presents with back pain, probe a bit more for the possibility of vertebral osteo or discitis. 

-percentage of patients with history of IVDA: 20.4% vs 4.6% … this number seems low, but also is somewhat in line with prior studies – thus making me wonder how many I’ve missed…

– percentage of patients with alcoholism with a spinal abscess: 19% vs 8% – the more I get interested in ID, the more I realize that alcoholism is basically a form of immunosuppression.

-percentage of spinal abscess patients with obesity 21.6% vs 2.3%; I’m surprised only 2.3% of controls were obese.  Not sure what role this plays as being a diabetic in and of itself was not associated with a higher increased risk in this study.

-fever was present 62.4% in those with a spinal abscess vs 13.6% of those without; this includes self reported fever, which I have to wonder how often we sweep this aside when the patient is afebrile in the ED.

-16% had no identifiable risk factors; a third of the patients  presented with back pain, fever, neurologic deficits vs 6%

-Other symptoms and signs related to potential spinal cord impingement were seen with similar frequencies and of similar durations among cases and controls- meaning, focal deficits seen in both groups.

-noncontiguous co-infection: 53.7% of time (pneumonia, distant osteo, endocarditis… of those with a co-infection, 20% had more than one).

-blood cultures were positive 63.4% of the time, and >75% of the time it was staph Aureus. 

-Majority of lesions were found in the L-spine at 56.2%  – which means almost half are elsewhere!

-while “admits” for spinal abscess were up from 2.5 to 8 in 10,000 admissions from 2005 to 2015, I have to believe that number is somewhat inflated as admits like chest pain, pneumonia and renal colic probably decreased, while MRI became more readily available. 

All in all, this paper is pretty much in line with others on this topic, and strengthens the signal a bit for certain key points: a good number of spinal abscesses are not in the L-spine; many patients are older than you think, and, among other things: its more than just IVDA. 

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Critical Care, Improving Outcomes, Mythbusting

Procalcitonin: Holy Grail, or Holy Sh*t ?

Procalcitonin is marketed as, “a marker of broad routine use, both for differential diagnosis of bacterial infection as well as for antibiotic stewardship.

But is it?  This study looks at 107 ICUs that had >25 sepsis cases in 2012, and had an ability to perform procalcitonin (PCT) levels on their septic patients, and essentially looked to compare the outcomes of those that had PCT ordered and those that did not.  All in all, there were about 17,000 septic patients without a PCT ordered, and about 3800 patients with a slightly lighter wallet and slightly more anemic after their admission than their comparators.

There was little difference in baseline characteristics – save for those having PCT ordered more likely hailing from the West (27.9% of PCT orders vs 12.7% of those not getting PCT ordered) and the opposite holding true for the South (55.3% without vs 49% with PCT).  PCT was slightly less ordered at teaching facilities (37.8% of septic patients without PCT orders vs 31.9% of those with a PCT ordered).  All other OR were <1.25.

There was no difference in length of stay and no differences in mortality.

There was an increase in days of antibiotic treatment for those in whom a PCT was ordered (relative risk increase 1.17), and with that an accompanying increase in Cdiff (OR 1.42) .  Of course, 1 PCT begets another (33% of the time, and about 3 days later).  Patients with serial PCT orders had higher rates of antibiotic use, higher Cdiff, and again, no mortality benefit.

Stop the madness.  Indiscriminately ordering tests that will not change management should not be done.  And they certainly should not be repeated.

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Critical Care

Who ya gonna call? #VancZosyn!

If there’s some strange cough in your resus room,

Who you gonna call? Vanc-ZoSyn!
If something’s fevered… and it don’t look good,
Who you gonna call? Vanc-ZoSyn!

I ain’t afraid of no Staph.
I ain’t afraid of no Strep.

If high lactates are running through your EMR,
Who you gonna call? Vanc-ZoSyn!

 

There’s been some FOAM rumblings about Vanc/ZoSyn causing AKI, but this was the first time it has been compared directly head to head with Vancomycin-Cefepime. This was a retrospective matched cohort study with 279 patients in each arm – one received combination therapy with vancomycin-cefepime (VC), the other received vancomycin-piptazobactam (VPT) for > 48 hours. Patients were excluded if their baseline serum creatinine was >1.2mg/dl or they were receiving RRT. Patients receiving VC were matched to patients receiving VPT based on severity of illness, ICU status, duration of combination therapy, vancomycin dose and number of concomitant nephrotoxins. The primary outcome was the incidence of RIFLE criteria-defined AKI, with a slew of secondary outcomes performed as well.

So, wait, what’s so special about RIFLE anyway? Glad you asked: In general, the worse the acute kidney injury, the higher the mortality.

Since this study shows an 11% AKI rate with VC and 29% AKI rate with VPT, maybe we can improve our mortality if we simply switch from zosyn to cefepime?

Except that this group reports mortality was actually worse in the VC group (though not statistically significant – 8.6% vs 5.7%). That’s right – the group with more AKI had less mortality. In other news, ICU stay was decreased (6 vs 8 days), which was statistically significant., and only ~1% of patients in both arms required long term hemodialysis.

While I was getting ready to click submit on this blog post, I found a second paper (published Nov 28, 2016) that looked at a matched cohort of 1633 VPT vs 578 VC patients, with essentially similar results – 21.4% AKI in VPT vs 12.5% VC.  This second paper found similar LoS, but also a similar trend in mortality-  6.9% for the VPT arm and 9.2 for VC.

So… I’m not certain what to make of this – but it seems more than fair to question whether drug induced AKI is a meaningful surrogate marker for sepsis mortality.  We need a long term look at mortality between VC vs VPT to see if VPT induced AKI follows the same trends. Maybe we’re trading a slight bump short term mortality for improved long term mortality with VC (or maybe not).  In the meantime, I think we need to pump the brakes on shouting about Vanc/Zosyn AKI until we sort this out a bit more.

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Improving Outcomes, Pediatrics

Baby LPs, ultrasounds, and fragility

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How fitting that the SMACCdub talk, What Scares You, has recently been released, and, to some extent, discusses pediatric bleeding. Well, this paper discusses high risk peds (febrile infant <60 days) and (post LP) bleeding, and whether or not ultrasound assisted guidance helps.

SPOILER ALERT: (it probably does).

From February 2007-December 2007 (wow, talk about a knowledge translation delay), the authors attempted to enroll 46 total patients to either standard LP without ultrasound vs ultrasound assisted LP. Here’s one key point – while ultrasound guidance means direct visualization of the needle into the desired space (like for central lines or paracentesis), ultrasound assisted means that landmarks were sonographically visualized, and then they marked the skin and estimated how deep was too deep for the needle, then performed the LP (without direct visualization.-Basically they performed an ultrasound to determine a “maximum safe depth” to limit needle advancement to avoid traumatic taps, since this is a common element of LP failure in this age group.

Patients with known spinal abnormality or VP shunt were excluded, and the procedures were done by either a house officer or pediatric NP with MD oversight (so, I’m not certain how applicable this is to those of us with significant experience in this age group). Unfortunately, the study was terminated prior to reaching their goal of enrolling 23 patients into each group due to academic calendar demands of the lead author (21 vs 22 patients in either arm – meh.) Success was defined as <10k RBC and whether or not CSF was obtained. Their 5 month historical failure rate was 44%.

The groups did not differ in terms of prematurity, patient weight or length, there was a lower median age in ultrasound assisted group (38 days vs 45 days p=0.02), which may give them a bit more of an uphill battle. The results are seen below:

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On first glance, these look good – less frequent traumatic taps, more frequently obtaining CSF with NNTs of 3.7 and 5.6 respectively. However, with such a small sample size, a Fragility index of 1, and having house officers and NP’s do the tap (with an unclear level of experience), I’m not certain this is broadly applicable to all providers, particularly when you add that 19 sono-assisted attempts are not enough to reach 80%  success in this study.  With that said, we commonly perform interventions with much lower NNTs with higher risks to the patient than a few ultrasonic waves. This is a cant hurt, will probably help intervention that we should probably be utilizing more frequently for all of our patients, not just our pediatric population.

For a great review on this topic check out sonomojo for more on ultrasound use for LPs.

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Cardiology, Improving Outcomes, Mythbusting, Neurology

Chronic viral infection & Coronary disease.

Are you openly ignoring a cardiac risk factor that is in the ballpark of smoking or early family history?   Even after controlling for numerous factors, well controlled HIV has a significantly higher cardiovascular MORTALITY rate – with an adjusted rate ratio of 1.53, while poorly controlled patients even moreso, with an adjusted rate ratio of 3.53, according to this paper.  It should be noted that this is one of several papers looking into HIV as a risk factor for early cardiac disease and death.

It is important to realize the limitations of our tools that we have at our disposal.  For instance, PERC and HEART are not validated in an HIV population.

I suspect many if not all chronic viral infections will portray a similar trend. It is already seen in HepC, albeit to a lesser extent. It will be interesting to see if the new age HepC drugs decrease the known risk of increased coronary artery disease and cerebrovascular disease after treatment.

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Critical Care, Improving Outcomes, Mythbusting, Neurology

Compazine… for infectious disease?

Today’s article’s (1, 23 ) are a break from the usual trials that are typically discussed and a bit more “benchside medicine” than bedside medicine.  In fact, let’s look at this as an early request for one of the 12 trials of Christmas.

Phenothiazines have demonstrated in vitro (as well as some in vivo) activity for gram positive cocci, mycobacteria, amoeba (4; 5), and some gram negative rods.

It should be noted that Klebsiellae, pseudomonads and acenetobacters were highly resistant to almost all of these drugs.

The MIC for phenothiazines are usually not reached with conventionally used doses, but these compounds do enhance the activity of various antibiotics to which various bacteria are susceptible (including vancomycin), and even decrease the MIC of resistant organisms.

So where am I going with all of this? For starters, lets look at some common causes of meningitis, in no specific order:

Strep pneumo (gram positive); group B strep (gram positive); staph aureus (gram positive); Listeria (gram positive); Neisseria meningitidis (gram neg diplococci); H flu (gram neg)

All things phenothiazines are thought to have activity against.

You’re likely to be giving patients with potential meningitis something for pain (I hope?), so why not go with compazine?  Likewise, patients whom you may suspect bacteremia from a cellulitis, why not give compazine to, ummm, “counteract the nausea” associated with the opiates you gave for pain control?

I think this falls into the unlikely to harm, might help category, and is seemingly a ripe area for research.  Is this practice changing?  Nope, not at all.  Food for thought, but until compazine is proven unsafe in an infectious process, I will continue my love affair with compazine for headaches, nausea, and vomiting (regardless of suspected etiology).

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