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.

Improving Outcomes, Pediatrics

Baby LPs, ultrasounds, and fragility



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:



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.

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.

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).

GI, Improving Outcomes, Mythbusting

Rethinking Diverticulitis

For those savvy FOAM early adopters that have been referring to diverticulitis as the sinusitis of the colon, this one is for you.

While diverticulitis management (or lack thereof) has been discussed periodically – specifically in regards to antibiotics being of no use in the uncomplicated form of diverticulitis – here comes a new study to suggest we have to at least rethink our referral patterns.

The Danish national registry was mined for a population-based cohort study, for a total of 445,456 included patients over 18 years, of whom 40,496 had a diagnosis of diverticulitis. They then compared other patients in a 1:10 ratio (diverticulitis: no diverticulitis) matched for sex and age within 1 year. Of note, the matched group also did not have a diagnosis of diverticulosis either.

Basically, the risk of developing colon cancer was 4.3% in the diverticulitis group and 2.3% in the matched cohort. This was statistically significant (P <0.001, incident ratio 1.86), and remained when adjusting for confounders (OR 2.20)…

Pro-inflammatory states cause more cancer? Perhaps. We know they cause more thromboembolism and early coronary disease already. Bottom line – while an NNT of 50 is nothing fantastic, we see this condition regularly, so reconsider providing strong follow up to your patient, whether that be PMD or GI, especially if they’re in the age where they are due for a colonoscopy anyway.


Molecular CAP testing is coming…

Two institutes in the UK collected sputum or endotracheal aspirate for multiplex real-time PCR assay in 323 patients with radiologically confirmed and admitted community acquired pneumonia patients. Essentially, a test looking for 26 bacterial and 8 viral pathogens. They go a step further and calculate bacterial loads for 8 pathogens they screened for. Notably, cystic fibrosis and HCAP patients were excluded. (49.4% of patients were CURB score of 0 or 1, while 25.4% of patients were PSI class 1 or 2 indicating that these patients could have gone home).

On the surface, seeing a pathogen detected 87% of the time vs 39% of the time for culture based methods seems like a win. Even after receiving antibiotics within 72 hours, 78% of the time a bacterial pathogen was detected vs 32% of the time in culture.

Of course, the authors set us up for more expensive testing: “It is difficult to interpret PCR results for typical respiratory bacteria in nonsterile samples such as sputum due to the potential for contamination with the same organisms from oropharyngeal flora. However, accurate molecular quantification of bacterial loads may aid in distinguishing infection from contamination in a way that is analogous to the use of quantitative cultures.”

But should be fall for this? Neither culture nor PCR positivity was associated with mortality. Polymicrobial infections were not associated with outcome. And while bacterial load of S pneumonia was associated with a higher 30 day mortality – so were higher PSI and CURB-65 scores…. and when you correct for CURB-65 scores, bacterial load was no longer associated with outcomes.

In an age where various medical entities have a history of expanded use resulting in increased costs with little to no net gains (“elective” cardiac caths, MRI for TIAs, outpatient PICC lines for infectious processes that there is an oral equivalent for, etc), I have a hard time believing this will impact the population to whom it will be pitched. There may be a chance to de-escalate antibiotic regimens, but antibiotics are a very small piece of the resuscitation puzzle. Focusing on early pressors, decreasing ED boarding, and aggressive source control in conjunction with an EGLS resuscitation will improve outcomes. Might we save a few ICU days or inpatient days? Perhaps. But we know we can do it with the above mentioned improvements for sepsis care which we are more often than not failing to do. Ultimately, this is looking for an easy fix that is already in front of us and we are opting not to do.

Now lets talk about the amount of money spent on this testing for which it will not be indicated: the outpatient treated patient. The COPD patient with a flare. The radiographically negative URI. FUO patients. Patients in whom many of us will still give zithromax because of sensitivity only at 87%…

Improving Outcomes

Spinal abscesses up 9 fold in 4 years??

When was the last time you diagnosed a spinal abscess? I’ve seen 4 in 6 months (before that, one in 6.5 years), and when I tweeted out today’s article, colleagues echoed similar experiences. This retrospective case series study reviewed the incidence of spinal abscesses in Kentucky at the University of Kentucky, as well as the association of spinal abscesses with IV drug abuse.

Kentucky ranks 26th in population in the US and also has the 4th highest number of prescribed scheduled medications. The authors report that legislation was passed in July of 2012 which focused on stricter monitoring and regulation of pain clinics and prescription drug abuse, partially through the use of an electronic prescription monitoring system. They go on to state that while prescription abuse decreased, there was a surge in IV heroin use (whether it was moving up the opiate abuse ladder, or because that was the only opiate they could find remain to be seen).


The number of spinal abscesses from 2010-2014 were as follows: 16, 26, 25, 38, 67.

The number of abscess with associated IVDA were as follows: 3, 5, 3, 7, 27.

Percentage of spinal abscesses with IVDA (2010-14): 19%, 19%, 12%, 18%, 40%


While the authors touted a 9 fold increased in the incidence of diagnosed spinal abscesses with a history of IVDA from 2010 to 2014, the number of times spinal abscess was diagnosed had increased over 4 fold (perhaps due to looking more, or from increased availability of MRI, or both). There was a big jump in 2014, as the percentage of patients with a spinal abscess has gone up to 40%; whether this high a percentage of spinal abscess patients are IVDA’ers or not remains to be seen. I reached out to a colleague who works in spinal surgery to pick his brain on this to see if his practice has seen similar change:

I would say the vast majority of epidural abscesses we see tend to be older patients with diabetes and remote h/o bacteremia or previous surgery. I would say we see a young- ish IVDA associated abscess every, 2 or 3 months”

Take home points? Spinal abscesses may be on the rise – but keep in mind that over 50% do NOT have a history of IVDA.