Category: Infectious Disease

Intracranial Extension of Sinusitis in Children

Interesting descriptive study of a decade’s worth of children transferred/admitted to Texas Children’s in Houston with intra-orbital or intra-cranial extension of their sinusitis.  It’s really just a summary of the clinical and hospital courses of 118 patients identified through retrospective chart review.

Interesting tidbits:
– Of these patients, 40% had been prescribed outpatient courses of antibiotics prior to the time of diagnosis of intra-cranial or intra-orbital extension.
– All patients with intra-orbital involvement presented with eye swelling.
– Intra-cranial extension had substantially (and significantly) more headache and vomiting, and only 67% received antibiotics prior to transfer.
– Identical numbers in each group – 16% – of patients were afebrile upon presentation.
– 33% of patients with intracranial extension of sinusitis did not complain of a URI-like syndrome at presentation.
– Frontal sinus involvement was associated with 84% of their intra-cranial extension.
– All organisms recovered were sensitive to clindamycin or vancomycin plus cefotaxime except for a single pseudomonal infection.
– There were no deaths, and four patients had persistent neurologic or visual sequelae.

Short summary – orbital cellulitis was a little more straightforward in diagnosis than intracranial extension of sinusitis, and a significant minority of both groups would definitely diagnostic challenges.  CT imaging, anathema as it may be, is the diagnostic modality of choice.

http://www.ncbi.nlm.nih.gov/pubmed/20970813

Fluoroquinolone-Resistant E. Coli

Doom and gloom from the Netherlands regarding antibiotic resistance in E. coli.  Although they focus on the resistance rates to fluoroquinolones, the more interesting take-home point from this article is the risk factors described for polypharmacy resistance.

Depending on your local resistance patterns, 88% susceptibility to E. coli for fluoroquinolones either sounds great or it sounds terrible.  What’s interesting is that the strains of E. coli in this study that had fluoroquinolone resistance also had 33% resistance to amoxicillin-clavulanate, 65% resistance to TMP-SMX, and 14% had an ESBL gene.  So, you can really extend their findings to more a listing of predictive factors for resistance to multiple antibiotics.  In there study, the main univariate risk factors were indwelling catheter (OR 6.0) and prior fluoroquinolone use within six months (OR 18.6).  Less prominent, but still statistically significant were underlying urinary tract disorder (OR 2.3), recurrent UTI (OR 2.2), or recent hospitalization (OR 2.3).
Their conclusion that the presence of any of these risk factors should result in a urine culture being sent, which is reasonable – although even in the absence of risk factors, there was still an 8.2% chance of fluoroquinolone resistance.

Antibiotics Are Unnecessary After MRSA Abscess Drainage

Almost a year old now, but it’s been dredged up for Journal Club (spoiler alert: the next two days might have something in common with vis-a-vis dredging).

Small study randomizing skin abscess to placebo vs. TMP-SMX after incision and drainage in children.  I think it’s a fair article with decent external validity, as I would say this directly addresses the practice pattern of pediatric emergency physicians, let alone community pediatricians.  The real issue is statistical power for their secondary endpoint and some minor differences between their two groups.  Treatment failures comparing placebo and TMP-SMX are identical – which just goes to show you that the I&D really is the most important element of treating abscesses.  They do a lot of packing!  I suppose I’m almost more surprised there isn’t more packing, since that’s the commonly accepted practice, but I digress.

The only fire remaining in their argument is that antibiotics will decrease recurrent abscesses.  And, I am willing to give them that – although, I really expect, if they had a longer follow-up period, a lot of those abscesses would return after the antibiotics were stopped because the environment requires eradication.  However, there’s a significant difference in the number of each group with a history of recurrent abscesses favoring the TMP-SMX group, which might explain the magnitude of their difference in recurrent lesions within 10 days.

Too small a study to change our practice – although, our practice probably should never have changed from not treating abscesses with antibiotics in the first place.

http://www.ncbi.nlm.nih.gov/pubmed/19409657

Heparin-Binding Protein for Bacterial Meningitis

This study came out highlighted by the last Emergency Medicine Journal Watch.

Now, I don’t want to steal Emergency Medical Abstracts thunder, since I’m sure they’re going to tear this article to shreds in a few months, but let me just comment on the conclusion of the Journal Watch reviewer that this is a “promising new biomarker that…might play the same role in bacterial meningitis that D-dimer does in venous thromboembolic disease” and that “an HBP level >20 ng/mL should prompt empirical therapy for bacterial meningitis” like this assay is something we should incorporate into our practice.

Part of the problem with this study is their methodology.  They used HBP to diagnose bacterial meningitis…in patients where they could diagnose bacterial meningitis.  Which means, these are all patients in which they already were able to make the diagnosis of bacterial meningitis without this magical new test.  So, immediately from that standpoint, it doesn’t add any value.

They also used two different samples, including, apparently, some they had on file from a decade ago – but their justification seems reasonable.

They compare the sensitivity and specificity of their test to the sensitivity and specificity of CSF polynuclear cells and CSF WBC count – and they’re statistically identical.  And, specifically, they are marginally better in absolute terms and likely in AUC vs. any of those tests individually, but when taken against the combined information given by all the CSF tests we already send off, there is likely no clinical difference.

Lastly, the most important words are on the first page: “Hansa Medical AB has filed a patent application on the use of HBP as a diagnostic tool in meningitis.  Dr. Linder, Dr. Christensson, Dr. Björck, and Dr. Åkesson are listed as inventors.”

My conclusion: this is an unnecessary test to add to your arsenal.  Read the article, make your own conclusion.

http://www.ncbi.nlm.nih.gov/pubmed/21200320

Carbapenem Resistant Bacteria in India

More public health doom and gloom from the infectious disease world – multiple bacterial found carrying stable and transmissible plasmids for the NDM-1 gene, a form of beta-lactamase that endows bacteria with carbapenem resistance.  In the sewage.  And in the drinking water.

…but only South Asia, for the time being.  But, they also note that India is a popular destination for “medical tourism” to save money on surgical procedures, and patients have returned as carriers for bacteria with the NDM-1 gene.
This is not a unique development – there’s MDR tuberculosis, inducible clindamycin resistance for MRSA, and, my favorite, macrolide-resistant streptococcus.  Macrolide resistance in streptococcus can be directly linked to the overuse of azithromycin, a patient-friendly drug with terrible pharmacokinetics.  In contrast to the medication it replaces, erythromycin, it has such a long half-life (68 hours when multiple doses are administered) after you take your fifth dose that it spends a long period in the body below its therapeutic concentration, just sitting there as substrate to induce resistance without bacteriostatic properties.
Grim.

Antibiotics for Acute Otitis Media

These are two articles coming to us from January’s NEJM – one from Pittsburgh and one from Finland.  For a ridiculously prevalent disease managed daily in the ambulatory setting by thousands of providers across the world, we really don’t know what we’re doing.  Firstly, we know there are bacteria in the middle ear – plenty of studies have aspirated out a variety of pathogens.  Secondly, undertreated AOM may lead to suppurative complications – the surgical emergency of mastoiditis.  Finally, however, we also know the natural history of AOM is to resolve without intervention and treatment in most cases.

The commentary accompanying these articles seemed to think these two studies tilted the balance in favor of routine antibiotic use for AOM.  And, you can read the articles in that fashion – the Finnish article makes an argument that by their standard of care, the placebo group had 45% treatment failure and required antibiotic rescue 30% of the time.  However, I read the article and their definitions of treatment failure are, for the most part, not clinically relevant.  A red ear that still looks red on day three does not predict much – and, actually, a lot of their primary outcome measures were not statistically significant until they added in the 30% they used rescue treatment on to boost their definition of treatment failure.  So, this study doesn’t tell much much – except that Augmentin causes diarrhea 40% of the time.

The Pittsburgh study reads much more straightforward and, partially, justifies my criticism of the Finnish study.  By day 7, 80% of their Augmentin group had symptom improvement compared to 74% of their placebo group.  However, the ears still looked terrible in the placebo group – but, obviously, weren’t correlating with symptoms.  So, is it clinically relevant to define treatment failure based on the appearance of the ear?  I would say that improvement in symptoms is the appropriate measure of clinical cure – and in that respect, the 80% vs 74% numbers match up better with previously published literature.

To me, these articles don’t help.  I don’t necessarily mind the AAP recommendations of treating AOM with antibiotics under a year of age – although, really, after their third set of immunizations, it’s not as though this is going to be a nidus for SBI.  Clearly, antibiotics offer some advantage – but not to everyone.  When I have a three year-old I have to hogtie to get a one-second glimpse at a red TM, how do I know whether this is a patient whose AOM will resolve on its own, or whether he falls into the subset of patients who will derive benefit from antibiotics?  And, is that 6% absolute difference in clinical outcome worth giving 40% of children horrible diarrhea (not that anyone uses Augmentin first-line for AOM, anyway).  With the NNT with antibiotics to prevent one case of mastoiditis estimated at 4100 from cohort data from the United Kingdom, that’s a lot of useless (and harmful) antibiotic prescriptions.  If we want to reduce the amount of antibiotic resistance in this country, I think these studies support a conservative non-antibiotic strategy initially in appropriately selected patients.

http://www.ncbi.nlm.nih.gov/pubmed/21226577
http://www.ncbi.nlm.nih.gov/pubmed/21226576

Addendum 5/11: Scott Weingart & David Newman did a bit of a rant on this topic on the most recent EM:RAP where they attacked the Pittsburgh article specifically regarding result reporting integrity.  Dr. Newman delved into far more detail regarding the multiple primary outcomes listed and found the original research protocol listed only time to resolution of symptoms as the primary outcome – which was statistically equivalent between the two groups.  He and Dr. Weingart seem to suggest there was not sufficient editorial oversight regarding the publication of this article due to these flaws, and that the author’s conclusions are suspect to the point of disingenuous.