Category: Infectious Disease

Here Comes Gonorrhea (Again)


Good news for the monogamous – bad news for the rest – Neiserria gonorrhoeae is rapidly becoming resistant to cefixime, an oral third-generation cephalosporin.  The resistance rates are low – a maximum of 17% in Honolulu – but the fear is that continued cefixime use will carry-over into an increased resistance for ceftriaxone.


This follows the 2007 declaration that fluoroquinolone resistance had obviated their use.


For now, the CDC recommendations have narrowed to 250mg IM/IV ceftriaxone plus 1g oral azithromycin once or 100mg oral doxycycline BID for seven days.

“Update to CDC’s Sexually Transmitted Diseases Treatment Guidelines, 2010: Oral Cephalosporins No Longer a Recommended Treatment for Gonococcal Infections”
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6131a3.htm?s_cid=mm6131a3_e

When Do Patients Need Blood Cultures?

Another lovely JAMA Rational Clinical Examination article relevant to the Emergency Department – this time regarding the utility of blood cultures.  Blood cultures are frequently requested for febrile inpatients, however, the incidence of false positive ranges between 2.5% and 8%.  This leads, unfortunately, to additional patient harms from additional treatment or observation.


This article is a systematic review of several studies gathering clinical features of patients for whom blood cultures were requested, as well as the clinical outcomes of the cultures, in an attempt to identify features predictive of positive or negative cultures.  They also examine a couple validated clinical decision instruments to determine their potential utility in stratifying the appropriateness of cultures.


Essentially, based on a few pieces of decent evidence and a few pieces of poor evidence, the authors determine a few general categories of infectious etiology with varying pretest probability for bacteremia.  These are:
 • Cellulitis, community-acquired pneumonia, community-acquired fever: low (<14%) probability
 • Pyelonephritis: mid (19-25%)
 • Severe sepsis, septic shock, bacterial meningitis: high (38-69%)


In general, however, no individual clinical feature had a positive or negative likelihood ratio of sufficient magnitude to guide testing.  Combinations of clinical features – such as patients with SIRS – were capable of excellent sensitivity & negative likelihood ratios, but only had specificities of 0.27 to 0.47.


However, the more important clinical aspect of blood cultures and bacteremia is not addressed in this article, which is how frequently the true positives even change clinical management.


“Does This Adult Patient With Suspected Bacteremia Require Blood Cultures?“

www.ncbi.nlm.nih.gov/pubmed/22851117

Cephalosporins Can Be Used in Penicillin Allergy

Did you know the literature describing the cross-reactivity between cephalosporins and penicillins is 30-40 years old?  It sort of takes the “modern” out of “modern medicine.”

At any rate, this is a literature review that aims to update the classical teaching that cross-reactivity between cephalosporins and PCN is ~10%.  They identified 406 articles on the topic and distilled it down to 27 respectable articles for inclusion in summary.  They rate the quality of the articles, and, unfortunately, find only a few good or outstanding articles and a preponderance of adequate evidence.
But, essentially, what they find is the cross-reactivity boils down to the presence of a shared R1 side chain present on first-generation and some second-generation cephalosporins.  Specific first-generation cephalosporins, such as cefadroxil (Duracef), were seen to have up to 28% cross-reactivity in some series, though the typical rate was lower, down to 0.11% with cefazolin (Ancef).  The largest meta-analyses estimated the true cross-reactivity at ~1% rather than 10%, with most of these occurring with first-generation cephalosporins.
In summary – 3rd-generation and greater cephalosporins with disimilar R1 side chains can probably be used in appropriate clinical situations despite a PCN allergy without incidence of allergy greater than in those patients who do not have a documented PCN allergy.
“The use of cephalosporins in penicillin-allergic patients: A literature review.”

Suprapubic Tap Should Be Used for Urinalysis in Children?

“Ideally, SPA should be used for microbiological assessment of urine in young children,” states the abstract conclusion for this article from Australia.


Looking retrospectively at urine samples from 599 children with an average age of 7 months, these authors conclude that suprapubic aspiration is superior to all other methods of obtaining urine samples for contamination rates.  Contamination rates were 46% with bag urine, 26% for clean catch, 12% for catheterization, and 1% for suprapubic aspiration.


We generally rely on catheterized urine samples in our Emergency Departments – and we even have difficulty convincing some parents that this is required, let alone a suprapubic aspiration.  In fact, I’m rather surprised they had 84 patients (14%) in their cohort receiving suprapubic aspiration, considering I have never seen it performed.


While I have no issue with their conclusion from a microbiologic accuracy standpoint, I’m not so sure such an invasive and painful procedure has a place in routine practice.


“Contamination rates of different urine collection methods for the diagnosis of urinary tract infections in young children: An observational cohort study.“
www.ncbi.nlm.nih.gov/pubmed/22537082

“Malodorous” Urine Isn’t Necessarily a UTI

Which is to say, when a parent brings in a child with a fever and the urine “smells bad”, plenty of those kids have normal urine cultures and plenty of children with Febreeze for urine have a urinary tract infection, regardless.


This is a prospective cohort study enrolling children receiving a urine culture as part of an evaluation for fever without a source in the Emergency Department – and then they went back and data mined for associations between the group diagnosed with UTI and not.  The overall incidence of UTI was 15%.  The overall incidence of UTI in those with “malodorous” urine was 24%.  It was the most significant contributing factor they found, but it’s still not sensitive or specific enough to use in isolation to change management.


Other interesting tidbits:  no circumcised male had a UTI, known high-grade vesicoureteral reflux predicted UTI.


“Association of Malodorous Urine With Urinary Tract Infection in Children Aged 1 to 36 Months”
http://www.ncbi.nlm.nih.gov/pubmed/22473364

Please Stop Using Azithromycin Indiscriminantly

There is a time and a place for a macrolide with a long half-life, and it is not empirically for pharyngitis.

And, it’s even less appropriate empirically for pharyngitis now that it’s been overused to the point where it’s nearly in the drinking water – because it can no longer be considered second-line for group A streptococcus for your penicillin allergic patients.

This is a case report and evidence review from Pediatrics that discusses two cases of rheumatic fever, both of which presented after treatment of GAS pharyngitis with azithromycin.  While rheumatic fever has been almost completely wiped out – there are so few of the RF emm types in circulation, that it’s almost nonexistent in the United States – there are still sporadic cases.  Macrolides are listed as second-line therapy for GAS, but single-institution studies have shown macrolide resistant streptococcus in up to 48% of patients.  Macrolide resistance varies greatly worldwide, from a low of 1.1% in Cyprus to 97.9% in Chinese children.

Why is macrolide resistance so high?  Azithromycin is the culprit; because it has such a long-half life, it spends a long time in the body at just below its mean inhibitory concentration, and preferentially selects for resistant strains.

Please stop using azithromycin.  Use doxycycline, or another alternative, when possible.  There has never been reported resistance to pencillin in GAS.

“Macrolide Treatment Failure in Streptococcal Pharyngitis Resulting in Acute Rheumatic Fever”
http://www.ncbi.nlm.nih.gov/pubmed/22311996

Ciprofloxacin is Better Than Cefpodoxime for UTI

…but don’t use either of them first-line.  And, of course, your mileage may vary based on local resistance patterns.


This study, in JAMA, is from Seattle, where their ciprofloxacin resistance in e. coli is extraordinarily low – only 4%.  Their e. coli resistance to cefpodoxime, a third-generation cephalosporin, was 8%.  They randomized 300 women with uncomplicated cystitis into, luckily, two rather similar groups – and found a 93% clinical cure rate for ciprofloxacin and an 82% cure rate with cefpodoxime.  Microbiologic cure rate at 5 days was 96% in the ciprofloxacin group and 81% in the cefpodoxime group.  And, then, there are a bunch of minor details in laborious text regarding the microbiology of the non-responders, but I’m not sure any of it’s actually relevant.  Seven women in the ciprofloxacin group required treatment for an “adverse effect” (nausea, headache, vaginal discomfort), compared with three in the cefpodoxime group.


However, neither of these agents should be considered first-line for uncomplicated cystitis.  Nitrofurantoin and fosfomycin are recommended as first-line therapy in the most recent guidelines, along with trimethoprim-sulfamethoxazole depending on local resistance.  After that, consult your local antibiogram to determine whether beta-lactams are viable, or whether a fluroquinolone or a third-generation cephalosporin should be your next option.


“Cefpodoxime vs ciprofloxacin for short-course treatment of acute uncomplicated cystitis: a randomized trial.”
http://www.ncbi.nlm.nih.gov/pubmed/22318279

The Tiniest Three Year Sinusitis Trial

Yet again, another article that saturated the lay press due to its publication in JAMA – this time regarding amoxicillin for acute sinusitis.

The problem is, I agree with the fundamental point the authors are making – according to the introduction, antibiotics for sinusitis account for 1 in 5 antibiotic prescriptions in the United States and they’re typically unnecessary, especially in an era where better antibiotic stewardship is needed.  However, I cannot imagine how a multicenter study of ten community clinics in St. Louis over three years only managed to enroll 166 adults into this study over the course of three years.  Their recruitment diagram states only 244 patients were assessed for eligibility – which seems like it ought to be a a couple months worth of URI presentations in an outpatient setting.

If you read the newspaper, you already know the main results – “no difference between 10 days of amoxicillin and placebo.”  But 11 of 85 intervention group patients discontinued treatment, as well of 12 of 81 placebo patients.  Due to lost data, 4 of 85 intervention patients were excluded from analysis, as well as 7 of 81 placebo patients.  Then, 32% of patients in the intervention group were non-compliant with the intervention – so, while this is valid in a real-world effectiveness sense, they’re increasingly no longer relevant to the actual efficacy of the intervention.  These are big holes in a small study.

And, bizarrely, the baseline characteristics they use to describe the two groups include more social characteristics than clinical characteristics – healthcare insurance, family income, etc.  Children living in the home, children in day care, etc., is an interesting demographic criteria, suggesting unique infectious exposure – 9% more intervention group patients had children at home, but this isn’t statistically significant because the sample sizes are so tiny.  Then, the clinical characteristics they chose only seem to partially reflect issues relevant to antibiotic efficacy – “usual health excellent or good” isn’t a very useful descriptor of whether they have impaired baseline immune function that places them at increased risk of significant bacterial superinfection.  For what it’s worth, the control group was significantly “healthier”, but also had significantly more smoking history.

Getting back to the main results – yes, the average SNOT-16 scores were equal at day 0, 3 and 10, but favored the intervention at day 7 – leading to their final conclusion that amoxicillin was of no benefit.  But, at the individual patient level, the control group patients were impaired from their usual activities almost 50% longer – 1.67 days vs. 1.15 days, and there was a 12% absolute difference in satisfaction with treatment favoring the intervention – 53% vs. 41 %.  But, due to the tiny sample size, none of these differences reached statistical significance.

In the end, it’s a fair real-world trial and addition to the literature, but it’s far too small and flawed a trial to stand on to as evidence.

Oddly, one of the authors receives royalties for the SNOT-16 scale.

“Amoxicillin for Acute Rhinosinusitis: A Randomized Controlled Trial”
http://jama.ama-assn.org/content/307/7/685

Lies, Damned Lies, and Tamiflu (oseltamivir)

Receiving quite a bit of press yesterday, and rightfully so, the Cochrane Collaboration published their analysis of oseltamivir – the miracle influenza antiviral that (at great cost) is part of our nation’s strategic stockpile for an influenza pandemic.  The story is interesting both regarding what they found, and what they didn’t find.

As for the data from the review, the numbers are similar to what we’ve been basing our practice upon – oseltamivir significantly shortens the length of time until symptom improvement from 160 hours to 139 hours.  However, it did not demonstrate any difference in hospitalization rates.  Additionally – whether through study bias or by direct medication effects – the oseltamivir groups were significantly less likely to have a confirmed diagnosis of influenza.

So, this suggests that it’s a little troubling that we’ve gone to all the expense to stockpile this expensive medication that does not appear to reduce hospitalizations from influenza – and it remains an individual decision whether that extra day of symptom improvement is worth exposure to the side effects of the medication.  But the reason this is national news is that Roche pharmaceuticals refused to supply the promised clinical data requested by the Cochrane Collaboration; the published analysis is based on 15 oseltamivir studies with complete information, and excludes 42 other studies with discrepancies in the data.  This sort of behavior is just another representative sample of the unethical, but completely understandable, profit-motivation of pharmaceutical corporations protecting their financial interests.

I would be greatly surprised if the clinical data Roche is holding onto supports oseltamivir efficacy.

“Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children – a review of clinical study reports”
http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD008965/abstract

“Flu Drugs: Search for evidence goes on”

Dog Bites and Antibiotics

Nicholas Genes of…well, multiple sites of fame, including recurring columns in several EM publications, SAEM leadership, and the long-standing medical blog “blogborygmi” beat me to this ACEP News item from today:

MedPage Today (12/9, Walsh) reports that a study presented in a poster session at the midyear clinical meeting of the American Society of Health-System Pharmacists (ASHP) found that only 64% of the patients presenting to the emergency department with animal bites “were discharged on the appropriate antibiotic.”


I won’t attempt to replicate his scathing criticism of ACEP News for publicizing a poster from an interim pharmacy conference, just read it for yourself:
http://blogborygmi.tumblr.com/post/13967004314/among-98-patients-seen-with-bites-over-the-course