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March 2012
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IDSA Journal Club
March 2012

In this feature, a panel of IDSA members identifies and critiques important new studies in the current literature that have a significant impact on the practice of infectious diseases medicine.

Click here for the previous edition of Journal Club. For a review of other recent research in the infectious diseases literature, see “In the Literature,” by Stanley Deresinski, MD, in each issue of Clinical Infectious Diseases.


S. aureus Decolonization for the Prevention of Recurrent SSTI in Children
Reviewed by Kathryn E. Stephenson, MD, MPH

Community-associated Staphylococcus aureus causes an increasing number of recurrent skin and soft tissue infections (SSTI), particularly among children. S. aureus transmission in the community is not well-characterized, but recurrent infections in children may be due to continued exposure to S. aureus-colonized household contacts.

In the March 15 issue of Clinical Infectious Diseases, researchers report the results of a randomized clinical trial of 183 pediatric patients with S. aureus SSTI, comparing two approaches to eradicating S. aureus: decolonizing the case alone versus decolonizing the entire household. Decolonization involved five days of mupirocin to the nares, showers/baths with Hibiclens, and standardized hygiene recommendations. The authors found that, one month after randomization, there was no difference in S. aureus eradication rates between the household group (51 percent) and the index group (50 percent, P = 1.00). Cases in the household group, however, were less likely than those in the index group to report recurrent SSTI after three months (28 percent vs. 47 percent; P = 0.02), six months (38 percent vs. 61 percent; P = 0.008), and 12 months (52 percent vs. 72 percent; P = 0.02). The authors conclude that decolonization of the entire household reduces the risk of recurrence of S. aureus SSTI in children.

The study’s strength is its randomized trial design, but its scope is limited. The results may not extend to adults, and the study did not address the fundamental question as to whether decolonization of the patient reduces subsequent S. aureus SSTI. In addition, as the authors emphasize, considerable improvement in S. aureus SSTI prevention is still needed, as more than 50 percent of cases in the household group reported recurrent SSTI over a one-year period.

 (Fritz et al. CID 2012:54:743-51.)

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Amoxicillin Alone Doesn’t Help Patients with Acute Sinusitis
Reviewed by Jason B. Weinberg, MD

A 10-day course of amoxicillin is no better than placebo at quickly improving symptoms in patients with acute rhinosinusitis, according to a study in the Feb. 15 issue of the Journal of the American Medical Association (JAMA).

Antibiotics are frequently prescribed for patients with sinusitis despite a lack of convincing evidence demonstrating their efficacy.  In addition, previous work suggests that many patients improve spontaneously without antibiotic therapy.  To determine whether antibiotic treatment had any effect on clinical outcomes, the authors of this study conducted a randomized, placebo-controlled trial in which 166 adult patients diagnosed with acute rhinosinusitis received either 10 days of amoxicillin or placebo in addition to symptomatic therapy.

The investigators assessed the primary outcome, sinusitis symptom severity and frequency, using the (brilliantly named) modified Sinonasal Outcome Test-16 (SNOT-16) scoring tool.  SNOT-16 scores and overall patient-reported improvement in symptoms were similar in amoxicillin and placebo groups on days 3 and 10 of therapy. Although scores were slightly better in patients receiving amoxicillin on day 7, the magnitude of this effect was not likely to be clinically significant. There were no differences between groups in satisfaction with treatment, missed days of work, disease relapse or recurrence, or adverse events.

Patients included in the study had at least 7 days of symptoms that were not improving or worsening, and the authors suggest that they were representative of patients who might receive antibiotics in general practice. Although the disease process is likely to be similar in pediatric patients, no children were included in the study. Importantly, the study also did not include patients with serious complications from sinusitis, a group for whom antibiotics are still likely to be beneficial. However, the results of this study suggest that amoxicillin therapy does not provide a substantial clinical benefit to the majority of patients with acute sinusitis.

IDSA clinical practice guidelines for acute bacterial rhinosinusitis released after this article was published advocate treating adult and pediatric patients who have persistent (≥10 days), severe, or worsening symptoms with amoxicillin/clavulanate. Because the JAMA study included some patients with a shorter duration of symptoms (<10 days) and treated patients with amoxicillin instead of amoxicillin/clavulanate, it is difficult to predict how they would have fared if treated according to the new guidelines. The consistent application of consensus definitions for the diagnosis of acute bacterial rhinosinusitis will be important for ongoing evaluation of the new practice guidelines.

(Garbutt et al. JAMA 2012; 307(7):685-92.)

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Treatment for Acute Uncomplicated Cystitis: Cefpodoxime vs. Ciprofloxacin
Reviewed by Kathryn E. Stephenson, MD, MPH

Fluoroquinolones are a popular antimicrobial choice for the treatment of uncomplicated cystitis because they are highly effective and have minimal side effects. There has been growing concern, however, that widespread fluoroquinolone use is leading to dangerous bacterial drug resistance within our environment. Cefpodoxime is an oral third-generation cephalosporin with fewer ecological adverse effects that has been proposed as a potential alternative to fluoroquinolones for the treatment of cystitis.

In the Feb. 8 issue of The Journal of the American Medical Association, a report describes the results of a randomized double-blind non-inferiority trial of 300 women with acute uncomplicated cystitis comparing 250 mg of ciprofloxacin to 100 mg of cefpodoxime, taken orally twice a day for three days. The primary outcome was clinical cure at the 30-day follow up visit; clinical cure was defined as not needing repeat antimicrobial therapy. The authors found that in the intent-to-treat analysis, patients having clinical cure was 93 percent for ciprofloxacin compared with 82 percent for cefpodoxime (P = .57). Study outcomes were not changed by the per-protocol analysis. In addition, 16 percent of women in the ciprofloxacin group compared with 40 percent in the cefpodoxime group had vaginal Escherichia coli colonization at the first follow-up visit.

This study demonstrates in an elegant fashion that cefpodoxime is not as effective as ciprofloxacin for the treatment of acute cystitis. The authors speculate that the reason cefpodoxime fails more often than ciprofloxacin is because it is not as effective at eradicating uropathogens from vaginal flora.

(Hooton et al. JAMA 2012:307:583-9.)

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Improving Accessibility to Fecal Transplantation for C. difficile Infections
Reviewed by Jonathan Li, MD

Fecal bacteriotherapy, commonly known as fecal or stool transplants, has been demonstrated in small studies to be a safe and efficacious method of treating recurrent C. difficile infection (CDI). Despite impressive outcomes and significant clinical need, the availability of fecal transplantation is limited by both practical (e.g., aesthetics and equipment/space for stool processing) and reimbursement (e.g., cost of donor screening) concerns. Two recent studies describe streamlined procedures that may help lower these barriers. 

In a study published online in the American Journal of Gastroenterology in January, researchers describe 43 patients treated with fecal microbiota transplantation (FMT) including the use of standard volunteer fecal donors and the banking of frozen processed fecal material. All patients had to have at least two documented recurrences, at least one of which was on a long vancomycin course and/or with a rifaximin “chaser.”

Overall, patients had a mean of almost six CDI recurrences over 12 months. There was no significant difference in the initial success rates at two months by type of donor material: 70 percent (7/10) in those receiving stool from a personalized donor, 92 percent (11/12) in participants receiving fresh material from a standard donor, and 90 percent (19/21) in those receiving previously frozen fecal material from a standard donor. In the six individuals with recurrence despite FMT, four elected to retry the procedure with standard donor stool, and all were successfully cured. The use of frozen fecal material from standard donors was preferred by the patients and removed significant practical barriers to FMT while reducing the costs associated with screening potential donors.

In a research letter published in the Jan. 23 issue of the Annals of Internal Medicine, investigators report the efficacy of standard donor fecal transplantation by rectal retention enema in 27 patients with refractory or recurrent CDI. The mean duration of diarrhea was 153 days. After one fecal transplant, 81 percent (22/27) of participants experienced clinical resolution of symptoms within seven days. The remaining five patients received a second stool enema, with three patients experiencing symptom resolution and a total clinical response rate of 93 percent (25/27). No additional relapses or adverse events were reported with a mean 427 days of follow-up after transplant. 

While both studies are relatively small, the protocols they describe may help overcome some of the practical and cost challenges limiting use of fecal transplantation for recurrent CDI and could play a role in improving patient access to these potentially life-saving therapies.

(Hamilton et al. Am J Gastroenterol. 2012; doi: 10.1038/ajg.2011.482. published online Jan. 31, 2012 and Kassam et al. Arch Intern Med. 2012;172(2):191-3.)

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For a review of other recent research in the infectious diseases literature, see “In the Literature,” by Stanley Deresinski, MD, in each issue of Clinical Infectious Diseases:

March 15

  • The Black Death and Modern Plague
  • Acute Drug-Induced Liver Injury—Some Cases May Actually Be Due to Hepatitis E Virus Infection

March 1

  • What’s in a Name? Canis Lupus Familiaris Hosts Rickettsia Felis
  • Men (and Women) Are Not Mice—Deferasirox Fails as Adjunctive Treatment of Mucormycosis
  • Cytotoxic Antiviral Therapy of Multicentric Castleman Disease

 
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