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September 2012
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IDSA Journal Club
September 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.


Doxycycline’s Effect on Clostridium difficile in Patients with Community-Acquired Pneumonia

Reviewed by Ed Dominguez, MD

Hospital-acquired Clostridium difficile infection (CDI) occurs at a rate of 6.5–8.5 per 10,000 patient-days with an attributable mortality of 5.7 to 6.9 percent. Currently, up to 7 percent of people receiving antibiotics develop CDI within 30 days. While there is renewed interest in developing new compounds (e.g., fidaxomicin) for CDI, there is also interest in prescribing available antibiotics that promote less selective pressure. In vitro studies and anecdotal reports have identified tetracyclines and glycylcyclines as such drugs. A historical cohort study reported in the Sept. 1 Clinical Infectious Diseases evaluated doxycycline’s effect on CDI in patients with community-acquired pneumonia (CAP) admitted to a single center.

Investigators evaluated 2,734 CAP hospitalizations for five and half  years through December 2010. The primary outcome was development of CDI within 30 days of the first dose of ceftriaxone. CDI was defined as a positive stool enzyme immunoassay for toxins A and B. All patients received at least one dose of ceftriaxone and 39 percent received doxycycline. Forty-three patients developed CDI, an overall incidence 5.60 per 10,000 patient-days. Five of 1,066 doxycycline recipients developed CDI, an incidence of 1.67 per 10,000 patient-days. The incidence for the 38 patients with CDI not receiving doxycycline was 8.11 per 10,000 patient-days.

There was a 27 percent lower rate of CDI for each additional day of doxycycline when adjusted for multiple variables. Comparing hazard ratios for five-day courses of ceftriaxone plus doxycyline to ceftriaxone plus either a macrolide or a flouroquinolone antibiotic, doxycycline proved protective with a hazard ratio of 0.15 or less. However, the strongest predictor of CDI was remaining in the hospital with a hazard 15.1-fold that of outpatients. Unfortunately, investigators did not rule out a clonal outbreak. Regardless, the study findings suggest centers with a high CDI incidence might substitute doxycycline for macrolides or fluoroquinolones for use with ceftriaxone in patients with CAP.

(Doernberg et al. Clin Infect Dis. 2012;55(5): 615-620.)

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Sinus Irrigation with Tap Water via Neti Pots and Fatal Naegleria Meningoencephalitis
Reviewed by Christopher J. Graber, MD, MPH

A recent article published in Clinical Infectious Diseases describes two cases of fatal amebic meningoencephalitis in Louisiana from 2011 that resulted from sinus irrigation with tap water contaminated with Naegleria fowleri. Both patients, a 28-year-old male and a 51-year-old female, presented with altered mental status and fever and died within 4 days of admission; N. fowleri was isolated from the cerebrospinal fluid of the first patient and from brain tissue of the second patient.

Neither patient had a history of recreational freshwater exposure, but they both regularly used neti pots for the treatment of sinus congestion. An investigation of the patients’ homes resulted in the isolation of N. fowleri (either by culture or PCR) from the tankless water heater of one patient and the kitchen faucet, shower, bathtub faucet, and bathroom sink faucet of the other patient. 

Neti pots, when used properly, can provide effective relief for chronic sinus congestion, but water used in these devices should be distilled, sterile, previously boiled then cooled, or filtered using a filter with an absolute pore size of 1 μm or smaller. After use, the device should be rinsed with the same treated water as above. Premanufactured salt packets are also available, but the investigators in this study tested them and found no decrease in N. fowleri load or degradation after four hours. Further guidance for patients can be found in a recent Food and Drug Administration alert.  While these cases represent uncommon presentations of a rare illness, the press that this report has received presents an opportunity for educating our patients in prevention of waterborne illness. 

(Yoder et al. Clin Infect Dis 2012; published online Aug. 22, advance access)

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When a Good Vaccine Gets Better: Evidence of Herd Immunity Against HPV
Reviewed by Christian B. Ramers, MD, MPH

Human papillomavirus (HPV) causes common warts as well as cervical, anal, and oropharyngeal carcinoma. Two vaccines have been shown to be safe and effective in preventing HPV infection and cervical intraepithelial neoplasia. The first vaccine, Gardasil, which protects against HPV types 6, 11, 16, and 18, was approved in June 2006 and recommended by the U.S. Advisory Committee on Immunization Practices shortly thereafter. While the individual benefit of these vaccines was demonstrated in the clinical trials that led to their approval, the effect of vaccine introduction on rates of HPV infection in real-world, community settings has been uncertain.

A study in the August 2012 issue of Pediatrics aimed to describe the effect of vaccine introduction on HPV rates in both immunized and unimmunized young women. In 2006-2007, the authors recruited 368 sexually active young women aged 13-26 for a pre-vaccination surveillance study. A separate sample of 409 women was recruited in 2009-2010 for post-vaccination surveillance. Fifty-nine percent of these women had received the quadrivalent HPV vaccine. Subjects completed behavioral questionnaires and had cervicovaginal samples submitted for HPV DNA PCR and type identification using a blot detection system.

Although overall HPV infection rates actually increased during the study period, there was a decrease of 60-70 percent in vaccine-type HPV infection. Prior to the introduction of HPV vaccine, the overall prevalence of vaccine-type HPV was 31.7 percent and this decreased to 13.4 percent (p<0.0001). This effect was seen both in vaccinated (31.8 percent à 9.9 percent, p < 0.0001), and unvaccinated young women (30.2 percent à 15.4 percent, p < 0.0001). The proportion of non-vaccine HPV types did increase in vaccinated individuals (60.7 percent à 75.9 percent, p < 0.0001). 

This simple study demonstrates yet another triumph of public health prevention through immunization. The pre-vaccination prevalence was extremely high, indicating early and significant impact of widespread vaccination. The observation of ‘type replacement’ by non-vaccine strains warrants further study.  

(Kahn et al. Pediatrics. 2012;130(2): e249-256.)

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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:

Sept. 15

  • Intravenously Administered Voriconazole in Patients With Renal Insufficiency
  • Human T-Lymphotrophic Virus Type 1 and Organ Transplantation

Sept. 1

  • Two Novel Treatable Immunodeficiency Diseases With Presentation in Adulthood: MonoMAC and WHIM
  • Eczema Herpeticum

 
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