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February 2013
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IDSA Journal Club
February 2013

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.

Daily Chlorhexidine Bathing Reduces Hospital-Acquired Bloodstream Infections
Reviewed by George R. Thompson III, MD

Multiple strategies to reduce the spread of multidrug-resistant organisms (MDROs) within the hospital have been proposed with varying amounts of success. Typically these policies require strict adherence by a large number of hospital personnel and are difficult to sustain.

In the Feb. 7, 2013, issue of theNew England Journal of Medicine, researchers report the results of a multicenter crossover trial to evaluate the effect of daily bathing with chlorhexidine-impregnated washcloths on the acquisition of MDROs and the incidence of hospital-acquired infections. Patients within the intensive care or bone marrow transplant unit were randomly assigned to bathing with no-rinse 2 percent chlorhexidine or nonantimicrobial washcloths for a six-month period, with exchange for the alternate product for the subsequent six months.

More than 7,000 patients were enrolled in this study, and a significant reduction in MDRO acquisition was observed in the chlorhexidine group (5.1 cases per 1,000 patient-days) compared with the nonantimicrobial group (6.6 per 1,000 patient-days) (p=0.03), a reduction of 23 percent. Bloodstream infections were also reduced in the chlorhexidine group (4.78 cases per 1,000 patient-days vs. 6.6 cases per 1,000 patient days in the nonantimicrobial group) (P=0.007).

No serious adverse effects with daily chlorhexidine bathing were observed, although if this practice is adopted into widescale use, it is important to note that serious allergic reactions, albeit rare, have been reported. Resistance to chlorhexidine has also been observed and may be an important limitation to adoption of this practice.  Nevertheless, the authors’ results are compelling and support daily bathing with chlorhexidine impregnated washcloths as a feasible strategy to reduce MDRO acquisition and bloodstream infections.

(Climo et al.  N Engl J Med. 2013;368(6) :533-542.)

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Donor-Feces Infusion for the Treatment of Recurrent C. difficile Infection
Reviewed by Kathryn E. Stephenson, MD, MPH

Clostridium difficile infection can be difficult to treat, with one-quarter of patients suffering recurrent disease. Most patients with recurrent C. difficile are treated with prolonged courses of vancomycin that are only intermittently effective in improving symptoms, probably because of persistent reduced diversity of bacteria within the bowel. Thus, it has been hypothesized that restoring bacterial diversity with an infusion of donor feces might be a superior treatment to vancomycin alone for recurrent C. difficile.

To test this hypothesis, researchers in the Netherlands, whose results appear in the Jan. 31, 2013, issue of the New England Journal of Medicine, performed an open-label, randomized, controlled trial comparing three treatment regimens for recurrent C. difficile infection: (1) donor-feces infusion through a nasoduodenal tube, after vancomycin for five days and bowel lavage; (2) vancomycin for two weeks; or (3) vancomycin for two weeks and bowel lavage. The primary end point was cure without relapse within 10 weeks after the initiation of therapy.

Investigators randomized 43 patients before the study was terminated early after an interim analysis showed donor-feces infusion to be markedly superior to the control treatments. Fifteen of 16 patients were cured in the donor-feces group (94 percent), compared to four of 13 patients (31 percent) in the vancomycin-alone group and three of 13 patients (23 percent) in the vancomycin-lavage group (P<0.001 for both comparisons). The primary adverse event associated with donor-feces infusion was diarrhea resolving within three hours. There was also a significant increase in the diversity of fecal microbiota after donor-feces infusion (P<0.001).

This randomized trial clearly demonstrates the superior efficacy of donor-feces infusion over vancomycin-based therapy for recurrent C. difficile infection. Future studies will need to address the efficacy of this treatment compared to newer bactericidal agents such as fidaxomicin, as well as in larger groups of patients, including those with prolonged immunodeficiency and critically ill patients, who were excluded from the trial.

(van Nood et al. N Engl J Med. 2013:368:407-415.)

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Ampicillin-Ceftriaxone for E. faecalis Endocarditis: An Emerging Alternative to Ampicillin-Gentamicin?
Reviewed by Christopher J. Graber, MD, MPH

An observational comparative study recently published in Clinical Infectious Diseases provides more clinical data to support the use of combination therapy with ampicillin and ceftriaxone (AC) for Enterococcus faecalis infective endocarditis (EFIE) as an alternative to conventional ampicillin and gentamicin (AG) therapy.

The study followed 159 AC-treated and 87 AG-treated EFIE patients at 17 Spanish hospitals and one Italian hospital from 2005 to 2011. Despite the AC-treated patients having a higher rate of baseline chronic renal insufficiency, malignancy, history of transplantation, and health care-acquired infection, AC- and AG-treated patients had similar rates of mortality, either during treatment (22 percent vs. 21 percent) or after treatment to three month follow-up (8 percent vs. 7 percent). AC-treated patients had significantly less adverse effects requiring treatment withdrawal (1 percent vs. 25 percent, p<.001) but similar rates of treatment failure requiring change of antimicrobials (1 percent vs. 2 percent) and relapse (3 percent vs. 4 percent). Ceftriaxone was dosed at 2 gm every 12 hours in the AC group. Gentamicin was not dosed uniformly across the study: Only 31 (36 percent) of AG-treated patients received a full four-six week course of gentamicin, and, among the 80 patients for whom dose scheduling was reported, only 37 patients received gentamicin three times a day.

The editorial accompanying the paper examines the data in the context of prior work and comes to a mixed verdict on when AC therapy should be preferred to AG therapy in the management of EFIE, though AC certainly does seem like a reasonable option in patients with isolates with high-level aminoglycoside resistance or in patients with pre-existing renal insufficiency or other risk factors for poor outcomes with aminoglycoside therapy. The role of other adjunctive treatments (i.e., daptomycin) in the management of EFIE likely needs more exploration as well.

(Fernández-Hidalgoet al. Clin Infect Dis. (2013) doi: 10.1093/cid/cit052 and Munita et al. Clin Infect Dis. (2013) doi: 10.1093/cid/cit050)

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Early Observations from the 2012 Fungal Meningitis Outbreak
Reviewed by Sheila Mitsuma, MD

In the Feb. 5, 2013, issue of the Annals of Internal Medicine, investigators in Virginia present early clinical findings and their experience in managing patients affected by fungal meningitis related to contaminated epidural steroid injections that occurred in the United States in late 2012.

In October 2012, 172 patients were screened for meningitis based on exposure to contaminated product. Of these, 131 patients had symptoms concerning for meningitis, with a median time to onset of 19 days. Twenty-five patients (19 percent) found to have neutrophilic pleocytosis on cerebrospinal fluid (CSF) analysis were diagnosed with meningitis and treated with voriconazole.

Exserohilum species was detected in culture or by PCR in six patients (24 percent) and Cladosporium species in two of the 25 patients. Mycologic diagnosis in the remainder was pending at the time of writing. MRI findings revealed leptomeningeal enhancement in seven patients, ventriculitis in four, and hemorrhagic infarction in two; 10 of 18 patients with back pain had arachnoiditis, one had epidural abscess, and one myelitis. CSF pleocytosis declined on therapy in the majority, with a shift from neutrophilic to lymphocytic predominance.

Most patients improved with voriconazole, and eight were discharged on oral voriconazole. However, 10 developed worsening symptoms, rising CSF leukocytosis, or new stroke (three patients), prompting a change to amphotericin. Eight of those 10 improved with change in therapy; outcomes for the other two were not reported. An additional two patients, not included in the above series, presented with fatal stroke. Connection to the outbreak and diagnosis of Exserohilum central nervous system infection were made retrospectively.

In sum, symptoms of meningitis associated with the outbreak were similar to those of typical meningitis. A relatively high incidence of arachnoiditis was found, theoretically related to the inoculation site. Stroke was a prominent feature and may suggest that Exserohilum has angioinvasive potential. Further data will be needed to characterize the natural history and the long-term sequellae of these infections.

(Kerkering et al. Ann Intern Med. 2013;158:154-161.)

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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:

Feb. 15

  • Fluoroquinolones and the Eye
  • Community-Acquired Pneumonia and the Heart
  • Another Route to Susceptibility to Mycobacterial Infection

Feb. 1

  • Ceftriaxone for Treatment of Infection due to Methicillin-Susceptible Staphylococcus aureus?
  • Infection of Percutaneously Implanted Prosthetic Aortic Valves
  • Nasal Carriage of Staphylococcus aureus: Not All Nostrils Are Equal

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