Medical Grand Rounds

Update in infectious disease treatment

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ABSTRACTStudies published during the past year on the treatment of several infectious diseases provide valuable information that should enable us to treat our patients more effectively. Among those findings:

  • Oral vancomycin (Vancocin) is superior to oral metronidazole (Flagyl) for treating patients with severe Clostridium difficile-associated disease.

  • The risk of death from any cause may be higher with the use of cefepime (Maxipime) than with other betalactam antibiotics.

  • In patients presenting to primary care physicians with symptoms of acute maxillary sinusitis, antibiotics and topical nasal steroids do not seem to be effective, either alone or in combination.

  • For patients with Bell palsy, early treatment with prednisolone improves the chance of complete recovery; antiviral therapy may be indicated for patients with complete facial nerve paralysis.

  • In patients undergoing chemotherapy for acute myelogenous leukemia or myelodysplasia, posaconazole (Noxafil) prevented fungal infections more effectively than fluconazole (Diflucan) or itraconazole (Sporanox) and improved overall survival.

  • Anidulafungin (Eraxis) was not inferior to fluconazole in the treatment of invasive candidiasis.


 

References

Studies published during the past year provide information that could influence how we treat several infectious diseases in daily practice. Here is a brief overview of these “impact” studies.

VANCOMYCIN BEATS METRONIDAZOLE FOR SEVERE C DIFFICILE DIARRHEA

Zar FA, Bakkanagari SR, Moorthi KM, Davis MB. A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile-assoicated diarrhea, stratified by disease severity. Clin Infect Dis 2007; 45:302–307.

Clostridium difficile is the most common infectious cause of nosocomial diarrhea. Furthermore, a unique and highly virulent strain has emerged.

Which drug should be the treatment of choice: metronidazole (Flagyl) or oral vancomycin (Vancocin)? Over time, some infectious disease practitioners have believed that oral vancomycin is superior to oral metronidazole for the treatment of severe C difficile-associated diarrhea. Indeed, in a recently published survey, more than 25% of infectious disease practitioners said they used vancomycin as initial therapy for C difficile-associated diarrhea.1 Until recently, there has been no evidence to support this preference.

Ever since the first description of C difficile-associated diarrhea in the late 1970s, only two head-to-head studies have compared the efficacy of metronidazole vs vancomycin for the treatment of this disorder. Both studies were underpowered and neither was blinded. In 1983, Teasley et al2 treated 101 patients with metronidazole or vancomycin in a non-blinded, nonrandomized study and found no difference in efficacy. In 1996, Wenisch et al,3 in a prospective, randomized, but nonblinded study in 119 patients, compared vancomycin, metronidazole, fusidic acid, and teicoplanin (Targocid) and also found no significant difference in efficacy.

The study. Zar et al,4 in a prospective, double-blind trial at a single institution over an 8-year period, randomized 172 patients with C difficile-associated diarrhea to receive either oral metronidazole 250 mg four times a day or oral vancomycin 125 mg four times a day, both for 10 days. (The appropriate dosage of vancomycin has been debated over the years. In 1989, Fekety et al5 treated patients who had antibiotic-associated C difficile colitis with either 125 or 500 mg of vancomycin, four times a day, and found that the low dosage was as effective as the high dosage.) Both groups also received an oral placebo in addition to the study drug.

In the study of Zar et al, criteria for inclusion were diarrhea (defined as having more than two nonformed stools per 24 hours) and the finding of either toxin A in the stool or pseudomembranes on endoscopic examination. Patients were excluded if they were pregnant, had suspected or proven life-threatening intra-abdominal complications, were allergic to either study drug, had taken one of the study drugs during the last 14 days, or had previously had C difficile-associated diarrhea that did not respond to either study drug.

Patients were followed for up to 21 days. The primary end points were cure, treatment failure, or relapse. Cure was defined as the resolution of diarrhea and no C difficile toxin A detected on stool assay at days 6 and 10.

Disease severity was classified as either mild or severe based on a point system: patients received a single point each for being older than 60 years, being febrile, having an albumin level of less than 2.5 mg/dL, or having a white blood cell count of more than 15 × 109/L. Patients were classified as having severe disease if they had two or more points. They received two points (ie, they were automatically classified as having severe disease) if they had pseudomembranous colitis or if they developed C difficile infection that required treatment in an intensive care unit.

Findings. The overall cure rate in patients receiving vancomycin was 97%, compared with 84% for those on metronidazole (P = .006). This difference was attributable to the group of patients with severe disease; no difference in treatment outcome was found in patients with mild disease. The relapse rates did not differ significantly between treatment groups in patients with either mild or severe disease.

Comments. The study was limited in that it was done at a single center and was done before the current highly virulent strain emerged. Whether these data can be extrapolated to today’s epidemic is unclear. Moreover, the investigators did not test for antimicrobial susceptibility (although metronidazole resistance is still uncommon). Finally, the development of colonization with vancomycin-resistant enterococci, one of the reasons that oral vancomycin is often not recommended, was not assessed.

Despite the study’s limitations, it shows that for severely ill patients with C difficile-associated diarrhea, oral vancomycin should be the treatment of choice.

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