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North America has new outbreaks of antibiotic associated C difficile

New York Janice Tanne

Outbreaks of severe Clostridium difficile diarrhoea with a high death rate have occurred among hospital patients in Quebec and in at least 16 US states. In the United States people at low risk in the community have also been affected. Use of fluoroquinolones and cephalosporins has been implicated.

Although the infection usually affects hospital patients or elderly people in long term care facilities, the US Centers for Disease Control and Prevention (CDC) reported severe C difficile disease among healthy people in the community and among peripartum women (Morbidity and Mortality Weekly Report 2005;54:1201-5).

Ten cases among peripartum women and 23 cases among people in the community were reported from four states between February 2003 and June 2005. The patients in the community ranged in age from 6 months to 72 years. One person, one of the peripartum women, died.

Most patients in the CDC reports said they had not used antimicrobial agents in the three months before their illness: 15 of the community patients and nine of the peripartum patients. However, seven of the 23 community patients had had contact with someone with a diarrhoeal illness.

Two reports and an editorial in the New England Journal of Medicine (2005;353:2442-9, 2433-41, and 2503-5) were released early to coincide with the CDC report.

In the first report, researchers describe a prospective study conducted in Quebec hospitals. Between January and June 2004, a team led by Vivian Loo, of the Department of Microbiology at McGill University Health Center in Montreal, did a prospective study of 1703 patients with 1719 episodes of nosocomial C difficile diarrhoea at 12 Quebec hospitals.

The incidence of the disease was 22.5 in every 1000 admissions—almost four times the incidence described in a 1997 survey of Canadian institutions. Elderly patients were more likely than younger patients to be infected. The 30 day mortality attributable to the infection was 6.9% (117 patients); the infection contributed to death in another 7.5% of patients (127 patients).

Patients were more likely than matched controls to have received fluoroquinolones or cephalosporins. One strain of the bacterium resistant to fluoroquinolones was found in 129 of 157 isolates (82%). Binary toxin genes and partial deletions in the tcdC gene (which is thought to be a negative regulator of toxin production) were present in 132 isolates (84%). These characteristics probably contributed to the strain’s virulence.

In the second report in the journal a CDC team led by Clifford McDonald said that in the past two years a growing number of health centres had reported C difficile disease that led to admission of the patient to intensive care units, colectomies, and deaths. A national survey by the emerging infections network of the Infectious Diseases Society of America found that about 39% of respondents reported an increase in the severity of C difficile disease among their patients.

The CDC team analysed 187 C difficile isolates from eight healthcare facilities in six US states that had had outbreaks of C difficile disease since 2001 and compared them with a database of more than 6000 isolates collected before 2001.

The team used restriction endonuclease analysis to characterise isolates. One group of isolates was identified in specimens from patients at all eight facilities and accounted for at least half the isolates from five facilities. This group was uncommon in isolates in the pre-2001 database. All of the current isolates but none of the old isolates were resistant to gatifloxacin and moxifloxacin.

In the editorial John Bartlett and Trish Perl of the Department of Medicine at Johns Hopkins University School of Medicine say that about 3% of healthy adults and 20% to 40% of hospitalised patients are colonised with C difficile. In healthy individuals the bacterium is in inactive spore form, but a disruption of competing flora promotes a conversion to forms that produce toxins.

The classic features of C difficile disease are diarrhoea, fever, leucocytosis, and hypoalbuminaemia or toxic megacolon (or both). The editorial warns that standard stool assays do not identify the current epidemic strain.

Treatment involves stopping the implicated antibiotic and giving oral metronidazole. Severely ill patients and patients who do not respond promptly to metronidazole may need oral vancomycin.

The authors advise restraint in using antibiotics such as second and third generation cephalosporins, clindamycin, and fluoroquinolones. Healthcare workers should wash their hands with soap and water, because alcohol based cleansers do not kill C difficile. Treatment should involve barrier precautions, isolation of patients, and careful cleaning of surroundings with sporicidal agents that are active against C difficile.

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