Emerging Diseases

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Emerging Diseases

C. difficile is more virulent, more resistant and affecting younger,

healthier patients

CDC urges physicians to consider this diagnosis in patients with

severe diarrhea, even if they don't have traditional risk factors.

by Marie Rosenthal

IDC Editor in Chief

http://www.idinchildren.com/200608/frameset.asp?article=difficile.asp

August 2006

WASHINGTON – Clostridium difficile is following the path of

methicillin-resistant Staphylococcus aureus (MRSA) – out the

hospital door and into the community.

In addition, strains are becoming more virulent and resistant, and

are starting to affect non-traditional populations, such as

children, according to Trish M. Perl, MD, director of hospital

epidemiology and infection control at s Hopkins in Baltimore.

" What happened is this disease remade itself – it got a face-lift, "

Perl said at a press briefing sponsored here by the National

Foundation for Infectious Diseases. " The perception is that there is

an increase in incidence of this, and it has emerged in the

community. We also think there is an increase in disease severity. "

This gram-positive, spore-forming bacillus, which produces

exotoxins, is a leading cause of nosocomial infections,

traditionally in the elderly or severely immunocompromised

patients. " It is the most commonly reported enteric pathogen and it

is the leading cause of nosocomial diarrheal diseases, " Perl

said. " It has been well described to cause epidemics, but it is

actually quite endemic. "

Associated with antibiotic use, C. difficile diarrhea used to be

only considered a nuisance in the health care setting, but Perl said

she would not characterize it as such today. " It truly is much more

than a nuisance; I think that is an underestimate of its

importance, " she said.

The organism colonizes the gastrointestinal tract and at any given

time, 3% of the population is colonized. " If we look at neonates

almost all of them are colonized. So it is something that normally

hangs out in the GI tract, " she said. Antibiotic exposure alters the

flora of the GI tract and can lead to proliferation of the C.

difficile.

Carol Baker, MD, a pediatric infectious disease physician at Texas

Children's Hospital, said that she is also seeing C. difficile in

children. " We also have begun to see C. difficile in kids, " she

said. This was " something I did not see previously, except in

adolescents with cystic fibrosis and years of antibiotic exposure. "

" The CDC's Morbidity and Mortality Weekly Report described several

cases of community-acquired C. difficile-associated disease (CA-

CDAD) among 23 healthy residents in the community and 10 peripartum

women, two populations previously considered at low-risk for CDAD.

The CDC highlighted some of the cases.

The first case involved a pregnant woman, 31, who presented at a

local emergency department with a history of three weeks of

intermittent diarrhea, followed by three days of cramping and

watery, black stools. She reported one antimicrobial exposure, a

course of trimethoprim-sulfamethoxazole (TMP-SMX) for a urinary

tract infection three months earlier. She was discharged after

receiving metronidazole. The next day, she was readmitted and spent

18 days in the hospital for treatment of severe colitis; she

received metronidazole, cholestyramine and oral vancomycin. She

improved and was discharged, but was readmitted with diarrhea and

hypotension. She lost the twins she was carrying and despite

aggressive treatment, she died. Histopathology of the colon showed a

megacolon with pseudomembranous colitis.

Another case involved a 10-year-old girl who presented to a local

children's hospital with intractable diarrhea, projectile vomiting,

abdominal pain and fever. She had no history of antibiotic use

during the preceding year. " The child had been healthy until two

weeks before the ED visit, when she became symptomatic within days

of her younger brother having a febrile diarrheal illness, " the

report said.

After a week of illness, a clinician performed a rapid strep test,

which was positive. She received amoxicillin, but could not keep it

down. She was admitted to the hospital and received intravenous

fluids, electrolytes and metronidazole; her symptoms finally

resolved.

" This was very unusual. I'm not a pediatrician; I'm an adult

infectious disease doctor. But there are pediatricians here who

would tell you that this is not a common disease in children. This

is really an adult disease. So, this was very unusual, " Perl said.

Another remarkable trend in the CDC report was that 24% of the

reported cases had not received antibiotics.

The CDC report suggested that clinicians " consider the diagnosis of

CDAD in patients with severe diarrhea even if the patients do not

necessarily have traditional risk factors, such as recent

hospitalization or antimicrobial use. "

The mortality associated with this disease appears to be increasing,

too. Perl said that when she was in training, it was highly unusual

for someone to die from C. difficile. Today, it is more likely to

happen. In 2000, one Pittsburgh institution reported that life-

threatening C. difficile almost doubled with 44 colectomies and 20

deaths, Perl said. Data from Portland, Ore. indicated that mortality

from C. difficile rose from 3.5% to 15%.

The reason is a new toxic strain called NAP1/B1 toxinotype III.

According to a report by the CDC, " the epidemic strain produces 16

times more toxin A and 23 times more toxin B compared with other

common strains.

" Virulent strains, which cause more severe disease in populations at

high risk, might also cause more frequent, severe disease in

populations previously at low risk (eg, otherwise health persons

with little or no exposure to health-care settings or antimicrobial

use), " the CDC went on to explain.

Research done in Quebec " helped us wake up to the potential change

in the epidemiology that was going on with severe outcomes and

deaths, " Perl said. The strain seen in Quebec has moved south into

the United States and is being seen in pockets of this country,

particularly in the Mid-Atlantic region. Seventeen states have

reported this toxic strain, she said.

Quebec reported that C. difficile rates increased from 36 per

100,000 population to 156 per 100,000 population between 1991 and

2003. " I also would point out that they showed similar data as that

reported by Portland with a similar mortality increase, so the same

kind of pattern is emerging – a tripling of the mortality associated

with the disease, " Perl said.

Fluoroquinolones traditionally have been associated with a fourfold

increase in CDAD, but other antibiotics, especially clindamycin, are

also putting patients at risk. Clindamycin is now a favored drug to

deal with community-associated MRSA; but in some communities, it

might not be the best choice, she said.

" As an adult ID doc, we use a lot of TMP-SMX in this particular

setting. It is not as well liked [in pediatrics], but the

pediatrician certainly will use that, " Perl said.

" I don't know that any of us at this point think that emergence of

C. diff is related to the clindamycin that we have been using for CA-

MRSA, " she cautioned. " But we have to be vigilant and we have to

watch for unintended consequences of anything that we do. "

Controlling CDAD

She said new practice guidelines are being developed to try to

control CDAD. One institution restricted fluoroquinolone use and saw

a decrease in C. difficile.

" There may be a push to restrict these other agents that have been

implicated, particularly, clindamycin, " she said.

Institutions should enforce hand washing with soap and water and the

use of gloves by anyone caring for a patient in the community. " It

is going to become more important not only in the health care

setting, but in the community, if these community cases are truly a

new wave of this disease, " she said.

Cleaning the environment is also important, but it is difficult

because the spores linger in the environment for a long time. New

technologies are needed to solve this problem, she said.

" Bleach clearly works very well, but it is destructive to equipment,

and when used in high concentrations, it burns your eyes. That is

not well tolerated in day care settings, hospitals or long-term care

facilities, " she said.

In addition to new cleaning methods, immune globulin, a promising

vaccine, and strategies to decolonize the patient are being studied

for treatment.

The disease may increase the average patient cost by $3,600 per

patient, Perl said.

For more information:

CDC. Severe Clostridium difficile-associated disease in populations

previously at low risk – four states, 2005. MMWR. 2005:54(47);1201-

1205