Miriam E. Tucker

WASHINGTON — Quebec's recent outbreak of Clostridium difficile-associated diarrhea does not appear to have been associated with any specific antibiotic use pattern. Rather, poor infection control practices are likely to blame.

That was the conclusion of an analysis from four Canadian hospitals conducted by Dr. Karl A. Weiss and his associates at Maisonneuve-Rosemont Hospital, Montreal, and reported in a poster at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

The outbreak of C. difficile-associated diarrhea (CDAD), which occurred in 2002–2004 at several Quebec hospitals, was caused by a new strain of C. difficile found to be more virulent than those previously seen (N. Engl. J. Med. 2005;353:2442–9).

Although antibiotic usage has been strongly associated with the occurrence of CDAD, the circumstances of this outbreak were at odds with that explanation: No increase in CDAD cases was seen in any province other than Quebec, which actually has the lowest per capita antibiotic consumption of all the Canadian provinces.

The investigators analyzed antibiotic use data for the time periods 1999–2001, 2002, and 2003 from two hospitals that were affected by the new C. difficile strain outbreak and two that were not. In one of the affected hospitals, the number of CD diagnoses per 1,000 population rose from 9 in 1999–2001 to 14 in 2002 to 33 in 2003. In contrast, rates in one of the unaffected hospitals remained stable, from 5/1,000 in 1999–2001 to 4 in 2002 to 5.5 in 2003.

A comparison of affected and unaffected hospitals showed no significant association between the number of CDAD cases per 1,000 admissions and the daily consumption of cephalosporins, carbapenems, β-lactams/β-lactamase inhibitors, fluoroquinolones, or intravenous clindamycin. There was no significant protective effect from any class of antibiotics, Dr. Weiss and his associates reported at the meeting, sponsored by the American Society for Microbiology.

Proper antibiotic use is key to controlling the emergence of resistant organisms, but in the case of CDAD antibiotics appear to be acting mainly as triggering agents in patients who acquire the new strain during their hospital stay.

Instead, the Quebec outbreak appeared to be mostly caused by poor infection control practices. The situation improved dramatically in 2004–2005 following substantial investment by the provincial government and the implementation of infection control measures.

WASHINGTON — Quebec's recent outbreak of Clostridium difficile-associated diarrhea does not appear to have been associated with any specific antibiotic use pattern. Rather, poor infection control practices are likely to blame.

That was the conclusion of an analysis from four Canadian hospitals conducted by Dr. Karl A. Weiss and his associates at Maisonneuve-Rosemont Hospital, Montreal, and reported in a poster at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

The outbreak of C. difficile-associated diarrhea (CDAD), which occurred in 2002–2004 at several Quebec hospitals, was caused by a new strain of C. difficile found to be more virulent than those previously seen (N. Engl. J. Med. 2005;353:2442–9).

Although antibiotic usage has been strongly associated with the occurrence of CDAD, the circumstances of this outbreak were at odds with that explanation: No increase in CDAD cases was seen in any province other than Quebec, which actually has the lowest per capita antibiotic consumption of all the Canadian provinces.

The investigators analyzed antibiotic use data for the time periods 1999–2001, 2002, and 2003 from two hospitals that were affected by the new C. difficile strain outbreak and two that were not. In one of the affected hospitals, the number of CD diagnoses per 1,000 population rose from 9 in 1999–2001 to 14 in 2002 to 33 in 2003. In contrast, rates in one of the unaffected hospitals remained stable, from 5/1,000 in 1999–2001 to 4 in 2002 to 5.5 in 2003.

A comparison of affected and unaffected hospitals showed no significant association between the number of CDAD cases per 1,000 admissions and the daily consumption of cephalosporins, carbapenems, β-lactams/β-lactamase inhibitors, fluoroquinolones, or intravenous clindamycin. There was no significant protective effect from any class of antibiotics, Dr. Weiss and his associates reported at the meeting, sponsored by the American Society for Microbiology.

Proper antibiotic use is key to controlling the emergence of resistant organisms, but in the case of CDAD antibiotics appear to be acting mainly as triggering agents in patients who acquire the new strain during their hospital stay.

Instead, the Quebec outbreak appeared to be mostly caused by poor infection control practices. The situation improved dramatically in 2004–2005 following substantial investment by the provincial government and the implementation of infection control measures.

WASHINGTON — Quebec's recent outbreak of Clostridium difficile-associated diarrhea does not appear to have been associated with any specific antibiotic use pattern. Rather, poor infection control practices are likely to blame.

That was the conclusion of an analysis from four Canadian hospitals conducted by Dr. Karl A. Weiss and his associates at Maisonneuve-Rosemont Hospital, Montreal, and reported in a poster at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

The outbreak of C. difficile-associated diarrhea (CDAD), which occurred in 2002–2004 at several Quebec hospitals, was caused by a new strain of C. difficile found to be more virulent than those previously seen (N. Engl. J. Med. 2005;353:2442–9).

Although antibiotic usage has been strongly associated with the occurrence of CDAD, the circumstances of this outbreak were at odds with that explanation: No increase in CDAD cases was seen in any province other than Quebec, which actually has the lowest per capita antibiotic consumption of all the Canadian provinces.

The investigators analyzed antibiotic use data for the time periods 1999–2001, 2002, and 2003 from two hospitals that were affected by the new C. difficile strain outbreak and two that were not. In one of the affected hospitals, the number of CD diagnoses per 1,000 population rose from 9 in 1999–2001 to 14 in 2002 to 33 in 2003. In contrast, rates in one of the unaffected hospitals remained stable, from 5/1,000 in 1999–2001 to 4 in 2002 to 5.5 in 2003.

A comparison of affected and unaffected hospitals showed no significant association between the number of CDAD cases per 1,000 admissions and the daily consumption of cephalosporins, carbapenems, β-lactams/β-lactamase inhibitors, fluoroquinolones, or intravenous clindamycin. There was no significant protective effect from any class of antibiotics, Dr. Weiss and his associates reported at the meeting, sponsored by the American Society for Microbiology.

Proper antibiotic use is key to controlling the emergence of resistant organisms, but in the case of CDAD antibiotics appear to be acting mainly as triggering agents in patients who acquire the new strain during their hospital stay.

Instead, the Quebec outbreak appeared to be mostly caused by poor infection control practices. The situation improved dramatically in 2004–2005 following substantial investment by the provincial government and the implementation of infection control measures.

U.S. Activity Levels Stagnant

Most U.S. adults did not engage in the minimum recommended level of physical activity in 2003, according to the Centers for Disease Control and Prevention.

Results from the nationwide Behavioral Risk Factor Surveillance System (BRFSS) suggest that between 2001 and 2003 there were no significant changes in the proportion of U.S. adults who engage in the recommended amount of physical activity or in the proportion who don't exercise at all, the CDC said (MMWR 2005;54:1208–12).

Responses from 214,500 participants in the 2001 BRFSS were compared with those of 264,684 in the 2003 survey. To meet the minimum recommended activity level, an individual had to engage in moderate activity for at least 30 minutes per day, 5 or more days a week, or vigorous activity at least 20 minutes per day, 3 or more days per week. Inactivity was defined as no moderate or vigorous activity of at least 10 minutes.

In 2003, the age-adjusted proportion of adults engaging in the minimum recommended activity level was 45.9%, up only slightly from the 45.3% reported in 2001. Increases occurred in 41 states and territories, while levels decreased in 12 states and territories. There was also no major change in lifestyle inactivity between 2001 (16.0%) and 2003 (15.6%), although there were decreases in 32 states and territories.

Bariatric Surgery Rates Balloon

The recent growth of bariatric surgery in the United States appears highly correlated with the development of laparoscopic bariatric surgery, reported Dr. Ninh T. Nguyen and colleagues at the University of California, Irvine.

From 1998 through 2002, a total of 188,599 morbidly obese patients underwent bariatric surgery in the United States. The number of procedures rose from 12,775 in 1998 to 70,256 in 2002, according to the investigators. During the same period, the rate of bariatric procedures rose from 6.3 per 100,000 adults in 1998 to 32.7 per 100,000 adults in 2002 (Arch. Surg. 2005;140:1198–202).

“The increased enthusiasm for bariatric surgery coincides with the development and dissemination of the laparoscopic approach,” the investigators wrote.

The overall annual rate of laparoscopic procedures increased exponentially, from 0.1 procedures per 100,000 adults in 1998 to 5.9 procedures in 2002. This compares with the smaller linear rise of open procedures, from 6.2 procedures per 100,000 adults in 1998 to 26.8 procedures per 100,000 adults in 2002. The percentage of laparoscopic procedures increased from 2.1% of the total in 1998 to nearly 18% in 2002.

The percentage of laparoscopic procedures increased from 2.1% of the total in 1998 to nearly 18% in 2002.

A previous study reported that bariatric procedures increased from 9,189 in 1993 to 12,541 in 1997, while the American Society for Bariatric Surgery (ASBS) has estimated that there were around 140,000 bariatric procedures in 2004, Dr. Nguyen and colleagues said.

The ASBS reported that their membership has risen from 258 in 1998 to 631 in 2002, a 144% increase in membership over 5 years.

Same Old, Same Old Aids Weight Loss

Limiting the variety of snack foods consumed to a subject's favorite snack may decrease the craving for that food, according to Hollie A. Raynor, Ph.D., and her colleagues at Brown University, Providence, R.I.

Thirty overweight and obese adults were randomized to one of two 8-week behavioral weight-loss interventions. The subjects, 27 of whom were female, were assigned a daily caloric goal of 1,200–1,500 kcal, with 20% of the calories coming from fat.

Half the subjects were randomized to an intervention that limited variety to one chosen snack food. They were told to eat this favorite snack at least four times a week in any amount, as long as their overall calorie restrictions were met. The 15 control subjects were told to keep their snack food servings to less than one per day, but they had no restriction on variety (Eat. Behav. 2006;7:1–14).

Both groups lost nearly 8 pounds, as was expected based on the calorie prescription. But the subjects in the reduced-variety group showed a decreased sense of pleasantness in response to their chosen snack food over time, compared with other snack foods given to them by researchers at the end of the study (−17.9 vs. −3.4 on a 100-mm visual analog scale, respectively). The pleasantness of the chosen snack food increased in the first 3 weeks but decreased steadily as the study went on, the investigators said.

In contrast, the controls showed no long-term sensory-specific satiety or feelings of monotony in response to the snack foods they ate.

By the end of the study, the reduced-variety group decreased energy consumption from snack food by 1,732 calories/week, while controls had a reduction of 1,448 calories/week, they said.

U.S. Activity Levels Stagnant

Most U.S. adults did not engage in the minimum recommended level of physical activity in 2003, according to the Centers for Disease Control and Prevention.

Results from the nationwide Behavioral Risk Factor Surveillance System (BRFSS) suggest that between 2001 and 2003 there were no significant changes in the proportion of U.S. adults who engage in the recommended amount of physical activity or in the proportion who don't exercise at all, the CDC said (MMWR 2005;54:1208–12).

Responses from 214,500 participants in the 2001 BRFSS were compared with those of 264,684 in the 2003 survey. To meet the minimum recommended activity level, an individual had to engage in moderate activity for at least 30 minutes per day, 5 or more days a week, or vigorous activity at least 20 minutes per day, 3 or more days per week. Inactivity was defined as no moderate or vigorous activity of at least 10 minutes.

In 2003, the age-adjusted proportion of adults engaging in the minimum recommended activity level was 45.9%, up only slightly from the 45.3% reported in 2001. Increases occurred in 41 states and territories, while levels decreased in 12 states and territories. There was also no major change in lifestyle inactivity between 2001 (16.0%) and 2003 (15.6%), although there were decreases in 32 states and territories.

Bariatric Surgery Rates Balloon

The recent growth of bariatric surgery in the United States appears highly correlated with the development of laparoscopic bariatric surgery, reported Dr. Ninh T. Nguyen and colleagues at the University of California, Irvine.

From 1998 through 2002, a total of 188,599 morbidly obese patients underwent bariatric surgery in the United States. The number of procedures rose from 12,775 in 1998 to 70,256 in 2002, according to the investigators. During the same period, the rate of bariatric procedures rose from 6.3 per 100,000 adults in 1998 to 32.7 per 100,000 adults in 2002 (Arch. Surg. 2005;140:1198–202).

“The increased enthusiasm for bariatric surgery coincides with the development and dissemination of the laparoscopic approach,” the investigators wrote.

The overall annual rate of laparoscopic procedures increased exponentially, from 0.1 procedures per 100,000 adults in 1998 to 5.9 procedures in 2002. This compares with the smaller linear rise of open procedures, from 6.2 procedures per 100,000 adults in 1998 to 26.8 procedures per 100,000 adults in 2002. The percentage of laparoscopic procedures increased from 2.1% of the total in 1998 to nearly 18% in 2002.

The percentage of laparoscopic procedures increased from 2.1% of the total in 1998 to nearly 18% in 2002.

A previous study reported that bariatric procedures increased from 9,189 in 1993 to 12,541 in 1997, while the American Society for Bariatric Surgery (ASBS) has estimated that there were around 140,000 bariatric procedures in 2004, Dr. Nguyen and colleagues said.

The ASBS reported that their membership has risen from 258 in 1998 to 631 in 2002, a 144% increase in membership over 5 years.

Same Old, Same Old Aids Weight Loss

Limiting the variety of snack foods consumed to a subject's favorite snack may decrease the craving for that food, according to Hollie A. Raynor, Ph.D., and her colleagues at Brown University, Providence, R.I.

Thirty overweight and obese adults were randomized to one of two 8-week behavioral weight-loss interventions. The subjects, 27 of whom were female, were assigned a daily caloric goal of 1,200–1,500 kcal, with 20% of the calories coming from fat.

Half the subjects were randomized to an intervention that limited variety to one chosen snack food. They were told to eat this favorite snack at least four times a week in any amount, as long as their overall calorie restrictions were met. The 15 control subjects were told to keep their snack food servings to less than one per day, but they had no restriction on variety (Eat. Behav. 2006;7:1–14).

Both groups lost nearly 8 pounds, as was expected based on the calorie prescription. But the subjects in the reduced-variety group showed a decreased sense of pleasantness in response to their chosen snack food over time, compared with other snack foods given to them by researchers at the end of the study (−17.9 vs. −3.4 on a 100-mm visual analog scale, respectively). The pleasantness of the chosen snack food increased in the first 3 weeks but decreased steadily as the study went on, the investigators said.

In contrast, the controls showed no long-term sensory-specific satiety or feelings of monotony in response to the snack foods they ate.

By the end of the study, the reduced-variety group decreased energy consumption from snack food by 1,732 calories/week, while controls had a reduction of 1,448 calories/week, they said.

U.S. Activity Levels Stagnant

Most U.S. adults did not engage in the minimum recommended level of physical activity in 2003, according to the Centers for Disease Control and Prevention.

Results from the nationwide Behavioral Risk Factor Surveillance System (BRFSS) suggest that between 2001 and 2003 there were no significant changes in the proportion of U.S. adults who engage in the recommended amount of physical activity or in the proportion who don't exercise at all, the CDC said (MMWR 2005;54:1208–12).

Responses from 214,500 participants in the 2001 BRFSS were compared with those of 264,684 in the 2003 survey. To meet the minimum recommended activity level, an individual had to engage in moderate activity for at least 30 minutes per day, 5 or more days a week, or vigorous activity at least 20 minutes per day, 3 or more days per week. Inactivity was defined as no moderate or vigorous activity of at least 10 minutes.

In 2003, the age-adjusted proportion of adults engaging in the minimum recommended activity level was 45.9%, up only slightly from the 45.3% reported in 2001. Increases occurred in 41 states and territories, while levels decreased in 12 states and territories. There was also no major change in lifestyle inactivity between 2001 (16.0%) and 2003 (15.6%), although there were decreases in 32 states and territories.

Bariatric Surgery Rates Balloon

The recent growth of bariatric surgery in the United States appears highly correlated with the development of laparoscopic bariatric surgery, reported Dr. Ninh T. Nguyen and colleagues at the University of California, Irvine.

From 1998 through 2002, a total of 188,599 morbidly obese patients underwent bariatric surgery in the United States. The number of procedures rose from 12,775 in 1998 to 70,256 in 2002, according to the investigators. During the same period, the rate of bariatric procedures rose from 6.3 per 100,000 adults in 1998 to 32.7 per 100,000 adults in 2002 (Arch. Surg. 2005;140:1198–202).

“The increased enthusiasm for bariatric surgery coincides with the development and dissemination of the laparoscopic approach,” the investigators wrote.

The overall annual rate of laparoscopic procedures increased exponentially, from 0.1 procedures per 100,000 adults in 1998 to 5.9 procedures in 2002. This compares with the smaller linear rise of open procedures, from 6.2 procedures per 100,000 adults in 1998 to 26.8 procedures per 100,000 adults in 2002. The percentage of laparoscopic procedures increased from 2.1% of the total in 1998 to nearly 18% in 2002.

The percentage of laparoscopic procedures increased from 2.1% of the total in 1998 to nearly 18% in 2002.

A previous study reported that bariatric procedures increased from 9,189 in 1993 to 12,541 in 1997, while the American Society for Bariatric Surgery (ASBS) has estimated that there were around 140,000 bariatric procedures in 2004, Dr. Nguyen and colleagues said.

The ASBS reported that their membership has risen from 258 in 1998 to 631 in 2002, a 144% increase in membership over 5 years.

Same Old, Same Old Aids Weight Loss

Limiting the variety of snack foods consumed to a subject's favorite snack may decrease the craving for that food, according to Hollie A. Raynor, Ph.D., and her colleagues at Brown University, Providence, R.I.

Thirty overweight and obese adults were randomized to one of two 8-week behavioral weight-loss interventions. The subjects, 27 of whom were female, were assigned a daily caloric goal of 1,200–1,500 kcal, with 20% of the calories coming from fat.

Half the subjects were randomized to an intervention that limited variety to one chosen snack food. They were told to eat this favorite snack at least four times a week in any amount, as long as their overall calorie restrictions were met. The 15 control subjects were told to keep their snack food servings to less than one per day, but they had no restriction on variety (Eat. Behav. 2006;7:1–14).

Both groups lost nearly 8 pounds, as was expected based on the calorie prescription. But the subjects in the reduced-variety group showed a decreased sense of pleasantness in response to their chosen snack food over time, compared with other snack foods given to them by researchers at the end of the study (−17.9 vs. −3.4 on a 100-mm visual analog scale, respectively). The pleasantness of the chosen snack food increased in the first 3 weeks but decreased steadily as the study went on, the investigators said.

In contrast, the controls showed no long-term sensory-specific satiety or feelings of monotony in response to the snack foods they ate.

By the end of the study, the reduced-variety group decreased energy consumption from snack food by 1,732 calories/week, while controls had a reduction of 1,448 calories/week, they said.

WASHINGTON — Officially, the lack of delayed language skills is what separates a child with Asperger's disorder from one with high-functioning autism. But the reality is far more complex, Dr. Chris Plauche Johnson said at the annual meeting of the American Academy of Pediatrics.

Both Asperger's disorder and autism are included in the Diagnostic and Statistical Manual-IV, Text Revision (DSM-IV-TR) under “Pervasive Developmental Disorders,” a term which itself is now falling out of use in favor of “autism spectrum disorders.” Asperger's disorder is a unique diagnostic category in DSM-IV-TR, while children who meet the criteria for autism except for having normal intelligence are often classified under “atypical autism.”

Both Asperger's and high-functioning autism share criteria regarding social skills and restricted interests, but they differ in language ability and age of onset. However, not everyone agrees that the two are actually separate entities, and some experts feel the DSM-IV-TR criteria for Asperger's disorder are too restrictive, said Dr. Johnson, a developmental pediatrician and clinical professor of pediatrics at the University of Texas Health Science Center, San Antonio.

The American Academy of Pediatrics plans to issue a revised clinical report on autism spectrum disorders sometime in 2006–2007, she said.

Unlike autism, for which the parents' first concern is about language development and which arises when the child is 18–24 months old, parents of children with Asperger's disorder often don't become concerned until the child is in preschool and has difficulties with peer social interactions or in general behavior.

But the syndromes are beginning to blend now that comorbid mental retardation is being diagnosed less and less often among children with autism. Before 1990, about 90% of autistic children also had mental retardation. Now the rate has dropped to 50% or even lower in some studies. A major reason for this is that better diagnostic tools and improved clinician training have reduced the number of children whose intelligence was considered “untestable” and who therefore were listed as mentally retarded.

These days, it's highly unusual for a child to be considered untestable, which calls into question the whole phenomenon of atypical autism. “High-functioning autism may not be atypical in the new millennium,” Dr. Johnson said.

But even children with high-functioning autism have delayed speech, with few words or with inconsistent, “pop-up” use of words. They may be able to label things or repeat song lyrics or phrases, but have difficulty constructing meaningful sentences on their own. They often don't respond to verbal or body language cues from others, and may interrupt others. In contrast, children with Asperger's disorder have no significant delay in language.

Any child suspected of having either disorder should be referred for comprehensive testing so that interventions such as speech and social skills training can begin early. In the end, the diagnosis may hinge on practical issues: Insurance companies, for example, will usually pay for therapy for autism but not always for Asperger's.

How the Criteria Delineate the Two

According to the DSM-IV-TR, criteria for autism and Asperger's disorder include:

In both autistic disorder and Asperger's disorder, there is qualitative impairment in social interaction, as manifested by at least two of the following:

Marked impairment in the use of multiple nonverbal behaviors such as eye-to-eye gaze, facial expression, body postures, and gestures to regulate social interaction.

Failure to develop peer relationships appropriate to developmental level.

A lack of spontaneous seeking to share enjoyment, interests, or achievements with other people.

Lack of social or emotional reciprocity.

In both autistic disorder and Asperger's disorder, there are restricted, repetitive, and stereotyped patterns of behavior, interests, and activities, as manifested by at least one of the following:

Encompassing preoccupation with one or more stereotyped and restricted patterns of interest that is abnormal either in intensity or focus.

Apparently inflexible adherence to specific, nonfunctional routines or rituals.

Stereotyped and repetitive motor mannerisms (hand or finger flapping or twisting, or complex whole-body movements).

Persistent preoccupation with parts of objects.

In autistic disorder, there are qualitative impairments in communication as manifested by at least one of the following:

Delay in, or total lack of, the development of spoken language (not accompanied by an attempt to compensate through alternative modes of communication such as gesture or mime).

In individuals with adequate speech, marked impairment in the ability to initiate or sustain a conversation with others.

Stereotyped and repetitive use of language or use of idiosyncratic language.

Lack of varied, spontaneous, make-believe play or social imitative play appropriate to developmental level.

Conversely, in Asperger's disorder, there is no clinically significant general delay in language (single words used by age 2 years, communicative phrases by age 3 years).

Although not specified in the DSM-IV, children with autistic disorder who have IQs higher than 70 are often classified as having “high-functioning autism.”

The criterion for high-functioning autism is sometimes considered to be an IQ greater than 85 or even greater than 100.

WASHINGTON — Officially, the lack of delayed language skills is what separates a child with Asperger's disorder from one with high-functioning autism. But the reality is far more complex, Dr. Chris Plauche Johnson said at the annual meeting of the American Academy of Pediatrics.

Both Asperger's disorder and autism are included in the Diagnostic and Statistical Manual-IV, Text Revision (DSM-IV-TR) under “Pervasive Developmental Disorders,” a term which itself is now falling out of use in favor of “autism spectrum disorders.” Asperger's disorder is a unique diagnostic category in DSM-IV-TR, while children who meet the criteria for autism except for having normal intelligence are often classified under “atypical autism.”

Both Asperger's and high-functioning autism share criteria regarding social skills and restricted interests, but they differ in language ability and age of onset. However, not everyone agrees that the two are actually separate entities, and some experts feel the DSM-IV-TR criteria for Asperger's disorder are too restrictive, said Dr. Johnson, a developmental pediatrician and clinical professor of pediatrics at the University of Texas Health Science Center, San Antonio.

The American Academy of Pediatrics plans to issue a revised clinical report on autism spectrum disorders sometime in 2006–2007, she said.

Unlike autism, for which the parents' first concern is about language development and which arises when the child is 18–24 months old, parents of children with Asperger's disorder often don't become concerned until the child is in preschool and has difficulties with peer social interactions or in general behavior.

But the syndromes are beginning to blend now that comorbid mental retardation is being diagnosed less and less often among children with autism. Before 1990, about 90% of autistic children also had mental retardation. Now the rate has dropped to 50% or even lower in some studies. A major reason for this is that better diagnostic tools and improved clinician training have reduced the number of children whose intelligence was considered “untestable” and who therefore were listed as mentally retarded.

These days, it's highly unusual for a child to be considered untestable, which calls into question the whole phenomenon of atypical autism. “High-functioning autism may not be atypical in the new millennium,” Dr. Johnson said.

But even children with high-functioning autism have delayed speech, with few words or with inconsistent, “pop-up” use of words. They may be able to label things or repeat song lyrics or phrases, but have difficulty constructing meaningful sentences on their own. They often don't respond to verbal or body language cues from others, and may interrupt others. In contrast, children with Asperger's disorder have no significant delay in language.

Any child suspected of having either disorder should be referred for comprehensive testing so that interventions such as speech and social skills training can begin early. In the end, the diagnosis may hinge on practical issues: Insurance companies, for example, will usually pay for therapy for autism but not always for Asperger's.

How the Criteria Delineate the Two

According to the DSM-IV-TR, criteria for autism and Asperger's disorder include:

In both autistic disorder and Asperger's disorder, there is qualitative impairment in social interaction, as manifested by at least two of the following:

Marked impairment in the use of multiple nonverbal behaviors such as eye-to-eye gaze, facial expression, body postures, and gestures to regulate social interaction.

Failure to develop peer relationships appropriate to developmental level.

A lack of spontaneous seeking to share enjoyment, interests, or achievements with other people.

Lack of social or emotional reciprocity.

In both autistic disorder and Asperger's disorder, there are restricted, repetitive, and stereotyped patterns of behavior, interests, and activities, as manifested by at least one of the following:

Encompassing preoccupation with one or more stereotyped and restricted patterns of interest that is abnormal either in intensity or focus.

Apparently inflexible adherence to specific, nonfunctional routines or rituals.

Stereotyped and repetitive motor mannerisms (hand or finger flapping or twisting, or complex whole-body movements).

Persistent preoccupation with parts of objects.

In autistic disorder, there are qualitative impairments in communication as manifested by at least one of the following:

Delay in, or total lack of, the development of spoken language (not accompanied by an attempt to compensate through alternative modes of communication such as gesture or mime).

In individuals with adequate speech, marked impairment in the ability to initiate or sustain a conversation with others.

Stereotyped and repetitive use of language or use of idiosyncratic language.

Lack of varied, spontaneous, make-believe play or social imitative play appropriate to developmental level.

Conversely, in Asperger's disorder, there is no clinically significant general delay in language (single words used by age 2 years, communicative phrases by age 3 years).

Although not specified in the DSM-IV, children with autistic disorder who have IQs higher than 70 are often classified as having “high-functioning autism.”

The criterion for high-functioning autism is sometimes considered to be an IQ greater than 85 or even greater than 100.

WASHINGTON — Officially, the lack of delayed language skills is what separates a child with Asperger's disorder from one with high-functioning autism. But the reality is far more complex, Dr. Chris Plauche Johnson said at the annual meeting of the American Academy of Pediatrics.

Both Asperger's disorder and autism are included in the Diagnostic and Statistical Manual-IV, Text Revision (DSM-IV-TR) under “Pervasive Developmental Disorders,” a term which itself is now falling out of use in favor of “autism spectrum disorders.” Asperger's disorder is a unique diagnostic category in DSM-IV-TR, while children who meet the criteria for autism except for having normal intelligence are often classified under “atypical autism.”

Both Asperger's and high-functioning autism share criteria regarding social skills and restricted interests, but they differ in language ability and age of onset. However, not everyone agrees that the two are actually separate entities, and some experts feel the DSM-IV-TR criteria for Asperger's disorder are too restrictive, said Dr. Johnson, a developmental pediatrician and clinical professor of pediatrics at the University of Texas Health Science Center, San Antonio.

The American Academy of Pediatrics plans to issue a revised clinical report on autism spectrum disorders sometime in 2006–2007, she said.

Unlike autism, for which the parents' first concern is about language development and which arises when the child is 18–24 months old, parents of children with Asperger's disorder often don't become concerned until the child is in preschool and has difficulties with peer social interactions or in general behavior.

But the syndromes are beginning to blend now that comorbid mental retardation is being diagnosed less and less often among children with autism. Before 1990, about 90% of autistic children also had mental retardation. Now the rate has dropped to 50% or even lower in some studies. A major reason for this is that better diagnostic tools and improved clinician training have reduced the number of children whose intelligence was considered “untestable” and who therefore were listed as mentally retarded.

These days, it's highly unusual for a child to be considered untestable, which calls into question the whole phenomenon of atypical autism. “High-functioning autism may not be atypical in the new millennium,” Dr. Johnson said.

But even children with high-functioning autism have delayed speech, with few words or with inconsistent, “pop-up” use of words. They may be able to label things or repeat song lyrics or phrases, but have difficulty constructing meaningful sentences on their own. They often don't respond to verbal or body language cues from others, and may interrupt others. In contrast, children with Asperger's disorder have no significant delay in language.

Any child suspected of having either disorder should be referred for comprehensive testing so that interventions such as speech and social skills training can begin early. In the end, the diagnosis may hinge on practical issues: Insurance companies, for example, will usually pay for therapy for autism but not always for Asperger's.

How the Criteria Delineate the Two

According to the DSM-IV-TR, criteria for autism and Asperger's disorder include:

In both autistic disorder and Asperger's disorder, there is qualitative impairment in social interaction, as manifested by at least two of the following:

Marked impairment in the use of multiple nonverbal behaviors such as eye-to-eye gaze, facial expression, body postures, and gestures to regulate social interaction.

Failure to develop peer relationships appropriate to developmental level.

A lack of spontaneous seeking to share enjoyment, interests, or achievements with other people.

Lack of social or emotional reciprocity.

In both autistic disorder and Asperger's disorder, there are restricted, repetitive, and stereotyped patterns of behavior, interests, and activities, as manifested by at least one of the following:

Encompassing preoccupation with one or more stereotyped and restricted patterns of interest that is abnormal either in intensity or focus.

Apparently inflexible adherence to specific, nonfunctional routines or rituals.

Stereotyped and repetitive motor mannerisms (hand or finger flapping or twisting, or complex whole-body movements).

Persistent preoccupation with parts of objects.

In autistic disorder, there are qualitative impairments in communication as manifested by at least one of the following:

Delay in, or total lack of, the development of spoken language (not accompanied by an attempt to compensate through alternative modes of communication such as gesture or mime).

In individuals with adequate speech, marked impairment in the ability to initiate or sustain a conversation with others.

Stereotyped and repetitive use of language or use of idiosyncratic language.

Lack of varied, spontaneous, make-believe play or social imitative play appropriate to developmental level.

Conversely, in Asperger's disorder, there is no clinically significant general delay in language (single words used by age 2 years, communicative phrases by age 3 years).

Although not specified in the DSM-IV, children with autistic disorder who have IQs higher than 70 are often classified as having “high-functioning autism.”

The criterion for high-functioning autism is sometimes considered to be an IQ greater than 85 or even greater than 100.

ATLANTA — Adolescents with type 1 diabetes may have early evidence of atherosclerosis, Dr. Maria V. Karantza reported at the annual scientific sessions of the American Diabetes Association.

The increased risk appears to be related to conventional cardiovascular disease risk factors such as dyslipidemia, hemoglobin A_1c, and tobacco exposure rather than nontraditional risk factors related to endothelial function, suggesting that strategies targeting modifiable risk factors could benefit these patients, said Dr. Karantza of the University of California, Los Angeles.

Carotid artery intima-medial thickening (IMT), considered an indirect measure of cardiovascular disease (CVD), was evaluated by B-mode ultrasound in 90 adolescents with type 1 diabetes (mean age 16.6 years) with 16 of their healthy siblings (mean age 16.7 years). Overall, IMT was significantly greater among the diabetic group than the controls (0.564 mm vs. 0.54 mm), she reported.

There were no differences between the two groups in body mass index, blood pressure, gender, or family history of diabetes/CVD. None of the controls smoked, while six of the diabetics (all male) were smokers; the difference was not statistically significant.

The two groups also did not differ by conventional risk factors such as cholesterol, triglycerides, or microalbumin/creatinine ratio, or by nontraditional risk factors such as fibrinogen, von Willebrand factor antigen, plasminogen activator inhibitor-1, or IL-6.

When broken down by gender, significant differences in IMT between diabetic and control subjects were only seen among the males (0.582 mm vs. 0.524 mm), and not the females (0.548 mm vs. 0.556 mm).

Among the males with diabetes, IMT was significantly correlated with HbA_1c and tobacco exposure, as well as with total cholesterol and apolipoprotein B. Among the female diabetics, IMT was correlated positively with a family history of CVD and negatively correlated with HDL cholesterol.

The findings suggest that conventional CVD risk factors result in increased IMT, and probably cause the initial endothelial dysfunction in these young people. The subsequent loss of normal endothelial homeostatic properties would eventually lead to a “proinflammatory, proadhesive, and procoagulant endothelial surface that is not yet present in our cohort. Early treatment of modifiable risk factors could avert the chronic inflammatory process which, if unabated, will result in the advanced chronic plaque formation,” she said.

ATLANTA — Adolescents with type 1 diabetes may have early evidence of atherosclerosis, Dr. Maria V. Karantza reported at the annual scientific sessions of the American Diabetes Association.

The increased risk appears to be related to conventional cardiovascular disease risk factors such as dyslipidemia, hemoglobin A_1c, and tobacco exposure rather than nontraditional risk factors related to endothelial function, suggesting that strategies targeting modifiable risk factors could benefit these patients, said Dr. Karantza of the University of California, Los Angeles.

Carotid artery intima-medial thickening (IMT), considered an indirect measure of cardiovascular disease (CVD), was evaluated by B-mode ultrasound in 90 adolescents with type 1 diabetes (mean age 16.6 years) with 16 of their healthy siblings (mean age 16.7 years). Overall, IMT was significantly greater among the diabetic group than the controls (0.564 mm vs. 0.54 mm), she reported.

There were no differences between the two groups in body mass index, blood pressure, gender, or family history of diabetes/CVD. None of the controls smoked, while six of the diabetics (all male) were smokers; the difference was not statistically significant.

The two groups also did not differ by conventional risk factors such as cholesterol, triglycerides, or microalbumin/creatinine ratio, or by nontraditional risk factors such as fibrinogen, von Willebrand factor antigen, plasminogen activator inhibitor-1, or IL-6.

When broken down by gender, significant differences in IMT between diabetic and control subjects were only seen among the males (0.582 mm vs. 0.524 mm), and not the females (0.548 mm vs. 0.556 mm).

Among the males with diabetes, IMT was significantly correlated with HbA_1c and tobacco exposure, as well as with total cholesterol and apolipoprotein B. Among the female diabetics, IMT was correlated positively with a family history of CVD and negatively correlated with HDL cholesterol.

The findings suggest that conventional CVD risk factors result in increased IMT, and probably cause the initial endothelial dysfunction in these young people. The subsequent loss of normal endothelial homeostatic properties would eventually lead to a “proinflammatory, proadhesive, and procoagulant endothelial surface that is not yet present in our cohort. Early treatment of modifiable risk factors could avert the chronic inflammatory process which, if unabated, will result in the advanced chronic plaque formation,” she said.

ATLANTA — Adolescents with type 1 diabetes may have early evidence of atherosclerosis, Dr. Maria V. Karantza reported at the annual scientific sessions of the American Diabetes Association.

The increased risk appears to be related to conventional cardiovascular disease risk factors such as dyslipidemia, hemoglobin A_1c, and tobacco exposure rather than nontraditional risk factors related to endothelial function, suggesting that strategies targeting modifiable risk factors could benefit these patients, said Dr. Karantza of the University of California, Los Angeles.

Carotid artery intima-medial thickening (IMT), considered an indirect measure of cardiovascular disease (CVD), was evaluated by B-mode ultrasound in 90 adolescents with type 1 diabetes (mean age 16.6 years) with 16 of their healthy siblings (mean age 16.7 years). Overall, IMT was significantly greater among the diabetic group than the controls (0.564 mm vs. 0.54 mm), she reported.

There were no differences between the two groups in body mass index, blood pressure, gender, or family history of diabetes/CVD. None of the controls smoked, while six of the diabetics (all male) were smokers; the difference was not statistically significant.

The two groups also did not differ by conventional risk factors such as cholesterol, triglycerides, or microalbumin/creatinine ratio, or by nontraditional risk factors such as fibrinogen, von Willebrand factor antigen, plasminogen activator inhibitor-1, or IL-6.

When broken down by gender, significant differences in IMT between diabetic and control subjects were only seen among the males (0.582 mm vs. 0.524 mm), and not the females (0.548 mm vs. 0.556 mm).

Among the males with diabetes, IMT was significantly correlated with HbA_1c and tobacco exposure, as well as with total cholesterol and apolipoprotein B. Among the female diabetics, IMT was correlated positively with a family history of CVD and negatively correlated with HDL cholesterol.

The findings suggest that conventional CVD risk factors result in increased IMT, and probably cause the initial endothelial dysfunction in these young people. The subsequent loss of normal endothelial homeostatic properties would eventually lead to a “proinflammatory, proadhesive, and procoagulant endothelial surface that is not yet present in our cohort. Early treatment of modifiable risk factors could avert the chronic inflammatory process which, if unabated, will result in the advanced chronic plaque formation,” she said.

One-fifth of the U.S. population aged 40 years and older has lower extremity disease, the Centers for Disease Control and Prevention reported.

In the 1999–2002 National Health and Nutrition Examination Survey, about 5% of adults aged 40 and above had peripheral arterial disease (PAD), 13% had peripheral insensate neuropathy (PN), and 4% reported a foot ulcer or were observed to have a current foot lesion or toe/foot amputation. Overall, 18.6% had one or more of these lower extremity disease (LED) conditions, the CDC said (MMWR 2005;54:1158–60).

The majority of these cases—including two-thirds of those with PAD and three fourths with PN—were asymptomatic. About one-fourth of the cases of both conditions were severe, defined as an ankle-brachial blood pressure index of less than 0.7 in either leg with PAD, or three or more insensate areas with PN.

The prevalence of LED was about twice as high in people diagnosed with diabetes as in those without, and 53% of the diabetics were symptomatic, compared with 31% of nondiabetics. Among individuals with PN, 42% of the diabetics were symptomatic versus 21% of nondiabetics, whereas one-third of the PAD group was symptomatic regardless of diabetes status.

Not surprisingly, the prevalence of LED increased with age, from 12.3% among those aged 40–59 years to 26.2% of 60- to 74-year-olds, to 40.8% of those aged 75 and older.

The conditions also were more common overall in men than in women (23% vs. 17%) and were higher among blacks (27%) than either whites (19%) or Mexican Americans (21%).

Diabetics had higher LEDrates than nondiabetics in all age, sex, and racial/ethnic groups, the CDC noted.

In 2003, the American Diabetes Association issued guidelines for the diagnosis and management of PAD, including a recommendation that an ankle-brachial index be obtained in all diabetic patients over age 50 (Diabetes Care 2003;26:3333–41).

One-fifth of the U.S. population aged 40 years and older has lower extremity disease, the Centers for Disease Control and Prevention reported.

In the 1999–2002 National Health and Nutrition Examination Survey, about 5% of adults aged 40 and above had peripheral arterial disease (PAD), 13% had peripheral insensate neuropathy (PN), and 4% reported a foot ulcer or were observed to have a current foot lesion or toe/foot amputation. Overall, 18.6% had one or more of these lower extremity disease (LED) conditions, the CDC said (MMWR 2005;54:1158–60).

The majority of these cases—including two-thirds of those with PAD and three fourths with PN—were asymptomatic. About one-fourth of the cases of both conditions were severe, defined as an ankle-brachial blood pressure index of less than 0.7 in either leg with PAD, or three or more insensate areas with PN.

The prevalence of LED was about twice as high in people diagnosed with diabetes as in those without, and 53% of the diabetics were symptomatic, compared with 31% of nondiabetics. Among individuals with PN, 42% of the diabetics were symptomatic versus 21% of nondiabetics, whereas one-third of the PAD group was symptomatic regardless of diabetes status.

Not surprisingly, the prevalence of LED increased with age, from 12.3% among those aged 40–59 years to 26.2% of 60- to 74-year-olds, to 40.8% of those aged 75 and older.

The conditions also were more common overall in men than in women (23% vs. 17%) and were higher among blacks (27%) than either whites (19%) or Mexican Americans (21%).

Diabetics had higher LEDrates than nondiabetics in all age, sex, and racial/ethnic groups, the CDC noted.

In 2003, the American Diabetes Association issued guidelines for the diagnosis and management of PAD, including a recommendation that an ankle-brachial index be obtained in all diabetic patients over age 50 (Diabetes Care 2003;26:3333–41).

One-fifth of the U.S. population aged 40 years and older has lower extremity disease, the Centers for Disease Control and Prevention reported.

In the 1999–2002 National Health and Nutrition Examination Survey, about 5% of adults aged 40 and above had peripheral arterial disease (PAD), 13% had peripheral insensate neuropathy (PN), and 4% reported a foot ulcer or were observed to have a current foot lesion or toe/foot amputation. Overall, 18.6% had one or more of these lower extremity disease (LED) conditions, the CDC said (MMWR 2005;54:1158–60).

The majority of these cases—including two-thirds of those with PAD and three fourths with PN—were asymptomatic. About one-fourth of the cases of both conditions were severe, defined as an ankle-brachial blood pressure index of less than 0.7 in either leg with PAD, or three or more insensate areas with PN.

The prevalence of LED was about twice as high in people diagnosed with diabetes as in those without, and 53% of the diabetics were symptomatic, compared with 31% of nondiabetics. Among individuals with PN, 42% of the diabetics were symptomatic versus 21% of nondiabetics, whereas one-third of the PAD group was symptomatic regardless of diabetes status.

Not surprisingly, the prevalence of LED increased with age, from 12.3% among those aged 40–59 years to 26.2% of 60- to 74-year-olds, to 40.8% of those aged 75 and older.

The conditions also were more common overall in men than in women (23% vs. 17%) and were higher among blacks (27%) than either whites (19%) or Mexican Americans (21%).

Diabetics had higher LEDrates than nondiabetics in all age, sex, and racial/ethnic groups, the CDC noted.

In 2003, the American Diabetes Association issued guidelines for the diagnosis and management of PAD, including a recommendation that an ankle-brachial index be obtained in all diabetic patients over age 50 (Diabetes Care 2003;26:3333–41).

The diagnosis of Clostridium difficile-associated disease should be considered in patients with severe diarrhea, even if they don't have traditional risk factors such as recent hospitalization or antimicrobial use, the Centers for Disease Control and Prevention advised.

During May and June 2005, a total of 10 peripartum and 23 C. difficile-associated disease (CDAD) cases from previously healthy individuals in the community were voluntarily reported from four U.S. states following a request from the CDC. The findings suggest that the epidemiology of the disease might be changing to include features that have been uncommon in the past, such as close-contact transmission, high recurrence rate, young patient age, bloody diarrhea, and lack of antimicrobial exposure, the CDC warned (MMWR 2005;54:1201–5).

All but 1 of the 33 cases occurred during 2004–2005. Hospitalization was required for 15 (46%), and relapses occurred in 13 (39%). Transmission to close contacts was evident in four cases. Eight of the 33 patients (24%)—including 5 children—reported no exposure to antimicrobial agents within 3 months prior to CDAD onset. Of those eight, two reported close contact with a person who had diarrheal illness.

Clindamycin was the most common antimicrobial exposure noted prior to CDAD, representing 10 (33%) of the 33 cases. These included two patients who had taken just one dose for group B streptococcal prophylaxis before CDAD onset.

Among the cases was a 31-year-old woman who was 14 weeks pregnant with twins whose only antimicrobial exposure during the previous year had been trimethoprim-sulfamethoxazole for a urinary tract infection 3 months before she developed severe diarrhea. Despite treatment with metronidazole, cholestyramine, and oral vancomycin, she spontaneously aborted her fetuses and died 3 days later, even after receiving subtotal colectomy, intubation, and inotropic medication.

Another case was a 10-year-old girl who had not taken antimicrobials in the previous year. She had been completely healthy until 2 weeks before developing intractable diarrhea, projectile vomiting, and abdominal pain. Her symptoms eventually resolved after she received intravenous fluids, electrolytes, and metronidazole in the hospital.

The diagnosis of Clostridium difficile-associated disease should be considered in patients with severe diarrhea, even if they don't have traditional risk factors such as recent hospitalization or antimicrobial use, the Centers for Disease Control and Prevention advised.

During May and June 2005, a total of 10 peripartum and 23 C. difficile-associated disease (CDAD) cases from previously healthy individuals in the community were voluntarily reported from four U.S. states following a request from the CDC. The findings suggest that the epidemiology of the disease might be changing to include features that have been uncommon in the past, such as close-contact transmission, high recurrence rate, young patient age, bloody diarrhea, and lack of antimicrobial exposure, the CDC warned (MMWR 2005;54:1201–5).

All but 1 of the 33 cases occurred during 2004–2005. Hospitalization was required for 15 (46%), and relapses occurred in 13 (39%). Transmission to close contacts was evident in four cases. Eight of the 33 patients (24%)—including 5 children—reported no exposure to antimicrobial agents within 3 months prior to CDAD onset. Of those eight, two reported close contact with a person who had diarrheal illness.

Clindamycin was the most common antimicrobial exposure noted prior to CDAD, representing 10 (33%) of the 33 cases. These included two patients who had taken just one dose for group B streptococcal prophylaxis before CDAD onset.

Among the cases was a 31-year-old woman who was 14 weeks pregnant with twins whose only antimicrobial exposure during the previous year had been trimethoprim-sulfamethoxazole for a urinary tract infection 3 months before she developed severe diarrhea. Despite treatment with metronidazole, cholestyramine, and oral vancomycin, she spontaneously aborted her fetuses and died 3 days later, even after receiving subtotal colectomy, intubation, and inotropic medication.

Another case was a 10-year-old girl who had not taken antimicrobials in the previous year. She had been completely healthy until 2 weeks before developing intractable diarrhea, projectile vomiting, and abdominal pain. Her symptoms eventually resolved after she received intravenous fluids, electrolytes, and metronidazole in the hospital.

The diagnosis of Clostridium difficile-associated disease should be considered in patients with severe diarrhea, even if they don't have traditional risk factors such as recent hospitalization or antimicrobial use, the Centers for Disease Control and Prevention advised.

During May and June 2005, a total of 10 peripartum and 23 C. difficile-associated disease (CDAD) cases from previously healthy individuals in the community were voluntarily reported from four U.S. states following a request from the CDC. The findings suggest that the epidemiology of the disease might be changing to include features that have been uncommon in the past, such as close-contact transmission, high recurrence rate, young patient age, bloody diarrhea, and lack of antimicrobial exposure, the CDC warned (MMWR 2005;54:1201–5).

All but 1 of the 33 cases occurred during 2004–2005. Hospitalization was required for 15 (46%), and relapses occurred in 13 (39%). Transmission to close contacts was evident in four cases. Eight of the 33 patients (24%)—including 5 children—reported no exposure to antimicrobial agents within 3 months prior to CDAD onset. Of those eight, two reported close contact with a person who had diarrheal illness.

Clindamycin was the most common antimicrobial exposure noted prior to CDAD, representing 10 (33%) of the 33 cases. These included two patients who had taken just one dose for group B streptococcal prophylaxis before CDAD onset.

Among the cases was a 31-year-old woman who was 14 weeks pregnant with twins whose only antimicrobial exposure during the previous year had been trimethoprim-sulfamethoxazole for a urinary tract infection 3 months before she developed severe diarrhea. Despite treatment with metronidazole, cholestyramine, and oral vancomycin, she spontaneously aborted her fetuses and died 3 days later, even after receiving subtotal colectomy, intubation, and inotropic medication.

Another case was a 10-year-old girl who had not taken antimicrobials in the previous year. She had been completely healthy until 2 weeks before developing intractable diarrhea, projectile vomiting, and abdominal pain. Her symptoms eventually resolved after she received intravenous fluids, electrolytes, and metronidazole in the hospital.

Fluoroquinolone use may be driving the emergence of newer and more virulent strains of Clostridium difficile, Dr. John G. Bartlett and Dr. Trish M. Perl said in an editorial accompanying two simultaneous reports in the New England Journal of Medicine.

“Particularly important is antibiotic stewardship with restraint in the use of epidemiologically implicated antimicrobial agents, usually second- and third-generation cephalosporins, clindamycin, or fluoroquinolones, or a combination of the three,” said Dr. Bartlett and Dr. Perl of Johns Hopkins University, Baltimore (N. Engl. J. Med. 2005;353:2503–5).

Several recent studies have documented a rise in the number and severity of C. difficile-associated disease cases in the United States and elsewhere. Now two new reports of detailed microbial analysis suggest that a more virulent strain of C. difficile is causing epidemic disease at selected locations and is associated with more frequent and more severe disease.

In one study, 187 isolates were collected from eight health care facilities in six states in which outbreaks of C. difficile-associated enteric disease had occurred between 2000 and 2003. In five of the facilities (two located in Maine and one each in Georgia, New Jersey, and Pennsylvania), one particular epidemic strain accounted for 50% or more of the isolates.

Among 29 of those isolates selected for further genetic testing, 25 were related by 90% or more, and all were more than 80% related. In contrast, very few of the other strains were more than 80% related, Dr. L. Clifford McDonald of the Centers for Disease Control and Prevention, Atlanta, and associates reported (N. Engl. J. Med. 2005;353:2433–41).

All 24 of the epidemic strain isolates that were tested for susceptibility were resistant to levofloxacin, gatifloxacin, and moxifloxacin, while 19 of the 24 (79%) were also resistant to clindamycin. In contrast, among 24 other C. difficile strains, 23 (96%) were resistant to levofloxacin, 19 (79%) to clindamycin, and just 10 each (42%) to gatifloxacin and moxifloxacin.

Even though resistance to clindamycin and levofloxacin was common among all the strains, the minimum inhibitory concentrations were higher for those of the epidemic strain. “The increasing use of fluoroquinolones in U.S. health care facilities may have provided a selective advantage for this epidemic strain and promoted its widespread emergence,” said Dr. McDonald and associates.

In the other study, Dr. Vivian G. Loo of McGill University and associates prospectively identified a total of 1,703 patients with 1,719 episodes that met the case definition for nosocomial C. difficile-associated diarrhea at 12 Canadian hospitals from January to June of 2004. The overall incidence was 23 per 1,000 admissions, a rate nearly four times greater than the 6/1,000 found in a 1997 survey of 18 Canadian institutions.

Among the 422 patients who died within 30 days of diagnosis of C. difficile-associated diarrhea, the disease was attributed to be the cause of death in 117, or 6.9% of the total 1,703 patients. In contrast, the attributable mortality rate was just 1.5% in the 1997 survey, Dr. Loo and her associates noted (N. Engl. J. Med. 2005;353:2442–9).

A total of 237 patients were compared with 237 hospitalized patients who did not have C. difficile-associated diarrhea, matched for age, sex, and Charlson (comorbidity) index. The case patients were significantly more likely than controls to have been exposed to antibiotics (79% vs. 60%) and enteral feeding (19% vs. 12%). Exposure to fluoroquinolones was a significant independent risk factor for C. difficile-associated diarrhea (odds ratio 3.9), as was cephalosporin exposure (OR 3.8).

Results of pulsed-gel electrophoresis in 157 of the isolates indicated that 82% had an identical pattern, known as a “pulsovar,” that was universally resistant to fluoroquinolones. Of those 129 patients, 16% had severe C. difficile-associated diarrhea, compared with just 7% of 28 patients whose isolates had other pulsovars.

Polymerase chain reaction revealed that 84% of the 157 isolates possessed genes encoding for two major toxins associated with C. difficile virulence, as well as a partial deletion of a gene that downregulates those toxin genes. Among those 132 patients, 17% had severe C. difficile-associated diarrhea, compared with 0 of the 25 patients who had none of those genes.

In addition to more judicious antimicrobial use, control of C. difficile-associated disease also hinges on better recognition of cases and optimal disease management, Dr. Bartlett and Dr. Perl said.

Fluoroquinolone use may be driving the emergence of newer and more virulent strains of Clostridium difficile, Dr. John G. Bartlett and Dr. Trish M. Perl said in an editorial accompanying two simultaneous reports in the New England Journal of Medicine.

“Particularly important is antibiotic stewardship with restraint in the use of epidemiologically implicated antimicrobial agents, usually second- and third-generation cephalosporins, clindamycin, or fluoroquinolones, or a combination of the three,” said Dr. Bartlett and Dr. Perl of Johns Hopkins University, Baltimore (N. Engl. J. Med. 2005;353:2503–5).

Several recent studies have documented a rise in the number and severity of C. difficile-associated disease cases in the United States and elsewhere. Now two new reports of detailed microbial analysis suggest that a more virulent strain of C. difficile is causing epidemic disease at selected locations and is associated with more frequent and more severe disease.

In one study, 187 isolates were collected from eight health care facilities in six states in which outbreaks of C. difficile-associated enteric disease had occurred between 2000 and 2003. In five of the facilities (two located in Maine and one each in Georgia, New Jersey, and Pennsylvania), one particular epidemic strain accounted for 50% or more of the isolates.

Among 29 of those isolates selected for further genetic testing, 25 were related by 90% or more, and all were more than 80% related. In contrast, very few of the other strains were more than 80% related, Dr. L. Clifford McDonald of the Centers for Disease Control and Prevention, Atlanta, and associates reported (N. Engl. J. Med. 2005;353:2433–41).

All 24 of the epidemic strain isolates that were tested for susceptibility were resistant to levofloxacin, gatifloxacin, and moxifloxacin, while 19 of the 24 (79%) were also resistant to clindamycin. In contrast, among 24 other C. difficile strains, 23 (96%) were resistant to levofloxacin, 19 (79%) to clindamycin, and just 10 each (42%) to gatifloxacin and moxifloxacin.

Even though resistance to clindamycin and levofloxacin was common among all the strains, the minimum inhibitory concentrations were higher for those of the epidemic strain. “The increasing use of fluoroquinolones in U.S. health care facilities may have provided a selective advantage for this epidemic strain and promoted its widespread emergence,” said Dr. McDonald and associates.

In the other study, Dr. Vivian G. Loo of McGill University and associates prospectively identified a total of 1,703 patients with 1,719 episodes that met the case definition for nosocomial C. difficile-associated diarrhea at 12 Canadian hospitals from January to June of 2004. The overall incidence was 23 per 1,000 admissions, a rate nearly four times greater than the 6/1,000 found in a 1997 survey of 18 Canadian institutions.

Among the 422 patients who died within 30 days of diagnosis of C. difficile-associated diarrhea, the disease was attributed to be the cause of death in 117, or 6.9% of the total 1,703 patients. In contrast, the attributable mortality rate was just 1.5% in the 1997 survey, Dr. Loo and her associates noted (N. Engl. J. Med. 2005;353:2442–9).

A total of 237 patients were compared with 237 hospitalized patients who did not have C. difficile-associated diarrhea, matched for age, sex, and Charlson (comorbidity) index. The case patients were significantly more likely than controls to have been exposed to antibiotics (79% vs. 60%) and enteral feeding (19% vs. 12%). Exposure to fluoroquinolones was a significant independent risk factor for C. difficile-associated diarrhea (odds ratio 3.9), as was cephalosporin exposure (OR 3.8).

Results of pulsed-gel electrophoresis in 157 of the isolates indicated that 82% had an identical pattern, known as a “pulsovar,” that was universally resistant to fluoroquinolones. Of those 129 patients, 16% had severe C. difficile-associated diarrhea, compared with just 7% of 28 patients whose isolates had other pulsovars.

Polymerase chain reaction revealed that 84% of the 157 isolates possessed genes encoding for two major toxins associated with C. difficile virulence, as well as a partial deletion of a gene that downregulates those toxin genes. Among those 132 patients, 17% had severe C. difficile-associated diarrhea, compared with 0 of the 25 patients who had none of those genes.

In addition to more judicious antimicrobial use, control of C. difficile-associated disease also hinges on better recognition of cases and optimal disease management, Dr. Bartlett and Dr. Perl said.

Fluoroquinolone use may be driving the emergence of newer and more virulent strains of Clostridium difficile, Dr. John G. Bartlett and Dr. Trish M. Perl said in an editorial accompanying two simultaneous reports in the New England Journal of Medicine.

“Particularly important is antibiotic stewardship with restraint in the use of epidemiologically implicated antimicrobial agents, usually second- and third-generation cephalosporins, clindamycin, or fluoroquinolones, or a combination of the three,” said Dr. Bartlett and Dr. Perl of Johns Hopkins University, Baltimore (N. Engl. J. Med. 2005;353:2503–5).

Several recent studies have documented a rise in the number and severity of C. difficile-associated disease cases in the United States and elsewhere. Now two new reports of detailed microbial analysis suggest that a more virulent strain of C. difficile is causing epidemic disease at selected locations and is associated with more frequent and more severe disease.

In one study, 187 isolates were collected from eight health care facilities in six states in which outbreaks of C. difficile-associated enteric disease had occurred between 2000 and 2003. In five of the facilities (two located in Maine and one each in Georgia, New Jersey, and Pennsylvania), one particular epidemic strain accounted for 50% or more of the isolates.

Among 29 of those isolates selected for further genetic testing, 25 were related by 90% or more, and all were more than 80% related. In contrast, very few of the other strains were more than 80% related, Dr. L. Clifford McDonald of the Centers for Disease Control and Prevention, Atlanta, and associates reported (N. Engl. J. Med. 2005;353:2433–41).

All 24 of the epidemic strain isolates that were tested for susceptibility were resistant to levofloxacin, gatifloxacin, and moxifloxacin, while 19 of the 24 (79%) were also resistant to clindamycin. In contrast, among 24 other C. difficile strains, 23 (96%) were resistant to levofloxacin, 19 (79%) to clindamycin, and just 10 each (42%) to gatifloxacin and moxifloxacin.

Even though resistance to clindamycin and levofloxacin was common among all the strains, the minimum inhibitory concentrations were higher for those of the epidemic strain. “The increasing use of fluoroquinolones in U.S. health care facilities may have provided a selective advantage for this epidemic strain and promoted its widespread emergence,” said Dr. McDonald and associates.

In the other study, Dr. Vivian G. Loo of McGill University and associates prospectively identified a total of 1,703 patients with 1,719 episodes that met the case definition for nosocomial C. difficile-associated diarrhea at 12 Canadian hospitals from January to June of 2004. The overall incidence was 23 per 1,000 admissions, a rate nearly four times greater than the 6/1,000 found in a 1997 survey of 18 Canadian institutions.

Among the 422 patients who died within 30 days of diagnosis of C. difficile-associated diarrhea, the disease was attributed to be the cause of death in 117, or 6.9% of the total 1,703 patients. In contrast, the attributable mortality rate was just 1.5% in the 1997 survey, Dr. Loo and her associates noted (N. Engl. J. Med. 2005;353:2442–9).

A total of 237 patients were compared with 237 hospitalized patients who did not have C. difficile-associated diarrhea, matched for age, sex, and Charlson (comorbidity) index. The case patients were significantly more likely than controls to have been exposed to antibiotics (79% vs. 60%) and enteral feeding (19% vs. 12%). Exposure to fluoroquinolones was a significant independent risk factor for C. difficile-associated diarrhea (odds ratio 3.9), as was cephalosporin exposure (OR 3.8).

Results of pulsed-gel electrophoresis in 157 of the isolates indicated that 82% had an identical pattern, known as a “pulsovar,” that was universally resistant to fluoroquinolones. Of those 129 patients, 16% had severe C. difficile-associated diarrhea, compared with just 7% of 28 patients whose isolates had other pulsovars.

Polymerase chain reaction revealed that 84% of the 157 isolates possessed genes encoding for two major toxins associated with C. difficile virulence, as well as a partial deletion of a gene that downregulates those toxin genes. Among those 132 patients, 17% had severe C. difficile-associated diarrhea, compared with 0 of the 25 patients who had none of those genes.

In addition to more judicious antimicrobial use, control of C. difficile-associated disease also hinges on better recognition of cases and optimal disease management, Dr. Bartlett and Dr. Perl said.

WASHINGTON — Perioperative statin use may significantly reduce the incidence of cerebrovascular events and mortality in patients undergoing carotid endarterectomy, Bruce A. Perler, M.D., reported at a conference for science reporters sponsored by the American Medical Association.

Dr. Perler and his associates conducted a retrospective analysis of 1,566 patients who underwent carotid endarterectomy (CEA) between 1994 and 2004 at Johns Hopkins Hospital. Those who had been taking a statin for at least 1 week prior to the procedure had a threefold reduction in stroke and fivefold reduction in death in the subsequent 30 days, compared with those not on a perioperative statin. The effects were independent of other risk factors, and both were highly significant. “The results were quite remarkable to us, really eye-opening,” Dr. Perler, professor and chief of vascular surgery at Johns Hopkins University, Baltimore.

“Because this was a retrospective study and not designed to establish clinical practice, I can't make a blanket statement … that everybody ought to be on a statin before they have a carotid endarterectomy. But one can certainly speculate that it's a reasonable thing to do,” Dr. Perler said.

Results of the study, which was not industry funded, were published in November (J. Vasc. Surg. 2005;42:829–36).

Of the 1,566 patients, 92% underwent solitary CEA; the other 8% had simultaneous coronary artery bypass grafting (CABG). Mean age was 72 years, and 63% were male. Indications for CEA were symptomatic disease in 42% (14% with a history of stroke and 28% with transient ischemic attacks) and asymptomatic stenosis in 58%.

Forty-two percent of the patients had been using statins for at least 1 week prior to the procedure. The most commonly used statins were atorvastatin (51%) and simvastatin (29%), both at a mean dose of 20 mg/day. Although the duration of statin therapy was unknown, most of the patients had been taking them for quite a bit longer, Dr. Perler noted.

At 30 days after CEA, the incidence of stroke among the 657 statin users was 1.2%, compared with 4.5% of the 909 not on statins. Mortality among patients on statins was 0.3% versus 2.1% in patients not taking the agent. Perioperative MIs were also less frequent among the statin users (1.2% vs. 2.1%), a nonsignificant difference. Although overall statin use increased with time over the 10-year period, differences between statin users and nonusers remained significant throughout, he said.

After adjustment for all comorbidities found to be associated with stroke (symptomatic carotid disease, chronic atrial fibrillation, hyperlipidemia, use of intraluminal shunt and patch grafting, and combined CEA/CABG), statin use remained associated with a threefold reduction in the 30-day risk for stroke (odds ratio 0.29).

Although this study is the first ever to investigate the impact of statin use on CEA outcome, there have been several previous clinical trials supporting the use of statin therapy to reduce complications after other vascular procedures, including CABG (Circulation 2000;110[suppl. 2]:1145–9 and Am. J. Cardiol. 2000;86:1128–30).

The fact that statins reduce the risk of stroke in individuals with both normal and elevated cholesterol levels—and that no similar effect has been seen with nonstatin cholesterol-lowering agents—suggests the mechanism is related to the statins' non-lipid-mediated actions. These include stabilization of atherosclerotic plaques and improvement of endothelial function, along with antithrombotic, anti-inflammatory, and antioxidant effects.

Given their plaque-stabilizing potential, it would be reasonable to assume statins would have a similar protective effect as adjunctive therapy for patients undergoing carotid angioplasty and stenting, as well. “It certainly ought to be considered—although that's pure speculation, because our study didn't address that,” Dr. Perler said in response to a reporter's question.

But what this study does point to, he noted, is a potential way to enhance the safety of CEA, the most commonly performed of all noncardiac vascular procedures. Although still considered the “gold standard” for treating occlusive carotid disease, that status is now being challenged by data suggesting that the minimally invasive alternative of carotid stenting is not inferior with regard to outcomes (N. Engl. J. Med. 2004;351:1493–501).

WASHINGTON — Perioperative statin use may significantly reduce the incidence of cerebrovascular events and mortality in patients undergoing carotid endarterectomy, Bruce A. Perler, M.D., reported at a conference for science reporters sponsored by the American Medical Association.

Dr. Perler and his associates conducted a retrospective analysis of 1,566 patients who underwent carotid endarterectomy (CEA) between 1994 and 2004 at Johns Hopkins Hospital. Those who had been taking a statin for at least 1 week prior to the procedure had a threefold reduction in stroke and fivefold reduction in death in the subsequent 30 days, compared with those not on a perioperative statin. The effects were independent of other risk factors, and both were highly significant. “The results were quite remarkable to us, really eye-opening,” Dr. Perler, professor and chief of vascular surgery at Johns Hopkins University, Baltimore.

“Because this was a retrospective study and not designed to establish clinical practice, I can't make a blanket statement … that everybody ought to be on a statin before they have a carotid endarterectomy. But one can certainly speculate that it's a reasonable thing to do,” Dr. Perler said.

Results of the study, which was not industry funded, were published in November (J. Vasc. Surg. 2005;42:829–36).

Of the 1,566 patients, 92% underwent solitary CEA; the other 8% had simultaneous coronary artery bypass grafting (CABG). Mean age was 72 years, and 63% were male. Indications for CEA were symptomatic disease in 42% (14% with a history of stroke and 28% with transient ischemic attacks) and asymptomatic stenosis in 58%.

Forty-two percent of the patients had been using statins for at least 1 week prior to the procedure. The most commonly used statins were atorvastatin (51%) and simvastatin (29%), both at a mean dose of 20 mg/day. Although the duration of statin therapy was unknown, most of the patients had been taking them for quite a bit longer, Dr. Perler noted.

At 30 days after CEA, the incidence of stroke among the 657 statin users was 1.2%, compared with 4.5% of the 909 not on statins. Mortality among patients on statins was 0.3% versus 2.1% in patients not taking the agent. Perioperative MIs were also less frequent among the statin users (1.2% vs. 2.1%), a nonsignificant difference. Although overall statin use increased with time over the 10-year period, differences between statin users and nonusers remained significant throughout, he said.

After adjustment for all comorbidities found to be associated with stroke (symptomatic carotid disease, chronic atrial fibrillation, hyperlipidemia, use of intraluminal shunt and patch grafting, and combined CEA/CABG), statin use remained associated with a threefold reduction in the 30-day risk for stroke (odds ratio 0.29).

Although this study is the first ever to investigate the impact of statin use on CEA outcome, there have been several previous clinical trials supporting the use of statin therapy to reduce complications after other vascular procedures, including CABG (Circulation 2000;110[suppl. 2]:1145–9 and Am. J. Cardiol. 2000;86:1128–30).

The fact that statins reduce the risk of stroke in individuals with both normal and elevated cholesterol levels—and that no similar effect has been seen with nonstatin cholesterol-lowering agents—suggests the mechanism is related to the statins' non-lipid-mediated actions. These include stabilization of atherosclerotic plaques and improvement of endothelial function, along with antithrombotic, anti-inflammatory, and antioxidant effects.

Given their plaque-stabilizing potential, it would be reasonable to assume statins would have a similar protective effect as adjunctive therapy for patients undergoing carotid angioplasty and stenting, as well. “It certainly ought to be considered—although that's pure speculation, because our study didn't address that,” Dr. Perler said in response to a reporter's question.

But what this study does point to, he noted, is a potential way to enhance the safety of CEA, the most commonly performed of all noncardiac vascular procedures. Although still considered the “gold standard” for treating occlusive carotid disease, that status is now being challenged by data suggesting that the minimally invasive alternative of carotid stenting is not inferior with regard to outcomes (N. Engl. J. Med. 2004;351:1493–501).

WASHINGTON — Perioperative statin use may significantly reduce the incidence of cerebrovascular events and mortality in patients undergoing carotid endarterectomy, Bruce A. Perler, M.D., reported at a conference for science reporters sponsored by the American Medical Association.

Dr. Perler and his associates conducted a retrospective analysis of 1,566 patients who underwent carotid endarterectomy (CEA) between 1994 and 2004 at Johns Hopkins Hospital. Those who had been taking a statin for at least 1 week prior to the procedure had a threefold reduction in stroke and fivefold reduction in death in the subsequent 30 days, compared with those not on a perioperative statin. The effects were independent of other risk factors, and both were highly significant. “The results were quite remarkable to us, really eye-opening,” Dr. Perler, professor and chief of vascular surgery at Johns Hopkins University, Baltimore.

“Because this was a retrospective study and not designed to establish clinical practice, I can't make a blanket statement … that everybody ought to be on a statin before they have a carotid endarterectomy. But one can certainly speculate that it's a reasonable thing to do,” Dr. Perler said.

Results of the study, which was not industry funded, were published in November (J. Vasc. Surg. 2005;42:829–36).

Of the 1,566 patients, 92% underwent solitary CEA; the other 8% had simultaneous coronary artery bypass grafting (CABG). Mean age was 72 years, and 63% were male. Indications for CEA were symptomatic disease in 42% (14% with a history of stroke and 28% with transient ischemic attacks) and asymptomatic stenosis in 58%.

Forty-two percent of the patients had been using statins for at least 1 week prior to the procedure. The most commonly used statins were atorvastatin (51%) and simvastatin (29%), both at a mean dose of 20 mg/day. Although the duration of statin therapy was unknown, most of the patients had been taking them for quite a bit longer, Dr. Perler noted.

At 30 days after CEA, the incidence of stroke among the 657 statin users was 1.2%, compared with 4.5% of the 909 not on statins. Mortality among patients on statins was 0.3% versus 2.1% in patients not taking the agent. Perioperative MIs were also less frequent among the statin users (1.2% vs. 2.1%), a nonsignificant difference. Although overall statin use increased with time over the 10-year period, differences between statin users and nonusers remained significant throughout, he said.

After adjustment for all comorbidities found to be associated with stroke (symptomatic carotid disease, chronic atrial fibrillation, hyperlipidemia, use of intraluminal shunt and patch grafting, and combined CEA/CABG), statin use remained associated with a threefold reduction in the 30-day risk for stroke (odds ratio 0.29).

Although this study is the first ever to investigate the impact of statin use on CEA outcome, there have been several previous clinical trials supporting the use of statin therapy to reduce complications after other vascular procedures, including CABG (Circulation 2000;110[suppl. 2]:1145–9 and Am. J. Cardiol. 2000;86:1128–30).

The fact that statins reduce the risk of stroke in individuals with both normal and elevated cholesterol levels—and that no similar effect has been seen with nonstatin cholesterol-lowering agents—suggests the mechanism is related to the statins' non-lipid-mediated actions. These include stabilization of atherosclerotic plaques and improvement of endothelial function, along with antithrombotic, anti-inflammatory, and antioxidant effects.

Given their plaque-stabilizing potential, it would be reasonable to assume statins would have a similar protective effect as adjunctive therapy for patients undergoing carotid angioplasty and stenting, as well. “It certainly ought to be considered—although that's pure speculation, because our study didn't address that,” Dr. Perler said in response to a reporter's question.

But what this study does point to, he noted, is a potential way to enhance the safety of CEA, the most commonly performed of all noncardiac vascular procedures. Although still considered the “gold standard” for treating occlusive carotid disease, that status is now being challenged by data suggesting that the minimally invasive alternative of carotid stenting is not inferior with regard to outcomes (N. Engl. J. Med. 2004;351:1493–501).

The diagnosis of Clostridium difficile-associated disease should be considered in patients with severe diarrhea, even if they don't have traditional risk factors such as recent hospitalization or antimicrobial use, the Centers for Disease Control and Prevention advised.

During May and June 2005, a total of 10 peripartum and 23 C. difficile-associated disease (CDAD) cases from previously healthy individuals in the community were voluntarily reported from four U.S. states following a request from the CDC.

The findings suggest that the epidemiology of the disease might be changing to include features that have been uncommon in the past, such as close-contact transmission, high recurrence rate, young patient age, bloody diarrhea, and lack of antimicrobial exposure, the CDC warned (MMWR 2005;54:1201–5).

All but 1 of the 33 cases occurred during 2004–2005. Hospitalization was required for 15 (46%), and relapses occurred in 13 (39%). Transmission to close contacts was evident in four cases. Eight of the 33 patients (24%)—including 5 children—reported no exposure to antimicrobial agents within 3 months prior to CDAD onset. Of those eight, two reported close contact with a person who had diarrheal illness.

Clindamycin was the most common antimicrobial exposure noted prior to onset of CDAD, representing 10 (33%) of the 33 cases. These included two patients who had taken just one dose for group B streptococcal prophylaxis before CDAD onset, the CDC noted.

Among the cases was a 31-year-old woman who was 14 weeks pregnant with twins whose only antimicrobial exposure during the previous year had been trimethoprim-sulfamethoxazole for a urinary tract infection 3 months before she developed severe diarrhea. Despite treatment with metronidazole, cholestyramine, and oral vancomycin, she spontaneously aborted her fetuses and died 3 days later.

Another case was a 10-year-old girl who had not taken antimicrobials in the previous year. She had been completely healthy until 2 weeks before developing intractable diarrhea, projectile vomiting, and abdominal pain. Her brother also had a febrile diarrheal illness but recovered within 2–3 days without treatment. The girl's symptoms eventually resolved after she received intravenous fluids, electrolytes, and metronidazole in the hospital.

The diagnosis of Clostridium difficile-associated disease should be considered in patients with severe diarrhea, even if they don't have traditional risk factors such as recent hospitalization or antimicrobial use, the Centers for Disease Control and Prevention advised.

During May and June 2005, a total of 10 peripartum and 23 C. difficile-associated disease (CDAD) cases from previously healthy individuals in the community were voluntarily reported from four U.S. states following a request from the CDC.

The findings suggest that the epidemiology of the disease might be changing to include features that have been uncommon in the past, such as close-contact transmission, high recurrence rate, young patient age, bloody diarrhea, and lack of antimicrobial exposure, the CDC warned (MMWR 2005;54:1201–5).

All but 1 of the 33 cases occurred during 2004–2005. Hospitalization was required for 15 (46%), and relapses occurred in 13 (39%). Transmission to close contacts was evident in four cases. Eight of the 33 patients (24%)—including 5 children—reported no exposure to antimicrobial agents within 3 months prior to CDAD onset. Of those eight, two reported close contact with a person who had diarrheal illness.

Clindamycin was the most common antimicrobial exposure noted prior to onset of CDAD, representing 10 (33%) of the 33 cases. These included two patients who had taken just one dose for group B streptococcal prophylaxis before CDAD onset, the CDC noted.

Among the cases was a 31-year-old woman who was 14 weeks pregnant with twins whose only antimicrobial exposure during the previous year had been trimethoprim-sulfamethoxazole for a urinary tract infection 3 months before she developed severe diarrhea. Despite treatment with metronidazole, cholestyramine, and oral vancomycin, she spontaneously aborted her fetuses and died 3 days later.

Another case was a 10-year-old girl who had not taken antimicrobials in the previous year. She had been completely healthy until 2 weeks before developing intractable diarrhea, projectile vomiting, and abdominal pain. Her brother also had a febrile diarrheal illness but recovered within 2–3 days without treatment. The girl's symptoms eventually resolved after she received intravenous fluids, electrolytes, and metronidazole in the hospital.

The diagnosis of Clostridium difficile-associated disease should be considered in patients with severe diarrhea, even if they don't have traditional risk factors such as recent hospitalization or antimicrobial use, the Centers for Disease Control and Prevention advised.

During May and June 2005, a total of 10 peripartum and 23 C. difficile-associated disease (CDAD) cases from previously healthy individuals in the community were voluntarily reported from four U.S. states following a request from the CDC.

The findings suggest that the epidemiology of the disease might be changing to include features that have been uncommon in the past, such as close-contact transmission, high recurrence rate, young patient age, bloody diarrhea, and lack of antimicrobial exposure, the CDC warned (MMWR 2005;54:1201–5).

All but 1 of the 33 cases occurred during 2004–2005. Hospitalization was required for 15 (46%), and relapses occurred in 13 (39%). Transmission to close contacts was evident in four cases. Eight of the 33 patients (24%)—including 5 children—reported no exposure to antimicrobial agents within 3 months prior to CDAD onset. Of those eight, two reported close contact with a person who had diarrheal illness.

Clindamycin was the most common antimicrobial exposure noted prior to onset of CDAD, representing 10 (33%) of the 33 cases. These included two patients who had taken just one dose for group B streptococcal prophylaxis before CDAD onset, the CDC noted.

Among the cases was a 31-year-old woman who was 14 weeks pregnant with twins whose only antimicrobial exposure during the previous year had been trimethoprim-sulfamethoxazole for a urinary tract infection 3 months before she developed severe diarrhea. Despite treatment with metronidazole, cholestyramine, and oral vancomycin, she spontaneously aborted her fetuses and died 3 days later.

Another case was a 10-year-old girl who had not taken antimicrobials in the previous year. She had been completely healthy until 2 weeks before developing intractable diarrhea, projectile vomiting, and abdominal pain. Her brother also had a febrile diarrheal illness but recovered within 2–3 days without treatment. The girl's symptoms eventually resolved after she received intravenous fluids, electrolytes, and metronidazole in the hospital.

Fluoroquinolone use may be driving the emergence of newer and more virulent strains of Clostridium difficile, Dr. John G. Bartlett and Dr. Trish M. Perl said in an editorial accompanying two simultaneous reports in the New England Journal of Medicine.

“Particularly important is antibiotic stewardship with restraint in the use of epidemiologically implicated antimicrobial agents, usually second- and third-generation cephalosporins, clindamycin, or fluoroquinolones, or a combination of the three,” said Dr. Bartlett and Dr. Perl of Johns Hopkins University, Baltimore (N. Engl. J. Med. 2005;353:2503–5).

Several recent studies have documented a rise in the number and severity of C. difficile-associated disease cases in the United States and elsewhere. Now two new reports of detailed microbial analysis suggest that a more virulent strain of C. difficile is causing epidemic disease at selected locations and is associated with more frequent and more severe disease.

In one study, 187 isolates were collected from eight health care facilities in six states in which outbreaks of C. difficile-associated enteric disease had occurred between 2000 and 2003. In five of the facilities (two located in Maine and one each in Georgia, New Jersey, and Pennsylvania), one particular epidemic strain accounted for 50% or more of the isolates.

Among 29 of those isolates selected for further genetic testing, 25 were related by 90% or more, and all were more than 80% related. In contrast, very few of the other strains were more than 80% related, Dr. L. Clifford McDonald of the Centers for Disease Control and Prevention, Atlanta, and associates reported (N. Engl. J. Med. 2005;353:2433–41).

All 24 of the epidemic strain isolates that were tested for susceptibility were resistant to levofloxacin, gatifloxacin, and moxifloxacin, while 19 of the 24 (79%) were also resistant to clindamycin. In contrast, among 24 other C. difficile strains, 23 (96%) were resistant to levofloxacin, 19 (79%) to clindamycin, and just 10 each (42%) to gatifloxacin and moxifloxacin.

Even though resistance to clindamycin and levofloxacin was common among all the strains, the minimum inhibitory concentrations were higher for those of the epidemic strain. “The increasing use of fluoroquinolones in U.S. health care facilities may have provided a selective advantage for this epidemic strain and promoted its widespread emergence,” said Dr. McDonald and associates.

In the other study, Dr. Vivian G. Loo of McGill University and her associates prospectively identified a total of 1,703 patients with 1,719 episodes that met the case definition for nosocomial C. difficile-associated diarrhea at 12 Canadian hospitals between January and June of 2004. The overall incidence was 23 per 1,000 admissions, a rate nearly four times greater than the 6/1,000 found in a 1997 survey of 18 Canadian institutions.

Among the 422 patients who died within 30 days of diagnosis of C. difficile-associated diarrhea, the disease was attributed to be the cause of death in 117, or 6.9% of the total 1,703 patients. In contrast, the attributable mortality rate was just 1.5% in the 1997 survey, Dr. Loo and her associates noted (N. Engl. J. Med. 2005;353:2442–9).

A total of 237 patients were compared with 237 hospitalized patients who did not have C. difficile-associated diarrhea, matched for age, sex, and Charlson (comorbidity) index. The case patients were significantly more likely than controls to have been exposed to antibiotics (79% vs. 60%) and enteral feeding (19% vs. 12%). Exposure to fluoroquinolones was a significant independent risk factor for C. difficile-associated diarrhea (odds ratio 3.9), as was cephalosporin exposure (OR 3.8).

Results of pulsed-gel electrophoresis in 157 of the isolates indicated that 82% had an identical pattern, known as a “pulsovar,” that was universally resistant to fluoroquinolones. Of those 129 patients, 16% had severe C. difficile-associated diarrhea, compared with just 7% of 28 patients whose isolates had other pulsovars.

Polymerase chain reaction revealed that 84% of the 157 isolates possessed genes encoding for two major toxins associated with C. difficile virulence, as well as a partial deletion of a gene that downregulates those toxin genes.

Among those 132 patients, 17% had severe C. difficile-associated diarrhea, compared with 0 of the 25 patients who had none of those genes.

Control of C. difficile-associated disease also hinges on better recognition of cases and optimal disease management, Dr. Bartlett and Dr. Perl said.

Fluoroquinolone use may be driving the emergence of newer and more virulent strains of Clostridium difficile, Dr. John G. Bartlett and Dr. Trish M. Perl said in an editorial accompanying two simultaneous reports in the New England Journal of Medicine.

“Particularly important is antibiotic stewardship with restraint in the use of epidemiologically implicated antimicrobial agents, usually second- and third-generation cephalosporins, clindamycin, or fluoroquinolones, or a combination of the three,” said Dr. Bartlett and Dr. Perl of Johns Hopkins University, Baltimore (N. Engl. J. Med. 2005;353:2503–5).

Several recent studies have documented a rise in the number and severity of C. difficile-associated disease cases in the United States and elsewhere. Now two new reports of detailed microbial analysis suggest that a more virulent strain of C. difficile is causing epidemic disease at selected locations and is associated with more frequent and more severe disease.

In one study, 187 isolates were collected from eight health care facilities in six states in which outbreaks of C. difficile-associated enteric disease had occurred between 2000 and 2003. In five of the facilities (two located in Maine and one each in Georgia, New Jersey, and Pennsylvania), one particular epidemic strain accounted for 50% or more of the isolates.

Among 29 of those isolates selected for further genetic testing, 25 were related by 90% or more, and all were more than 80% related. In contrast, very few of the other strains were more than 80% related, Dr. L. Clifford McDonald of the Centers for Disease Control and Prevention, Atlanta, and associates reported (N. Engl. J. Med. 2005;353:2433–41).

All 24 of the epidemic strain isolates that were tested for susceptibility were resistant to levofloxacin, gatifloxacin, and moxifloxacin, while 19 of the 24 (79%) were also resistant to clindamycin. In contrast, among 24 other C. difficile strains, 23 (96%) were resistant to levofloxacin, 19 (79%) to clindamycin, and just 10 each (42%) to gatifloxacin and moxifloxacin.

Even though resistance to clindamycin and levofloxacin was common among all the strains, the minimum inhibitory concentrations were higher for those of the epidemic strain. “The increasing use of fluoroquinolones in U.S. health care facilities may have provided a selective advantage for this epidemic strain and promoted its widespread emergence,” said Dr. McDonald and associates.

In the other study, Dr. Vivian G. Loo of McGill University and her associates prospectively identified a total of 1,703 patients with 1,719 episodes that met the case definition for nosocomial C. difficile-associated diarrhea at 12 Canadian hospitals between January and June of 2004. The overall incidence was 23 per 1,000 admissions, a rate nearly four times greater than the 6/1,000 found in a 1997 survey of 18 Canadian institutions.

Among the 422 patients who died within 30 days of diagnosis of C. difficile-associated diarrhea, the disease was attributed to be the cause of death in 117, or 6.9% of the total 1,703 patients. In contrast, the attributable mortality rate was just 1.5% in the 1997 survey, Dr. Loo and her associates noted (N. Engl. J. Med. 2005;353:2442–9).

A total of 237 patients were compared with 237 hospitalized patients who did not have C. difficile-associated diarrhea, matched for age, sex, and Charlson (comorbidity) index. The case patients were significantly more likely than controls to have been exposed to antibiotics (79% vs. 60%) and enteral feeding (19% vs. 12%). Exposure to fluoroquinolones was a significant independent risk factor for C. difficile-associated diarrhea (odds ratio 3.9), as was cephalosporin exposure (OR 3.8).

Results of pulsed-gel electrophoresis in 157 of the isolates indicated that 82% had an identical pattern, known as a “pulsovar,” that was universally resistant to fluoroquinolones. Of those 129 patients, 16% had severe C. difficile-associated diarrhea, compared with just 7% of 28 patients whose isolates had other pulsovars.

Polymerase chain reaction revealed that 84% of the 157 isolates possessed genes encoding for two major toxins associated with C. difficile virulence, as well as a partial deletion of a gene that downregulates those toxin genes.

Among those 132 patients, 17% had severe C. difficile-associated diarrhea, compared with 0 of the 25 patients who had none of those genes.

Control of C. difficile-associated disease also hinges on better recognition of cases and optimal disease management, Dr. Bartlett and Dr. Perl said.

Fluoroquinolone use may be driving the emergence of newer and more virulent strains of Clostridium difficile, Dr. John G. Bartlett and Dr. Trish M. Perl said in an editorial accompanying two simultaneous reports in the New England Journal of Medicine.

“Particularly important is antibiotic stewardship with restraint in the use of epidemiologically implicated antimicrobial agents, usually second- and third-generation cephalosporins, clindamycin, or fluoroquinolones, or a combination of the three,” said Dr. Bartlett and Dr. Perl of Johns Hopkins University, Baltimore (N. Engl. J. Med. 2005;353:2503–5).

Several recent studies have documented a rise in the number and severity of C. difficile-associated disease cases in the United States and elsewhere. Now two new reports of detailed microbial analysis suggest that a more virulent strain of C. difficile is causing epidemic disease at selected locations and is associated with more frequent and more severe disease.

In one study, 187 isolates were collected from eight health care facilities in six states in which outbreaks of C. difficile-associated enteric disease had occurred between 2000 and 2003. In five of the facilities (two located in Maine and one each in Georgia, New Jersey, and Pennsylvania), one particular epidemic strain accounted for 50% or more of the isolates.

Among 29 of those isolates selected for further genetic testing, 25 were related by 90% or more, and all were more than 80% related. In contrast, very few of the other strains were more than 80% related, Dr. L. Clifford McDonald of the Centers for Disease Control and Prevention, Atlanta, and associates reported (N. Engl. J. Med. 2005;353:2433–41).

All 24 of the epidemic strain isolates that were tested for susceptibility were resistant to levofloxacin, gatifloxacin, and moxifloxacin, while 19 of the 24 (79%) were also resistant to clindamycin. In contrast, among 24 other C. difficile strains, 23 (96%) were resistant to levofloxacin, 19 (79%) to clindamycin, and just 10 each (42%) to gatifloxacin and moxifloxacin.

Even though resistance to clindamycin and levofloxacin was common among all the strains, the minimum inhibitory concentrations were higher for those of the epidemic strain. “The increasing use of fluoroquinolones in U.S. health care facilities may have provided a selective advantage for this epidemic strain and promoted its widespread emergence,” said Dr. McDonald and associates.

In the other study, Dr. Vivian G. Loo of McGill University and her associates prospectively identified a total of 1,703 patients with 1,719 episodes that met the case definition for nosocomial C. difficile-associated diarrhea at 12 Canadian hospitals between January and June of 2004. The overall incidence was 23 per 1,000 admissions, a rate nearly four times greater than the 6/1,000 found in a 1997 survey of 18 Canadian institutions.

Among the 422 patients who died within 30 days of diagnosis of C. difficile-associated diarrhea, the disease was attributed to be the cause of death in 117, or 6.9% of the total 1,703 patients. In contrast, the attributable mortality rate was just 1.5% in the 1997 survey, Dr. Loo and her associates noted (N. Engl. J. Med. 2005;353:2442–9).

A total of 237 patients were compared with 237 hospitalized patients who did not have C. difficile-associated diarrhea, matched for age, sex, and Charlson (comorbidity) index. The case patients were significantly more likely than controls to have been exposed to antibiotics (79% vs. 60%) and enteral feeding (19% vs. 12%). Exposure to fluoroquinolones was a significant independent risk factor for C. difficile-associated diarrhea (odds ratio 3.9), as was cephalosporin exposure (OR 3.8).

Results of pulsed-gel electrophoresis in 157 of the isolates indicated that 82% had an identical pattern, known as a “pulsovar,” that was universally resistant to fluoroquinolones. Of those 129 patients, 16% had severe C. difficile-associated diarrhea, compared with just 7% of 28 patients whose isolates had other pulsovars.

Polymerase chain reaction revealed that 84% of the 157 isolates possessed genes encoding for two major toxins associated with C. difficile virulence, as well as a partial deletion of a gene that downregulates those toxin genes.

Among those 132 patients, 17% had severe C. difficile-associated diarrhea, compared with 0 of the 25 patients who had none of those genes.

Control of C. difficile-associated disease also hinges on better recognition of cases and optimal disease management, Dr. Bartlett and Dr. Perl said.