European Society of Clinical Microbiology and Infectious Diseases (ESCMID): European Congress of Clinical Microbiology and Infectious Diseases (ECCMID)

LONDON – Fidaxomicin was noninferior to vancomycin in achieving clinical cure of Clostridium difficile infection after 10 days of treatment but was superior to vancomycin in attaining lower recurrence rates and higher sustained response rates at 4 weeks.

The findings come from a multicenter, randomized, controlled, double-blind study conducted in seven European countries, Canada, and the United States. It was funded by Optimer Pharmaceuticals, manufacturer of fidaxomicin, a novel macrocyclic antibiotic with a narrow spectrum of activity against gram-positive bacteria and minimal activity against normal gut flora. It was approved for treatment of C. difficile infection in the United States in May 2011 and in Europe in December 2011. A previous phase III trial in Canada and the United States showed fidaxomicin to be noninferior to vancomycin for clinical cure and superior for sustained response at 4 weeks after treatment completion (N. Engl. J. Med. 2011;364:422-31).

The current study, identical in design and procedures, compared the efficacy of fidaxomicin in Europe as well as in the United States and Canada, said Dr. Oliver A. Cornely of University Hospital, Cologne, Germany. The findings were published online prior to the ECCMID meeting (Lancet Infect. Dis. 2012;12:281-9).

The 509 patients included in the intent to treat analysis were all aged 16 years or older, had more than three unformed bowel movements per 24 hours, had C. diff infection confirmed by toxin A and/or B in stool, and had a first episode or recurrence within 90 days. They were randomized to either twice-daily 200-mg doses of fidaxomicin with twice-daily intervening placebo or the standard 125-mg doses of vancomycin four times daily.

The 198 patients from Europe were slightly older than those from the United States and Canada (66.9 vs. 61.2 years), and fewer were women (54.5% vs. 65%). More of the European group were inpatients at the time of study enrollment (84.3% vs. 57.9%), but fewer in Europe had had a previous episode of C. diff within the prior 90 days (10.1% vs. 18.0%). As expected, the hypervirulent, fluoroquinolone-resistant C. difficile strain NAP1/BI/027 was more common in the U.S./Canada (45.9% vs. 10.4%).

Use of concomitant antibiotics to treat other infections was more common in Europe than in the United States during both treatment and follow-up (34.8% vs. 26.7% for either time period), Dr. Cornely reported.

For the primary study end point ("resolution of diarrhea and no further need for treatment"), fidaxomicin was noninferior to vancomycin, 87.7% vs. 86.8%, well within the prespecified 10% margin. However, fidaxomicin was superior in recurrence, defined as return of diarrhea within 4 weeks of completing therapy plus a positive toxin test (12.7% vs. 26.9%). Fidaxomicin was also superior for sustained response, defined as clinical cure maintained for 4 weeks (76.6% vs. 63.4%). The median time to resolution of diarrhea did not differ between fidaxomicin and vancomycin (56 vs. 58 hours, respectively). (Time to resolution was defined as the number of hours from the first dose of the study drug to the last unformed bowel movement preceding 2 days of three or fewer unformed stools per day.)

Resolution of diarrhea was significantly delayed among patients who received antibiotics to treat other infections at the same time as they were being treated for CDI (median time to resolution 92 hours vs. 54 hours). Among the patients who were receiving concomitant antibiotics, fidaxomicin was superior to vancomycin in clinical cure rate (90.2% of 51 vs. 73.3% of 45), Dr. Cornely reported.

When Europe and the U.S./Canada were analyzed separately, fidaxomicin remained noninferior for clinical cure and superior for recurrence and sustained response. However, recurrence rates overall were slightly higher and sustained response slightly lower in the U.S./Canada, compared with Europe, although the confidence intervals were broad. Early resolution (in less than 72 hours) was more common in Europe (51 vs. 60 hours), but the overall trend was not significantly different for Europe and North America, he said.

There were no significant differences in cure rates between fidaxomicin and vancomycin for other subgroups, including those stratified by age, prior C. diff. infection, inpatient/outpatient, severity, strain, or location.

No fidaxomicin-resistant clones were isolated at baseline or at the end of treatment, although a single isolate recovered at recurrence in Canada has reduced susceptibility, Dr. Cornely noted.

The study was funded by Optimer Pharmaceuticals. Dr. Cornely disclosed that he has received research grants or lecture honoraria or is an adviser to Optimer and multiple other firms, including Actelion, Astellas, Basilea, Bayer, BioCryst, Celgene, F2G, Genzyme, Gilead, Merck, Miltenyi, Pfizer, Quintiles, and ViroPharma.

LONDON – Fidaxomicin was noninferior to vancomycin in achieving clinical cure of Clostridium difficile infection after 10 days of treatment but was superior to vancomycin in attaining lower recurrence rates and higher sustained response rates at 4 weeks.

The findings come from a multicenter, randomized, controlled, double-blind study conducted in seven European countries, Canada, and the United States. It was funded by Optimer Pharmaceuticals, manufacturer of fidaxomicin, a novel macrocyclic antibiotic with a narrow spectrum of activity against gram-positive bacteria and minimal activity against normal gut flora. It was approved for treatment of C. difficile infection in the United States in May 2011 and in Europe in December 2011. A previous phase III trial in Canada and the United States showed fidaxomicin to be noninferior to vancomycin for clinical cure and superior for sustained response at 4 weeks after treatment completion (N. Engl. J. Med. 2011;364:422-31).

The current study, identical in design and procedures, compared the efficacy of fidaxomicin in Europe as well as in the United States and Canada, said Dr. Oliver A. Cornely of University Hospital, Cologne, Germany. The findings were published online prior to the ECCMID meeting (Lancet Infect. Dis. 2012;12:281-9).

The 509 patients included in the intent to treat analysis were all aged 16 years or older, had more than three unformed bowel movements per 24 hours, had C. diff infection confirmed by toxin A and/or B in stool, and had a first episode or recurrence within 90 days. They were randomized to either twice-daily 200-mg doses of fidaxomicin with twice-daily intervening placebo or the standard 125-mg doses of vancomycin four times daily.

The 198 patients from Europe were slightly older than those from the United States and Canada (66.9 vs. 61.2 years), and fewer were women (54.5% vs. 65%). More of the European group were inpatients at the time of study enrollment (84.3% vs. 57.9%), but fewer in Europe had had a previous episode of C. diff within the prior 90 days (10.1% vs. 18.0%). As expected, the hypervirulent, fluoroquinolone-resistant C. difficile strain NAP1/BI/027 was more common in the U.S./Canada (45.9% vs. 10.4%).

Use of concomitant antibiotics to treat other infections was more common in Europe than in the United States during both treatment and follow-up (34.8% vs. 26.7% for either time period), Dr. Cornely reported.

For the primary study end point ("resolution of diarrhea and no further need for treatment"), fidaxomicin was noninferior to vancomycin, 87.7% vs. 86.8%, well within the prespecified 10% margin. However, fidaxomicin was superior in recurrence, defined as return of diarrhea within 4 weeks of completing therapy plus a positive toxin test (12.7% vs. 26.9%). Fidaxomicin was also superior for sustained response, defined as clinical cure maintained for 4 weeks (76.6% vs. 63.4%). The median time to resolution of diarrhea did not differ between fidaxomicin and vancomycin (56 vs. 58 hours, respectively). (Time to resolution was defined as the number of hours from the first dose of the study drug to the last unformed bowel movement preceding 2 days of three or fewer unformed stools per day.)

Resolution of diarrhea was significantly delayed among patients who received antibiotics to treat other infections at the same time as they were being treated for CDI (median time to resolution 92 hours vs. 54 hours). Among the patients who were receiving concomitant antibiotics, fidaxomicin was superior to vancomycin in clinical cure rate (90.2% of 51 vs. 73.3% of 45), Dr. Cornely reported.

When Europe and the U.S./Canada were analyzed separately, fidaxomicin remained noninferior for clinical cure and superior for recurrence and sustained response. However, recurrence rates overall were slightly higher and sustained response slightly lower in the U.S./Canada, compared with Europe, although the confidence intervals were broad. Early resolution (in less than 72 hours) was more common in Europe (51 vs. 60 hours), but the overall trend was not significantly different for Europe and North America, he said.

There were no significant differences in cure rates between fidaxomicin and vancomycin for other subgroups, including those stratified by age, prior C. diff. infection, inpatient/outpatient, severity, strain, or location.

No fidaxomicin-resistant clones were isolated at baseline or at the end of treatment, although a single isolate recovered at recurrence in Canada has reduced susceptibility, Dr. Cornely noted.

The study was funded by Optimer Pharmaceuticals. Dr. Cornely disclosed that he has received research grants or lecture honoraria or is an adviser to Optimer and multiple other firms, including Actelion, Astellas, Basilea, Bayer, BioCryst, Celgene, F2G, Genzyme, Gilead, Merck, Miltenyi, Pfizer, Quintiles, and ViroPharma.

LONDON – Fidaxomicin was noninferior to vancomycin in achieving clinical cure of Clostridium difficile infection after 10 days of treatment but was superior to vancomycin in attaining lower recurrence rates and higher sustained response rates at 4 weeks.

The findings come from a multicenter, randomized, controlled, double-blind study conducted in seven European countries, Canada, and the United States. It was funded by Optimer Pharmaceuticals, manufacturer of fidaxomicin, a novel macrocyclic antibiotic with a narrow spectrum of activity against gram-positive bacteria and minimal activity against normal gut flora. It was approved for treatment of C. difficile infection in the United States in May 2011 and in Europe in December 2011. A previous phase III trial in Canada and the United States showed fidaxomicin to be noninferior to vancomycin for clinical cure and superior for sustained response at 4 weeks after treatment completion (N. Engl. J. Med. 2011;364:422-31).

The current study, identical in design and procedures, compared the efficacy of fidaxomicin in Europe as well as in the United States and Canada, said Dr. Oliver A. Cornely of University Hospital, Cologne, Germany. The findings were published online prior to the ECCMID meeting (Lancet Infect. Dis. 2012;12:281-9).

The 509 patients included in the intent to treat analysis were all aged 16 years or older, had more than three unformed bowel movements per 24 hours, had C. diff infection confirmed by toxin A and/or B in stool, and had a first episode or recurrence within 90 days. They were randomized to either twice-daily 200-mg doses of fidaxomicin with twice-daily intervening placebo or the standard 125-mg doses of vancomycin four times daily.

The 198 patients from Europe were slightly older than those from the United States and Canada (66.9 vs. 61.2 years), and fewer were women (54.5% vs. 65%). More of the European group were inpatients at the time of study enrollment (84.3% vs. 57.9%), but fewer in Europe had had a previous episode of C. diff within the prior 90 days (10.1% vs. 18.0%). As expected, the hypervirulent, fluoroquinolone-resistant C. difficile strain NAP1/BI/027 was more common in the U.S./Canada (45.9% vs. 10.4%).

Use of concomitant antibiotics to treat other infections was more common in Europe than in the United States during both treatment and follow-up (34.8% vs. 26.7% for either time period), Dr. Cornely reported.

For the primary study end point ("resolution of diarrhea and no further need for treatment"), fidaxomicin was noninferior to vancomycin, 87.7% vs. 86.8%, well within the prespecified 10% margin. However, fidaxomicin was superior in recurrence, defined as return of diarrhea within 4 weeks of completing therapy plus a positive toxin test (12.7% vs. 26.9%). Fidaxomicin was also superior for sustained response, defined as clinical cure maintained for 4 weeks (76.6% vs. 63.4%). The median time to resolution of diarrhea did not differ between fidaxomicin and vancomycin (56 vs. 58 hours, respectively). (Time to resolution was defined as the number of hours from the first dose of the study drug to the last unformed bowel movement preceding 2 days of three or fewer unformed stools per day.)

Resolution of diarrhea was significantly delayed among patients who received antibiotics to treat other infections at the same time as they were being treated for CDI (median time to resolution 92 hours vs. 54 hours). Among the patients who were receiving concomitant antibiotics, fidaxomicin was superior to vancomycin in clinical cure rate (90.2% of 51 vs. 73.3% of 45), Dr. Cornely reported.

When Europe and the U.S./Canada were analyzed separately, fidaxomicin remained noninferior for clinical cure and superior for recurrence and sustained response. However, recurrence rates overall were slightly higher and sustained response slightly lower in the U.S./Canada, compared with Europe, although the confidence intervals were broad. Early resolution (in less than 72 hours) was more common in Europe (51 vs. 60 hours), but the overall trend was not significantly different for Europe and North America, he said.

There were no significant differences in cure rates between fidaxomicin and vancomycin for other subgroups, including those stratified by age, prior C. diff. infection, inpatient/outpatient, severity, strain, or location.

No fidaxomicin-resistant clones were isolated at baseline or at the end of treatment, although a single isolate recovered at recurrence in Canada has reduced susceptibility, Dr. Cornely noted.

The study was funded by Optimer Pharmaceuticals. Dr. Cornely disclosed that he has received research grants or lecture honoraria or is an adviser to Optimer and multiple other firms, including Actelion, Astellas, Basilea, Bayer, BioCryst, Celgene, F2G, Genzyme, Gilead, Merck, Miltenyi, Pfizer, Quintiles, and ViroPharma.

LONDON – Hospital-acquired infections occurred in more than one in four intensive care unit stays and increased the cost per stay by nearly $16,000, a retrospective analysis of data from a large U.S. hospital database revealed.

"The prevalence and burden of hospital-acquired infections in the ICU are high and clearly associated with a major economic impact," said Florence Joly, Pharm.D., of Sanofi R&D, France.

The study was conducted by Sanofi to inform the development of a new drug to combat hospital-associated infections (HAIs) including bloodstream infections, hospital-acquired pneumonia (HAP), and surgical site infections (SSIs). The data came from Premier Perspective, a large U.S. hospital database containing information from more than 700 hospitals and representing about 20% of all hospital discharges in the United States.

The analysis included 463,491 adults aged 18 years and older who were admitted in 2007 for a total of 511,815 ICU stays of more than 48 hours. The patients were 53% male and had a mean age of 64 years. A third (33%) had diabetes, 26% had a central venous catheter/central line, and 22% were on mechanical ventilation. Most of the patients (91.5%) had just one ICU stay, but 7% had two stays and 1.5% had three or more stays.

At least one HAI occurred in 27% of all ICU stays, including pneumonia in 17%, bloodstream infections in 14.5%, and SSIs in 1.5%. In addition, severe sepsis occurred in 40%, she reported at the European Congress of Clinical Microbiology and Infectious Diseases.

Length of stay (LOS) was 23 days for SSIs, at a cost of $59,905 per stay. For bloodstream infections, the stay was 18 days at $43,071 per stay, and for HAP, 15 days at $36,467/stay. Mortality was 25% for bloodstream infections, 17% for HAP, and 11% for SSIs. In total, the length of stay for all that involved HAI was 16 days at a cost of $37,539 per stay, compared with just 8 days at $21,541 per stay for those without HAI. Overall mortality rates were 19% with HAI vs. 4.5% without. All of the HAI/no HAI differences were highly statistically significant, she noted.

Similar results were found using data from 2008 and 2009.

"The increase in mortality rates and longer LOS findings as the drivers of higher ICU costs indicate the need for specific measures to reduce the prevalence of these major types of hospital-acquired infections," Dr. Joly concluded.

In a separate poster presentation by Dr. Caroline Amand-Bourdon, also of Sanofi R&D, the same database of 463,491 patients was analyzed for risk factors predicting HAI for just the first hospitalization per patient. In all, 26% of the patients (119,616) experienced a HAI, including 17% with pneumonia, 14% with a bloodstream infection, and 1% with an SSI. Compared with the 343,875 patients who did not have a HAI, patients who did were older (mean age 66 vs. 63 years) and had more device procedures, including central catheter placements (49% vs. 18%) and mechanical ventilation hookups (42% vs. 15%). The HAI patients were also more often admitted via the emergency department (71% vs. 56%).

Central catheter and mechanical ventilation were identified as the two main risk factors for HAI, with adjusted odds ratios of 3.4 and 2.8, respectively, Dr. Amand-Bourdon and her associates reported.

"These findings illustrate the changing nature of hospital inpatient populations over the years that are more vulnerable to HAI," according to the investigators.

Both Dr. Joly and Dr. Amand-Bourdon are employees of Sanofi, which funded and conducted the study.

LONDON – Hospital-acquired infections occurred in more than one in four intensive care unit stays and increased the cost per stay by nearly $16,000, a retrospective analysis of data from a large U.S. hospital database revealed.

"The prevalence and burden of hospital-acquired infections in the ICU are high and clearly associated with a major economic impact," said Florence Joly, Pharm.D., of Sanofi R&D, France.

The study was conducted by Sanofi to inform the development of a new drug to combat hospital-associated infections (HAIs) including bloodstream infections, hospital-acquired pneumonia (HAP), and surgical site infections (SSIs). The data came from Premier Perspective, a large U.S. hospital database containing information from more than 700 hospitals and representing about 20% of all hospital discharges in the United States.

The analysis included 463,491 adults aged 18 years and older who were admitted in 2007 for a total of 511,815 ICU stays of more than 48 hours. The patients were 53% male and had a mean age of 64 years. A third (33%) had diabetes, 26% had a central venous catheter/central line, and 22% were on mechanical ventilation. Most of the patients (91.5%) had just one ICU stay, but 7% had two stays and 1.5% had three or more stays.

At least one HAI occurred in 27% of all ICU stays, including pneumonia in 17%, bloodstream infections in 14.5%, and SSIs in 1.5%. In addition, severe sepsis occurred in 40%, she reported at the European Congress of Clinical Microbiology and Infectious Diseases.

Length of stay (LOS) was 23 days for SSIs, at a cost of $59,905 per stay. For bloodstream infections, the stay was 18 days at $43,071 per stay, and for HAP, 15 days at $36,467/stay. Mortality was 25% for bloodstream infections, 17% for HAP, and 11% for SSIs. In total, the length of stay for all that involved HAI was 16 days at a cost of $37,539 per stay, compared with just 8 days at $21,541 per stay for those without HAI. Overall mortality rates were 19% with HAI vs. 4.5% without. All of the HAI/no HAI differences were highly statistically significant, she noted.

Similar results were found using data from 2008 and 2009.

"The increase in mortality rates and longer LOS findings as the drivers of higher ICU costs indicate the need for specific measures to reduce the prevalence of these major types of hospital-acquired infections," Dr. Joly concluded.

In a separate poster presentation by Dr. Caroline Amand-Bourdon, also of Sanofi R&D, the same database of 463,491 patients was analyzed for risk factors predicting HAI for just the first hospitalization per patient. In all, 26% of the patients (119,616) experienced a HAI, including 17% with pneumonia, 14% with a bloodstream infection, and 1% with an SSI. Compared with the 343,875 patients who did not have a HAI, patients who did were older (mean age 66 vs. 63 years) and had more device procedures, including central catheter placements (49% vs. 18%) and mechanical ventilation hookups (42% vs. 15%). The HAI patients were also more often admitted via the emergency department (71% vs. 56%).

Central catheter and mechanical ventilation were identified as the two main risk factors for HAI, with adjusted odds ratios of 3.4 and 2.8, respectively, Dr. Amand-Bourdon and her associates reported.

"These findings illustrate the changing nature of hospital inpatient populations over the years that are more vulnerable to HAI," according to the investigators.

Both Dr. Joly and Dr. Amand-Bourdon are employees of Sanofi, which funded and conducted the study.

LONDON – Hospital-acquired infections occurred in more than one in four intensive care unit stays and increased the cost per stay by nearly $16,000, a retrospective analysis of data from a large U.S. hospital database revealed.

"The prevalence and burden of hospital-acquired infections in the ICU are high and clearly associated with a major economic impact," said Florence Joly, Pharm.D., of Sanofi R&D, France.

The study was conducted by Sanofi to inform the development of a new drug to combat hospital-associated infections (HAIs) including bloodstream infections, hospital-acquired pneumonia (HAP), and surgical site infections (SSIs). The data came from Premier Perspective, a large U.S. hospital database containing information from more than 700 hospitals and representing about 20% of all hospital discharges in the United States.

The analysis included 463,491 adults aged 18 years and older who were admitted in 2007 for a total of 511,815 ICU stays of more than 48 hours. The patients were 53% male and had a mean age of 64 years. A third (33%) had diabetes, 26% had a central venous catheter/central line, and 22% were on mechanical ventilation. Most of the patients (91.5%) had just one ICU stay, but 7% had two stays and 1.5% had three or more stays.

At least one HAI occurred in 27% of all ICU stays, including pneumonia in 17%, bloodstream infections in 14.5%, and SSIs in 1.5%. In addition, severe sepsis occurred in 40%, she reported at the European Congress of Clinical Microbiology and Infectious Diseases.

Length of stay (LOS) was 23 days for SSIs, at a cost of $59,905 per stay. For bloodstream infections, the stay was 18 days at $43,071 per stay, and for HAP, 15 days at $36,467/stay. Mortality was 25% for bloodstream infections, 17% for HAP, and 11% for SSIs. In total, the length of stay for all that involved HAI was 16 days at a cost of $37,539 per stay, compared with just 8 days at $21,541 per stay for those without HAI. Overall mortality rates were 19% with HAI vs. 4.5% without. All of the HAI/no HAI differences were highly statistically significant, she noted.

Similar results were found using data from 2008 and 2009.

"The increase in mortality rates and longer LOS findings as the drivers of higher ICU costs indicate the need for specific measures to reduce the prevalence of these major types of hospital-acquired infections," Dr. Joly concluded.

In a separate poster presentation by Dr. Caroline Amand-Bourdon, also of Sanofi R&D, the same database of 463,491 patients was analyzed for risk factors predicting HAI for just the first hospitalization per patient. In all, 26% of the patients (119,616) experienced a HAI, including 17% with pneumonia, 14% with a bloodstream infection, and 1% with an SSI. Compared with the 343,875 patients who did not have a HAI, patients who did were older (mean age 66 vs. 63 years) and had more device procedures, including central catheter placements (49% vs. 18%) and mechanical ventilation hookups (42% vs. 15%). The HAI patients were also more often admitted via the emergency department (71% vs. 56%).

Central catheter and mechanical ventilation were identified as the two main risk factors for HAI, with adjusted odds ratios of 3.4 and 2.8, respectively, Dr. Amand-Bourdon and her associates reported.

"These findings illustrate the changing nature of hospital inpatient populations over the years that are more vulnerable to HAI," according to the investigators.

Both Dr. Joly and Dr. Amand-Bourdon are employees of Sanofi, which funded and conducted the study.

LONDON – Being obese increased the risk of surgical site infection nearly fourfold among patients who underwent operations in the United Kingdom from 2006 through 2010.

The findings pose questions such as whether preoperative dosing of antibiotics might be adjusted upward or whether preoperative weight loss should be advocated, said Dr. Simon Thelwall of the Health Protection Agency, London.

The analysis was done using nationwide data from the UK’s Health Protection Agency (HPA) Surgical Site Infection Surveillance Service, comprising data submitted from all 212 of the National Health Service hospitals in England on a cumulative total of 326,880 adult patients who underwent one of five operations: abdominal hysterectomy, coronary artery bypass graft (CABG), hip replacement, knee replacement, and large bowel surgery.

Of those, surgical site infections (SSIs) were detected in inpatients and at readmission for 4,453, and body mass index (BMI) data were available for 43%. Of these 112,048 (79.3%) were overweight or obese, said Dr. Thelwall.

The rates of SSIs didn’t differ among those with and without available body mass index data except among CABG patients, for whom the rate of SSIs was double among those with and without BMI data (5.17% vs. 2.71%). The CABG patients with BMI data were also significantly more likely to have received implants (85% vs. 61%), to have undergone emergency operations (1.29% vs. 0.76%), and to have had significantly longer operations (205 vs. 220 minutes).

Thus, "CABG patients with BMI data are more likely to have risk factors predisposing them to SSI," Dr. Thelwall noted.

Obesity significantly increased the risk for SSI in all surgical groups except for abdominal hysterectomy, with risk ratios ranging from 1.62 for knee replacement to 1.87 for large bowel surgery. Obesity still increased the SSI risk among abdominal hysterectomy patients with a risk ratio of 1.81, but that did not reach statistical significance, he said.

Overall, the SSI risk increased with increasing BMI. In multivariate analysis adjusting for a variety of potential confounders including age, trauma, category of surgery, implant, and emergency surgery, the odds ratios for SSI increased from 1.44 among the overweight patients to 1.89 for those with BMIs of 30-34.99 kg/m², to 2.94 for BMIs of 35-39.99 kg/m², and to 3.73 for BMIs greater than 40 kg/m². In the highest BMI category, even the SSI rate for abdominal hysterectomy became significantly greater, compared with that of patients of normal weight (risk ratio, 3.90), Dr. Thelwall said.

Among the morbidly obese (BMI greater than 40 kg/m²), between 65% and 78% of the risk for SSI was attributable to being very obese. And in that group of morbidly obese patients, the risk of SSI among abdominal hysterectomy patients became significantly elevated three- to fivefold, compared with that of women of normal weight, he noted.

Dr. Thelwall declared that he had no disclosures.

LONDON – Being obese increased the risk of surgical site infection nearly fourfold among patients who underwent operations in the United Kingdom from 2006 through 2010.

The findings pose questions such as whether preoperative dosing of antibiotics might be adjusted upward or whether preoperative weight loss should be advocated, said Dr. Simon Thelwall of the Health Protection Agency, London.

The analysis was done using nationwide data from the UK’s Health Protection Agency (HPA) Surgical Site Infection Surveillance Service, comprising data submitted from all 212 of the National Health Service hospitals in England on a cumulative total of 326,880 adult patients who underwent one of five operations: abdominal hysterectomy, coronary artery bypass graft (CABG), hip replacement, knee replacement, and large bowel surgery.

Of those, surgical site infections (SSIs) were detected in inpatients and at readmission for 4,453, and body mass index (BMI) data were available for 43%. Of these 112,048 (79.3%) were overweight or obese, said Dr. Thelwall.

The rates of SSIs didn’t differ among those with and without available body mass index data except among CABG patients, for whom the rate of SSIs was double among those with and without BMI data (5.17% vs. 2.71%). The CABG patients with BMI data were also significantly more likely to have received implants (85% vs. 61%), to have undergone emergency operations (1.29% vs. 0.76%), and to have had significantly longer operations (205 vs. 220 minutes).

Thus, "CABG patients with BMI data are more likely to have risk factors predisposing them to SSI," Dr. Thelwall noted.

Obesity significantly increased the risk for SSI in all surgical groups except for abdominal hysterectomy, with risk ratios ranging from 1.62 for knee replacement to 1.87 for large bowel surgery. Obesity still increased the SSI risk among abdominal hysterectomy patients with a risk ratio of 1.81, but that did not reach statistical significance, he said.

Overall, the SSI risk increased with increasing BMI. In multivariate analysis adjusting for a variety of potential confounders including age, trauma, category of surgery, implant, and emergency surgery, the odds ratios for SSI increased from 1.44 among the overweight patients to 1.89 for those with BMIs of 30-34.99 kg/m², to 2.94 for BMIs of 35-39.99 kg/m², and to 3.73 for BMIs greater than 40 kg/m². In the highest BMI category, even the SSI rate for abdominal hysterectomy became significantly greater, compared with that of patients of normal weight (risk ratio, 3.90), Dr. Thelwall said.

Among the morbidly obese (BMI greater than 40 kg/m²), between 65% and 78% of the risk for SSI was attributable to being very obese. And in that group of morbidly obese patients, the risk of SSI among abdominal hysterectomy patients became significantly elevated three- to fivefold, compared with that of women of normal weight, he noted.

Dr. Thelwall declared that he had no disclosures.

LONDON – Being obese increased the risk of surgical site infection nearly fourfold among patients who underwent operations in the United Kingdom from 2006 through 2010.

The findings pose questions such as whether preoperative dosing of antibiotics might be adjusted upward or whether preoperative weight loss should be advocated, said Dr. Simon Thelwall of the Health Protection Agency, London.

The analysis was done using nationwide data from the UK’s Health Protection Agency (HPA) Surgical Site Infection Surveillance Service, comprising data submitted from all 212 of the National Health Service hospitals in England on a cumulative total of 326,880 adult patients who underwent one of five operations: abdominal hysterectomy, coronary artery bypass graft (CABG), hip replacement, knee replacement, and large bowel surgery.

Of those, surgical site infections (SSIs) were detected in inpatients and at readmission for 4,453, and body mass index (BMI) data were available for 43%. Of these 112,048 (79.3%) were overweight or obese, said Dr. Thelwall.

The rates of SSIs didn’t differ among those with and without available body mass index data except among CABG patients, for whom the rate of SSIs was double among those with and without BMI data (5.17% vs. 2.71%). The CABG patients with BMI data were also significantly more likely to have received implants (85% vs. 61%), to have undergone emergency operations (1.29% vs. 0.76%), and to have had significantly longer operations (205 vs. 220 minutes).

Thus, "CABG patients with BMI data are more likely to have risk factors predisposing them to SSI," Dr. Thelwall noted.

Obesity significantly increased the risk for SSI in all surgical groups except for abdominal hysterectomy, with risk ratios ranging from 1.62 for knee replacement to 1.87 for large bowel surgery. Obesity still increased the SSI risk among abdominal hysterectomy patients with a risk ratio of 1.81, but that did not reach statistical significance, he said.

Overall, the SSI risk increased with increasing BMI. In multivariate analysis adjusting for a variety of potential confounders including age, trauma, category of surgery, implant, and emergency surgery, the odds ratios for SSI increased from 1.44 among the overweight patients to 1.89 for those with BMIs of 30-34.99 kg/m², to 2.94 for BMIs of 35-39.99 kg/m², and to 3.73 for BMIs greater than 40 kg/m². In the highest BMI category, even the SSI rate for abdominal hysterectomy became significantly greater, compared with that of patients of normal weight (risk ratio, 3.90), Dr. Thelwall said.

Among the morbidly obese (BMI greater than 40 kg/m²), between 65% and 78% of the risk for SSI was attributable to being very obese. And in that group of morbidly obese patients, the risk of SSI among abdominal hysterectomy patients became significantly elevated three- to fivefold, compared with that of women of normal weight, he noted.

Dr. Thelwall declared that he had no disclosures.

LONDON – The use of acid-suppression therapy was associated with a significantly increased risk for Clostridium difficile infection in a systematic review and meta-analysis of data from 30 studies.

Previous observational studies have suggested a link between proton pump inhibitor (PPI) use and an increased risk of developing Clostridium difficile infection (CDI). In February, the Food and Drug Administration issued an alert about the use of PPIs because of the increased CDI risk.

This new meta-analysis supports this association, with a significantly increased risk of CDI with acid suppression (odds ratio, 1.58; P less than .05), Dr. Iman Tleyjeh said at the European Congress of Clinical Microbiology and Infectious Diseases.

"We found a robust association between acid-suppression therapy and the appearance of CDI," said Dr. Tleyjeh, director of the research and scientific publication center and a consultant in infectious disease at King Fahad Medical City, Riyadh, Saudi Arabia.

"Our findings have major global implications, particularly that most of the use of acid-suppression therapy [is] unjustified based on available evidence," he added.

The analysis included studies published through January 2012. Inclusion criteria were that each study had to be an analytical study reporting the effect of acid suppression on CDI incidence, and had to be adjusted for confounders such as antibiotic use.

A total of 30 studies from the United States, United Kingdom, Canada, and Israel met the criteria. There were no randomized clinical trials. Twenty-one were cohort studies, and nine were case-control studies, with a total of 52 effect estimates. All of the included studies were of very good quality, said Dr. Tleyjeh, who is also with the Mayo Clinic, Rochester, Minn.

Separate analyses were done for the different types of studies, and the investigators addressed statistical issues including heterogeneity, publication bias, and residual confounding. Twenty-four studies were from single centers, five were multicenter, two were from general practice research databases, and one was from a general practice clinic. Five studies exclusively addressed community-acquired CDI, 24 addressed hospital-acquired CDI, 1 covered both community- and hospital-acquired CDI, and 1 examined CDI rates in a long-term care facility.

A random-effect meta-analysis revealed that use of acid-suppression therapy (PPIs or H₂ blockers) was associated with a significantly increased risk for CDI, with an odds ratio of 1.58 (95% confidence interval [CI], 1.38-1.80). The pooled proportion of CDI patients who were exposed to antibiotics was 0.70 (95% CI, 0.64-0.75). Thus, on average, 30% of CDI patients were not exposed to antibiotics, based on pharmacy records, discharge summaries, or other data sources, Dr. Tleyjeh noted.

Each of the separate analyses showed a significant association (P less than 0.05) between acid suppression and CDI, with pooled effect estimates of 1.67 for studies investigating PPIs, 1.44 for those looking at H₂ blockers, 1.46 for the cohort studies, and 1.63 for the case-control studies.

Analysis of the heterogeneity between studies revealed that the main driver was an overall lower pooled effect size for the Canadian studies compared with those from the other three countries. Among the Canadian studies, the odds ratio for the effect of acid suppression on CDI was just 1.08, compared with 1.79 for the U.S. studies, 1.91 for the U.K. studies, and 2.52 for the Israeli studies.

The "meta-regression analysis" technique was used to further explore the heterogeneity between studies with regard to study design, study location, journal impact factor, method of ascertainment of antibiotic use, and proportion with antibiotic exposure.

That analysis revealed that the country where the study was performed was a significant independent variable, whereas patient’s sex had a small independent impact. A comparison of different country-specific study characteristics revealed that CDI cases in Canadian studies had a higher exposure to antibiotics than did those in the three other countries, 90% vs. 72%.

Further analysis also revealed that potential publication bias, the tendency for negative studies to remain unpublished, and adjustment for that factor using a novel regression-based method resulted in an adjusted average odds ratio of 1.38 (95% CI, 1.21-1.58). "So, there is resistant association even if we assume there is [publication] bias and we adjust for it," Dr. Tleyjeh said.

Because the included studies were all observational, a final sensitivity analysis was done to assess the possible effect of unknown and unmeasured confounders. This revealed that an unmeasured confounder would have to be severely imbalanced between the acid-suppression users and nonusers, by an odds ratio of 10, or would have to increase the risk of CDI by at least twofold to account for this association. Such a confounder would have to be even stronger than antibiotic use, he commented.

The exact reason for the association between acid suppression and CDI has not been clearly elucidated. Gastric acid does not kill C. difficile spores, but it does kill the vegetative form of C. difficile, the survival of which with acid-suppression therapy could play a role in pathogenesis. Acid-suppression therapy has also been shown to delay gastric emptying, which could improve survival of the vegetative form, he explained.

Dr. Tleyjeh stated that he had no relevant financial disclosures.

LONDON – The use of acid-suppression therapy was associated with a significantly increased risk for Clostridium difficile infection in a systematic review and meta-analysis of data from 30 studies.

Previous observational studies have suggested a link between proton pump inhibitor (PPI) use and an increased risk of developing Clostridium difficile infection (CDI). In February, the Food and Drug Administration issued an alert about the use of PPIs because of the increased CDI risk.

This new meta-analysis supports this association, with a significantly increased risk of CDI with acid suppression (odds ratio, 1.58; P less than .05), Dr. Iman Tleyjeh said at the European Congress of Clinical Microbiology and Infectious Diseases.

"We found a robust association between acid-suppression therapy and the appearance of CDI," said Dr. Tleyjeh, director of the research and scientific publication center and a consultant in infectious disease at King Fahad Medical City, Riyadh, Saudi Arabia.

"Our findings have major global implications, particularly that most of the use of acid-suppression therapy [is] unjustified based on available evidence," he added.

The analysis included studies published through January 2012. Inclusion criteria were that each study had to be an analytical study reporting the effect of acid suppression on CDI incidence, and had to be adjusted for confounders such as antibiotic use.

A total of 30 studies from the United States, United Kingdom, Canada, and Israel met the criteria. There were no randomized clinical trials. Twenty-one were cohort studies, and nine were case-control studies, with a total of 52 effect estimates. All of the included studies were of very good quality, said Dr. Tleyjeh, who is also with the Mayo Clinic, Rochester, Minn.

Separate analyses were done for the different types of studies, and the investigators addressed statistical issues including heterogeneity, publication bias, and residual confounding. Twenty-four studies were from single centers, five were multicenter, two were from general practice research databases, and one was from a general practice clinic. Five studies exclusively addressed community-acquired CDI, 24 addressed hospital-acquired CDI, 1 covered both community- and hospital-acquired CDI, and 1 examined CDI rates in a long-term care facility.

A random-effect meta-analysis revealed that use of acid-suppression therapy (PPIs or H₂ blockers) was associated with a significantly increased risk for CDI, with an odds ratio of 1.58 (95% confidence interval [CI], 1.38-1.80). The pooled proportion of CDI patients who were exposed to antibiotics was 0.70 (95% CI, 0.64-0.75). Thus, on average, 30% of CDI patients were not exposed to antibiotics, based on pharmacy records, discharge summaries, or other data sources, Dr. Tleyjeh noted.

Each of the separate analyses showed a significant association (P less than 0.05) between acid suppression and CDI, with pooled effect estimates of 1.67 for studies investigating PPIs, 1.44 for those looking at H₂ blockers, 1.46 for the cohort studies, and 1.63 for the case-control studies.

Analysis of the heterogeneity between studies revealed that the main driver was an overall lower pooled effect size for the Canadian studies compared with those from the other three countries. Among the Canadian studies, the odds ratio for the effect of acid suppression on CDI was just 1.08, compared with 1.79 for the U.S. studies, 1.91 for the U.K. studies, and 2.52 for the Israeli studies.

The "meta-regression analysis" technique was used to further explore the heterogeneity between studies with regard to study design, study location, journal impact factor, method of ascertainment of antibiotic use, and proportion with antibiotic exposure.

That analysis revealed that the country where the study was performed was a significant independent variable, whereas patient’s sex had a small independent impact. A comparison of different country-specific study characteristics revealed that CDI cases in Canadian studies had a higher exposure to antibiotics than did those in the three other countries, 90% vs. 72%.

Further analysis also revealed that potential publication bias, the tendency for negative studies to remain unpublished, and adjustment for that factor using a novel regression-based method resulted in an adjusted average odds ratio of 1.38 (95% CI, 1.21-1.58). "So, there is resistant association even if we assume there is [publication] bias and we adjust for it," Dr. Tleyjeh said.

Because the included studies were all observational, a final sensitivity analysis was done to assess the possible effect of unknown and unmeasured confounders. This revealed that an unmeasured confounder would have to be severely imbalanced between the acid-suppression users and nonusers, by an odds ratio of 10, or would have to increase the risk of CDI by at least twofold to account for this association. Such a confounder would have to be even stronger than antibiotic use, he commented.

The exact reason for the association between acid suppression and CDI has not been clearly elucidated. Gastric acid does not kill C. difficile spores, but it does kill the vegetative form of C. difficile, the survival of which with acid-suppression therapy could play a role in pathogenesis. Acid-suppression therapy has also been shown to delay gastric emptying, which could improve survival of the vegetative form, he explained.

Dr. Tleyjeh stated that he had no relevant financial disclosures.

LONDON – The use of acid-suppression therapy was associated with a significantly increased risk for Clostridium difficile infection in a systematic review and meta-analysis of data from 30 studies.

Previous observational studies have suggested a link between proton pump inhibitor (PPI) use and an increased risk of developing Clostridium difficile infection (CDI). In February, the Food and Drug Administration issued an alert about the use of PPIs because of the increased CDI risk.

This new meta-analysis supports this association, with a significantly increased risk of CDI with acid suppression (odds ratio, 1.58; P less than .05), Dr. Iman Tleyjeh said at the European Congress of Clinical Microbiology and Infectious Diseases.

"We found a robust association between acid-suppression therapy and the appearance of CDI," said Dr. Tleyjeh, director of the research and scientific publication center and a consultant in infectious disease at King Fahad Medical City, Riyadh, Saudi Arabia.

"Our findings have major global implications, particularly that most of the use of acid-suppression therapy [is] unjustified based on available evidence," he added.

The analysis included studies published through January 2012. Inclusion criteria were that each study had to be an analytical study reporting the effect of acid suppression on CDI incidence, and had to be adjusted for confounders such as antibiotic use.

A total of 30 studies from the United States, United Kingdom, Canada, and Israel met the criteria. There were no randomized clinical trials. Twenty-one were cohort studies, and nine were case-control studies, with a total of 52 effect estimates. All of the included studies were of very good quality, said Dr. Tleyjeh, who is also with the Mayo Clinic, Rochester, Minn.

Separate analyses were done for the different types of studies, and the investigators addressed statistical issues including heterogeneity, publication bias, and residual confounding. Twenty-four studies were from single centers, five were multicenter, two were from general practice research databases, and one was from a general practice clinic. Five studies exclusively addressed community-acquired CDI, 24 addressed hospital-acquired CDI, 1 covered both community- and hospital-acquired CDI, and 1 examined CDI rates in a long-term care facility.

A random-effect meta-analysis revealed that use of acid-suppression therapy (PPIs or H₂ blockers) was associated with a significantly increased risk for CDI, with an odds ratio of 1.58 (95% confidence interval [CI], 1.38-1.80). The pooled proportion of CDI patients who were exposed to antibiotics was 0.70 (95% CI, 0.64-0.75). Thus, on average, 30% of CDI patients were not exposed to antibiotics, based on pharmacy records, discharge summaries, or other data sources, Dr. Tleyjeh noted.

Each of the separate analyses showed a significant association (P less than 0.05) between acid suppression and CDI, with pooled effect estimates of 1.67 for studies investigating PPIs, 1.44 for those looking at H₂ blockers, 1.46 for the cohort studies, and 1.63 for the case-control studies.

Analysis of the heterogeneity between studies revealed that the main driver was an overall lower pooled effect size for the Canadian studies compared with those from the other three countries. Among the Canadian studies, the odds ratio for the effect of acid suppression on CDI was just 1.08, compared with 1.79 for the U.S. studies, 1.91 for the U.K. studies, and 2.52 for the Israeli studies.

The "meta-regression analysis" technique was used to further explore the heterogeneity between studies with regard to study design, study location, journal impact factor, method of ascertainment of antibiotic use, and proportion with antibiotic exposure.

That analysis revealed that the country where the study was performed was a significant independent variable, whereas patient’s sex had a small independent impact. A comparison of different country-specific study characteristics revealed that CDI cases in Canadian studies had a higher exposure to antibiotics than did those in the three other countries, 90% vs. 72%.

Further analysis also revealed that potential publication bias, the tendency for negative studies to remain unpublished, and adjustment for that factor using a novel regression-based method resulted in an adjusted average odds ratio of 1.38 (95% CI, 1.21-1.58). "So, there is resistant association even if we assume there is [publication] bias and we adjust for it," Dr. Tleyjeh said.

Because the included studies were all observational, a final sensitivity analysis was done to assess the possible effect of unknown and unmeasured confounders. This revealed that an unmeasured confounder would have to be severely imbalanced between the acid-suppression users and nonusers, by an odds ratio of 10, or would have to increase the risk of CDI by at least twofold to account for this association. Such a confounder would have to be even stronger than antibiotic use, he commented.

The exact reason for the association between acid suppression and CDI has not been clearly elucidated. Gastric acid does not kill C. difficile spores, but it does kill the vegetative form of C. difficile, the survival of which with acid-suppression therapy could play a role in pathogenesis. Acid-suppression therapy has also been shown to delay gastric emptying, which could improve survival of the vegetative form, he explained.

Dr. Tleyjeh stated that he had no relevant financial disclosures.

LONDON – An elevated red blood cell distribution width predicted poor outcomes from community-acquired pneumonia in a retrospective analysis of more than 3,000 adult patients.

Red blood cell distribution width (RDW) is routinely measured as a check for anemia, but there have been several previous reports that the marker predicts poor outcome in a variety of conditions, including heart failure and sepsis. "It’s used in hematology, but it proves to be an outstanding marker of adverse outcome in some very important diseases of internal medicine. ... We found it actually works in community-acquired pneumonia [CAP] as well," Dr. Eyal Braun said in an interview at the European Congress of Clinical Microbiology and Infectious Diseases.

Last year, Dr. Braun and his associates at Rambam Health Care Campus, Haifa, Israel, reported that among 637 CAP patients aged 60 years and younger, elevated RDW levels on admission were associated with significantly higher rates of mortality and severe morbidity (Crit. Care 2011;15:R194).

The current study looked at the overall general population of internal medicine wards, comprising a total of 3,815 patients aged 18 years and older seen between Jan. 1, 2005, and Dec. 31, 2010. The patients had a mean age of 69.6 years, and 56% were men.

In the multivariate analysis, factors associated with mortality at 90 days were age greater than 80 years, a high Charlson comorbidity index (above 7), a bloodstream infection (BSI), a blood urea nitrogen (BUN) level greater than 30 mg/dL, an abnormal white blood cell (WBC) count, a systolic blood pressure less than 90 mm Hg, and an elevated RDW greater than 15% (odds ratio, 2.1). Variables associated with complicated hospitalization included a high Charlson comorbidity index, an abnormal WBC count, a BUN greater than 30 mg/dL, a hemoglobin level less than 10 g/dL, a BSI on admission, and an elevated RDW (OR 1.5), Dr. Braun reported in a poster.

The rates of mortality and complicated hospitalization were significantly higher among patients with an increased RDW, regardless of the WBC count or hemoglobin levels, he and his associates found.

In the interview, Dr. Braun said that an elevated RDW might help identify which patients who present with CAP need to be admitted to the hospital. Despite many existing scores aimed at identifying increased risk among CAP patients, "people are still dying from CAP. ... The bottom line is mortality from CAP is still high."

Dr. Braun stated that he has no relevant financial disclosures.

LONDON – An elevated red blood cell distribution width predicted poor outcomes from community-acquired pneumonia in a retrospective analysis of more than 3,000 adult patients.

Red blood cell distribution width (RDW) is routinely measured as a check for anemia, but there have been several previous reports that the marker predicts poor outcome in a variety of conditions, including heart failure and sepsis. "It’s used in hematology, but it proves to be an outstanding marker of adverse outcome in some very important diseases of internal medicine. ... We found it actually works in community-acquired pneumonia [CAP] as well," Dr. Eyal Braun said in an interview at the European Congress of Clinical Microbiology and Infectious Diseases.

Last year, Dr. Braun and his associates at Rambam Health Care Campus, Haifa, Israel, reported that among 637 CAP patients aged 60 years and younger, elevated RDW levels on admission were associated with significantly higher rates of mortality and severe morbidity (Crit. Care 2011;15:R194).

The current study looked at the overall general population of internal medicine wards, comprising a total of 3,815 patients aged 18 years and older seen between Jan. 1, 2005, and Dec. 31, 2010. The patients had a mean age of 69.6 years, and 56% were men.

In the multivariate analysis, factors associated with mortality at 90 days were age greater than 80 years, a high Charlson comorbidity index (above 7), a bloodstream infection (BSI), a blood urea nitrogen (BUN) level greater than 30 mg/dL, an abnormal white blood cell (WBC) count, a systolic blood pressure less than 90 mm Hg, and an elevated RDW greater than 15% (odds ratio, 2.1). Variables associated with complicated hospitalization included a high Charlson comorbidity index, an abnormal WBC count, a BUN greater than 30 mg/dL, a hemoglobin level less than 10 g/dL, a BSI on admission, and an elevated RDW (OR 1.5), Dr. Braun reported in a poster.

The rates of mortality and complicated hospitalization were significantly higher among patients with an increased RDW, regardless of the WBC count or hemoglobin levels, he and his associates found.

In the interview, Dr. Braun said that an elevated RDW might help identify which patients who present with CAP need to be admitted to the hospital. Despite many existing scores aimed at identifying increased risk among CAP patients, "people are still dying from CAP. ... The bottom line is mortality from CAP is still high."

Dr. Braun stated that he has no relevant financial disclosures.

LONDON – An elevated red blood cell distribution width predicted poor outcomes from community-acquired pneumonia in a retrospective analysis of more than 3,000 adult patients.

Red blood cell distribution width (RDW) is routinely measured as a check for anemia, but there have been several previous reports that the marker predicts poor outcome in a variety of conditions, including heart failure and sepsis. "It’s used in hematology, but it proves to be an outstanding marker of adverse outcome in some very important diseases of internal medicine. ... We found it actually works in community-acquired pneumonia [CAP] as well," Dr. Eyal Braun said in an interview at the European Congress of Clinical Microbiology and Infectious Diseases.

Last year, Dr. Braun and his associates at Rambam Health Care Campus, Haifa, Israel, reported that among 637 CAP patients aged 60 years and younger, elevated RDW levels on admission were associated with significantly higher rates of mortality and severe morbidity (Crit. Care 2011;15:R194).

The current study looked at the overall general population of internal medicine wards, comprising a total of 3,815 patients aged 18 years and older seen between Jan. 1, 2005, and Dec. 31, 2010. The patients had a mean age of 69.6 years, and 56% were men.

In the multivariate analysis, factors associated with mortality at 90 days were age greater than 80 years, a high Charlson comorbidity index (above 7), a bloodstream infection (BSI), a blood urea nitrogen (BUN) level greater than 30 mg/dL, an abnormal white blood cell (WBC) count, a systolic blood pressure less than 90 mm Hg, and an elevated RDW greater than 15% (odds ratio, 2.1). Variables associated with complicated hospitalization included a high Charlson comorbidity index, an abnormal WBC count, a BUN greater than 30 mg/dL, a hemoglobin level less than 10 g/dL, a BSI on admission, and an elevated RDW (OR 1.5), Dr. Braun reported in a poster.

The rates of mortality and complicated hospitalization were significantly higher among patients with an increased RDW, regardless of the WBC count or hemoglobin levels, he and his associates found.

In the interview, Dr. Braun said that an elevated RDW might help identify which patients who present with CAP need to be admitted to the hospital. Despite many existing scores aimed at identifying increased risk among CAP patients, "people are still dying from CAP. ... The bottom line is mortality from CAP is still high."

Dr. Braun stated that he has no relevant financial disclosures.

LONDON – Hemodialysis and injection drug use were major risk factors for recurrent episodes of infective endocarditis among patients enrolled in a large international prospective study.

Repeat infective endocarditis (IE) is a serious complication of patients who survive an initial episode. In previous studies, the incidence has ranged from 2% to 31%. "Repeat IE is associated with significant mortality. It is an uncommon complication but can be highly relevant among specific groups of patients," Dr. Laura Alagna of San Raffaele Hospital, Milan, said at the European Congress of Clinical Microbiology and Infectious Diseases.

The findings come from The International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS), a contemporary cohort of more than 5,000 patients with infective endocarditis (IE) from 64 centers in 28 countries worldwide. Patients included in the current analysis were those enrolled from June 2000 to December 2006, with a diagnosis of definite IE on native or prosthetic valves who had at least a 1-year follow-up.

Of 1,857 patients who met inclusion criteria, 1,783 had one episode of IE and 91 (5%) had a repeat IE. Of those, 17 had a presumed relapse, defined clinically as infection with the same pathogen isolated within 6 months of the initial episode. The other 74 had a presumed new infection, defined clinically as a repeat episode with a different pathogen or the same pathogen isolated greater than 6 months from the initial episode.

On bivariate analysis, being from North America, infection with Staphylococcus aureus, hemodialysis dependence, intravenous drug use (IDU), HIV infection, history of previous IE, and non-nosocomial health care as a presumed source of infection were all associated with repeat IE. However, on multivariate analysis, only four independent risk factors emerged: North American location (odds ratio, 1.96), hemodialysis (OR, 2.54), IDU (OR, 2.89), and history of previous IE (2.76).

At 1-year follow-up, survival was significantly lower for those with repeat IE, 80% compared to 91% for those with only one episode (P = .0034), Dr. Alagna reported.

Molecular analysis with pulsed-gel electrophoresis performed in 12 of the repeat IE patients demonstrated concordance with the clinical definition in 10, including eight confirmed relapses and two confirmed new infections. Of the other two patients, one had S. aureus with the same molecular pattern isolated more than a year after the first episode. That patient was hemodialysis-dependent and had other risk factors. In the other discordant patient, S. bovis with the same molecular pattern was isolated after nearly 9 months. In that patient, a cardiac device had not been removed during the first episode, she explained.

"The clinical classification of repeat IE is satisfactory, but can be improved with molecular analysis," she concluded.

Dr. Alagna stated that she had no disclosures.

LONDON – Hemodialysis and injection drug use were major risk factors for recurrent episodes of infective endocarditis among patients enrolled in a large international prospective study.

Repeat infective endocarditis (IE) is a serious complication of patients who survive an initial episode. In previous studies, the incidence has ranged from 2% to 31%. "Repeat IE is associated with significant mortality. It is an uncommon complication but can be highly relevant among specific groups of patients," Dr. Laura Alagna of San Raffaele Hospital, Milan, said at the European Congress of Clinical Microbiology and Infectious Diseases.

The findings come from The International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS), a contemporary cohort of more than 5,000 patients with infective endocarditis (IE) from 64 centers in 28 countries worldwide. Patients included in the current analysis were those enrolled from June 2000 to December 2006, with a diagnosis of definite IE on native or prosthetic valves who had at least a 1-year follow-up.

Of 1,857 patients who met inclusion criteria, 1,783 had one episode of IE and 91 (5%) had a repeat IE. Of those, 17 had a presumed relapse, defined clinically as infection with the same pathogen isolated within 6 months of the initial episode. The other 74 had a presumed new infection, defined clinically as a repeat episode with a different pathogen or the same pathogen isolated greater than 6 months from the initial episode.

On bivariate analysis, being from North America, infection with Staphylococcus aureus, hemodialysis dependence, intravenous drug use (IDU), HIV infection, history of previous IE, and non-nosocomial health care as a presumed source of infection were all associated with repeat IE. However, on multivariate analysis, only four independent risk factors emerged: North American location (odds ratio, 1.96), hemodialysis (OR, 2.54), IDU (OR, 2.89), and history of previous IE (2.76).

At 1-year follow-up, survival was significantly lower for those with repeat IE, 80% compared to 91% for those with only one episode (P = .0034), Dr. Alagna reported.

Molecular analysis with pulsed-gel electrophoresis performed in 12 of the repeat IE patients demonstrated concordance with the clinical definition in 10, including eight confirmed relapses and two confirmed new infections. Of the other two patients, one had S. aureus with the same molecular pattern isolated more than a year after the first episode. That patient was hemodialysis-dependent and had other risk factors. In the other discordant patient, S. bovis with the same molecular pattern was isolated after nearly 9 months. In that patient, a cardiac device had not been removed during the first episode, she explained.

"The clinical classification of repeat IE is satisfactory, but can be improved with molecular analysis," she concluded.

Dr. Alagna stated that she had no disclosures.

LONDON – Hemodialysis and injection drug use were major risk factors for recurrent episodes of infective endocarditis among patients enrolled in a large international prospective study.

Repeat infective endocarditis (IE) is a serious complication of patients who survive an initial episode. In previous studies, the incidence has ranged from 2% to 31%. "Repeat IE is associated with significant mortality. It is an uncommon complication but can be highly relevant among specific groups of patients," Dr. Laura Alagna of San Raffaele Hospital, Milan, said at the European Congress of Clinical Microbiology and Infectious Diseases.

The findings come from The International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS), a contemporary cohort of more than 5,000 patients with infective endocarditis (IE) from 64 centers in 28 countries worldwide. Patients included in the current analysis were those enrolled from June 2000 to December 2006, with a diagnosis of definite IE on native or prosthetic valves who had at least a 1-year follow-up.

Of 1,857 patients who met inclusion criteria, 1,783 had one episode of IE and 91 (5%) had a repeat IE. Of those, 17 had a presumed relapse, defined clinically as infection with the same pathogen isolated within 6 months of the initial episode. The other 74 had a presumed new infection, defined clinically as a repeat episode with a different pathogen or the same pathogen isolated greater than 6 months from the initial episode.

On bivariate analysis, being from North America, infection with Staphylococcus aureus, hemodialysis dependence, intravenous drug use (IDU), HIV infection, history of previous IE, and non-nosocomial health care as a presumed source of infection were all associated with repeat IE. However, on multivariate analysis, only four independent risk factors emerged: North American location (odds ratio, 1.96), hemodialysis (OR, 2.54), IDU (OR, 2.89), and history of previous IE (2.76).

At 1-year follow-up, survival was significantly lower for those with repeat IE, 80% compared to 91% for those with only one episode (P = .0034), Dr. Alagna reported.

Molecular analysis with pulsed-gel electrophoresis performed in 12 of the repeat IE patients demonstrated concordance with the clinical definition in 10, including eight confirmed relapses and two confirmed new infections. Of the other two patients, one had S. aureus with the same molecular pattern isolated more than a year after the first episode. That patient was hemodialysis-dependent and had other risk factors. In the other discordant patient, S. bovis with the same molecular pattern was isolated after nearly 9 months. In that patient, a cardiac device had not been removed during the first episode, she explained.

"The clinical classification of repeat IE is satisfactory, but can be improved with molecular analysis," she concluded.

Dr. Alagna stated that she had no disclosures.