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

AT ECCMID 2016

AMSTERDAM – Daptomycin successfully treated infective endocarditis in 90% of patients who developed it after undergoing heart valve replacement, according to a report presented at the annual congress of the European Society of Clinical Microbiology and Infectious Diseases.

Dr. Achyut Guleri, clinical director of laboratory medicine at Blackpool Victoria Hospital, Lancashire, England, said the lipopeptide antibiotic was equally effective against methicillin- and penicillin-resistant Staphylococcus aureus, coagulase-negative staphylococcus, and enterococci.

“This is particularly good to know because sometimes in real life, on the shop floor, you don’t always have a very clear insight into what you’re trying to treat,” said Dr. Guleri. “It’s reassuring to see that the success rate is similar in all these infections.”

He presented a subgroup analysis of patients enrolled in European Cubicin Outcomes Registry and Experience (EUCORE), a retrospective, noninterventional, postmarketing registry. The 4-year study reported real-world clinical experience of daptomycin use for the treatment of Gram-positive infections in patients with infective endocarditis who had undergone heart valve replacement.

Typically, Dr. Guleri said, vancomycin, either alone or with rifampicin, is recommended for the infection. “However, with increasing antibiotic resistance, vancomycin doesn’t inspire much confidence, especially for MRSA infections,” he noted.

Daptomycin is increasingly employed as an alternative treatment. It exhibits rapid bactericidal activity against a wide range of Gram-positive pathogens, including MRSA. It’s approved for the treatment of right-sided infective endocarditis due to S. aureus, at a dose of 6 mg/kg per day. However, higher doses are now recommended by several international guidelines and are often used for hard-to-treat infections, Dr. Guleri said.

EUCORE comprised 6,075 patients from 18 countries who were enrolled from 2006 to 2012. Patients were followed until 2014. Of this group, 610 had infective endocarditis and 198 underwent valve replacement. Most were male (70%); mean age was 58 years. Medical comorbidities were common and included renal disease, sepsis, diabetes, pulmonary disease, gastrointestinal disease, cerebrovascular disease and inflammatory diseases.

Culture results were available for 87%. Of these, 68% were positive. The most common pathogen was S. aureus (37%). Half of these isolates were penicillin resistant and 35% were methicillin resistant. Enterococci were responsible for 14% of the infections, and coagulase-negative staph for 32%. The rest were caused by other pathogens.

Before trying daptomycin, most patients (83%) had already been treated with an antibiotic, which was employed in conjunction with another antibiotic in 77% of cases. The concomitant medications included rifampicin (31%), aminoglycosides (29%) and carbapenems (18%).

The overall clinical cure rate at 2 years was 90%. Daptomycin was equally effective in left- and right-sided disease, and was more effective in penicillin-resistant staph (95%) than methicillin-resistant staph (80%). The cure rate was also good in coagulase-negative staph (81%) and enterococci (75%).

High doses were more effective than low doses. At 4 mg/kg per day, the cure rate was 61%. At 6 mg/kg per day, it was 86%, and at more than 6 mg/kg per day, it was 90%.

Adverse events were rare (3%). Three patients developed increased creatine phosphokinase levels; one patient developed rhabdomyolysis and one developed cholestasis. Agranulocytosis developed in three patients and eosinophilic pneumonia in three. One patient developed a rash. No one discontinued the drug due to a side effect.

Dr. Guleri had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

AT ECCMID 2016

AMSTERDAM – Daptomycin successfully treated infective endocarditis in 90% of patients who developed it after undergoing heart valve replacement, according to a report presented at the annual congress of the European Society of Clinical Microbiology and Infectious Diseases.

Dr. Achyut Guleri, clinical director of laboratory medicine at Blackpool Victoria Hospital, Lancashire, England, said the lipopeptide antibiotic was equally effective against methicillin- and penicillin-resistant Staphylococcus aureus, coagulase-negative staphylococcus, and enterococci.

“This is particularly good to know because sometimes in real life, on the shop floor, you don’t always have a very clear insight into what you’re trying to treat,” said Dr. Guleri. “It’s reassuring to see that the success rate is similar in all these infections.”

He presented a subgroup analysis of patients enrolled in European Cubicin Outcomes Registry and Experience (EUCORE), a retrospective, noninterventional, postmarketing registry. The 4-year study reported real-world clinical experience of daptomycin use for the treatment of Gram-positive infections in patients with infective endocarditis who had undergone heart valve replacement.

Typically, Dr. Guleri said, vancomycin, either alone or with rifampicin, is recommended for the infection. “However, with increasing antibiotic resistance, vancomycin doesn’t inspire much confidence, especially for MRSA infections,” he noted.

Daptomycin is increasingly employed as an alternative treatment. It exhibits rapid bactericidal activity against a wide range of Gram-positive pathogens, including MRSA. It’s approved for the treatment of right-sided infective endocarditis due to S. aureus, at a dose of 6 mg/kg per day. However, higher doses are now recommended by several international guidelines and are often used for hard-to-treat infections, Dr. Guleri said.

EUCORE comprised 6,075 patients from 18 countries who were enrolled from 2006 to 2012. Patients were followed until 2014. Of this group, 610 had infective endocarditis and 198 underwent valve replacement. Most were male (70%); mean age was 58 years. Medical comorbidities were common and included renal disease, sepsis, diabetes, pulmonary disease, gastrointestinal disease, cerebrovascular disease and inflammatory diseases.

Culture results were available for 87%. Of these, 68% were positive. The most common pathogen was S. aureus (37%). Half of these isolates were penicillin resistant and 35% were methicillin resistant. Enterococci were responsible for 14% of the infections, and coagulase-negative staph for 32%. The rest were caused by other pathogens.

Before trying daptomycin, most patients (83%) had already been treated with an antibiotic, which was employed in conjunction with another antibiotic in 77% of cases. The concomitant medications included rifampicin (31%), aminoglycosides (29%) and carbapenems (18%).

The overall clinical cure rate at 2 years was 90%. Daptomycin was equally effective in left- and right-sided disease, and was more effective in penicillin-resistant staph (95%) than methicillin-resistant staph (80%). The cure rate was also good in coagulase-negative staph (81%) and enterococci (75%).

High doses were more effective than low doses. At 4 mg/kg per day, the cure rate was 61%. At 6 mg/kg per day, it was 86%, and at more than 6 mg/kg per day, it was 90%.

Adverse events were rare (3%). Three patients developed increased creatine phosphokinase levels; one patient developed rhabdomyolysis and one developed cholestasis. Agranulocytosis developed in three patients and eosinophilic pneumonia in three. One patient developed a rash. No one discontinued the drug due to a side effect.

Dr. Guleri had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

AT ECCMID 2016

AMSTERDAM – Daptomycin successfully treated infective endocarditis in 90% of patients who developed it after undergoing heart valve replacement, according to a report presented at the annual congress of the European Society of Clinical Microbiology and Infectious Diseases.

Dr. Achyut Guleri, clinical director of laboratory medicine at Blackpool Victoria Hospital, Lancashire, England, said the lipopeptide antibiotic was equally effective against methicillin- and penicillin-resistant Staphylococcus aureus, coagulase-negative staphylococcus, and enterococci.

“This is particularly good to know because sometimes in real life, on the shop floor, you don’t always have a very clear insight into what you’re trying to treat,” said Dr. Guleri. “It’s reassuring to see that the success rate is similar in all these infections.”

He presented a subgroup analysis of patients enrolled in European Cubicin Outcomes Registry and Experience (EUCORE), a retrospective, noninterventional, postmarketing registry. The 4-year study reported real-world clinical experience of daptomycin use for the treatment of Gram-positive infections in patients with infective endocarditis who had undergone heart valve replacement.

Typically, Dr. Guleri said, vancomycin, either alone or with rifampicin, is recommended for the infection. “However, with increasing antibiotic resistance, vancomycin doesn’t inspire much confidence, especially for MRSA infections,” he noted.

Daptomycin is increasingly employed as an alternative treatment. It exhibits rapid bactericidal activity against a wide range of Gram-positive pathogens, including MRSA. It’s approved for the treatment of right-sided infective endocarditis due to S. aureus, at a dose of 6 mg/kg per day. However, higher doses are now recommended by several international guidelines and are often used for hard-to-treat infections, Dr. Guleri said.

EUCORE comprised 6,075 patients from 18 countries who were enrolled from 2006 to 2012. Patients were followed until 2014. Of this group, 610 had infective endocarditis and 198 underwent valve replacement. Most were male (70%); mean age was 58 years. Medical comorbidities were common and included renal disease, sepsis, diabetes, pulmonary disease, gastrointestinal disease, cerebrovascular disease and inflammatory diseases.

Culture results were available for 87%. Of these, 68% were positive. The most common pathogen was S. aureus (37%). Half of these isolates were penicillin resistant and 35% were methicillin resistant. Enterococci were responsible for 14% of the infections, and coagulase-negative staph for 32%. The rest were caused by other pathogens.

Before trying daptomycin, most patients (83%) had already been treated with an antibiotic, which was employed in conjunction with another antibiotic in 77% of cases. The concomitant medications included rifampicin (31%), aminoglycosides (29%) and carbapenems (18%).

The overall clinical cure rate at 2 years was 90%. Daptomycin was equally effective in left- and right-sided disease, and was more effective in penicillin-resistant staph (95%) than methicillin-resistant staph (80%). The cure rate was also good in coagulase-negative staph (81%) and enterococci (75%).

High doses were more effective than low doses. At 4 mg/kg per day, the cure rate was 61%. At 6 mg/kg per day, it was 86%, and at more than 6 mg/kg per day, it was 90%.

Adverse events were rare (3%). Three patients developed increased creatine phosphokinase levels; one patient developed rhabdomyolysis and one developed cholestasis. Agranulocytosis developed in three patients and eosinophilic pneumonia in three. One patient developed a rash. No one discontinued the drug due to a side effect.

Dr. Guleri had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

AMSTERDAM – Neither cycling through a regular schedule of antibiotics on a unit-wide basis, nor randomly mixing them on a patient-level basis reduced the prevalence of antibiotic resistance in eight European intensive care units, a randomized study has determined.

Lead investigator Dr. Pleun Joppe van Duijn of University Medical Center Utrecht (the Netherlands), said he and his colleagues did, however, discover a few common sense findings that seemed to positively affect antibiotic resistance, including compliance with hand hygiene, shorter lengths of stay, staff ratio, and unit occupancy rate. He reported the results of his research at the European Society of Clinical Microbiology and Infectious Diseases annual congress.

Edwin Verin/©Thinkstock

Many ICUs in Europe have one preferred empirical treatment strategy which, Dr. van Duijn said, may create selective pressure for a single resistance type. “An alternative to this is a program of antibiotic rotation,” he noted. “By constantly changing the preferred first-line treatment, selective pressure is constantly changing, which may reduce selection of antibiotic resistance.”

Dr. van Duijn and his colleagues examined this idea in a randomized crossover trial that compared antibiotic cycling and mixing. The protocols employed three antibiotic classes: third- and fourth-generation cephalosporins, piperacillin/tazobactam, and carbapenems. The trial was conducted in eight ICUs in Belgium, Germany, France, Slovenia, and Portugal.

The sites were randomized to two 9-month interventions of cycling or mixing antibiotics, with a 1-month washout period between the two interventions. In cycling protocol, the preferred empiric antibiotic was changed every 6 weeks. In the mixing protocol, every consecutive patient received a different antibiotic. However, treating physicians were allowed to deviate from any protocol for patient safety or to optimize treatment.

The primary endpoint was the monthly prevalence of perineal and/or respiratory carriage of two classes of bacteria:

• Enterobacteriaceae species that were piperacillin/tazobactam–resistant or that showed extended spectrum beta-lactamase production.

• Pseudomonas aeruginosa and Acinetobacter species that were either piperacillin/tazobactam– or carbapenem-resistant.

In all, 8,945 patients were involved, with 4,238 exposed to cycling and 4,707 to mixing. Patients were a mean of 62 years old, with a mean 7-day length of stay. About 4.5% were already colonized with resistant bacteria upon admission. A quarter were on contact isolation; 2% were on both droplet and respiratory isolation.

The overall mortality rate was 11% and did not differ between the cycling and mixing groups (10.9% vs. 11.6%). Antibiotic resistance developed in 22.6% of the cycling group and 21.5% of the mixing group – not a significant difference. Neither protocol significantly reduced over time the amount of antibiotic resistance that was observed in the baseline period.

A multivariate analysis did, however, find a few things associated with resistance prevalence. Women were about 58% less likely to develop a resistant bacterial strain than men. Patients who stayed less than 48 hours had a 38% decreased risk of developing a resistant strain. Good staff compliance with hand hygiene reduced the risk by 12%, and having one-on-one nursing reduced it by 53%.

The study was funded by the European Community’s Seventh Framework Programme. Dr. van Duijn had no financial declarations.

msullivan@frontlinemedcom.com

AMSTERDAM – Neither cycling through a regular schedule of antibiotics on a unit-wide basis, nor randomly mixing them on a patient-level basis reduced the prevalence of antibiotic resistance in eight European intensive care units, a randomized study has determined.

Lead investigator Dr. Pleun Joppe van Duijn of University Medical Center Utrecht (the Netherlands), said he and his colleagues did, however, discover a few common sense findings that seemed to positively affect antibiotic resistance, including compliance with hand hygiene, shorter lengths of stay, staff ratio, and unit occupancy rate. He reported the results of his research at the European Society of Clinical Microbiology and Infectious Diseases annual congress.

Edwin Verin/©Thinkstock

Many ICUs in Europe have one preferred empirical treatment strategy which, Dr. van Duijn said, may create selective pressure for a single resistance type. “An alternative to this is a program of antibiotic rotation,” he noted. “By constantly changing the preferred first-line treatment, selective pressure is constantly changing, which may reduce selection of antibiotic resistance.”

Dr. van Duijn and his colleagues examined this idea in a randomized crossover trial that compared antibiotic cycling and mixing. The protocols employed three antibiotic classes: third- and fourth-generation cephalosporins, piperacillin/tazobactam, and carbapenems. The trial was conducted in eight ICUs in Belgium, Germany, France, Slovenia, and Portugal.

The sites were randomized to two 9-month interventions of cycling or mixing antibiotics, with a 1-month washout period between the two interventions. In cycling protocol, the preferred empiric antibiotic was changed every 6 weeks. In the mixing protocol, every consecutive patient received a different antibiotic. However, treating physicians were allowed to deviate from any protocol for patient safety or to optimize treatment.

The primary endpoint was the monthly prevalence of perineal and/or respiratory carriage of two classes of bacteria:

• Enterobacteriaceae species that were piperacillin/tazobactam–resistant or that showed extended spectrum beta-lactamase production.

• Pseudomonas aeruginosa and Acinetobacter species that were either piperacillin/tazobactam– or carbapenem-resistant.

In all, 8,945 patients were involved, with 4,238 exposed to cycling and 4,707 to mixing. Patients were a mean of 62 years old, with a mean 7-day length of stay. About 4.5% were already colonized with resistant bacteria upon admission. A quarter were on contact isolation; 2% were on both droplet and respiratory isolation.

The overall mortality rate was 11% and did not differ between the cycling and mixing groups (10.9% vs. 11.6%). Antibiotic resistance developed in 22.6% of the cycling group and 21.5% of the mixing group – not a significant difference. Neither protocol significantly reduced over time the amount of antibiotic resistance that was observed in the baseline period.

A multivariate analysis did, however, find a few things associated with resistance prevalence. Women were about 58% less likely to develop a resistant bacterial strain than men. Patients who stayed less than 48 hours had a 38% decreased risk of developing a resistant strain. Good staff compliance with hand hygiene reduced the risk by 12%, and having one-on-one nursing reduced it by 53%.

The study was funded by the European Community’s Seventh Framework Programme. Dr. van Duijn had no financial declarations.

msullivan@frontlinemedcom.com

AMSTERDAM – Neither cycling through a regular schedule of antibiotics on a unit-wide basis, nor randomly mixing them on a patient-level basis reduced the prevalence of antibiotic resistance in eight European intensive care units, a randomized study has determined.

Lead investigator Dr. Pleun Joppe van Duijn of University Medical Center Utrecht (the Netherlands), said he and his colleagues did, however, discover a few common sense findings that seemed to positively affect antibiotic resistance, including compliance with hand hygiene, shorter lengths of stay, staff ratio, and unit occupancy rate. He reported the results of his research at the European Society of Clinical Microbiology and Infectious Diseases annual congress.

Edwin Verin/©Thinkstock

Many ICUs in Europe have one preferred empirical treatment strategy which, Dr. van Duijn said, may create selective pressure for a single resistance type. “An alternative to this is a program of antibiotic rotation,” he noted. “By constantly changing the preferred first-line treatment, selective pressure is constantly changing, which may reduce selection of antibiotic resistance.”

Dr. van Duijn and his colleagues examined this idea in a randomized crossover trial that compared antibiotic cycling and mixing. The protocols employed three antibiotic classes: third- and fourth-generation cephalosporins, piperacillin/tazobactam, and carbapenems. The trial was conducted in eight ICUs in Belgium, Germany, France, Slovenia, and Portugal.

The sites were randomized to two 9-month interventions of cycling or mixing antibiotics, with a 1-month washout period between the two interventions. In cycling protocol, the preferred empiric antibiotic was changed every 6 weeks. In the mixing protocol, every consecutive patient received a different antibiotic. However, treating physicians were allowed to deviate from any protocol for patient safety or to optimize treatment.

The primary endpoint was the monthly prevalence of perineal and/or respiratory carriage of two classes of bacteria:

• Enterobacteriaceae species that were piperacillin/tazobactam–resistant or that showed extended spectrum beta-lactamase production.

• Pseudomonas aeruginosa and Acinetobacter species that were either piperacillin/tazobactam– or carbapenem-resistant.

In all, 8,945 patients were involved, with 4,238 exposed to cycling and 4,707 to mixing. Patients were a mean of 62 years old, with a mean 7-day length of stay. About 4.5% were already colonized with resistant bacteria upon admission. A quarter were on contact isolation; 2% were on both droplet and respiratory isolation.

The overall mortality rate was 11% and did not differ between the cycling and mixing groups (10.9% vs. 11.6%). Antibiotic resistance developed in 22.6% of the cycling group and 21.5% of the mixing group – not a significant difference. Neither protocol significantly reduced over time the amount of antibiotic resistance that was observed in the baseline period.

A multivariate analysis did, however, find a few things associated with resistance prevalence. Women were about 58% less likely to develop a resistant bacterial strain than men. Patients who stayed less than 48 hours had a 38% decreased risk of developing a resistant strain. Good staff compliance with hand hygiene reduced the risk by 12%, and having one-on-one nursing reduced it by 53%.

The study was funded by the European Community’s Seventh Framework Programme. Dr. van Duijn had no financial declarations.

msullivan@frontlinemedcom.com

AMSTERDAM – Infection is a major cause of death among patients waiting for a liver transplant, killing more than half of those who contracted one.

Infection also was the biggest reason that patients with end-stage liver disease withdrew from the transplant waiting list, a 9-year-long study has shown. Patients who developed an infection were six times more likely to withdraw than were those who did not, Dr. Loes Alferink wrote in a poster presented at the European Society of Clinical Microbiology and Infectious Diseases annual congress.

“We need to focus on better prophylactic antibiotic strategies to save lives in patients with end-stage liver disease who are on the waiting list,” said Dr. Alferink of Erasmus Medical Center, Rotterdam, the Netherlands.

She and her colleagues examined the effect of infections on 312 patients who were waiting for a transplant at Erasmus Medical Center from the period of 2006-2013. During that time, a total of 317 infections developed in 144 patients. The infections were fatal in 58% of these patients.

These included spontaneous primary cholangitis (75); spontaneous bacterial peritonitis (61); urogenital (38), respiratory (30), and skin (25) infections; as well as primary bacteremia (22). Also, there were 18 cases of gastroenteritis and 12 cases of Candida esophagitis. The remainder were unspecified infections.

The death rate was highest in primary bacteremia, which killed about 40% of those who developed it. The rate was about 25% in respiratory infections, 20% in spontaneous primary bacteremia, 15% in esophagitis, 10% in gastroenteritis and urinary tract infections, and 10% in patients with multiple site infections.

The pathogens were gram negative (70) and gram positive (37) bacteria; Enterococcus faecium (15) and faecalis (3); yeasts (13); viruses (7); and mold (2). The remainder of the infections yielded a negative culture.

In 24 patients, multiple pathogens were identified. These patients had the highest rate of mortality, with almost half of them dying from their infection; one of the two patients with a mold infection also died. The death rate was 20% in patients with yeast infections, 18% in those with E. faecium, 15% in gram-positive infections, and 10% in gram-negative infections.

A multivariate analysis found several factors that increased the risk of dying from an infection. For every 10 years of increasing age, the risk of infection-related mortality doubled (odds ratio, 2); worse MELD (Model for End-Stage Liver Disease) scores increased the risk by 12%.

Patients with hepatic encephalopathy were 76% more likely to die from an infection, and those with refractory ascites faced a 2.5-fold increased risk. Mechanical ventilation was associated with more than a fivefold increased risk (OR, 5.72).

Patients who developed an infection were almost six times more likely to be withdrawn from the transplant waiting list (hazard ratio, 5.87). The regression analysis for withdrawal identified several factors that significantly increased the risk, including age, MELD score, and serum albumin. The biggest risk factor for withdrawal related to infection was refractory ascites, which more than doubled the risk (HR, 2.2).

Dr. Alferink had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

AMSTERDAM – Infection is a major cause of death among patients waiting for a liver transplant, killing more than half of those who contracted one.

Infection also was the biggest reason that patients with end-stage liver disease withdrew from the transplant waiting list, a 9-year-long study has shown. Patients who developed an infection were six times more likely to withdraw than were those who did not, Dr. Loes Alferink wrote in a poster presented at the European Society of Clinical Microbiology and Infectious Diseases annual congress.

“We need to focus on better prophylactic antibiotic strategies to save lives in patients with end-stage liver disease who are on the waiting list,” said Dr. Alferink of Erasmus Medical Center, Rotterdam, the Netherlands.

She and her colleagues examined the effect of infections on 312 patients who were waiting for a transplant at Erasmus Medical Center from the period of 2006-2013. During that time, a total of 317 infections developed in 144 patients. The infections were fatal in 58% of these patients.

These included spontaneous primary cholangitis (75); spontaneous bacterial peritonitis (61); urogenital (38), respiratory (30), and skin (25) infections; as well as primary bacteremia (22). Also, there were 18 cases of gastroenteritis and 12 cases of Candida esophagitis. The remainder were unspecified infections.

The death rate was highest in primary bacteremia, which killed about 40% of those who developed it. The rate was about 25% in respiratory infections, 20% in spontaneous primary bacteremia, 15% in esophagitis, 10% in gastroenteritis and urinary tract infections, and 10% in patients with multiple site infections.

The pathogens were gram negative (70) and gram positive (37) bacteria; Enterococcus faecium (15) and faecalis (3); yeasts (13); viruses (7); and mold (2). The remainder of the infections yielded a negative culture.

In 24 patients, multiple pathogens were identified. These patients had the highest rate of mortality, with almost half of them dying from their infection; one of the two patients with a mold infection also died. The death rate was 20% in patients with yeast infections, 18% in those with E. faecium, 15% in gram-positive infections, and 10% in gram-negative infections.

A multivariate analysis found several factors that increased the risk of dying from an infection. For every 10 years of increasing age, the risk of infection-related mortality doubled (odds ratio, 2); worse MELD (Model for End-Stage Liver Disease) scores increased the risk by 12%.

Patients with hepatic encephalopathy were 76% more likely to die from an infection, and those with refractory ascites faced a 2.5-fold increased risk. Mechanical ventilation was associated with more than a fivefold increased risk (OR, 5.72).

Patients who developed an infection were almost six times more likely to be withdrawn from the transplant waiting list (hazard ratio, 5.87). The regression analysis for withdrawal identified several factors that significantly increased the risk, including age, MELD score, and serum albumin. The biggest risk factor for withdrawal related to infection was refractory ascites, which more than doubled the risk (HR, 2.2).

Dr. Alferink had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

AMSTERDAM – Infection is a major cause of death among patients waiting for a liver transplant, killing more than half of those who contracted one.

Infection also was the biggest reason that patients with end-stage liver disease withdrew from the transplant waiting list, a 9-year-long study has shown. Patients who developed an infection were six times more likely to withdraw than were those who did not, Dr. Loes Alferink wrote in a poster presented at the European Society of Clinical Microbiology and Infectious Diseases annual congress.

“We need to focus on better prophylactic antibiotic strategies to save lives in patients with end-stage liver disease who are on the waiting list,” said Dr. Alferink of Erasmus Medical Center, Rotterdam, the Netherlands.

She and her colleagues examined the effect of infections on 312 patients who were waiting for a transplant at Erasmus Medical Center from the period of 2006-2013. During that time, a total of 317 infections developed in 144 patients. The infections were fatal in 58% of these patients.

These included spontaneous primary cholangitis (75); spontaneous bacterial peritonitis (61); urogenital (38), respiratory (30), and skin (25) infections; as well as primary bacteremia (22). Also, there were 18 cases of gastroenteritis and 12 cases of Candida esophagitis. The remainder were unspecified infections.

The death rate was highest in primary bacteremia, which killed about 40% of those who developed it. The rate was about 25% in respiratory infections, 20% in spontaneous primary bacteremia, 15% in esophagitis, 10% in gastroenteritis and urinary tract infections, and 10% in patients with multiple site infections.

The pathogens were gram negative (70) and gram positive (37) bacteria; Enterococcus faecium (15) and faecalis (3); yeasts (13); viruses (7); and mold (2). The remainder of the infections yielded a negative culture.

In 24 patients, multiple pathogens were identified. These patients had the highest rate of mortality, with almost half of them dying from their infection; one of the two patients with a mold infection also died. The death rate was 20% in patients with yeast infections, 18% in those with E. faecium, 15% in gram-positive infections, and 10% in gram-negative infections.

A multivariate analysis found several factors that increased the risk of dying from an infection. For every 10 years of increasing age, the risk of infection-related mortality doubled (odds ratio, 2); worse MELD (Model for End-Stage Liver Disease) scores increased the risk by 12%.

Patients with hepatic encephalopathy were 76% more likely to die from an infection, and those with refractory ascites faced a 2.5-fold increased risk. Mechanical ventilation was associated with more than a fivefold increased risk (OR, 5.72).

Patients who developed an infection were almost six times more likely to be withdrawn from the transplant waiting list (hazard ratio, 5.87). The regression analysis for withdrawal identified several factors that significantly increased the risk, including age, MELD score, and serum albumin. The biggest risk factor for withdrawal related to infection was refractory ascites, which more than doubled the risk (HR, 2.2).

Dr. Alferink had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

AMSTERDAM – Intravenous tigecycline was significantly more effective than standard therapy at curing refractory Clostridium difficile infections, according to a case-control study presented at the European Society of Clinical Microbiology and Infectious Diseases annual congress.

Tigecycline effected a 76% clinical cure rate, compared with 53% for the combination regimen of intravenous metronidazole and oral vancomycin, Dr. Baltin Gergely Szabo reported. And despite the fact that those who took tigecycline had more clinically severe disease, no colectomies were required in that group, while two patients in the standard treatment arm did need the procedure.

However, tigecycline didn’t significantly improve relapse rates or mortality, noted Dr. Szabo of the St. Stephan and St. Ladislaus Hospital-Clinic, Budapest, Hungary.

He presented the results of a matched case-control study of 90 patients with severe C. difficile infections, who were treated with either of the protocols. Patients who took tigecycline were more likely to have a recurrent infection (38% vs. 29%). Thus, they were also more likely to have previously been treated with metronidazole (38% vs. 24%) and vancomycin (24% vs. 7%). Prior tigecycline use was very rare in both groups (2% vs. 0%).

Those who took tigecycline were significantly younger as well (72 vs. 78 years), and more often men (56% vs. 30%). They were more likely to be hypertensive, have chronic obstructive pulmonary disease, have cancers, be immunosuppressed, and be chronic users of corticosteroids.

However, the Charlson comorbidity index was similar between the tigecycline and standard therapy groups (4.6 vs. 5). They were also matched for ATLAS scores (mean 7.8 in each group).

Significantly more patients taking tigecycline had acquired their infections during hospitalization (64% vs. 30%). They also had a longer duration of symptoms (17 vs. 10 days).

Imaging showed more severe disease in the tigecycline group with significantly more colonic distension, mural thickening, and ascites. Tigecycline patients had also undergone significantly more colonoscopies and blood cultures.

Tigecycline was given in the hospital for 7-10 days, with a 100-mg loading dose and subsequent 50-mg daily doses. The main duration of therapy was 10 days, but that varied widely, from 2 to 22 days. It was given only as first-line treatment to 15% of patients; the rest received tigecycline as an alternative treatment, often after the combination of metronidazole/vancomycin had failed. No adverse drug reactions occurred in the group.

Clinical cure was achieved in 76% of the tigecycline group and 53% of the standard protocol group – a significant difference. The drug was associated with a decreased rate of complicated disease course (29% vs. 53%) and significantly fewer colectomies (0 vs. 2).

Rates of toxic megacolon were equal (7% each group); ileus was more frequent in the tigecycline group (11% vs. 9%), but this difference was not statistically significant.

However, tigecycline had no impact on either in-hospital or 90-day relapse, or on in-hospital mortality (15 vs. 16 deaths). At 90 days, fewer patients taking the drug had died (17 vs. 21), but that difference was not statistically significant (P = 0.52).

A multivariate analysis identified several characteristics associated with a beneficial response to tigecycline:

• Male sex.

• Being immunosuppressed.

• Chronic steroid treatment.

• Malignancy.

• Longer duration of symptoms.

• Prior C. difficile infections.

• Nosocomial onset.

• Signs of severe infection on imaging.

Dr. Szabo said these characteristics can be used to create a profile of patients who might be good candidates for the drug.

He had no relevant financial declarations.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

AMSTERDAM – Intravenous tigecycline was significantly more effective than standard therapy at curing refractory Clostridium difficile infections, according to a case-control study presented at the European Society of Clinical Microbiology and Infectious Diseases annual congress.

Tigecycline effected a 76% clinical cure rate, compared with 53% for the combination regimen of intravenous metronidazole and oral vancomycin, Dr. Baltin Gergely Szabo reported. And despite the fact that those who took tigecycline had more clinically severe disease, no colectomies were required in that group, while two patients in the standard treatment arm did need the procedure.

However, tigecycline didn’t significantly improve relapse rates or mortality, noted Dr. Szabo of the St. Stephan and St. Ladislaus Hospital-Clinic, Budapest, Hungary.

He presented the results of a matched case-control study of 90 patients with severe C. difficile infections, who were treated with either of the protocols. Patients who took tigecycline were more likely to have a recurrent infection (38% vs. 29%). Thus, they were also more likely to have previously been treated with metronidazole (38% vs. 24%) and vancomycin (24% vs. 7%). Prior tigecycline use was very rare in both groups (2% vs. 0%).

Those who took tigecycline were significantly younger as well (72 vs. 78 years), and more often men (56% vs. 30%). They were more likely to be hypertensive, have chronic obstructive pulmonary disease, have cancers, be immunosuppressed, and be chronic users of corticosteroids.

However, the Charlson comorbidity index was similar between the tigecycline and standard therapy groups (4.6 vs. 5). They were also matched for ATLAS scores (mean 7.8 in each group).

Significantly more patients taking tigecycline had acquired their infections during hospitalization (64% vs. 30%). They also had a longer duration of symptoms (17 vs. 10 days).

Imaging showed more severe disease in the tigecycline group with significantly more colonic distension, mural thickening, and ascites. Tigecycline patients had also undergone significantly more colonoscopies and blood cultures.

Tigecycline was given in the hospital for 7-10 days, with a 100-mg loading dose and subsequent 50-mg daily doses. The main duration of therapy was 10 days, but that varied widely, from 2 to 22 days. It was given only as first-line treatment to 15% of patients; the rest received tigecycline as an alternative treatment, often after the combination of metronidazole/vancomycin had failed. No adverse drug reactions occurred in the group.

Clinical cure was achieved in 76% of the tigecycline group and 53% of the standard protocol group – a significant difference. The drug was associated with a decreased rate of complicated disease course (29% vs. 53%) and significantly fewer colectomies (0 vs. 2).

Rates of toxic megacolon were equal (7% each group); ileus was more frequent in the tigecycline group (11% vs. 9%), but this difference was not statistically significant.

However, tigecycline had no impact on either in-hospital or 90-day relapse, or on in-hospital mortality (15 vs. 16 deaths). At 90 days, fewer patients taking the drug had died (17 vs. 21), but that difference was not statistically significant (P = 0.52).

A multivariate analysis identified several characteristics associated with a beneficial response to tigecycline:

• Male sex.

• Being immunosuppressed.

• Chronic steroid treatment.

• Malignancy.

• Longer duration of symptoms.

• Prior C. difficile infections.

• Nosocomial onset.

• Signs of severe infection on imaging.

Dr. Szabo said these characteristics can be used to create a profile of patients who might be good candidates for the drug.

He had no relevant financial declarations.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

AMSTERDAM – Intravenous tigecycline was significantly more effective than standard therapy at curing refractory Clostridium difficile infections, according to a case-control study presented at the European Society of Clinical Microbiology and Infectious Diseases annual congress.

Tigecycline effected a 76% clinical cure rate, compared with 53% for the combination regimen of intravenous metronidazole and oral vancomycin, Dr. Baltin Gergely Szabo reported. And despite the fact that those who took tigecycline had more clinically severe disease, no colectomies were required in that group, while two patients in the standard treatment arm did need the procedure.

However, tigecycline didn’t significantly improve relapse rates or mortality, noted Dr. Szabo of the St. Stephan and St. Ladislaus Hospital-Clinic, Budapest, Hungary.

He presented the results of a matched case-control study of 90 patients with severe C. difficile infections, who were treated with either of the protocols. Patients who took tigecycline were more likely to have a recurrent infection (38% vs. 29%). Thus, they were also more likely to have previously been treated with metronidazole (38% vs. 24%) and vancomycin (24% vs. 7%). Prior tigecycline use was very rare in both groups (2% vs. 0%).

Those who took tigecycline were significantly younger as well (72 vs. 78 years), and more often men (56% vs. 30%). They were more likely to be hypertensive, have chronic obstructive pulmonary disease, have cancers, be immunosuppressed, and be chronic users of corticosteroids.

However, the Charlson comorbidity index was similar between the tigecycline and standard therapy groups (4.6 vs. 5). They were also matched for ATLAS scores (mean 7.8 in each group).

Significantly more patients taking tigecycline had acquired their infections during hospitalization (64% vs. 30%). They also had a longer duration of symptoms (17 vs. 10 days).

Imaging showed more severe disease in the tigecycline group with significantly more colonic distension, mural thickening, and ascites. Tigecycline patients had also undergone significantly more colonoscopies and blood cultures.

Tigecycline was given in the hospital for 7-10 days, with a 100-mg loading dose and subsequent 50-mg daily doses. The main duration of therapy was 10 days, but that varied widely, from 2 to 22 days. It was given only as first-line treatment to 15% of patients; the rest received tigecycline as an alternative treatment, often after the combination of metronidazole/vancomycin had failed. No adverse drug reactions occurred in the group.

Clinical cure was achieved in 76% of the tigecycline group and 53% of the standard protocol group – a significant difference. The drug was associated with a decreased rate of complicated disease course (29% vs. 53%) and significantly fewer colectomies (0 vs. 2).

Rates of toxic megacolon were equal (7% each group); ileus was more frequent in the tigecycline group (11% vs. 9%), but this difference was not statistically significant.

However, tigecycline had no impact on either in-hospital or 90-day relapse, or on in-hospital mortality (15 vs. 16 deaths). At 90 days, fewer patients taking the drug had died (17 vs. 21), but that difference was not statistically significant (P = 0.52).

A multivariate analysis identified several characteristics associated with a beneficial response to tigecycline:

• Male sex.

• Being immunosuppressed.

• Chronic steroid treatment.

• Malignancy.

• Longer duration of symptoms.

• Prior C. difficile infections.

• Nosocomial onset.

• Signs of severe infection on imaging.

Dr. Szabo said these characteristics can be used to create a profile of patients who might be good candidates for the drug.

He had no relevant financial declarations.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

AMSTERDAM – Clostridium difficile infections are a major driver of death and nursing home placement in Americans older than 65 years, according to research presented at a major international conference on infectious diseases.

A Medicare database review of almost 1.6 million patients has determined that 36% of those with C. difficile died, compared with 25% of an age-matched control group – an 11% attributable mortality. The infections also doubled the risk of placement in a skilled care nursing facility and tripled the risk of nursing home admission, Dr. Erik Dubberke said at the European Society of Clinical Microbiology and Infectious Diseases annual congress.

Dr. Dubberke, an infectious disease specialist at Washington University, St. Louis, said these findings underscore not only the infection’s potential lethality, but its considerable impact on both short- and long-term quality of life.

His case-control study included 175,000 patients older than 65 years who were diagnosed with a C. difficile infection in 2011 – they were then matched with 1.45 million controls. This yielded 129,000 pairs matched for mortality, 105,000 matched for skilled nursing facility admission, and 93,500 matched for nursing home admission. The analysis controlled for age, gender, race, other infections, as well as health care utilization and a comprehensive group of acute and chronic conditions in the prior 12 months.

Overall, Dr. Dubberke found that 36% of cases and 25% of controls died during the year – a 44% increased risk of death and an 11% attributable mortality rate. During the same period, another 36% of the C. difficile cases were admitted to a skilled nursing facility, compared with 19% of controls – an 89% increased risk and 17% attributable admission rate.

C. difficile infections also exerted a significant impact on nursing home admissions: 15% of the cases in the study were admitted, compared with 5% of controls. This represented almost a tripling of risk (relative risk, 2.80), with an attributable admission rate of 10%, Dr. Dubberke said.

“These findings illustrate how C. difficile impacts quality of life, with short-term morbidity reflected in increasing admissions to skilled nursing facilities, and long-term morbidity by increasing admissions to nursing homes,” he said.

Dr. Dubberke had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

AMSTERDAM – Clostridium difficile infections are a major driver of death and nursing home placement in Americans older than 65 years, according to research presented at a major international conference on infectious diseases.

A Medicare database review of almost 1.6 million patients has determined that 36% of those with C. difficile died, compared with 25% of an age-matched control group – an 11% attributable mortality. The infections also doubled the risk of placement in a skilled care nursing facility and tripled the risk of nursing home admission, Dr. Erik Dubberke said at the European Society of Clinical Microbiology and Infectious Diseases annual congress.

Dr. Dubberke, an infectious disease specialist at Washington University, St. Louis, said these findings underscore not only the infection’s potential lethality, but its considerable impact on both short- and long-term quality of life.

His case-control study included 175,000 patients older than 65 years who were diagnosed with a C. difficile infection in 2011 – they were then matched with 1.45 million controls. This yielded 129,000 pairs matched for mortality, 105,000 matched for skilled nursing facility admission, and 93,500 matched for nursing home admission. The analysis controlled for age, gender, race, other infections, as well as health care utilization and a comprehensive group of acute and chronic conditions in the prior 12 months.

Overall, Dr. Dubberke found that 36% of cases and 25% of controls died during the year – a 44% increased risk of death and an 11% attributable mortality rate. During the same period, another 36% of the C. difficile cases were admitted to a skilled nursing facility, compared with 19% of controls – an 89% increased risk and 17% attributable admission rate.

C. difficile infections also exerted a significant impact on nursing home admissions: 15% of the cases in the study were admitted, compared with 5% of controls. This represented almost a tripling of risk (relative risk, 2.80), with an attributable admission rate of 10%, Dr. Dubberke said.

“These findings illustrate how C. difficile impacts quality of life, with short-term morbidity reflected in increasing admissions to skilled nursing facilities, and long-term morbidity by increasing admissions to nursing homes,” he said.

Dr. Dubberke had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

AMSTERDAM – Clostridium difficile infections are a major driver of death and nursing home placement in Americans older than 65 years, according to research presented at a major international conference on infectious diseases.

A Medicare database review of almost 1.6 million patients has determined that 36% of those with C. difficile died, compared with 25% of an age-matched control group – an 11% attributable mortality. The infections also doubled the risk of placement in a skilled care nursing facility and tripled the risk of nursing home admission, Dr. Erik Dubberke said at the European Society of Clinical Microbiology and Infectious Diseases annual congress.

Dr. Dubberke, an infectious disease specialist at Washington University, St. Louis, said these findings underscore not only the infection’s potential lethality, but its considerable impact on both short- and long-term quality of life.

His case-control study included 175,000 patients older than 65 years who were diagnosed with a C. difficile infection in 2011 – they were then matched with 1.45 million controls. This yielded 129,000 pairs matched for mortality, 105,000 matched for skilled nursing facility admission, and 93,500 matched for nursing home admission. The analysis controlled for age, gender, race, other infections, as well as health care utilization and a comprehensive group of acute and chronic conditions in the prior 12 months.

Overall, Dr. Dubberke found that 36% of cases and 25% of controls died during the year – a 44% increased risk of death and an 11% attributable mortality rate. During the same period, another 36% of the C. difficile cases were admitted to a skilled nursing facility, compared with 19% of controls – an 89% increased risk and 17% attributable admission rate.

C. difficile infections also exerted a significant impact on nursing home admissions: 15% of the cases in the study were admitted, compared with 5% of controls. This represented almost a tripling of risk (relative risk, 2.80), with an attributable admission rate of 10%, Dr. Dubberke said.

“These findings illustrate how C. difficile impacts quality of life, with short-term morbidity reflected in increasing admissions to skilled nursing facilities, and long-term morbidity by increasing admissions to nursing homes,” he said.

Dr. Dubberke had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

AMSTERDAM – The long-term safety of proton pump inhibitors has once again come into question, as they may quadruple the chance of carrying a bacterial strain highly resistant to both penicillin and cephalosporin antibiotics, a Dutch study suggested.

The observational study showed only association, not causation, according to Dr. Pepijn Huizinga of the Amphia Ziekenhuis Hospital, Breda, the Netherlands. But, he said, the association of PPIs and extended-spectrum beta-lactamase–producing enterobacteriaceae (ESBL-E) is biologically plausible, and strong enough to warrant deeper investigation. Dr. Huizinga reported the study results at the 2016 European Conference of Clinical Microbiology and Infectious Diseases.

“We are continuously exposed to ESBL-E from many sources – other humans, contaminated foods, and the environment,” Dr. Huizinga said. “The gastric acid barrier is one of the last barriers we have against developing carriage. As long as it is in the normal pH range of 1.5-3, it’s quite efficient at keeping these bacteria from entering our system. But PPIs decrease this to 3 or 4. We already know that this is associated with an increased risk of infections from campylobacteriae, salmonella, and C. [Clostridium] difficile.”

PPI use is exploding in the Netherlands, Dr. Huizinga said, following a worldwide pattern of escalating use. National statistics demonstrate a very sharp upward trend, beginning with the introduction of omeprazole in 1994. By 2013, with five PPIs on the market, there were more than 2.7 million users – 14% of the country’s adult population. About a third of people older than 65 years are using them on a daily basis, according to data from the Dutch Foundation for Pharmaceutical Statistics.

To examine the relationship, Dr. Huizinga mined data from an ESBL-E prevalence survey conducted at Amphia Ziekenhuis Hospital in 2014 and 2015. The study cohort comprised 570 adults who received a rectal culture within a day of admission. Of these, 5.4% (31) were positive for ESBL-E carriage.

He examined correlations between carriage and several patient characteristics. Women were slightly more likely to be carriers than men (6.6% vs. 4%). There was no difference in the incidence of antibiotic use on day of admission, with 6% of the positive patients taking an antibiotic and 5% not taking one. Carriers were younger than noncarriers (64 vs. 65 years). PPI use was significantly more common among those who carried ESBL-E (8.6% vs. 2.9%).

In a multivariate analysis, there were no significant associations with sex, age, or antibiotic use. PPI use conferred the only significant risk, a fourfold increase in the chance of carriage.

Dr. Huizinga noted that the model didn’t consider the length of time taking the drugs, only whether they were in use on the day of admission. Nor did the study account for any medical comorbidity.

“However,” he said, “I think we do need to consider the possibility that the frequent use of PPIs in the general population could be an important driver of the increase we are seeing in ESBL-E carriage.”

Dr. Huizinga had no relevant financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

AMSTERDAM – The long-term safety of proton pump inhibitors has once again come into question, as they may quadruple the chance of carrying a bacterial strain highly resistant to both penicillin and cephalosporin antibiotics, a Dutch study suggested.

The observational study showed only association, not causation, according to Dr. Pepijn Huizinga of the Amphia Ziekenhuis Hospital, Breda, the Netherlands. But, he said, the association of PPIs and extended-spectrum beta-lactamase–producing enterobacteriaceae (ESBL-E) is biologically plausible, and strong enough to warrant deeper investigation. Dr. Huizinga reported the study results at the 2016 European Conference of Clinical Microbiology and Infectious Diseases.

“We are continuously exposed to ESBL-E from many sources – other humans, contaminated foods, and the environment,” Dr. Huizinga said. “The gastric acid barrier is one of the last barriers we have against developing carriage. As long as it is in the normal pH range of 1.5-3, it’s quite efficient at keeping these bacteria from entering our system. But PPIs decrease this to 3 or 4. We already know that this is associated with an increased risk of infections from campylobacteriae, salmonella, and C. [Clostridium] difficile.”

PPI use is exploding in the Netherlands, Dr. Huizinga said, following a worldwide pattern of escalating use. National statistics demonstrate a very sharp upward trend, beginning with the introduction of omeprazole in 1994. By 2013, with five PPIs on the market, there were more than 2.7 million users – 14% of the country’s adult population. About a third of people older than 65 years are using them on a daily basis, according to data from the Dutch Foundation for Pharmaceutical Statistics.

To examine the relationship, Dr. Huizinga mined data from an ESBL-E prevalence survey conducted at Amphia Ziekenhuis Hospital in 2014 and 2015. The study cohort comprised 570 adults who received a rectal culture within a day of admission. Of these, 5.4% (31) were positive for ESBL-E carriage.

He examined correlations between carriage and several patient characteristics. Women were slightly more likely to be carriers than men (6.6% vs. 4%). There was no difference in the incidence of antibiotic use on day of admission, with 6% of the positive patients taking an antibiotic and 5% not taking one. Carriers were younger than noncarriers (64 vs. 65 years). PPI use was significantly more common among those who carried ESBL-E (8.6% vs. 2.9%).

In a multivariate analysis, there were no significant associations with sex, age, or antibiotic use. PPI use conferred the only significant risk, a fourfold increase in the chance of carriage.

Dr. Huizinga noted that the model didn’t consider the length of time taking the drugs, only whether they were in use on the day of admission. Nor did the study account for any medical comorbidity.

“However,” he said, “I think we do need to consider the possibility that the frequent use of PPIs in the general population could be an important driver of the increase we are seeing in ESBL-E carriage.”

Dr. Huizinga had no relevant financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

AMSTERDAM – The long-term safety of proton pump inhibitors has once again come into question, as they may quadruple the chance of carrying a bacterial strain highly resistant to both penicillin and cephalosporin antibiotics, a Dutch study suggested.

The observational study showed only association, not causation, according to Dr. Pepijn Huizinga of the Amphia Ziekenhuis Hospital, Breda, the Netherlands. But, he said, the association of PPIs and extended-spectrum beta-lactamase–producing enterobacteriaceae (ESBL-E) is biologically plausible, and strong enough to warrant deeper investigation. Dr. Huizinga reported the study results at the 2016 European Conference of Clinical Microbiology and Infectious Diseases.

“We are continuously exposed to ESBL-E from many sources – other humans, contaminated foods, and the environment,” Dr. Huizinga said. “The gastric acid barrier is one of the last barriers we have against developing carriage. As long as it is in the normal pH range of 1.5-3, it’s quite efficient at keeping these bacteria from entering our system. But PPIs decrease this to 3 or 4. We already know that this is associated with an increased risk of infections from campylobacteriae, salmonella, and C. [Clostridium] difficile.”

PPI use is exploding in the Netherlands, Dr. Huizinga said, following a worldwide pattern of escalating use. National statistics demonstrate a very sharp upward trend, beginning with the introduction of omeprazole in 1994. By 2013, with five PPIs on the market, there were more than 2.7 million users – 14% of the country’s adult population. About a third of people older than 65 years are using them on a daily basis, according to data from the Dutch Foundation for Pharmaceutical Statistics.

To examine the relationship, Dr. Huizinga mined data from an ESBL-E prevalence survey conducted at Amphia Ziekenhuis Hospital in 2014 and 2015. The study cohort comprised 570 adults who received a rectal culture within a day of admission. Of these, 5.4% (31) were positive for ESBL-E carriage.

He examined correlations between carriage and several patient characteristics. Women were slightly more likely to be carriers than men (6.6% vs. 4%). There was no difference in the incidence of antibiotic use on day of admission, with 6% of the positive patients taking an antibiotic and 5% not taking one. Carriers were younger than noncarriers (64 vs. 65 years). PPI use was significantly more common among those who carried ESBL-E (8.6% vs. 2.9%).

In a multivariate analysis, there were no significant associations with sex, age, or antibiotic use. PPI use conferred the only significant risk, a fourfold increase in the chance of carriage.

Dr. Huizinga noted that the model didn’t consider the length of time taking the drugs, only whether they were in use on the day of admission. Nor did the study account for any medical comorbidity.

“However,” he said, “I think we do need to consider the possibility that the frequent use of PPIs in the general population could be an important driver of the increase we are seeing in ESBL-E carriage.”

Dr. Huizinga had no relevant financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

AMSTERDAM – Fecal transplants effected a clinical cure in 97% of patients with recurrent Clostridium difficile infection, a small prospective study has determined.

However, the transplants, which were administered via duodenal intubation, were not without serious adverse events, Dr. Yvette van Beurden said at the European Society of Clinical Microbiology and Infectious Diseases annual congress.

Michele G. Sullivan/Frontline Medical News

Five patients regurgitated or vomited fecal material, and one of these patients died, presumably from aspiration pneumonia related to the event, said Dr. van Beurden of the VU University Medical Center, Amsterdam.

The study was relatively small – 39 patients – but provided up to 2 years of follow-up on them. All were treated at Academic Medical Center, Amsterdam, from 2010 to 1016.

They were a mean of 73 years old, but the age range was wide (14-97 years). All had experienced recurrent C. difficile infections. The mean recurrence rate was four, but again this varied widely, from one recurrence to 10.

Thus, they had also experienced a mean of four courses of antibiotic treatment, with a range similar to the recurrence range. At the time of transplant, they were a mean of 6 months past their last recurrence.

The transplant protocol called for a minimum of 4 days of vancomycin treatment before transplant, and a full bowel prep 1 day before. The transplant itself consisted of 500 mL of fresh donor feces in solution; it was obtained from a household contact or healthy volunteer and administered by duodenal tube. Patients were discharged on the same day of infusion.

The mean follow-up was 21 months, also with a wide range (3-68 months).

A clinical cure – not microbiologically confirmed – occurred in 82% of the patients. There were seven recurrences (18%), which all happened within the first 3 months. Of these, two were thought to be related to antibiotic use within the first month of the procedure; the cause of the other recurrences was unknown.

Four of the patients with recurrent infections received antibiotics without a repeat transplant; three received fidaxomicin and one, metronidazole. Two underwent a successful repeat transplant. One patient had multiple treatments, including a course of fidaxomicin. This patient experienced another recurrence that was successfully treated with a second transplant.

Six of these seven patients experienced a clinical cure, bringing the secondary cure rate of the entire cohort to 97%.

There were nine serious adverse events (23%), most of which occurred during or shortly after the transplant procedure. This included the single death; four hospitalizations (one related to the transplant); and four transplant-related events.

The patient who died had an uncomplicated transplant, but within an hour started to feel nauseated and regurgitated the fecal material. “This didn’t appear to be severe,” Dr. van Beurden said. “But within a week, pneumonia developed and the patient died despite antibiotic treatment.”

She added that this patient was “medically fragile,” with a swallowing disorder that required a percutaneous endoscopic gastrostomy feeding tube.

Of the other four patients with transplant complications:

• One, following an uncomplicated transplant, was discharged and ate a large meal, then shortly after vomited food and donor feces.

• One experienced abdominal cramping during the procedure, which was immediately stopped. When the cramping subsided, the procedure was completed. However, within a few hours the cramping recurred, along with diarrhea, nausea, and vomiting of fecal material.

• One patient was “very stressed and anxious” during the procedure and regurgitated a mix of gastric juices and donor feces. The infusion tube was immediately removed. The patient was discharged after being symptom-free for 3 hours, but vomited fecal material on the way home.

• One patient experienced nausea during the transplant, which was immediately stopped with tube removal. Upon removal, the patient regurgitated donor material. Nausea shortly resolved.

During the discussion period, Dr. van Beurden fielded a question about duodenal administration rather than delivering the donor feces colonoscopically. She said that decision was made because the duodenal tube doesn’t require anesthesia, and because many of the patients had severely inflamed colons. However, the hospital’s experience with complications did help refine its transplant protocol, she said.

• Colonoscopic administration is mandatory for any patient with a swallowing disorder.

• A smaller volume of feces is now infused.

• Donor material is infused very slowly and immediately discontinued if there is any nausea, cramping, or regurgitation.

• There is no eating or drinking for at least 1 hour after the transplant.

• To minimize the risk of recurrent C. difficile, patients should have no nonessential antibiotic treatment within the first month after transplant.

She had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

AMSTERDAM – Fecal transplants effected a clinical cure in 97% of patients with recurrent Clostridium difficile infection, a small prospective study has determined.

However, the transplants, which were administered via duodenal intubation, were not without serious adverse events, Dr. Yvette van Beurden said at the European Society of Clinical Microbiology and Infectious Diseases annual congress.

Michele G. Sullivan/Frontline Medical News

Five patients regurgitated or vomited fecal material, and one of these patients died, presumably from aspiration pneumonia related to the event, said Dr. van Beurden of the VU University Medical Center, Amsterdam.

The study was relatively small – 39 patients – but provided up to 2 years of follow-up on them. All were treated at Academic Medical Center, Amsterdam, from 2010 to 1016.

They were a mean of 73 years old, but the age range was wide (14-97 years). All had experienced recurrent C. difficile infections. The mean recurrence rate was four, but again this varied widely, from one recurrence to 10.

Thus, they had also experienced a mean of four courses of antibiotic treatment, with a range similar to the recurrence range. At the time of transplant, they were a mean of 6 months past their last recurrence.

The transplant protocol called for a minimum of 4 days of vancomycin treatment before transplant, and a full bowel prep 1 day before. The transplant itself consisted of 500 mL of fresh donor feces in solution; it was obtained from a household contact or healthy volunteer and administered by duodenal tube. Patients were discharged on the same day of infusion.

The mean follow-up was 21 months, also with a wide range (3-68 months).

A clinical cure – not microbiologically confirmed – occurred in 82% of the patients. There were seven recurrences (18%), which all happened within the first 3 months. Of these, two were thought to be related to antibiotic use within the first month of the procedure; the cause of the other recurrences was unknown.

Four of the patients with recurrent infections received antibiotics without a repeat transplant; three received fidaxomicin and one, metronidazole. Two underwent a successful repeat transplant. One patient had multiple treatments, including a course of fidaxomicin. This patient experienced another recurrence that was successfully treated with a second transplant.

Six of these seven patients experienced a clinical cure, bringing the secondary cure rate of the entire cohort to 97%.

There were nine serious adverse events (23%), most of which occurred during or shortly after the transplant procedure. This included the single death; four hospitalizations (one related to the transplant); and four transplant-related events.

The patient who died had an uncomplicated transplant, but within an hour started to feel nauseated and regurgitated the fecal material. “This didn’t appear to be severe,” Dr. van Beurden said. “But within a week, pneumonia developed and the patient died despite antibiotic treatment.”

She added that this patient was “medically fragile,” with a swallowing disorder that required a percutaneous endoscopic gastrostomy feeding tube.

Of the other four patients with transplant complications:

• One, following an uncomplicated transplant, was discharged and ate a large meal, then shortly after vomited food and donor feces.

• One experienced abdominal cramping during the procedure, which was immediately stopped. When the cramping subsided, the procedure was completed. However, within a few hours the cramping recurred, along with diarrhea, nausea, and vomiting of fecal material.

• One patient was “very stressed and anxious” during the procedure and regurgitated a mix of gastric juices and donor feces. The infusion tube was immediately removed. The patient was discharged after being symptom-free for 3 hours, but vomited fecal material on the way home.

• One patient experienced nausea during the transplant, which was immediately stopped with tube removal. Upon removal, the patient regurgitated donor material. Nausea shortly resolved.

During the discussion period, Dr. van Beurden fielded a question about duodenal administration rather than delivering the donor feces colonoscopically. She said that decision was made because the duodenal tube doesn’t require anesthesia, and because many of the patients had severely inflamed colons. However, the hospital’s experience with complications did help refine its transplant protocol, she said.

• Colonoscopic administration is mandatory for any patient with a swallowing disorder.

• A smaller volume of feces is now infused.

• Donor material is infused very slowly and immediately discontinued if there is any nausea, cramping, or regurgitation.

• There is no eating or drinking for at least 1 hour after the transplant.

• To minimize the risk of recurrent C. difficile, patients should have no nonessential antibiotic treatment within the first month after transplant.

She had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

AMSTERDAM – Fecal transplants effected a clinical cure in 97% of patients with recurrent Clostridium difficile infection, a small prospective study has determined.

However, the transplants, which were administered via duodenal intubation, were not without serious adverse events, Dr. Yvette van Beurden said at the European Society of Clinical Microbiology and Infectious Diseases annual congress.

Michele G. Sullivan/Frontline Medical News

Five patients regurgitated or vomited fecal material, and one of these patients died, presumably from aspiration pneumonia related to the event, said Dr. van Beurden of the VU University Medical Center, Amsterdam.

The study was relatively small – 39 patients – but provided up to 2 years of follow-up on them. All were treated at Academic Medical Center, Amsterdam, from 2010 to 1016.

They were a mean of 73 years old, but the age range was wide (14-97 years). All had experienced recurrent C. difficile infections. The mean recurrence rate was four, but again this varied widely, from one recurrence to 10.

Thus, they had also experienced a mean of four courses of antibiotic treatment, with a range similar to the recurrence range. At the time of transplant, they were a mean of 6 months past their last recurrence.

The transplant protocol called for a minimum of 4 days of vancomycin treatment before transplant, and a full bowel prep 1 day before. The transplant itself consisted of 500 mL of fresh donor feces in solution; it was obtained from a household contact or healthy volunteer and administered by duodenal tube. Patients were discharged on the same day of infusion.

The mean follow-up was 21 months, also with a wide range (3-68 months).

A clinical cure – not microbiologically confirmed – occurred in 82% of the patients. There were seven recurrences (18%), which all happened within the first 3 months. Of these, two were thought to be related to antibiotic use within the first month of the procedure; the cause of the other recurrences was unknown.

Four of the patients with recurrent infections received antibiotics without a repeat transplant; three received fidaxomicin and one, metronidazole. Two underwent a successful repeat transplant. One patient had multiple treatments, including a course of fidaxomicin. This patient experienced another recurrence that was successfully treated with a second transplant.

Six of these seven patients experienced a clinical cure, bringing the secondary cure rate of the entire cohort to 97%.

There were nine serious adverse events (23%), most of which occurred during or shortly after the transplant procedure. This included the single death; four hospitalizations (one related to the transplant); and four transplant-related events.

The patient who died had an uncomplicated transplant, but within an hour started to feel nauseated and regurgitated the fecal material. “This didn’t appear to be severe,” Dr. van Beurden said. “But within a week, pneumonia developed and the patient died despite antibiotic treatment.”

She added that this patient was “medically fragile,” with a swallowing disorder that required a percutaneous endoscopic gastrostomy feeding tube.

Of the other four patients with transplant complications:

• One, following an uncomplicated transplant, was discharged and ate a large meal, then shortly after vomited food and donor feces.

• One experienced abdominal cramping during the procedure, which was immediately stopped. When the cramping subsided, the procedure was completed. However, within a few hours the cramping recurred, along with diarrhea, nausea, and vomiting of fecal material.

• One patient was “very stressed and anxious” during the procedure and regurgitated a mix of gastric juices and donor feces. The infusion tube was immediately removed. The patient was discharged after being symptom-free for 3 hours, but vomited fecal material on the way home.

• One patient experienced nausea during the transplant, which was immediately stopped with tube removal. Upon removal, the patient regurgitated donor material. Nausea shortly resolved.

During the discussion period, Dr. van Beurden fielded a question about duodenal administration rather than delivering the donor feces colonoscopically. She said that decision was made because the duodenal tube doesn’t require anesthesia, and because many of the patients had severely inflamed colons. However, the hospital’s experience with complications did help refine its transplant protocol, she said.

• Colonoscopic administration is mandatory for any patient with a swallowing disorder.

• A smaller volume of feces is now infused.

• Donor material is infused very slowly and immediately discontinued if there is any nausea, cramping, or regurgitation.

• There is no eating or drinking for at least 1 hour after the transplant.

• To minimize the risk of recurrent C. difficile, patients should have no nonessential antibiotic treatment within the first month after transplant.

She had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

AMSTERDAM – Five people with confirmed Zika virus infections have died in Colombia, and all had medical comorbidities, including leukemia, diabetes, sickle cell anemia, and hypertension.

All of the deaths occurred last October in northern and central Colombia, Dr. Alfonso Rodriguez-Morales said at the European Society of Clinical Microbiology and Infectious Diseases annual congress.

Four of the cases were simultaneously published April 7 in the Lancet Infectious Diseases (2016 Apr 7. doi: 10.1016/S1473-3099[16]30006-8). The fifth case occurred in northern Colombia, and was reported in Emerging Infectious Diseases (2016 May. doi: 10.3201/eid2205.151934).

Reports of confirmed Zika-related deaths are rare. Brazil, the only other country to disclose them, has now reported three, said Dr. Rodriguez-Morales of the Universidad Tecnológica de Pereira, Colombia.

©bakhtiar_zein/Thinkstock

“Before the current outbreak in Latin America, Zika virus was not linked to deaths,” he noted. But the eight confirmed Zika-related deaths in South America “call attention to the need for evidence-based guidelines for clinical management of Zika, as well as the possible occurrence of atypical and severe cases, including possibly congenitally related microcephaly.”

Because they all occurred in medically compromised patients, Dr. Rodriguez-Morales also urged clinicians to cast a wary eye on such patients who present with arbovirus-type symptoms, including fever and rash.

From September 2015 to March 2016, Colombia had 58,838 reported cases of Zika. Of those, only 2,361 were lab confirmed. The rest were either diagnosed clinically or were suspected cases, Dr. Rodriguez-Morales said. Although Colombia has a much smaller population than Brazil (49 million vs. 210 million), its Zika case rate is much higher, 120 cases per 100,000 people vs. 34 cases per 100,000 people.

The group of four deaths occurred in central Colombia, and included a 2-year-old girl, a 30-year-old woman, a 61-year-old man, and a 72-year-old woman. All presented with 2-6 days of fever. All were initially suspected to have dengue fever or chikungunya. None tested positive for dengue, but the man was coinfected with chikungunya.

All patients presented with anemia. All but the older man also had severe thrombocytopenia.

The toddler presented with hepatomegaly, mucosal hemorrhage, progressive respiratory collapse, progressive thrombocytopenia, and intravascular coagulation. She died 5 days after symptom onset and was found to have had unrecognized lymphoblastic leukemia.

The 30-year-old woman presented with a severe rash on both arms. She also exhibited coagulation dysfunction, including severe thrombocytopenia and leukopenia that progressed to intracerebral and subarachnoid hemorrhage. She died 12 days after symptom onset. She was determined to have had unrecognized acute myeloid leukemia.

The elderly man had a history of medically controlled hypertension. He experienced mucosal hemorrhage and respiratory distress. He died 7 days after symptom onset. On autopsy, his liver showed necrotic areas, and his spleen indicated a systemic inflammatory response.

The elderly woman had a history of insulin-controlled type 2 diabetes. Her symptoms included gastrointestinal distress, thrombocytopenia, and acute respiratory failure. She died 48 hours after symptom onset; her brain showed edema and ischemic lesions.

The 15-year-old girl in northern Colombia had a 5-year history of sickle cell disease, which, Dr. Rodriguez-Morales pointed out, is a risk factor for arbovirus diseases. However, the patient had never been hospitalized for a vasoocclusive crisis. She presented with a high fever; joint, muscle, and abdominal pain; and jaundice. She was assumed to have dengue virus. Within another day, she had progressed into respiratory failure and was on a ventilator. She died less than 2 days later.

Her autopsy showed hepatic necrosis and severe decrease of splenic lymphoid tissue with splenic sequestration. Systemic inflammation probably triggered a fatal vasoocclusive crisis and splenic sequestration.

Dr. Rodriguez-Morales had no financial disclosures.

msullivan@frontlinemedcom.com

AMSTERDAM – Five people with confirmed Zika virus infections have died in Colombia, and all had medical comorbidities, including leukemia, diabetes, sickle cell anemia, and hypertension.

All of the deaths occurred last October in northern and central Colombia, Dr. Alfonso Rodriguez-Morales said at the European Society of Clinical Microbiology and Infectious Diseases annual congress.

Four of the cases were simultaneously published April 7 in the Lancet Infectious Diseases (2016 Apr 7. doi: 10.1016/S1473-3099[16]30006-8). The fifth case occurred in northern Colombia, and was reported in Emerging Infectious Diseases (2016 May. doi: 10.3201/eid2205.151934).

Reports of confirmed Zika-related deaths are rare. Brazil, the only other country to disclose them, has now reported three, said Dr. Rodriguez-Morales of the Universidad Tecnológica de Pereira, Colombia.

©bakhtiar_zein/Thinkstock

“Before the current outbreak in Latin America, Zika virus was not linked to deaths,” he noted. But the eight confirmed Zika-related deaths in South America “call attention to the need for evidence-based guidelines for clinical management of Zika, as well as the possible occurrence of atypical and severe cases, including possibly congenitally related microcephaly.”

Because they all occurred in medically compromised patients, Dr. Rodriguez-Morales also urged clinicians to cast a wary eye on such patients who present with arbovirus-type symptoms, including fever and rash.

From September 2015 to March 2016, Colombia had 58,838 reported cases of Zika. Of those, only 2,361 were lab confirmed. The rest were either diagnosed clinically or were suspected cases, Dr. Rodriguez-Morales said. Although Colombia has a much smaller population than Brazil (49 million vs. 210 million), its Zika case rate is much higher, 120 cases per 100,000 people vs. 34 cases per 100,000 people.

The group of four deaths occurred in central Colombia, and included a 2-year-old girl, a 30-year-old woman, a 61-year-old man, and a 72-year-old woman. All presented with 2-6 days of fever. All were initially suspected to have dengue fever or chikungunya. None tested positive for dengue, but the man was coinfected with chikungunya.

All patients presented with anemia. All but the older man also had severe thrombocytopenia.

The toddler presented with hepatomegaly, mucosal hemorrhage, progressive respiratory collapse, progressive thrombocytopenia, and intravascular coagulation. She died 5 days after symptom onset and was found to have had unrecognized lymphoblastic leukemia.

The 30-year-old woman presented with a severe rash on both arms. She also exhibited coagulation dysfunction, including severe thrombocytopenia and leukopenia that progressed to intracerebral and subarachnoid hemorrhage. She died 12 days after symptom onset. She was determined to have had unrecognized acute myeloid leukemia.

The elderly man had a history of medically controlled hypertension. He experienced mucosal hemorrhage and respiratory distress. He died 7 days after symptom onset. On autopsy, his liver showed necrotic areas, and his spleen indicated a systemic inflammatory response.

The elderly woman had a history of insulin-controlled type 2 diabetes. Her symptoms included gastrointestinal distress, thrombocytopenia, and acute respiratory failure. She died 48 hours after symptom onset; her brain showed edema and ischemic lesions.

The 15-year-old girl in northern Colombia had a 5-year history of sickle cell disease, which, Dr. Rodriguez-Morales pointed out, is a risk factor for arbovirus diseases. However, the patient had never been hospitalized for a vasoocclusive crisis. She presented with a high fever; joint, muscle, and abdominal pain; and jaundice. She was assumed to have dengue virus. Within another day, she had progressed into respiratory failure and was on a ventilator. She died less than 2 days later.

Her autopsy showed hepatic necrosis and severe decrease of splenic lymphoid tissue with splenic sequestration. Systemic inflammation probably triggered a fatal vasoocclusive crisis and splenic sequestration.

Dr. Rodriguez-Morales had no financial disclosures.

msullivan@frontlinemedcom.com

AMSTERDAM – Five people with confirmed Zika virus infections have died in Colombia, and all had medical comorbidities, including leukemia, diabetes, sickle cell anemia, and hypertension.

All of the deaths occurred last October in northern and central Colombia, Dr. Alfonso Rodriguez-Morales said at the European Society of Clinical Microbiology and Infectious Diseases annual congress.

Four of the cases were simultaneously published April 7 in the Lancet Infectious Diseases (2016 Apr 7. doi: 10.1016/S1473-3099[16]30006-8). The fifth case occurred in northern Colombia, and was reported in Emerging Infectious Diseases (2016 May. doi: 10.3201/eid2205.151934).

Reports of confirmed Zika-related deaths are rare. Brazil, the only other country to disclose them, has now reported three, said Dr. Rodriguez-Morales of the Universidad Tecnológica de Pereira, Colombia.

©bakhtiar_zein/Thinkstock

“Before the current outbreak in Latin America, Zika virus was not linked to deaths,” he noted. But the eight confirmed Zika-related deaths in South America “call attention to the need for evidence-based guidelines for clinical management of Zika, as well as the possible occurrence of atypical and severe cases, including possibly congenitally related microcephaly.”

Because they all occurred in medically compromised patients, Dr. Rodriguez-Morales also urged clinicians to cast a wary eye on such patients who present with arbovirus-type symptoms, including fever and rash.

From September 2015 to March 2016, Colombia had 58,838 reported cases of Zika. Of those, only 2,361 were lab confirmed. The rest were either diagnosed clinically or were suspected cases, Dr. Rodriguez-Morales said. Although Colombia has a much smaller population than Brazil (49 million vs. 210 million), its Zika case rate is much higher, 120 cases per 100,000 people vs. 34 cases per 100,000 people.

The group of four deaths occurred in central Colombia, and included a 2-year-old girl, a 30-year-old woman, a 61-year-old man, and a 72-year-old woman. All presented with 2-6 days of fever. All were initially suspected to have dengue fever or chikungunya. None tested positive for dengue, but the man was coinfected with chikungunya.

All patients presented with anemia. All but the older man also had severe thrombocytopenia.

The toddler presented with hepatomegaly, mucosal hemorrhage, progressive respiratory collapse, progressive thrombocytopenia, and intravascular coagulation. She died 5 days after symptom onset and was found to have had unrecognized lymphoblastic leukemia.

The 30-year-old woman presented with a severe rash on both arms. She also exhibited coagulation dysfunction, including severe thrombocytopenia and leukopenia that progressed to intracerebral and subarachnoid hemorrhage. She died 12 days after symptom onset. She was determined to have had unrecognized acute myeloid leukemia.

The elderly man had a history of medically controlled hypertension. He experienced mucosal hemorrhage and respiratory distress. He died 7 days after symptom onset. On autopsy, his liver showed necrotic areas, and his spleen indicated a systemic inflammatory response.

The elderly woman had a history of insulin-controlled type 2 diabetes. Her symptoms included gastrointestinal distress, thrombocytopenia, and acute respiratory failure. She died 48 hours after symptom onset; her brain showed edema and ischemic lesions.

The 15-year-old girl in northern Colombia had a 5-year history of sickle cell disease, which, Dr. Rodriguez-Morales pointed out, is a risk factor for arbovirus diseases. However, the patient had never been hospitalized for a vasoocclusive crisis. She presented with a high fever; joint, muscle, and abdominal pain; and jaundice. She was assumed to have dengue virus. Within another day, she had progressed into respiratory failure and was on a ventilator. She died less than 2 days later.

Her autopsy showed hepatic necrosis and severe decrease of splenic lymphoid tissue with splenic sequestration. Systemic inflammation probably triggered a fatal vasoocclusive crisis and splenic sequestration.

Dr. Rodriguez-Morales had no financial disclosures.

msullivan@frontlinemedcom.com