Interscience Conference on Antimicrobial Agents & Chemotherapy (ICAAC)

CHICAGO – Oral metronidazole was just as effective as oral vancomycin in treating Clostridium difficile diarrhea, regardless of the severity of illness, in a single-center study.

There also were no differences in mortality with use of either antibiotic, primary author Dr. Qamar Saleheen reported during a poster session at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

"Based on these findings, we ask this question to the medical community: ‘Is using one antibiotic over the other justified based upon severity of illness without consideration to the financial impact of using vancomycin, which is much more expensive than metronidazole?’ " the researchers asked in a press statement.

According to guidelines on the treatment of C. difficile diarrhea published in May 2010 by the Society for Healthcare Epidemiology of America, oral metronidazole is recommended for mild to moderate illness while oral vancomycin is recommend for severe illness (Infect. Control Hosp. Epidemiol. 2010;31:431-55).

Between Jan. 1, 2009 and March 31, 2010, Dr. Saleheen and his associates at Edward Hines Jr. VA Hospital in Hines, Ill., reviewed the charts of 147 patients with C. difficile positive stools. A total of 25 patients with a mean age of 67 years initially received oral vancomycin and 122 with a mean age of 68 years initially received oral metronidazole. Of 122 patients initially treated with metronidazole, 28 received crossover treatment with vancomycin.

Dr. Saleheen, an infectious diseases fellow at Loyola University Medical Center, Maywood, Ill., reported that in the vancomycin group, 14 patients (56%) had severe disease, of whom 3 patients (12%) had recurrence. Of the 11 patients (44%) who had nonsevere disease, none had a recurrence.

In the metronidazole group, 59 patients (48%) had severe disease, of whom 16 (13%) had recurrence; of the 63 (52%) with nonsevere disease, 11 (9%) had recurrence.

The researchers found that metronidazole was equivalent to vancomycin regardless of the severity of illness (P = .14). There were also no statistically significant differences between the two groups in the rate of recurrence or complications.

The researchers acknowledged certain limitations of the study, including its retrospective design, its relatively small sample size, and the fact that only two patients were female.

"There is a need for a prospective, head-to-head trial of these two medications, but I’m not sure who’s going to fund that study," Dr. Saleheen said in an interview at the meeting, which was sponsored by the American Society for Microbiology. "There is a paucity of data on this topic so it’s hard to say which antibiotic is better. We’re not jumping to any conclusions. There is no fixed management. We have to individualize each patient and treat accordingly."

The study’s principal investigators were Dr. Joseph R. Lentino and Dr. Constance Pachucki, both of Loyola University Chicago. The study’s fourth investigator was Dr. Mohammed Bilgrami, who is also an infectious diseases fellow at Loyola University Medical Center.

The researchers stated that they had no relevant financial conflicts to disclose.

CHICAGO – Oral metronidazole was just as effective as oral vancomycin in treating Clostridium difficile diarrhea, regardless of the severity of illness, in a single-center study.

There also were no differences in mortality with use of either antibiotic, primary author Dr. Qamar Saleheen reported during a poster session at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

"Based on these findings, we ask this question to the medical community: ‘Is using one antibiotic over the other justified based upon severity of illness without consideration to the financial impact of using vancomycin, which is much more expensive than metronidazole?’ " the researchers asked in a press statement.

According to guidelines on the treatment of C. difficile diarrhea published in May 2010 by the Society for Healthcare Epidemiology of America, oral metronidazole is recommended for mild to moderate illness while oral vancomycin is recommend for severe illness (Infect. Control Hosp. Epidemiol. 2010;31:431-55).

Between Jan. 1, 2009 and March 31, 2010, Dr. Saleheen and his associates at Edward Hines Jr. VA Hospital in Hines, Ill., reviewed the charts of 147 patients with C. difficile positive stools. A total of 25 patients with a mean age of 67 years initially received oral vancomycin and 122 with a mean age of 68 years initially received oral metronidazole. Of 122 patients initially treated with metronidazole, 28 received crossover treatment with vancomycin.

Dr. Saleheen, an infectious diseases fellow at Loyola University Medical Center, Maywood, Ill., reported that in the vancomycin group, 14 patients (56%) had severe disease, of whom 3 patients (12%) had recurrence. Of the 11 patients (44%) who had nonsevere disease, none had a recurrence.

In the metronidazole group, 59 patients (48%) had severe disease, of whom 16 (13%) had recurrence; of the 63 (52%) with nonsevere disease, 11 (9%) had recurrence.

The researchers found that metronidazole was equivalent to vancomycin regardless of the severity of illness (P = .14). There were also no statistically significant differences between the two groups in the rate of recurrence or complications.

The researchers acknowledged certain limitations of the study, including its retrospective design, its relatively small sample size, and the fact that only two patients were female.

"There is a need for a prospective, head-to-head trial of these two medications, but I’m not sure who’s going to fund that study," Dr. Saleheen said in an interview at the meeting, which was sponsored by the American Society for Microbiology. "There is a paucity of data on this topic so it’s hard to say which antibiotic is better. We’re not jumping to any conclusions. There is no fixed management. We have to individualize each patient and treat accordingly."

The study’s principal investigators were Dr. Joseph R. Lentino and Dr. Constance Pachucki, both of Loyola University Chicago. The study’s fourth investigator was Dr. Mohammed Bilgrami, who is also an infectious diseases fellow at Loyola University Medical Center.

The researchers stated that they had no relevant financial conflicts to disclose.

CHICAGO – Oral metronidazole was just as effective as oral vancomycin in treating Clostridium difficile diarrhea, regardless of the severity of illness, in a single-center study.

There also were no differences in mortality with use of either antibiotic, primary author Dr. Qamar Saleheen reported during a poster session at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

"Based on these findings, we ask this question to the medical community: ‘Is using one antibiotic over the other justified based upon severity of illness without consideration to the financial impact of using vancomycin, which is much more expensive than metronidazole?’ " the researchers asked in a press statement.

According to guidelines on the treatment of C. difficile diarrhea published in May 2010 by the Society for Healthcare Epidemiology of America, oral metronidazole is recommended for mild to moderate illness while oral vancomycin is recommend for severe illness (Infect. Control Hosp. Epidemiol. 2010;31:431-55).

Between Jan. 1, 2009 and March 31, 2010, Dr. Saleheen and his associates at Edward Hines Jr. VA Hospital in Hines, Ill., reviewed the charts of 147 patients with C. difficile positive stools. A total of 25 patients with a mean age of 67 years initially received oral vancomycin and 122 with a mean age of 68 years initially received oral metronidazole. Of 122 patients initially treated with metronidazole, 28 received crossover treatment with vancomycin.

Dr. Saleheen, an infectious diseases fellow at Loyola University Medical Center, Maywood, Ill., reported that in the vancomycin group, 14 patients (56%) had severe disease, of whom 3 patients (12%) had recurrence. Of the 11 patients (44%) who had nonsevere disease, none had a recurrence.

In the metronidazole group, 59 patients (48%) had severe disease, of whom 16 (13%) had recurrence; of the 63 (52%) with nonsevere disease, 11 (9%) had recurrence.

The researchers found that metronidazole was equivalent to vancomycin regardless of the severity of illness (P = .14). There were also no statistically significant differences between the two groups in the rate of recurrence or complications.

The researchers acknowledged certain limitations of the study, including its retrospective design, its relatively small sample size, and the fact that only two patients were female.

"There is a need for a prospective, head-to-head trial of these two medications, but I’m not sure who’s going to fund that study," Dr. Saleheen said in an interview at the meeting, which was sponsored by the American Society for Microbiology. "There is a paucity of data on this topic so it’s hard to say which antibiotic is better. We’re not jumping to any conclusions. There is no fixed management. We have to individualize each patient and treat accordingly."

The study’s principal investigators were Dr. Joseph R. Lentino and Dr. Constance Pachucki, both of Loyola University Chicago. The study’s fourth investigator was Dr. Mohammed Bilgrami, who is also an infectious diseases fellow at Loyola University Medical Center.

The researchers stated that they had no relevant financial conflicts to disclose.

CHICAGO – Intra-abdominal infections are the most common source of hospital-acquired bloodstream infections, results from a year-long, single-center study found.

"With the movement toward reducing all hospital-acquired infections, it is important to find out where to put our efforts," lead investigator Dr. Mohamad G. Fakih said in an interview before a poster session at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy, where the research was presented in poster form.

To better understand the main sources of hospital-acquired bloodstream infections, Dr. Fakih and his associates at the 804-bed St. John Hospital and Medical Center, Detroit, retrospectively evaluated 180 cases of patients with positive blood cultures from 10 adult nonintensive medical-surgical units at the hospital between October 2009 and September of 2010. They collected data on infection source, causative organism, and whether it was hospital-acquired (defined as the emergence of a bloodstream infection greater than 48 hours after admission).

In all, 47 of the cases were considered to be contaminants. That left 133 cases of bloodstream infections: 42 of them had a community-onset and 91 were acquired in the hospital.

Dr. Fakih, medical director of infection prevention and control at the hospital, reported that of the 91 hospital-acquired cases of bloodstream infection, 20 (22%) were related to Staphylococcus aureus, 3 (3.3%) to coagulase-negative staphylococci, 11 (12.1%) to other gram-positive organisms, 25 (27.5%) to gram-negative bacilli, 21 (23.1%) to mixed organisms, 5 (5.5%) to anaerobes, and 6 (6.6%) to Candida species.

As for common sources of hospital-acquired bloodstream infections, 32 (35.2%) were intra-abdominal, 19 (20.9%) were vascular catheter, 11 (12.9%) were urinary tract, and 9 (9.9%) were soft tissue.

Dr. Fakih noted that peripheral intravenous catheters were the source of 42.1% of bloodstream infections that were associated with vascular catheters.

He indicated certain limitations of the study, including its single-center design. Dr. Fakih also encouraged clinicians to cast a wide net when it comes to infection control practices. "Look at what is important in your hospital and not only what is mandated by external agencies or what is now considered to be hospital-acquired conditions," he advised.

The conference was sponsored by the American Society for Microbiology. Dr. Fakih said that he had no relevant financial conflicts to disclose.

CHICAGO – Intra-abdominal infections are the most common source of hospital-acquired bloodstream infections, results from a year-long, single-center study found.

"With the movement toward reducing all hospital-acquired infections, it is important to find out where to put our efforts," lead investigator Dr. Mohamad G. Fakih said in an interview before a poster session at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy, where the research was presented in poster form.

To better understand the main sources of hospital-acquired bloodstream infections, Dr. Fakih and his associates at the 804-bed St. John Hospital and Medical Center, Detroit, retrospectively evaluated 180 cases of patients with positive blood cultures from 10 adult nonintensive medical-surgical units at the hospital between October 2009 and September of 2010. They collected data on infection source, causative organism, and whether it was hospital-acquired (defined as the emergence of a bloodstream infection greater than 48 hours after admission).

In all, 47 of the cases were considered to be contaminants. That left 133 cases of bloodstream infections: 42 of them had a community-onset and 91 were acquired in the hospital.

Dr. Fakih, medical director of infection prevention and control at the hospital, reported that of the 91 hospital-acquired cases of bloodstream infection, 20 (22%) were related to Staphylococcus aureus, 3 (3.3%) to coagulase-negative staphylococci, 11 (12.1%) to other gram-positive organisms, 25 (27.5%) to gram-negative bacilli, 21 (23.1%) to mixed organisms, 5 (5.5%) to anaerobes, and 6 (6.6%) to Candida species.

As for common sources of hospital-acquired bloodstream infections, 32 (35.2%) were intra-abdominal, 19 (20.9%) were vascular catheter, 11 (12.9%) were urinary tract, and 9 (9.9%) were soft tissue.

Dr. Fakih noted that peripheral intravenous catheters were the source of 42.1% of bloodstream infections that were associated with vascular catheters.

He indicated certain limitations of the study, including its single-center design. Dr. Fakih also encouraged clinicians to cast a wide net when it comes to infection control practices. "Look at what is important in your hospital and not only what is mandated by external agencies or what is now considered to be hospital-acquired conditions," he advised.

The conference was sponsored by the American Society for Microbiology. Dr. Fakih said that he had no relevant financial conflicts to disclose.

CHICAGO – Intra-abdominal infections are the most common source of hospital-acquired bloodstream infections, results from a year-long, single-center study found.

"With the movement toward reducing all hospital-acquired infections, it is important to find out where to put our efforts," lead investigator Dr. Mohamad G. Fakih said in an interview before a poster session at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy, where the research was presented in poster form.

To better understand the main sources of hospital-acquired bloodstream infections, Dr. Fakih and his associates at the 804-bed St. John Hospital and Medical Center, Detroit, retrospectively evaluated 180 cases of patients with positive blood cultures from 10 adult nonintensive medical-surgical units at the hospital between October 2009 and September of 2010. They collected data on infection source, causative organism, and whether it was hospital-acquired (defined as the emergence of a bloodstream infection greater than 48 hours after admission).

In all, 47 of the cases were considered to be contaminants. That left 133 cases of bloodstream infections: 42 of them had a community-onset and 91 were acquired in the hospital.

Dr. Fakih, medical director of infection prevention and control at the hospital, reported that of the 91 hospital-acquired cases of bloodstream infection, 20 (22%) were related to Staphylococcus aureus, 3 (3.3%) to coagulase-negative staphylococci, 11 (12.1%) to other gram-positive organisms, 25 (27.5%) to gram-negative bacilli, 21 (23.1%) to mixed organisms, 5 (5.5%) to anaerobes, and 6 (6.6%) to Candida species.

As for common sources of hospital-acquired bloodstream infections, 32 (35.2%) were intra-abdominal, 19 (20.9%) were vascular catheter, 11 (12.9%) were urinary tract, and 9 (9.9%) were soft tissue.

Dr. Fakih noted that peripheral intravenous catheters were the source of 42.1% of bloodstream infections that were associated with vascular catheters.

He indicated certain limitations of the study, including its single-center design. Dr. Fakih also encouraged clinicians to cast a wide net when it comes to infection control practices. "Look at what is important in your hospital and not only what is mandated by external agencies or what is now considered to be hospital-acquired conditions," he advised.

The conference was sponsored by the American Society for Microbiology. Dr. Fakih said that he had no relevant financial conflicts to disclose.

CHICAGO – Patients with end-stage renal disease have sharply elevated rates of hospitalization for pneumonia throughout the renal transplantation trajectory, researchers reported at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

The findings underscore the importance of vaccinating this group against pneumococcal and other diseases, lead investigator Lise Haubjerg Nielsen recommended in an interview. Pneumonia "is a big economic burden for society and it is a huge [source of] mortality for these patients."

In a Danish nationwide population-based cohort study among more than 90,000 individuals, those with end-stage renal disease (ESRD) had an 8- to 14-fold higher incidence of such hospitalization, depending on whether they were wait-listed, posttransplant, or post–graft failure, when compared with their counterparts in the general population.

About one-third of the posttransplant group was hospitalized for pneumonia. Male sex and older age were among the significant risk factors for pneumonia hospitalization at this stage. On the other hand, risk fell after the first year posttransplant.

The marked increase in posttransplant risk was expected, given patients’ use of immunosuppressants, according to Ms. Nielsen, who is a medical student undertaking a research year in the department of infectious diseases at Aarhus University Hospital, Skejby. However, the fact that the elevations seen before and after transplantation were even greater was surprising, she said at the meeting, which was sponsored by the American Society for Microbiology.

The increase in pretransplant risk was probably caused by patients’ uremic state, while that post–graft failure "could also be just [a reflection of] these patients being more sick than the general population," she speculated.

The investigators analyzed data from the Danish National Hospital Registry, identifying all hospitalizations since 1977 having a discharge diagnosis of pneumonia, regardless of whether the infection was community or hospital acquired.

They assessed first hospitalizations for pneumonia (excluding those caused by Pneumocystis jiroveci) occurring during 1990-2009. Patients with ESRD who were wait-listed for and/or underwent transplantation were matched by age and sex with up to 19 unaffected individuals from the general population. Analyses were based on 4,973 individuals with and 85,899 individuals without ESRD.

The incidence of first pneumonia hospitalization was 46, 32, and 63 per 1,000 person-years among wait-listed patients, renal transplant recipients, and patients who experienced graft loss, respectively.

These groups had corresponding 10-, 9, and 14-fold increases in the incidence of such hospitalization compared with the general population, according to Ms. Nielsen.

In an analysis of risk factors among the renal transplant recipients, the adjusted incidence rate of pneumonia hospitalization was significantly higher for men; patients aged 50 years or older; those who underwent 1-3 years of dialysis pretransplantation versus none; and those whose renal disease was associated with diabetes, chronic interstitial nephritis, or polycystic kidney disease as compared with glomerulonephritis. The risk of pneumonia hospitalization was significantly lower for those who were at least 1 year out from transplantation.

Ms. Nielsen reported having no conflicts of interest.

CHICAGO – Patients with end-stage renal disease have sharply elevated rates of hospitalization for pneumonia throughout the renal transplantation trajectory, researchers reported at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

The findings underscore the importance of vaccinating this group against pneumococcal and other diseases, lead investigator Lise Haubjerg Nielsen recommended in an interview. Pneumonia "is a big economic burden for society and it is a huge [source of] mortality for these patients."

In a Danish nationwide population-based cohort study among more than 90,000 individuals, those with end-stage renal disease (ESRD) had an 8- to 14-fold higher incidence of such hospitalization, depending on whether they were wait-listed, posttransplant, or post–graft failure, when compared with their counterparts in the general population.

About one-third of the posttransplant group was hospitalized for pneumonia. Male sex and older age were among the significant risk factors for pneumonia hospitalization at this stage. On the other hand, risk fell after the first year posttransplant.

The marked increase in posttransplant risk was expected, given patients’ use of immunosuppressants, according to Ms. Nielsen, who is a medical student undertaking a research year in the department of infectious diseases at Aarhus University Hospital, Skejby. However, the fact that the elevations seen before and after transplantation were even greater was surprising, she said at the meeting, which was sponsored by the American Society for Microbiology.

The increase in pretransplant risk was probably caused by patients’ uremic state, while that post–graft failure "could also be just [a reflection of] these patients being more sick than the general population," she speculated.

The investigators analyzed data from the Danish National Hospital Registry, identifying all hospitalizations since 1977 having a discharge diagnosis of pneumonia, regardless of whether the infection was community or hospital acquired.

They assessed first hospitalizations for pneumonia (excluding those caused by Pneumocystis jiroveci) occurring during 1990-2009. Patients with ESRD who were wait-listed for and/or underwent transplantation were matched by age and sex with up to 19 unaffected individuals from the general population. Analyses were based on 4,973 individuals with and 85,899 individuals without ESRD.

The incidence of first pneumonia hospitalization was 46, 32, and 63 per 1,000 person-years among wait-listed patients, renal transplant recipients, and patients who experienced graft loss, respectively.

These groups had corresponding 10-, 9, and 14-fold increases in the incidence of such hospitalization compared with the general population, according to Ms. Nielsen.

In an analysis of risk factors among the renal transplant recipients, the adjusted incidence rate of pneumonia hospitalization was significantly higher for men; patients aged 50 years or older; those who underwent 1-3 years of dialysis pretransplantation versus none; and those whose renal disease was associated with diabetes, chronic interstitial nephritis, or polycystic kidney disease as compared with glomerulonephritis. The risk of pneumonia hospitalization was significantly lower for those who were at least 1 year out from transplantation.

Ms. Nielsen reported having no conflicts of interest.

CHICAGO – Patients with end-stage renal disease have sharply elevated rates of hospitalization for pneumonia throughout the renal transplantation trajectory, researchers reported at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

The findings underscore the importance of vaccinating this group against pneumococcal and other diseases, lead investigator Lise Haubjerg Nielsen recommended in an interview. Pneumonia "is a big economic burden for society and it is a huge [source of] mortality for these patients."

In a Danish nationwide population-based cohort study among more than 90,000 individuals, those with end-stage renal disease (ESRD) had an 8- to 14-fold higher incidence of such hospitalization, depending on whether they were wait-listed, posttransplant, or post–graft failure, when compared with their counterparts in the general population.

About one-third of the posttransplant group was hospitalized for pneumonia. Male sex and older age were among the significant risk factors for pneumonia hospitalization at this stage. On the other hand, risk fell after the first year posttransplant.

The marked increase in posttransplant risk was expected, given patients’ use of immunosuppressants, according to Ms. Nielsen, who is a medical student undertaking a research year in the department of infectious diseases at Aarhus University Hospital, Skejby. However, the fact that the elevations seen before and after transplantation were even greater was surprising, she said at the meeting, which was sponsored by the American Society for Microbiology.

The increase in pretransplant risk was probably caused by patients’ uremic state, while that post–graft failure "could also be just [a reflection of] these patients being more sick than the general population," she speculated.

The investigators analyzed data from the Danish National Hospital Registry, identifying all hospitalizations since 1977 having a discharge diagnosis of pneumonia, regardless of whether the infection was community or hospital acquired.

They assessed first hospitalizations for pneumonia (excluding those caused by Pneumocystis jiroveci) occurring during 1990-2009. Patients with ESRD who were wait-listed for and/or underwent transplantation were matched by age and sex with up to 19 unaffected individuals from the general population. Analyses were based on 4,973 individuals with and 85,899 individuals without ESRD.

The incidence of first pneumonia hospitalization was 46, 32, and 63 per 1,000 person-years among wait-listed patients, renal transplant recipients, and patients who experienced graft loss, respectively.

These groups had corresponding 10-, 9, and 14-fold increases in the incidence of such hospitalization compared with the general population, according to Ms. Nielsen.

In an analysis of risk factors among the renal transplant recipients, the adjusted incidence rate of pneumonia hospitalization was significantly higher for men; patients aged 50 years or older; those who underwent 1-3 years of dialysis pretransplantation versus none; and those whose renal disease was associated with diabetes, chronic interstitial nephritis, or polycystic kidney disease as compared with glomerulonephritis. The risk of pneumonia hospitalization was significantly lower for those who were at least 1 year out from transplantation.

Ms. Nielsen reported having no conflicts of interest.

CHICAGO – Doripenem was a safe and effective treatment for pediatric patients with septicemia, pneumonia, and other infections in a phase-III trial of 95 children.

Two or three 20-mg/kg doses of the parenteral carbapenem antibiotic cured the infections of 92 of the children enrolled in the multicenter trial. The microbiological cure rate among the 75 subjects in whom at least one bacterial pathogen was isolated at baseline was 92%, reported Dr. Keisuke Sunakawa of Kitasato University, Tokyo.

Doripenem (Doribax) is approved in the United States for the treatment of complicated intra-abdominal infections and complicated urinary tract infections in adults. It is also approved for nosocomial pneumonia in Europe and for a variety of bacterial infections, including septicemia and pneumonia, in Japan, Dr. Sunakawa said at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Because of the drug’s antibacterial activity against known causative pathogens in pediatric infections, including penicillin-resistant Streptococcus pneumoniae (PRSP) and beta-lactamase–nonproducing, ampicillin-resistant Haemophilus influenzae (BLNAR), the investigators sought to determine its safety and efficacy in children. Toward this end, they enrolled 100 children between the ages of 2 months and 13 years with pneumonia, urinary tract infections, middle otitis, septicemia, and other infections.

Because doripenem does not have specific pediatric dosing recommendation, the investigators performed a Monte Carlo simulation based on a pharmacokinetic-pharmacodynamic model, which suggested that 20 mg/kg given two or three times daily would provide optimal coverage, Dr. Sunakawa said in a poster presentation. Patients received infusions based on this dosing regimen for a maximum of 14 days and were followed up 7 days after the last dose. The primary end point was the clinical cure rate at the end of therapy.

Of the 95 children (50 boys and 45 girls) included in the final analysis, 58 had pneumonia, 12 had urinary tract infections, 8 had otitis media, and 17 had septicemia or other infections, with mean treatment durations of 6.4, 6.4, 6.5, and 6.1 days, respectively.

The clinical response rates by infection type at the end of therapy were 97% for pneumonia, 100% for urinary tract infections, 100% for middle otitis, and 94% for septicemia and other infections, he said.

The one treatment "failure" was a patient in the latter group with perimandibular phlegmon who stopped treatment because she underwent additional endodontic surgery at another hospital. The recurrence/reinfection rate at follow-up was 1.4%, Dr. Sunakawa at the meeting, which was sponsored by the American Society for Microbiology.

When assessed by microbiological response, 6 of the 75 patients in whom at least one baseline pathogen had been detected failed treatment, including one patient with gram-negative H. influenzae and five with polymicrobial (S. pneumoniae and H. influenzae) infection, he reported.

"Of the drug-resistant genes [identified by PCR], all but three were cured with doripenem," he said, including one PRSP infection, one BLNAR infection, and one beta-lactamase–producing, amoxicillin clavulanate–resistant H. influenzae infection.

Regarding safety, "the adverse events were consistent with those observed at the 250- to 1,000-mg dose in adults," Dr. Sunakawa stated. "There were no new safety signals, and there were no central nervous system events, such as seizures, which are a concern for this drug class."

At least one adverse event was reported in 2 of the patients who received twice-daily doses (40%) and 54 of those who had thrice-daily doses (57%). The most common adverse events were diarrhea or loose stool, followed by injection site reactions and increased platelet count, ALT, AST, and eosinophil count, Dr. Sunakawa said. No events observed in the twice-daily dosing group and 27 in the thrice-daily dosing group were considered to be drug related, he said.

The results suggest that treatment with doripenem may be a good option for severe, intractable pediatric infections, particularly in light of the increasing frequency of drug-resistant pathogens, Dr. Sunakawa concluded. The drug is not yet indicated for use in children in the United States, Europe, or Japan.

Dr. Sunakawa disclosed serving as a scientific advisor for Shionogi & Co.

CHICAGO – Doripenem was a safe and effective treatment for pediatric patients with septicemia, pneumonia, and other infections in a phase-III trial of 95 children.

Two or three 20-mg/kg doses of the parenteral carbapenem antibiotic cured the infections of 92 of the children enrolled in the multicenter trial. The microbiological cure rate among the 75 subjects in whom at least one bacterial pathogen was isolated at baseline was 92%, reported Dr. Keisuke Sunakawa of Kitasato University, Tokyo.

Doripenem (Doribax) is approved in the United States for the treatment of complicated intra-abdominal infections and complicated urinary tract infections in adults. It is also approved for nosocomial pneumonia in Europe and for a variety of bacterial infections, including septicemia and pneumonia, in Japan, Dr. Sunakawa said at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Because of the drug’s antibacterial activity against known causative pathogens in pediatric infections, including penicillin-resistant Streptococcus pneumoniae (PRSP) and beta-lactamase–nonproducing, ampicillin-resistant Haemophilus influenzae (BLNAR), the investigators sought to determine its safety and efficacy in children. Toward this end, they enrolled 100 children between the ages of 2 months and 13 years with pneumonia, urinary tract infections, middle otitis, septicemia, and other infections.

Because doripenem does not have specific pediatric dosing recommendation, the investigators performed a Monte Carlo simulation based on a pharmacokinetic-pharmacodynamic model, which suggested that 20 mg/kg given two or three times daily would provide optimal coverage, Dr. Sunakawa said in a poster presentation. Patients received infusions based on this dosing regimen for a maximum of 14 days and were followed up 7 days after the last dose. The primary end point was the clinical cure rate at the end of therapy.

Of the 95 children (50 boys and 45 girls) included in the final analysis, 58 had pneumonia, 12 had urinary tract infections, 8 had otitis media, and 17 had septicemia or other infections, with mean treatment durations of 6.4, 6.4, 6.5, and 6.1 days, respectively.

The clinical response rates by infection type at the end of therapy were 97% for pneumonia, 100% for urinary tract infections, 100% for middle otitis, and 94% for septicemia and other infections, he said.

The one treatment "failure" was a patient in the latter group with perimandibular phlegmon who stopped treatment because she underwent additional endodontic surgery at another hospital. The recurrence/reinfection rate at follow-up was 1.4%, Dr. Sunakawa at the meeting, which was sponsored by the American Society for Microbiology.

When assessed by microbiological response, 6 of the 75 patients in whom at least one baseline pathogen had been detected failed treatment, including one patient with gram-negative H. influenzae and five with polymicrobial (S. pneumoniae and H. influenzae) infection, he reported.

"Of the drug-resistant genes [identified by PCR], all but three were cured with doripenem," he said, including one PRSP infection, one BLNAR infection, and one beta-lactamase–producing, amoxicillin clavulanate–resistant H. influenzae infection.

Regarding safety, "the adverse events were consistent with those observed at the 250- to 1,000-mg dose in adults," Dr. Sunakawa stated. "There were no new safety signals, and there were no central nervous system events, such as seizures, which are a concern for this drug class."

At least one adverse event was reported in 2 of the patients who received twice-daily doses (40%) and 54 of those who had thrice-daily doses (57%). The most common adverse events were diarrhea or loose stool, followed by injection site reactions and increased platelet count, ALT, AST, and eosinophil count, Dr. Sunakawa said. No events observed in the twice-daily dosing group and 27 in the thrice-daily dosing group were considered to be drug related, he said.

The results suggest that treatment with doripenem may be a good option for severe, intractable pediatric infections, particularly in light of the increasing frequency of drug-resistant pathogens, Dr. Sunakawa concluded. The drug is not yet indicated for use in children in the United States, Europe, or Japan.

Dr. Sunakawa disclosed serving as a scientific advisor for Shionogi & Co.

CHICAGO – Doripenem was a safe and effective treatment for pediatric patients with septicemia, pneumonia, and other infections in a phase-III trial of 95 children.

Two or three 20-mg/kg doses of the parenteral carbapenem antibiotic cured the infections of 92 of the children enrolled in the multicenter trial. The microbiological cure rate among the 75 subjects in whom at least one bacterial pathogen was isolated at baseline was 92%, reported Dr. Keisuke Sunakawa of Kitasato University, Tokyo.

Doripenem (Doribax) is approved in the United States for the treatment of complicated intra-abdominal infections and complicated urinary tract infections in adults. It is also approved for nosocomial pneumonia in Europe and for a variety of bacterial infections, including septicemia and pneumonia, in Japan, Dr. Sunakawa said at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Because of the drug’s antibacterial activity against known causative pathogens in pediatric infections, including penicillin-resistant Streptococcus pneumoniae (PRSP) and beta-lactamase–nonproducing, ampicillin-resistant Haemophilus influenzae (BLNAR), the investigators sought to determine its safety and efficacy in children. Toward this end, they enrolled 100 children between the ages of 2 months and 13 years with pneumonia, urinary tract infections, middle otitis, septicemia, and other infections.

Because doripenem does not have specific pediatric dosing recommendation, the investigators performed a Monte Carlo simulation based on a pharmacokinetic-pharmacodynamic model, which suggested that 20 mg/kg given two or three times daily would provide optimal coverage, Dr. Sunakawa said in a poster presentation. Patients received infusions based on this dosing regimen for a maximum of 14 days and were followed up 7 days after the last dose. The primary end point was the clinical cure rate at the end of therapy.

Of the 95 children (50 boys and 45 girls) included in the final analysis, 58 had pneumonia, 12 had urinary tract infections, 8 had otitis media, and 17 had septicemia or other infections, with mean treatment durations of 6.4, 6.4, 6.5, and 6.1 days, respectively.

The clinical response rates by infection type at the end of therapy were 97% for pneumonia, 100% for urinary tract infections, 100% for middle otitis, and 94% for septicemia and other infections, he said.

The one treatment "failure" was a patient in the latter group with perimandibular phlegmon who stopped treatment because she underwent additional endodontic surgery at another hospital. The recurrence/reinfection rate at follow-up was 1.4%, Dr. Sunakawa at the meeting, which was sponsored by the American Society for Microbiology.

When assessed by microbiological response, 6 of the 75 patients in whom at least one baseline pathogen had been detected failed treatment, including one patient with gram-negative H. influenzae and five with polymicrobial (S. pneumoniae and H. influenzae) infection, he reported.

"Of the drug-resistant genes [identified by PCR], all but three were cured with doripenem," he said, including one PRSP infection, one BLNAR infection, and one beta-lactamase–producing, amoxicillin clavulanate–resistant H. influenzae infection.

Regarding safety, "the adverse events were consistent with those observed at the 250- to 1,000-mg dose in adults," Dr. Sunakawa stated. "There were no new safety signals, and there were no central nervous system events, such as seizures, which are a concern for this drug class."

At least one adverse event was reported in 2 of the patients who received twice-daily doses (40%) and 54 of those who had thrice-daily doses (57%). The most common adverse events were diarrhea or loose stool, followed by injection site reactions and increased platelet count, ALT, AST, and eosinophil count, Dr. Sunakawa said. No events observed in the twice-daily dosing group and 27 in the thrice-daily dosing group were considered to be drug related, he said.

The results suggest that treatment with doripenem may be a good option for severe, intractable pediatric infections, particularly in light of the increasing frequency of drug-resistant pathogens, Dr. Sunakawa concluded. The drug is not yet indicated for use in children in the United States, Europe, or Japan.

Dr. Sunakawa disclosed serving as a scientific advisor for Shionogi & Co.

CHICAGO – Hospitalized patients who maintained short-term glucose levels less than 110mg/dL were less likely than those with higher short-term levels to develop bloodstream infections, according to the findings of a retrospective study presented at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

By contrast, long-term glucose measures – hemoglobin A_1c – did not appear to be associated with the rates of bloodstream infections, said the study’s lead investigator Christie Y. Jeon, Sc.D., of Columbia University, New York.

"Given that people with diabetes are at increased risk of infections, monitoring glucose control may reduce the burden of bloodstream infections," she said at the conference, sponsored by the American Society for Microbiology.

There is currently a dearth of information on how short-term and long-term glucose control impact health care–associated bloodstream infections and what level of glucose control is optimal for reducing the risk of infection. Yet "health care–associated bloodstream infections are estimated to cause over 30,000 deaths in the United States annually," she said in an interview.

In the study, Dr. Jeon and associates analyzed 18,736 records from diabetes patients and 60,778 records from patients without diabetes admitted to one of three hospitals in New York City to examine the relationship between both short- and long-term glucose control on bloodstream infection rates.

For short-term glucose control, the researchers assessed glucose levels during three different periods leading up to the index date of infection: period 1, the index date and 2 days prior (day 0 to day -2); period 2, day -1 to day -3; and period 3, day -2 to day -4. Then they classified them into six categories: less than 80 mg/dL, 80-109 mg/dL, 110-139 mg/dL, 140-179 mg/dL, 180-199 mg/dL, and 200 mg/dL or higher.

Long-term glucose control was determined by hemoglobin A_1c.

The researchers controlled for confounding variables, including age, gender, severity of illness, malignancy, use of immunosuppressive medications, renal failure, prior hospitalization, use of mechanical ventilation, feeding tubes, and central venous and urinary catheterizations. The median age of patients was 53 years, and 54% were female.

Short-term glucose levels of 110 mg/dL or higher during period 1 were associated with an increase in bloodstream infections in people with diabetes (hazard ratio from 2.18 to 3.32) and in those without diabetes (HR from 1.62 to 1.80). Glucose levels measured more remotely in period 3 were not associated with bloodstream infections. Hypoglycemia and hemoglobin A_1c levels were not associated with bloodstream infections.

"The fact that long-term glucose control was not associated with bloodstream infection was surprising and informative to us, as it is an indication that for acute infections such as bloodstream infections, long-term glucose control is limited in its impact," Dr. Jeon said. "Further, the fact that glucose measured closest to the index date of infection was most predictive of bloodstream infections suggests that associations between glucose levels and infections may be due to hyperglycemia as an effect, and not a cause, of health care–associated infections."

The study was limited by its observational design. In addition, "there is a possibility that ... confounders may have influenced glucose levels as well as infection risk."

The study was funded by the National Institutes of Health. Dr. Jeon was supported by a National Research Service Award from the National Institute of Allergy and Infectious Diseases. Dr. Jeon’s coathors on the study were Dr. Emily Y. Furuya, Mandar Apte, and Elaine L. Larson, Ph.D.

Dr. Jeon said that she had no relevant financial conflicts of interest.

CHICAGO – Hospitalized patients who maintained short-term glucose levels less than 110mg/dL were less likely than those with higher short-term levels to develop bloodstream infections, according to the findings of a retrospective study presented at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

By contrast, long-term glucose measures – hemoglobin A_1c – did not appear to be associated with the rates of bloodstream infections, said the study’s lead investigator Christie Y. Jeon, Sc.D., of Columbia University, New York.

"Given that people with diabetes are at increased risk of infections, monitoring glucose control may reduce the burden of bloodstream infections," she said at the conference, sponsored by the American Society for Microbiology.

There is currently a dearth of information on how short-term and long-term glucose control impact health care–associated bloodstream infections and what level of glucose control is optimal for reducing the risk of infection. Yet "health care–associated bloodstream infections are estimated to cause over 30,000 deaths in the United States annually," she said in an interview.

In the study, Dr. Jeon and associates analyzed 18,736 records from diabetes patients and 60,778 records from patients without diabetes admitted to one of three hospitals in New York City to examine the relationship between both short- and long-term glucose control on bloodstream infection rates.

For short-term glucose control, the researchers assessed glucose levels during three different periods leading up to the index date of infection: period 1, the index date and 2 days prior (day 0 to day -2); period 2, day -1 to day -3; and period 3, day -2 to day -4. Then they classified them into six categories: less than 80 mg/dL, 80-109 mg/dL, 110-139 mg/dL, 140-179 mg/dL, 180-199 mg/dL, and 200 mg/dL or higher.

Long-term glucose control was determined by hemoglobin A_1c.

The researchers controlled for confounding variables, including age, gender, severity of illness, malignancy, use of immunosuppressive medications, renal failure, prior hospitalization, use of mechanical ventilation, feeding tubes, and central venous and urinary catheterizations. The median age of patients was 53 years, and 54% were female.

Short-term glucose levels of 110 mg/dL or higher during period 1 were associated with an increase in bloodstream infections in people with diabetes (hazard ratio from 2.18 to 3.32) and in those without diabetes (HR from 1.62 to 1.80). Glucose levels measured more remotely in period 3 were not associated with bloodstream infections. Hypoglycemia and hemoglobin A_1c levels were not associated with bloodstream infections.

"The fact that long-term glucose control was not associated with bloodstream infection was surprising and informative to us, as it is an indication that for acute infections such as bloodstream infections, long-term glucose control is limited in its impact," Dr. Jeon said. "Further, the fact that glucose measured closest to the index date of infection was most predictive of bloodstream infections suggests that associations between glucose levels and infections may be due to hyperglycemia as an effect, and not a cause, of health care–associated infections."

The study was limited by its observational design. In addition, "there is a possibility that ... confounders may have influenced glucose levels as well as infection risk."

The study was funded by the National Institutes of Health. Dr. Jeon was supported by a National Research Service Award from the National Institute of Allergy and Infectious Diseases. Dr. Jeon’s coathors on the study were Dr. Emily Y. Furuya, Mandar Apte, and Elaine L. Larson, Ph.D.

Dr. Jeon said that she had no relevant financial conflicts of interest.

CHICAGO – Hospitalized patients who maintained short-term glucose levels less than 110mg/dL were less likely than those with higher short-term levels to develop bloodstream infections, according to the findings of a retrospective study presented at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

By contrast, long-term glucose measures – hemoglobin A_1c – did not appear to be associated with the rates of bloodstream infections, said the study’s lead investigator Christie Y. Jeon, Sc.D., of Columbia University, New York.

"Given that people with diabetes are at increased risk of infections, monitoring glucose control may reduce the burden of bloodstream infections," she said at the conference, sponsored by the American Society for Microbiology.

There is currently a dearth of information on how short-term and long-term glucose control impact health care–associated bloodstream infections and what level of glucose control is optimal for reducing the risk of infection. Yet "health care–associated bloodstream infections are estimated to cause over 30,000 deaths in the United States annually," she said in an interview.

In the study, Dr. Jeon and associates analyzed 18,736 records from diabetes patients and 60,778 records from patients without diabetes admitted to one of three hospitals in New York City to examine the relationship between both short- and long-term glucose control on bloodstream infection rates.

For short-term glucose control, the researchers assessed glucose levels during three different periods leading up to the index date of infection: period 1, the index date and 2 days prior (day 0 to day -2); period 2, day -1 to day -3; and period 3, day -2 to day -4. Then they classified them into six categories: less than 80 mg/dL, 80-109 mg/dL, 110-139 mg/dL, 140-179 mg/dL, 180-199 mg/dL, and 200 mg/dL or higher.

Long-term glucose control was determined by hemoglobin A_1c.

The researchers controlled for confounding variables, including age, gender, severity of illness, malignancy, use of immunosuppressive medications, renal failure, prior hospitalization, use of mechanical ventilation, feeding tubes, and central venous and urinary catheterizations. The median age of patients was 53 years, and 54% were female.

Short-term glucose levels of 110 mg/dL or higher during period 1 were associated with an increase in bloodstream infections in people with diabetes (hazard ratio from 2.18 to 3.32) and in those without diabetes (HR from 1.62 to 1.80). Glucose levels measured more remotely in period 3 were not associated with bloodstream infections. Hypoglycemia and hemoglobin A_1c levels were not associated with bloodstream infections.

"The fact that long-term glucose control was not associated with bloodstream infection was surprising and informative to us, as it is an indication that for acute infections such as bloodstream infections, long-term glucose control is limited in its impact," Dr. Jeon said. "Further, the fact that glucose measured closest to the index date of infection was most predictive of bloodstream infections suggests that associations between glucose levels and infections may be due to hyperglycemia as an effect, and not a cause, of health care–associated infections."

The study was limited by its observational design. In addition, "there is a possibility that ... confounders may have influenced glucose levels as well as infection risk."

The study was funded by the National Institutes of Health. Dr. Jeon was supported by a National Research Service Award from the National Institute of Allergy and Infectious Diseases. Dr. Jeon’s coathors on the study were Dr. Emily Y. Furuya, Mandar Apte, and Elaine L. Larson, Ph.D.

Dr. Jeon said that she had no relevant financial conflicts of interest.