Kerri Wachter

WASHINGTON — Intravascular catheter infections were the most common cause of infective endocarditis in a 10-year retrospective study of more than 150 cases at one Veterans Affairs center.

The most common predisposing factor was an intravascular catheter, present in 20% of 163 cases of infective endocarditis in 155 patients, reported Dr. Ingrid Roig of Baylor College of Medicine, Houston. More than half (53%) of the catheters were located in either the jugular or subclavian vein.

Further, cardiac devices appear to represent an underappreciated source of infectious endocarditis, said Dr. Roig at the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy and the annual meeting of the Infectious Diseases Society of America. Implantable cardiac devices were identified as the source of infection in 8% of cases.

The retrospective chart review identified 280 patients with ICD-9 codes for endocarditis at the Michael E. DeBakey VA Medical Center in Houston between 1997 and 2007. Medical records of these patients were reviewed for the placement of an indwelling vascular catheter or implantable cardiac device in the 3 months prior to diagnosis.

In 35 cases, central catheters had been placed during the previous 3 months, and were the presumed source of the subsequent endocarditis in 25 cases. A prior episode of catheter-associated bacteremia resulted in four cases of endocarditis.

Implantable cardioverter devices were present in 21 patients and were the presumptive source of infection in 13.

WASHINGTON — Intravascular catheter infections were the most common cause of infective endocarditis in a 10-year retrospective study of more than 150 cases at one Veterans Affairs center.

The most common predisposing factor was an intravascular catheter, present in 20% of 163 cases of infective endocarditis in 155 patients, reported Dr. Ingrid Roig of Baylor College of Medicine, Houston. More than half (53%) of the catheters were located in either the jugular or subclavian vein.

Further, cardiac devices appear to represent an underappreciated source of infectious endocarditis, said Dr. Roig at the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy and the annual meeting of the Infectious Diseases Society of America. Implantable cardiac devices were identified as the source of infection in 8% of cases.

The retrospective chart review identified 280 patients with ICD-9 codes for endocarditis at the Michael E. DeBakey VA Medical Center in Houston between 1997 and 2007. Medical records of these patients were reviewed for the placement of an indwelling vascular catheter or implantable cardiac device in the 3 months prior to diagnosis.

In 35 cases, central catheters had been placed during the previous 3 months, and were the presumed source of the subsequent endocarditis in 25 cases. A prior episode of catheter-associated bacteremia resulted in four cases of endocarditis.

Implantable cardioverter devices were present in 21 patients and were the presumptive source of infection in 13.

WASHINGTON — Intravascular catheter infections were the most common cause of infective endocarditis in a 10-year retrospective study of more than 150 cases at one Veterans Affairs center.

The most common predisposing factor was an intravascular catheter, present in 20% of 163 cases of infective endocarditis in 155 patients, reported Dr. Ingrid Roig of Baylor College of Medicine, Houston. More than half (53%) of the catheters were located in either the jugular or subclavian vein.

Further, cardiac devices appear to represent an underappreciated source of infectious endocarditis, said Dr. Roig at the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy and the annual meeting of the Infectious Diseases Society of America. Implantable cardiac devices were identified as the source of infection in 8% of cases.

The retrospective chart review identified 280 patients with ICD-9 codes for endocarditis at the Michael E. DeBakey VA Medical Center in Houston between 1997 and 2007. Medical records of these patients were reviewed for the placement of an indwelling vascular catheter or implantable cardiac device in the 3 months prior to diagnosis.

In 35 cases, central catheters had been placed during the previous 3 months, and were the presumed source of the subsequent endocarditis in 25 cases. A prior episode of catheter-associated bacteremia resulted in four cases of endocarditis.

Implantable cardioverter devices were present in 21 patients and were the presumptive source of infection in 13.

SAN FRANCISCO — Treatment with paroxetine (Paxil) appears to put healthy men at greater risk of sperm DNA fragmentation, according to data from a small study presented at the annual meeting of the American Society for Reproductive Medicine.

In 35 healthy male volunteers, SSRI treatment was significantly correlated with increased DNA fragmentation (odds ratio 11.12, P = .0003) on multivariate logistic regression, after correcting for age and body mass index.

“Healthy volunteers demonstrated a dramatic increase in DNA fragmentation within just a few weeks of paroxetine treatment, without an apparent impact on standard semen parameters. This negative impact on sperm DNA fragmentation may affect reproductive outcomes,” even with intracytoplasmic sperm injection, study investigator Dr. Cigdem Tanrikut said in an interview.

“Certainly, one should query male patients about SSRI use. However, based on these preliminary findings, it would be premature to suggest a patient come off of SSRIs altogether or change to an alternate therapy given the lack of data regarding other newer antidepressants,” said Dr. Tanrikut, director of male reproductive medicine at Massachusetts General Hospital's fertility center in Boston.

Men in the study ranged in age from 18 to 65 years. Intake assessment included physical exam, semen analysis, and the Brief Sexual Function Inventory (BSFI). Repeat semen analysis was obtained before SSRI initiation.

Paroxetine was given for 5 weeks: 10 mg daily during week 1; 20 mg daily during week 2; 30 mg daily during weeks 3–4; and 20 mg daily during week 5. Semen analysis was performed at weeks 2 and 4. One month after cessation of the SSRI, a final semen analysis was then performed. The BSFI was completed at week 4 and at the final semen collection.

Standard World Health Organization evaluation of semen parameters was performed in a certified laboratory. TUNEL (terminal dUTP nick-end labeling) assays were performed at baseline and at week 4 to evaluate the percentage of sperm DNA fragmentation. Semen parameters and TUNEL assays for each participant were compared at each time point.

Semen parameters—including volume, concentration, motility, and morphology—were not significantly altered during SSRI treatment. However, the mean DNA fragmentation TUNEL score was significantly higher with SSRI use, compared with baseline measurements (30.3% vs. 13.8%, P = .0002). The unadjusted odds ratio of having abnormal DNA fragmentation while on paroxetine was 9.33.

In addition, the BSFI revealed significant sexual dysfunction on paroxetine as compared with baseline. Up to 35% of men noted significant changes in erectile function, and up to 47% of subjects reported ejaculatory difficulties while on paroxetine. At least partial recovery of sexual function was noted within 1 month after stopping treatment.

The study was supported by the Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust and Brady Urology Foundation.

Based on these preliminary findings, it would be premature to suggest changing to an alternate therapy. DR. TANRIKUT

SAN FRANCISCO — Treatment with paroxetine (Paxil) appears to put healthy men at greater risk of sperm DNA fragmentation, according to data from a small study presented at the annual meeting of the American Society for Reproductive Medicine.

In 35 healthy male volunteers, SSRI treatment was significantly correlated with increased DNA fragmentation (odds ratio 11.12, P = .0003) on multivariate logistic regression, after correcting for age and body mass index.

“Healthy volunteers demonstrated a dramatic increase in DNA fragmentation within just a few weeks of paroxetine treatment, without an apparent impact on standard semen parameters. This negative impact on sperm DNA fragmentation may affect reproductive outcomes,” even with intracytoplasmic sperm injection, study investigator Dr. Cigdem Tanrikut said in an interview.

“Certainly, one should query male patients about SSRI use. However, based on these preliminary findings, it would be premature to suggest a patient come off of SSRIs altogether or change to an alternate therapy given the lack of data regarding other newer antidepressants,” said Dr. Tanrikut, director of male reproductive medicine at Massachusetts General Hospital's fertility center in Boston.

Men in the study ranged in age from 18 to 65 years. Intake assessment included physical exam, semen analysis, and the Brief Sexual Function Inventory (BSFI). Repeat semen analysis was obtained before SSRI initiation.

Paroxetine was given for 5 weeks: 10 mg daily during week 1; 20 mg daily during week 2; 30 mg daily during weeks 3–4; and 20 mg daily during week 5. Semen analysis was performed at weeks 2 and 4. One month after cessation of the SSRI, a final semen analysis was then performed. The BSFI was completed at week 4 and at the final semen collection.

Standard World Health Organization evaluation of semen parameters was performed in a certified laboratory. TUNEL (terminal dUTP nick-end labeling) assays were performed at baseline and at week 4 to evaluate the percentage of sperm DNA fragmentation. Semen parameters and TUNEL assays for each participant were compared at each time point.

Semen parameters—including volume, concentration, motility, and morphology—were not significantly altered during SSRI treatment. However, the mean DNA fragmentation TUNEL score was significantly higher with SSRI use, compared with baseline measurements (30.3% vs. 13.8%, P = .0002). The unadjusted odds ratio of having abnormal DNA fragmentation while on paroxetine was 9.33.

In addition, the BSFI revealed significant sexual dysfunction on paroxetine as compared with baseline. Up to 35% of men noted significant changes in erectile function, and up to 47% of subjects reported ejaculatory difficulties while on paroxetine. At least partial recovery of sexual function was noted within 1 month after stopping treatment.

The study was supported by the Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust and Brady Urology Foundation.

Based on these preliminary findings, it would be premature to suggest changing to an alternate therapy. DR. TANRIKUT

SAN FRANCISCO — Treatment with paroxetine (Paxil) appears to put healthy men at greater risk of sperm DNA fragmentation, according to data from a small study presented at the annual meeting of the American Society for Reproductive Medicine.

In 35 healthy male volunteers, SSRI treatment was significantly correlated with increased DNA fragmentation (odds ratio 11.12, P = .0003) on multivariate logistic regression, after correcting for age and body mass index.

“Healthy volunteers demonstrated a dramatic increase in DNA fragmentation within just a few weeks of paroxetine treatment, without an apparent impact on standard semen parameters. This negative impact on sperm DNA fragmentation may affect reproductive outcomes,” even with intracytoplasmic sperm injection, study investigator Dr. Cigdem Tanrikut said in an interview.

“Certainly, one should query male patients about SSRI use. However, based on these preliminary findings, it would be premature to suggest a patient come off of SSRIs altogether or change to an alternate therapy given the lack of data regarding other newer antidepressants,” said Dr. Tanrikut, director of male reproductive medicine at Massachusetts General Hospital's fertility center in Boston.

Men in the study ranged in age from 18 to 65 years. Intake assessment included physical exam, semen analysis, and the Brief Sexual Function Inventory (BSFI). Repeat semen analysis was obtained before SSRI initiation.

Paroxetine was given for 5 weeks: 10 mg daily during week 1; 20 mg daily during week 2; 30 mg daily during weeks 3–4; and 20 mg daily during week 5. Semen analysis was performed at weeks 2 and 4. One month after cessation of the SSRI, a final semen analysis was then performed. The BSFI was completed at week 4 and at the final semen collection.

Standard World Health Organization evaluation of semen parameters was performed in a certified laboratory. TUNEL (terminal dUTP nick-end labeling) assays were performed at baseline and at week 4 to evaluate the percentage of sperm DNA fragmentation. Semen parameters and TUNEL assays for each participant were compared at each time point.

Semen parameters—including volume, concentration, motility, and morphology—were not significantly altered during SSRI treatment. However, the mean DNA fragmentation TUNEL score was significantly higher with SSRI use, compared with baseline measurements (30.3% vs. 13.8%, P = .0002). The unadjusted odds ratio of having abnormal DNA fragmentation while on paroxetine was 9.33.

In addition, the BSFI revealed significant sexual dysfunction on paroxetine as compared with baseline. Up to 35% of men noted significant changes in erectile function, and up to 47% of subjects reported ejaculatory difficulties while on paroxetine. At least partial recovery of sexual function was noted within 1 month after stopping treatment.

The study was supported by the Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust and Brady Urology Foundation.

Based on these preliminary findings, it would be premature to suggest changing to an alternate therapy. DR. TANRIKUT

WASHINGTON — The investigative antibiotic PTK 0796 appears to be comparable to linezolid in terms of efficacy against skin and skin structure infections and safety, based on the results of a phase II study of more than 200 patients.

Clinical success for the intention-to-treat population (those randomized, who received at least one dose) was 88% for the PTK 0796 group and 76% for the linezolid group, according to a poster presented at the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy and the annual meeting of the Infectious Diseases Society of America.

Clinical success was defined as the blinded evaluator's assessment that the infection was sufficiently resolved, such that no additional antibiotic therapy was required, at the test-of-cure visit. Patients who were not evaluated at a test-of-cure visit were considered clinical failures.

PTK 0796 is the first of a new class of antibiotics—the aminomethylcyclines—which are semisynthetic compounds that are related to tetracycline. The drug is being developed by Paratek Pharmaceuticals, which carried out the study.

Patients with complicated skin and skin structure infections were randomized to receive either intravenous PTK 0796 or linezolid (Zyvox) and could be switched to oral therapy at the investigator's discretion. Intravenous dosing was 100 mg PTK 0796 every 24 hours or 600 mg linezolid every 12 hours. Oral dosing was 200 mg PTK 0796 every 24 hours or 600 mg linezolid every 12 hours. If the investigator considered that a patient might require gram-negative coverage, patients on linezolid could receive aztreonam (Azactam) infusions and those on PTK 0796 could receive placebo infusions.

In all, 118 patients were randomized to receive PTK 0796 and 116 patients, to linezolid. Patients in both groups were similar in terms of demographics, type of infection, severity of infection, and comorbidities. Major abscesses were the most common type of infection in both groups—73 patients in the PTK 0796 group and 72 in the linezolid group.

Duration of treatment was similar for both groups. Intravenous duration was 4 days for the PTK 0976 group and 3 days for the linezolid group. Overall antibiotic duration was 10 days for both the PTK 0796 and linezolid groups.

In terms of microbiology, the primary pathogen was known for 84 patients in the PTK 0796 group and for 78 patients in the linezolid group. MRSA was the most common primary pathogen isolated in both the PTK 0796 and linezolid group—52% and 49%, respectively. Clinical efficacy against MRSA was 96% in the PTK 0796 group and 79% in the linezolid group.

There were no drug-related serious adverse events in either group. No patient discontinued PTK 0796 because of adverse events, compared with two patients in the linezolid group. The most common adverse events in both groups were gastrointestinal—21 in the PTK 0796 group and 18 in the linezolid group.

WASHINGTON — The investigative antibiotic PTK 0796 appears to be comparable to linezolid in terms of efficacy against skin and skin structure infections and safety, based on the results of a phase II study of more than 200 patients.

Clinical success for the intention-to-treat population (those randomized, who received at least one dose) was 88% for the PTK 0796 group and 76% for the linezolid group, according to a poster presented at the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy and the annual meeting of the Infectious Diseases Society of America.

Clinical success was defined as the blinded evaluator's assessment that the infection was sufficiently resolved, such that no additional antibiotic therapy was required, at the test-of-cure visit. Patients who were not evaluated at a test-of-cure visit were considered clinical failures.

PTK 0796 is the first of a new class of antibiotics—the aminomethylcyclines—which are semisynthetic compounds that are related to tetracycline. The drug is being developed by Paratek Pharmaceuticals, which carried out the study.

Patients with complicated skin and skin structure infections were randomized to receive either intravenous PTK 0796 or linezolid (Zyvox) and could be switched to oral therapy at the investigator's discretion. Intravenous dosing was 100 mg PTK 0796 every 24 hours or 600 mg linezolid every 12 hours. Oral dosing was 200 mg PTK 0796 every 24 hours or 600 mg linezolid every 12 hours. If the investigator considered that a patient might require gram-negative coverage, patients on linezolid could receive aztreonam (Azactam) infusions and those on PTK 0796 could receive placebo infusions.

In all, 118 patients were randomized to receive PTK 0796 and 116 patients, to linezolid. Patients in both groups were similar in terms of demographics, type of infection, severity of infection, and comorbidities. Major abscesses were the most common type of infection in both groups—73 patients in the PTK 0796 group and 72 in the linezolid group.

Duration of treatment was similar for both groups. Intravenous duration was 4 days for the PTK 0976 group and 3 days for the linezolid group. Overall antibiotic duration was 10 days for both the PTK 0796 and linezolid groups.

In terms of microbiology, the primary pathogen was known for 84 patients in the PTK 0796 group and for 78 patients in the linezolid group. MRSA was the most common primary pathogen isolated in both the PTK 0796 and linezolid group—52% and 49%, respectively. Clinical efficacy against MRSA was 96% in the PTK 0796 group and 79% in the linezolid group.

There were no drug-related serious adverse events in either group. No patient discontinued PTK 0796 because of adverse events, compared with two patients in the linezolid group. The most common adverse events in both groups were gastrointestinal—21 in the PTK 0796 group and 18 in the linezolid group.

WASHINGTON — The investigative antibiotic PTK 0796 appears to be comparable to linezolid in terms of efficacy against skin and skin structure infections and safety, based on the results of a phase II study of more than 200 patients.

Clinical success for the intention-to-treat population (those randomized, who received at least one dose) was 88% for the PTK 0796 group and 76% for the linezolid group, according to a poster presented at the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy and the annual meeting of the Infectious Diseases Society of America.

Clinical success was defined as the blinded evaluator's assessment that the infection was sufficiently resolved, such that no additional antibiotic therapy was required, at the test-of-cure visit. Patients who were not evaluated at a test-of-cure visit were considered clinical failures.

PTK 0796 is the first of a new class of antibiotics—the aminomethylcyclines—which are semisynthetic compounds that are related to tetracycline. The drug is being developed by Paratek Pharmaceuticals, which carried out the study.

Patients with complicated skin and skin structure infections were randomized to receive either intravenous PTK 0796 or linezolid (Zyvox) and could be switched to oral therapy at the investigator's discretion. Intravenous dosing was 100 mg PTK 0796 every 24 hours or 600 mg linezolid every 12 hours. Oral dosing was 200 mg PTK 0796 every 24 hours or 600 mg linezolid every 12 hours. If the investigator considered that a patient might require gram-negative coverage, patients on linezolid could receive aztreonam (Azactam) infusions and those on PTK 0796 could receive placebo infusions.

In all, 118 patients were randomized to receive PTK 0796 and 116 patients, to linezolid. Patients in both groups were similar in terms of demographics, type of infection, severity of infection, and comorbidities. Major abscesses were the most common type of infection in both groups—73 patients in the PTK 0796 group and 72 in the linezolid group.

Duration of treatment was similar for both groups. Intravenous duration was 4 days for the PTK 0976 group and 3 days for the linezolid group. Overall antibiotic duration was 10 days for both the PTK 0796 and linezolid groups.

In terms of microbiology, the primary pathogen was known for 84 patients in the PTK 0796 group and for 78 patients in the linezolid group. MRSA was the most common primary pathogen isolated in both the PTK 0796 and linezolid group—52% and 49%, respectively. Clinical efficacy against MRSA was 96% in the PTK 0796 group and 79% in the linezolid group.

There were no drug-related serious adverse events in either group. No patient discontinued PTK 0796 because of adverse events, compared with two patients in the linezolid group. The most common adverse events in both groups were gastrointestinal—21 in the PTK 0796 group and 18 in the linezolid group.

WASHINGTON — The investigational antibiotic ceftaroline was found to be effective against a range of gram-positive and gram-negative organisms that can cause complicated skin and skin structure infections, according to data from a phase III noninferiority study of more than 600 patients.

Clinical cure rates (8–15 days after therapy ended) were similar for patients who received at least one dose of ceftaroline or vancomycin/aztreonam (the modified intent-to-treat population)—87% for those on ceftaroline and 86% with vancomycin-aztreonam, according to data from the CANVAS-1 study presented as a poster at the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy and the annual meeting of the Infectious Diseases Society of America.

"Ceftaroline monotherapy was as effective and well tolerated as vancomycin plus aztreonam combination therapy in treating patients with complicated skin and skin structure infections due to both gram-positive and gram-negative pathogens," wrote Dr. Ralph Corey of Duke University, Durham, N.C., and his coinvestigators. The study was supported by Forrest Laboratories Inc., which is developing ceftaroline. Two of Dr. Corey's coinvestigators are employed by Cerexa Inc., which is a wholly-owned subsidiary of Forest. Dr. Corey disclosed having received research funding and serving as an adviser to Cerexa.

The randomized, double-blind study enrolled adults with local and systemic evidence of complicated skin and skin structure infections. Patients were randomized to either 600 mg intravenous ceftaroline every 12 hours for 5–14 days or 1 g intravenous vancomycin plus 1 g intravenous aztreonam (Azactam) every 12 hours for 5–14 days. Aztreonam was discontinued if gram-negative pathogens were not identified or suspected.

At enrollment, 353 patients were randomized to receive ceftaroline and 349 were randomized to receive vancomycin/aztreonam. The modified intention-to-treat population included all patients who had received any study drug—351 patients in the ceftaroline group and 347 patients in the vancomycin/aztreonam group.

Almost a quarter of the patients in each group had polymicrobial infection. The most common infection type was deep, extensive cellulitis (35% in both groups), followed by major abscess (28% of the ceftaroline group and 29% of the vancomycin/aztreonam group).

There were 471 patients—244 in the ceftaroline group and 227 in the vancomycin/aztreonam group—who were microbiologically evaluable. Microbiologic eradication was achieved in 92% of patients on ceftaroline and 93% of patients on vancomycin/aztreonam.

Staphylococcus aureus was the most commonly isolated organism, but ceftaroline was effective against a range of gram-positive and gram-negative organisms. (See table.)

Most adverse events were mild. The most common adverse events with ceftaroline were nausea (6%) and headache (5%). The most common adverse event in the vancomycin/aztreonam group was pruritus (8%), followed by nausea and generalized pruritus (5% each).

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — The investigational antibiotic ceftaroline was found to be effective against a range of gram-positive and gram-negative organisms that can cause complicated skin and skin structure infections, according to data from a phase III noninferiority study of more than 600 patients.

Clinical cure rates (8–15 days after therapy ended) were similar for patients who received at least one dose of ceftaroline or vancomycin/aztreonam (the modified intent-to-treat population)—87% for those on ceftaroline and 86% with vancomycin-aztreonam, according to data from the CANVAS-1 study presented as a poster at the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy and the annual meeting of the Infectious Diseases Society of America.

"Ceftaroline monotherapy was as effective and well tolerated as vancomycin plus aztreonam combination therapy in treating patients with complicated skin and skin structure infections due to both gram-positive and gram-negative pathogens," wrote Dr. Ralph Corey of Duke University, Durham, N.C., and his coinvestigators. The study was supported by Forrest Laboratories Inc., which is developing ceftaroline. Two of Dr. Corey's coinvestigators are employed by Cerexa Inc., which is a wholly-owned subsidiary of Forest. Dr. Corey disclosed having received research funding and serving as an adviser to Cerexa.

The randomized, double-blind study enrolled adults with local and systemic evidence of complicated skin and skin structure infections. Patients were randomized to either 600 mg intravenous ceftaroline every 12 hours for 5–14 days or 1 g intravenous vancomycin plus 1 g intravenous aztreonam (Azactam) every 12 hours for 5–14 days. Aztreonam was discontinued if gram-negative pathogens were not identified or suspected.

At enrollment, 353 patients were randomized to receive ceftaroline and 349 were randomized to receive vancomycin/aztreonam. The modified intention-to-treat population included all patients who had received any study drug—351 patients in the ceftaroline group and 347 patients in the vancomycin/aztreonam group.

Almost a quarter of the patients in each group had polymicrobial infection. The most common infection type was deep, extensive cellulitis (35% in both groups), followed by major abscess (28% of the ceftaroline group and 29% of the vancomycin/aztreonam group).

There were 471 patients—244 in the ceftaroline group and 227 in the vancomycin/aztreonam group—who were microbiologically evaluable. Microbiologic eradication was achieved in 92% of patients on ceftaroline and 93% of patients on vancomycin/aztreonam.

Staphylococcus aureus was the most commonly isolated organism, but ceftaroline was effective against a range of gram-positive and gram-negative organisms. (See table.)

Most adverse events were mild. The most common adverse events with ceftaroline were nausea (6%) and headache (5%). The most common adverse event in the vancomycin/aztreonam group was pruritus (8%), followed by nausea and generalized pruritus (5% each).

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — The investigational antibiotic ceftaroline was found to be effective against a range of gram-positive and gram-negative organisms that can cause complicated skin and skin structure infections, according to data from a phase III noninferiority study of more than 600 patients.

Clinical cure rates (8–15 days after therapy ended) were similar for patients who received at least one dose of ceftaroline or vancomycin/aztreonam (the modified intent-to-treat population)—87% for those on ceftaroline and 86% with vancomycin-aztreonam, according to data from the CANVAS-1 study presented as a poster at the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy and the annual meeting of the Infectious Diseases Society of America.

"Ceftaroline monotherapy was as effective and well tolerated as vancomycin plus aztreonam combination therapy in treating patients with complicated skin and skin structure infections due to both gram-positive and gram-negative pathogens," wrote Dr. Ralph Corey of Duke University, Durham, N.C., and his coinvestigators. The study was supported by Forrest Laboratories Inc., which is developing ceftaroline. Two of Dr. Corey's coinvestigators are employed by Cerexa Inc., which is a wholly-owned subsidiary of Forest. Dr. Corey disclosed having received research funding and serving as an adviser to Cerexa.

The randomized, double-blind study enrolled adults with local and systemic evidence of complicated skin and skin structure infections. Patients were randomized to either 600 mg intravenous ceftaroline every 12 hours for 5–14 days or 1 g intravenous vancomycin plus 1 g intravenous aztreonam (Azactam) every 12 hours for 5–14 days. Aztreonam was discontinued if gram-negative pathogens were not identified or suspected.

At enrollment, 353 patients were randomized to receive ceftaroline and 349 were randomized to receive vancomycin/aztreonam. The modified intention-to-treat population included all patients who had received any study drug—351 patients in the ceftaroline group and 347 patients in the vancomycin/aztreonam group.

Almost a quarter of the patients in each group had polymicrobial infection. The most common infection type was deep, extensive cellulitis (35% in both groups), followed by major abscess (28% of the ceftaroline group and 29% of the vancomycin/aztreonam group).

There were 471 patients—244 in the ceftaroline group and 227 in the vancomycin/aztreonam group—who were microbiologically evaluable. Microbiologic eradication was achieved in 92% of patients on ceftaroline and 93% of patients on vancomycin/aztreonam.

Staphylococcus aureus was the most commonly isolated organism, but ceftaroline was effective against a range of gram-positive and gram-negative organisms. (See table.)

Most adverse events were mild. The most common adverse events with ceftaroline were nausea (6%) and headache (5%). The most common adverse event in the vancomycin/aztreonam group was pruritus (8%), followed by nausea and generalized pruritus (5% each).

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — Staphylococcus aureus colonization increases significantly in the first 2 months of life and appears to be positively associated with maternal carriage, based on a study of 200 mother-neonate pairs.

At delivery, S. aureus detection among 165 infants was 8%; at discharge, detection among 190 infants was 7%. However, at age 2 months, 33% of infants were colonized with S. aureus—17% with methicillin-resistant S. aureus (MRSA), Dr. Clarence B. (Buddy) Creech II said at the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy and the annual meeting of the Infectious Diseases Society of America.

“In those mothers who had no evidence of nasal colonization at 2 months, the vast majority of their infants also remained uncolonized. However, among those mothers who had methicillin-susceptible S. aureus (MSSA) nasal colonization [at 2 months], 51% of their infants were nasally colonized with MSSA.” Of mothers with MRSA nasal colonization, 45% of their infants had nasal MRSA colonization at 2 months.

“We were able to detect MRSA carriage in a significant number of mothers and infants; however, we have not observed many infections in this cohort,” Dr. Creech said in an interview. The findings demonstrate that staphylococci are commensal organisms and part of normal flora. “The question that remains is whether certain strains of staphylococci, in certain hosts, are more likely to cause disease than others.”

Pregnant women were recruited at the time of group B streptococcus (GBS) screening between gestational weeks 35 and 37. At that time, nasal swabs for S. aureus and rectovaginal swabs for GBS and S. aureus were taken. Nasal swabs were repeated in the mother on the day of delivery and at 2 months post partum. Neonatal nasal and umbilical swabs were obtained within 2 hours of birth and nasal swabs were repeated on the day of discharge and at 2 months.

At the time of the presentation, 431 pregnant women had been enrolled. Dr. Creech, of the pediatric infectious diseases department at Vanderbilt University, Nashville, Tenn., presented data on the first 200 mother-neonate pairs with data out to the 2-month period. Mothers were primarily recruited from academic private practice and an obstetric resident clinic serving an inner-city Medicare population in Nashville.

Nasal S. aureus colonization of mothers in pregnancy was 23.5%—12% for MSSA and 11.5% for MRSA. Rectovaginal S. aureus colonization of mothers during pregnancy was 17%—13% for MSSA and 4% for MRSA. It was not always possible to obtain neonatal swabs within 2 hours of delivery. In all, 165 infants were evaluable at delivery. Neonatal MSSA detection at delivery (not necessarily colonization) was 5% and MRSA detection was 3%; 190 infants were evaluable at discharge. Neonatal MSSA detection at discharge was 2%; MRSA detection was 5%.

Of the 136 mothers who did not have S. aureus colonization during enrollment, 96% of their infants did not have S. aureus detected at delivery, 3% of infants had MSSA, and 1% had MRSA. Of the 21 mothers who had MSSA colonization at enrollment, 67% of their infants did not have S. aureus detected at delivery, 19% of infants had MSSA, and 14% had MRSA. Of the eight women who had MRSA colonization during enrollment, 62% of their infants did not have S. aureus detected at delivery, 13% of infants had MSSA, and 25% had MRSA.

Two babies developed disease during the first 5–7 weeks. One infant had an abscess that required drainage and intravenous antibiotics. The other infant developed purulent conjunctivitis. The isolates from these infections matched very closely the USA300 strain with staphylococcal cassette chromosome mecIV and were Panton-Valentine leukocidin toxin positive.

With regard to women colonized with S. aureus during pregnancy, “there [are] no data to suggest that prophylactic antibiotics that cover S. aureus would be of any benefit. Many infants in whom MRSA was detected within 2 hours of birth had no evidence of S. aureus at discharge or at 2 months follow-up,” he said.

Dr. Creech disclosed financial relationships with several pharmaceutical companies.

WASHINGTON — Staphylococcus aureus colonization increases significantly in the first 2 months of life and appears to be positively associated with maternal carriage, based on a study of 200 mother-neonate pairs.

At delivery, S. aureus detection among 165 infants was 8%; at discharge, detection among 190 infants was 7%. However, at age 2 months, 33% of infants were colonized with S. aureus—17% with methicillin-resistant S. aureus (MRSA), Dr. Clarence B. (Buddy) Creech II said at the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy and the annual meeting of the Infectious Diseases Society of America.

“In those mothers who had no evidence of nasal colonization at 2 months, the vast majority of their infants also remained uncolonized. However, among those mothers who had methicillin-susceptible S. aureus (MSSA) nasal colonization [at 2 months], 51% of their infants were nasally colonized with MSSA.” Of mothers with MRSA nasal colonization, 45% of their infants had nasal MRSA colonization at 2 months.

“We were able to detect MRSA carriage in a significant number of mothers and infants; however, we have not observed many infections in this cohort,” Dr. Creech said in an interview. The findings demonstrate that staphylococci are commensal organisms and part of normal flora. “The question that remains is whether certain strains of staphylococci, in certain hosts, are more likely to cause disease than others.”

Pregnant women were recruited at the time of group B streptococcus (GBS) screening between gestational weeks 35 and 37. At that time, nasal swabs for S. aureus and rectovaginal swabs for GBS and S. aureus were taken. Nasal swabs were repeated in the mother on the day of delivery and at 2 months post partum. Neonatal nasal and umbilical swabs were obtained within 2 hours of birth and nasal swabs were repeated on the day of discharge and at 2 months.

At the time of the presentation, 431 pregnant women had been enrolled. Dr. Creech, of the pediatric infectious diseases department at Vanderbilt University, Nashville, Tenn., presented data on the first 200 mother-neonate pairs with data out to the 2-month period. Mothers were primarily recruited from academic private practice and an obstetric resident clinic serving an inner-city Medicare population in Nashville.

Nasal S. aureus colonization of mothers in pregnancy was 23.5%—12% for MSSA and 11.5% for MRSA. Rectovaginal S. aureus colonization of mothers during pregnancy was 17%—13% for MSSA and 4% for MRSA. It was not always possible to obtain neonatal swabs within 2 hours of delivery. In all, 165 infants were evaluable at delivery. Neonatal MSSA detection at delivery (not necessarily colonization) was 5% and MRSA detection was 3%; 190 infants were evaluable at discharge. Neonatal MSSA detection at discharge was 2%; MRSA detection was 5%.

Of the 136 mothers who did not have S. aureus colonization during enrollment, 96% of their infants did not have S. aureus detected at delivery, 3% of infants had MSSA, and 1% had MRSA. Of the 21 mothers who had MSSA colonization at enrollment, 67% of their infants did not have S. aureus detected at delivery, 19% of infants had MSSA, and 14% had MRSA. Of the eight women who had MRSA colonization during enrollment, 62% of their infants did not have S. aureus detected at delivery, 13% of infants had MSSA, and 25% had MRSA.

Two babies developed disease during the first 5–7 weeks. One infant had an abscess that required drainage and intravenous antibiotics. The other infant developed purulent conjunctivitis. The isolates from these infections matched very closely the USA300 strain with staphylococcal cassette chromosome mecIV and were Panton-Valentine leukocidin toxin positive.

With regard to women colonized with S. aureus during pregnancy, “there [are] no data to suggest that prophylactic antibiotics that cover S. aureus would be of any benefit. Many infants in whom MRSA was detected within 2 hours of birth had no evidence of S. aureus at discharge or at 2 months follow-up,” he said.

Dr. Creech disclosed financial relationships with several pharmaceutical companies.

WASHINGTON — Staphylococcus aureus colonization increases significantly in the first 2 months of life and appears to be positively associated with maternal carriage, based on a study of 200 mother-neonate pairs.

At delivery, S. aureus detection among 165 infants was 8%; at discharge, detection among 190 infants was 7%. However, at age 2 months, 33% of infants were colonized with S. aureus—17% with methicillin-resistant S. aureus (MRSA), Dr. Clarence B. (Buddy) Creech II said at the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy and the annual meeting of the Infectious Diseases Society of America.

“In those mothers who had no evidence of nasal colonization at 2 months, the vast majority of their infants also remained uncolonized. However, among those mothers who had methicillin-susceptible S. aureus (MSSA) nasal colonization [at 2 months], 51% of their infants were nasally colonized with MSSA.” Of mothers with MRSA nasal colonization, 45% of their infants had nasal MRSA colonization at 2 months.

“We were able to detect MRSA carriage in a significant number of mothers and infants; however, we have not observed many infections in this cohort,” Dr. Creech said in an interview. The findings demonstrate that staphylococci are commensal organisms and part of normal flora. “The question that remains is whether certain strains of staphylococci, in certain hosts, are more likely to cause disease than others.”

Pregnant women were recruited at the time of group B streptococcus (GBS) screening between gestational weeks 35 and 37. At that time, nasal swabs for S. aureus and rectovaginal swabs for GBS and S. aureus were taken. Nasal swabs were repeated in the mother on the day of delivery and at 2 months post partum. Neonatal nasal and umbilical swabs were obtained within 2 hours of birth and nasal swabs were repeated on the day of discharge and at 2 months.

At the time of the presentation, 431 pregnant women had been enrolled. Dr. Creech, of the pediatric infectious diseases department at Vanderbilt University, Nashville, Tenn., presented data on the first 200 mother-neonate pairs with data out to the 2-month period. Mothers were primarily recruited from academic private practice and an obstetric resident clinic serving an inner-city Medicare population in Nashville.

Nasal S. aureus colonization of mothers in pregnancy was 23.5%—12% for MSSA and 11.5% for MRSA. Rectovaginal S. aureus colonization of mothers during pregnancy was 17%—13% for MSSA and 4% for MRSA. It was not always possible to obtain neonatal swabs within 2 hours of delivery. In all, 165 infants were evaluable at delivery. Neonatal MSSA detection at delivery (not necessarily colonization) was 5% and MRSA detection was 3%; 190 infants were evaluable at discharge. Neonatal MSSA detection at discharge was 2%; MRSA detection was 5%.

Of the 136 mothers who did not have S. aureus colonization during enrollment, 96% of their infants did not have S. aureus detected at delivery, 3% of infants had MSSA, and 1% had MRSA. Of the 21 mothers who had MSSA colonization at enrollment, 67% of their infants did not have S. aureus detected at delivery, 19% of infants had MSSA, and 14% had MRSA. Of the eight women who had MRSA colonization during enrollment, 62% of their infants did not have S. aureus detected at delivery, 13% of infants had MSSA, and 25% had MRSA.

Two babies developed disease during the first 5–7 weeks. One infant had an abscess that required drainage and intravenous antibiotics. The other infant developed purulent conjunctivitis. The isolates from these infections matched very closely the USA300 strain with staphylococcal cassette chromosome mecIV and were Panton-Valentine leukocidin toxin positive.

With regard to women colonized with S. aureus during pregnancy, “there [are] no data to suggest that prophylactic antibiotics that cover S. aureus would be of any benefit. Many infants in whom MRSA was detected within 2 hours of birth had no evidence of S. aureus at discharge or at 2 months follow-up,” he said.

Dr. Creech disclosed financial relationships with several pharmaceutical companies.

The cognitive-reserve hypothesis is a concept that has been proposed to account for findings that the brains of certain individuals with pathological Alzheimer's disease burden are somehow able to compensate and minimize the effect of this burden on cognitive function. It's been suggested that greater abilities in thinking, learning, and memory—which can result in part from regularly challenging the brain—makes some individuals less susceptible to the damage caused by the disease. Education is commonly used as a surrogate for cognitive function in investigations of this hypothesis.

Previous studies have suggested that a greater amyloid β (Aβ) burden in the brain is required among individuals with more education to manifest mild dementia of the Alzheimer type (DAT) than in those with less education.

Catherine M. Roe, Ph.D., a research instructor in neurology, and her colleagues at Washington University in St. Louis used Pittsburgh Compound-B (PIB) PET imaging to test whether education and level of fibrillar brain Aβ interact to affect cognitive function in both nondemented individuals and those with DAT.

“We were really interested in the association between the amyloid uptake, their scores on these tests, and how education might mediate that,” said Dr. Roe.

The data were obtained from participants in longitudinal studies conducted at Washington University's Alzheimer's disease research center.

All of the participants underwent PET imaging using PIB, as well as anatomical T1-weighted MRI. Each participant's MRI was registered to a standard atlas target to minimize bias due to atrophy. PET images were aligned with the MR images. For the analysis, the cerebellum was chosen as the reference region because there is little specific PIB binding in this region, even in individuals with Alzheimer's.

Binding potentials (BPs) were calculated for each region of interest. “Binding potential is a number that is essentially proportional to the number of binding sites. It's a number that combines both the number of binding sites and the affinity of that particular molecule [in this case, Aβ] for the binding sites,” said Dr. Mark A. Mintun, a professor of radiology, psychiatry, and bioengineering at Washington University, and also the director of the center for clinical imaging research there. Theoretically, BP should be very highly related to the amount of amyloid present.

Mean BP was calculated for the prefrontal cortex, gyrus rectus, lateral temporal cortex, and precuneus regions.

“These regions were chosen based on previous work that we've done, where we looked at patients who had a clinical diagnosis [of DAT] with very obvious amyloid plaques using PIB scans,” said Dr. Mintun. For this study, “we looked at the four regions that we thought were the most clearly associated with Alzheimer's disease.”

It's been hypothesized that amyloid plaques would show up first in those areas for individuals who were previously healthy.

Mean BPs from these regions were used to calculate mean cortical BP based on regions known to have high PIB uptake among patients with DAT. The participants were categorized based on their mean cortical BP.

In all, 198 participants were included: 161 who were cognitively normal and 37 with DAT. In all, 139 were determined to be PIB negative and 59 PIB positive. the participants were also categorized based on their level of education: high school or less; some college or college graduate; and post college. Among the PIB-negative group, 22 had a high school education or less, 69 had some college or had graduated from college, and 48 had postcollege education. In the PIB-positive group, 16 had a high school education or less, 29 had some college or had graduated from college, and 14 had postcollege education.

“What we found on the global tests is that the people who had little PIB uptake (the people who had few if any plaques at all) all scored very well and basically had no dementia. It was kind of a ceiling effect,” said Dr. Roe.

In that group, scores on the tests were unrelated to education. “For the people who had high PIB uptake—more plaques in their brains—the scores were related to the amount of education that they had.”

These findings lend support for the cognitive-reserve hypothesis because those with greater education maintained better global cognitive functioning in the presence of Aβ pathology.

PIB binding was limited (top row) or moderate (middle; yellow, orange, and red) in 2 nondemented women but was very pronounced in a woman with Alzheimer's (bottom). IMAGES COURTESY DR. MARK A. MINTUN

The cognitive-reserve hypothesis is a concept that has been proposed to account for findings that the brains of certain individuals with pathological Alzheimer's disease burden are somehow able to compensate and minimize the effect of this burden on cognitive function. It's been suggested that greater abilities in thinking, learning, and memory—which can result in part from regularly challenging the brain—makes some individuals less susceptible to the damage caused by the disease. Education is commonly used as a surrogate for cognitive function in investigations of this hypothesis.

Previous studies have suggested that a greater amyloid β (Aβ) burden in the brain is required among individuals with more education to manifest mild dementia of the Alzheimer type (DAT) than in those with less education.

Catherine M. Roe, Ph.D., a research instructor in neurology, and her colleagues at Washington University in St. Louis used Pittsburgh Compound-B (PIB) PET imaging to test whether education and level of fibrillar brain Aβ interact to affect cognitive function in both nondemented individuals and those with DAT.

“We were really interested in the association between the amyloid uptake, their scores on these tests, and how education might mediate that,” said Dr. Roe.

The data were obtained from participants in longitudinal studies conducted at Washington University's Alzheimer's disease research center.

All of the participants underwent PET imaging using PIB, as well as anatomical T1-weighted MRI. Each participant's MRI was registered to a standard atlas target to minimize bias due to atrophy. PET images were aligned with the MR images. For the analysis, the cerebellum was chosen as the reference region because there is little specific PIB binding in this region, even in individuals with Alzheimer's.

Binding potentials (BPs) were calculated for each region of interest. “Binding potential is a number that is essentially proportional to the number of binding sites. It's a number that combines both the number of binding sites and the affinity of that particular molecule [in this case, Aβ] for the binding sites,” said Dr. Mark A. Mintun, a professor of radiology, psychiatry, and bioengineering at Washington University, and also the director of the center for clinical imaging research there. Theoretically, BP should be very highly related to the amount of amyloid present.

Mean BP was calculated for the prefrontal cortex, gyrus rectus, lateral temporal cortex, and precuneus regions.

“These regions were chosen based on previous work that we've done, where we looked at patients who had a clinical diagnosis [of DAT] with very obvious amyloid plaques using PIB scans,” said Dr. Mintun. For this study, “we looked at the four regions that we thought were the most clearly associated with Alzheimer's disease.”

It's been hypothesized that amyloid plaques would show up first in those areas for individuals who were previously healthy.

Mean BPs from these regions were used to calculate mean cortical BP based on regions known to have high PIB uptake among patients with DAT. The participants were categorized based on their mean cortical BP.

In all, 198 participants were included: 161 who were cognitively normal and 37 with DAT. In all, 139 were determined to be PIB negative and 59 PIB positive. the participants were also categorized based on their level of education: high school or less; some college or college graduate; and post college. Among the PIB-negative group, 22 had a high school education or less, 69 had some college or had graduated from college, and 48 had postcollege education. In the PIB-positive group, 16 had a high school education or less, 29 had some college or had graduated from college, and 14 had postcollege education.

“What we found on the global tests is that the people who had little PIB uptake (the people who had few if any plaques at all) all scored very well and basically had no dementia. It was kind of a ceiling effect,” said Dr. Roe.

In that group, scores on the tests were unrelated to education. “For the people who had high PIB uptake—more plaques in their brains—the scores were related to the amount of education that they had.”

These findings lend support for the cognitive-reserve hypothesis because those with greater education maintained better global cognitive functioning in the presence of Aβ pathology.

PIB binding was limited (top row) or moderate (middle; yellow, orange, and red) in 2 nondemented women but was very pronounced in a woman with Alzheimer's (bottom). IMAGES COURTESY DR. MARK A. MINTUN

The cognitive-reserve hypothesis is a concept that has been proposed to account for findings that the brains of certain individuals with pathological Alzheimer's disease burden are somehow able to compensate and minimize the effect of this burden on cognitive function. It's been suggested that greater abilities in thinking, learning, and memory—which can result in part from regularly challenging the brain—makes some individuals less susceptible to the damage caused by the disease. Education is commonly used as a surrogate for cognitive function in investigations of this hypothesis.

Previous studies have suggested that a greater amyloid β (Aβ) burden in the brain is required among individuals with more education to manifest mild dementia of the Alzheimer type (DAT) than in those with less education.

Catherine M. Roe, Ph.D., a research instructor in neurology, and her colleagues at Washington University in St. Louis used Pittsburgh Compound-B (PIB) PET imaging to test whether education and level of fibrillar brain Aβ interact to affect cognitive function in both nondemented individuals and those with DAT.

“We were really interested in the association between the amyloid uptake, their scores on these tests, and how education might mediate that,” said Dr. Roe.

The data were obtained from participants in longitudinal studies conducted at Washington University's Alzheimer's disease research center.

All of the participants underwent PET imaging using PIB, as well as anatomical T1-weighted MRI. Each participant's MRI was registered to a standard atlas target to minimize bias due to atrophy. PET images were aligned with the MR images. For the analysis, the cerebellum was chosen as the reference region because there is little specific PIB binding in this region, even in individuals with Alzheimer's.

Binding potentials (BPs) were calculated for each region of interest. “Binding potential is a number that is essentially proportional to the number of binding sites. It's a number that combines both the number of binding sites and the affinity of that particular molecule [in this case, Aβ] for the binding sites,” said Dr. Mark A. Mintun, a professor of radiology, psychiatry, and bioengineering at Washington University, and also the director of the center for clinical imaging research there. Theoretically, BP should be very highly related to the amount of amyloid present.

Mean BP was calculated for the prefrontal cortex, gyrus rectus, lateral temporal cortex, and precuneus regions.

“These regions were chosen based on previous work that we've done, where we looked at patients who had a clinical diagnosis [of DAT] with very obvious amyloid plaques using PIB scans,” said Dr. Mintun. For this study, “we looked at the four regions that we thought were the most clearly associated with Alzheimer's disease.”

It's been hypothesized that amyloid plaques would show up first in those areas for individuals who were previously healthy.

Mean BPs from these regions were used to calculate mean cortical BP based on regions known to have high PIB uptake among patients with DAT. The participants were categorized based on their mean cortical BP.

In all, 198 participants were included: 161 who were cognitively normal and 37 with DAT. In all, 139 were determined to be PIB negative and 59 PIB positive. the participants were also categorized based on their level of education: high school or less; some college or college graduate; and post college. Among the PIB-negative group, 22 had a high school education or less, 69 had some college or had graduated from college, and 48 had postcollege education. In the PIB-positive group, 16 had a high school education or less, 29 had some college or had graduated from college, and 14 had postcollege education.

“What we found on the global tests is that the people who had little PIB uptake (the people who had few if any plaques at all) all scored very well and basically had no dementia. It was kind of a ceiling effect,” said Dr. Roe.

In that group, scores on the tests were unrelated to education. “For the people who had high PIB uptake—more plaques in their brains—the scores were related to the amount of education that they had.”

These findings lend support for the cognitive-reserve hypothesis because those with greater education maintained better global cognitive functioning in the presence of Aβ pathology.

PIB binding was limited (top row) or moderate (middle; yellow, orange, and red) in 2 nondemented women but was very pronounced in a woman with Alzheimer's (bottom). IMAGES COURTESY DR. MARK A. MINTUN

Use of paroxetine (Paxil) appears to put healthy men at greater risk of sperm DNA fragmentation, according to data from a small study.

In a study of 35 healthy male volunteers, SSRI treatment was significantly correlated with increased DNA fragmentation (odds ratio 11.12, P = 0.0003) on multivariate logistic regression, after correcting for age and body mass index.

“Healthy volunteers demonstrated a dramatic increase in DNA fragmentation within just a few weeks of paroxetine treatment, without an apparent impact on standard semen parameters. This negative impact on sperm DNA fragmentation may affect reproductive outcomes, even with [intracytoplasmic sperm injection],” study investigator Dr. Cigdem Tanrikut said in an interview.

“Certainly, one should query male patients about SSRI use. However, based on these preliminary findings, it would be premature to suggest a patient come off of SSRIs altogether or change to an alternate therapy given the lack of data regarding other newer antidepressants,” said Dr. Tanrikut, Director of Male Reproductive Medicine at Massachusetts General Hospital's Fertility Center in Boston.

Men in the study ranged in age from 18 to 65 years. Intake assessment included physical exam, semen analysis, and the Brief Sexual Function Inventory (BSFI). Repeat semen analysis was obtained before SSRI initiation.

Paroxetine was given for 5 weeks: 10 mg daily during week 1; 20 mg daily during week 2; 30 mg daily during weeks 3–4; and 20 mg daily during week 5. Semen analysis was performed at weeks 2 and 4. One month after cessation of the SSRI, a final semen analysis was then performed. The BSFI was completed at week 4 and at the final semen collection.

The unadjusted odds ratio of having abnormal DNA fragmentation while on paroxetine was 9.33. In addition, BSFI revealed significant sexual dysfunction on paroxetine as compared with baseline. Up to 35% of men noted significant changes in erectile function, and up to 47% of subjects reported ejaculatory difficulties while on paroxetine. At least partial recovery of sexual function was noted within 1 month after stopping treatment.

The study was supported by the Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust and Brady Urology Foundation.

Use of paroxetine (Paxil) appears to put healthy men at greater risk of sperm DNA fragmentation, according to data from a small study.

In a study of 35 healthy male volunteers, SSRI treatment was significantly correlated with increased DNA fragmentation (odds ratio 11.12, P = 0.0003) on multivariate logistic regression, after correcting for age and body mass index.

“Healthy volunteers demonstrated a dramatic increase in DNA fragmentation within just a few weeks of paroxetine treatment, without an apparent impact on standard semen parameters. This negative impact on sperm DNA fragmentation may affect reproductive outcomes, even with [intracytoplasmic sperm injection],” study investigator Dr. Cigdem Tanrikut said in an interview.

“Certainly, one should query male patients about SSRI use. However, based on these preliminary findings, it would be premature to suggest a patient come off of SSRIs altogether or change to an alternate therapy given the lack of data regarding other newer antidepressants,” said Dr. Tanrikut, Director of Male Reproductive Medicine at Massachusetts General Hospital's Fertility Center in Boston.

Men in the study ranged in age from 18 to 65 years. Intake assessment included physical exam, semen analysis, and the Brief Sexual Function Inventory (BSFI). Repeat semen analysis was obtained before SSRI initiation.

Paroxetine was given for 5 weeks: 10 mg daily during week 1; 20 mg daily during week 2; 30 mg daily during weeks 3–4; and 20 mg daily during week 5. Semen analysis was performed at weeks 2 and 4. One month after cessation of the SSRI, a final semen analysis was then performed. The BSFI was completed at week 4 and at the final semen collection.

The unadjusted odds ratio of having abnormal DNA fragmentation while on paroxetine was 9.33. In addition, BSFI revealed significant sexual dysfunction on paroxetine as compared with baseline. Up to 35% of men noted significant changes in erectile function, and up to 47% of subjects reported ejaculatory difficulties while on paroxetine. At least partial recovery of sexual function was noted within 1 month after stopping treatment.

The study was supported by the Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust and Brady Urology Foundation.

Use of paroxetine (Paxil) appears to put healthy men at greater risk of sperm DNA fragmentation, according to data from a small study.

In a study of 35 healthy male volunteers, SSRI treatment was significantly correlated with increased DNA fragmentation (odds ratio 11.12, P = 0.0003) on multivariate logistic regression, after correcting for age and body mass index.

“Healthy volunteers demonstrated a dramatic increase in DNA fragmentation within just a few weeks of paroxetine treatment, without an apparent impact on standard semen parameters. This negative impact on sperm DNA fragmentation may affect reproductive outcomes, even with [intracytoplasmic sperm injection],” study investigator Dr. Cigdem Tanrikut said in an interview.

“Certainly, one should query male patients about SSRI use. However, based on these preliminary findings, it would be premature to suggest a patient come off of SSRIs altogether or change to an alternate therapy given the lack of data regarding other newer antidepressants,” said Dr. Tanrikut, Director of Male Reproductive Medicine at Massachusetts General Hospital's Fertility Center in Boston.

Men in the study ranged in age from 18 to 65 years. Intake assessment included physical exam, semen analysis, and the Brief Sexual Function Inventory (BSFI). Repeat semen analysis was obtained before SSRI initiation.

Paroxetine was given for 5 weeks: 10 mg daily during week 1; 20 mg daily during week 2; 30 mg daily during weeks 3–4; and 20 mg daily during week 5. Semen analysis was performed at weeks 2 and 4. One month after cessation of the SSRI, a final semen analysis was then performed. The BSFI was completed at week 4 and at the final semen collection.

The unadjusted odds ratio of having abnormal DNA fragmentation while on paroxetine was 9.33. In addition, BSFI revealed significant sexual dysfunction on paroxetine as compared with baseline. Up to 35% of men noted significant changes in erectile function, and up to 47% of subjects reported ejaculatory difficulties while on paroxetine. At least partial recovery of sexual function was noted within 1 month after stopping treatment.

The study was supported by the Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust and Brady Urology Foundation.

PARIS — Nonbiologic systemic drugs can be effective choices for the treatment of psoriasis if they are chosen properly, according to Dr. Jonathan Barker.

“The important message is that standard, traditional systemic drugs work,” said Dr. Barker at the annual congress of the European Academy of Dermatology and Venereology. However, these drugs are not always effective and are often associated with considerable toxicity.

“To optimize systemic therapy, we're talking about maximizing efficacy and minimizing toxicity,” said Dr. Barker, head of the skin inflammation unit at St. John's Institute of Dermatology, King's College, London, who gave an overview of several standard systemic drugs.

▸ Methotrexate. The preferred drug for unrelenting disease that is likely to require long-term therapy, it is also effective for treating psoriatic arthritis said Dr. Barker. The key to avoiding adverse events with the drug is to start with a low dose and increase it slowly.

Dr. Barker said he and his colleagues begin psoriasis patients on 5 mg/week and increase the dose by 5 mg/week up to 15 mg for the first 3 months. The maximum dose they use for psoriasis patients is 25 mg.

It's not commonly recognized that most causes of death that are associated with methotrexate are attributable to bone marrow suppression, not hepatotoxicity. These deaths are usually a result of some confusion over the dosing regimen or folic acid deficiency, he said. Bone marrow suppression is rare when patients are on folic acid supplementation.

Dr. Barker noted that it is possible to monitor liver function without routine liver biopsy by monitoring serum procollagen III aminopeptide (Br. J. Dermatol. 2005;152:444–50). For his psoriasis patients on long-term methotrexate, he checks serum procollagen III aminopeptide every 3 months.

“If this practice were to be widely adopted, then methotrexate would become a more acceptable option for many patients who are dissuaded from considering it because of the threat of repeated liver biopsy,” he said.

▸ Cyclosporine. It is a fast-acting drug that “presents a different set of problems with respect to usage,” Dr. Barker noted. “It's a very good drug for patients with intermittent disease, where they need a quick fix but you're hoping that the duration of therapy will be very short.”

Glomerular sclerosis is extremely unlikely to occur in patients who are treated with cyclosporine for less than 12 months and in whom there is an insignificant rise in creatinine levels. Glomerular sclerosis is much more likely to occur when cyclosporine is used for more than a year.

In addition, long-term cyclosporine A—the main form of this drug—is associated with an increased risk of nonmelanoma skin cancer. However, this risk can be minimized by limiting both dosage and duration of use (no longer than 1–2 years), said Dr. Barker. Cyclosporine use should be minimized in patients who have had significant phototherapy.

▸ Acitretin. It can be used “occasionally in moderate chronic plaque psoriasis, more so in palmo-plantar pustulosis,” said Dr. Barker, who added that he starts with the lowest dosage (25 mg/day) and uses it with narrow-band UVB phototherapy.

However, one should use extreme caution when treating women of child-bearing age with acitretin because it can cause major fetal abnormalities, he cautioned.

In addition, it is very helpful as an adjunctive treatment for patients with severe disease and multiple squamoproliferative lesions who have been on phototherapy in the past.

“This is not an immunosuppressive drug and there is some evidence that it has chemoprotective activity for malignancy,” he said.

Dr. Barker has consulted for several pharmaceutical companies making biologics but noted that none was relevant to his presentation.

PARIS — Nonbiologic systemic drugs can be effective choices for the treatment of psoriasis if they are chosen properly, according to Dr. Jonathan Barker.

“The important message is that standard, traditional systemic drugs work,” said Dr. Barker at the annual congress of the European Academy of Dermatology and Venereology. However, these drugs are not always effective and are often associated with considerable toxicity.

“To optimize systemic therapy, we're talking about maximizing efficacy and minimizing toxicity,” said Dr. Barker, head of the skin inflammation unit at St. John's Institute of Dermatology, King's College, London, who gave an overview of several standard systemic drugs.

▸ Methotrexate. The preferred drug for unrelenting disease that is likely to require long-term therapy, it is also effective for treating psoriatic arthritis said Dr. Barker. The key to avoiding adverse events with the drug is to start with a low dose and increase it slowly.

Dr. Barker said he and his colleagues begin psoriasis patients on 5 mg/week and increase the dose by 5 mg/week up to 15 mg for the first 3 months. The maximum dose they use for psoriasis patients is 25 mg.

It's not commonly recognized that most causes of death that are associated with methotrexate are attributable to bone marrow suppression, not hepatotoxicity. These deaths are usually a result of some confusion over the dosing regimen or folic acid deficiency, he said. Bone marrow suppression is rare when patients are on folic acid supplementation.

Dr. Barker noted that it is possible to monitor liver function without routine liver biopsy by monitoring serum procollagen III aminopeptide (Br. J. Dermatol. 2005;152:444–50). For his psoriasis patients on long-term methotrexate, he checks serum procollagen III aminopeptide every 3 months.

“If this practice were to be widely adopted, then methotrexate would become a more acceptable option for many patients who are dissuaded from considering it because of the threat of repeated liver biopsy,” he said.

▸ Cyclosporine. It is a fast-acting drug that “presents a different set of problems with respect to usage,” Dr. Barker noted. “It's a very good drug for patients with intermittent disease, where they need a quick fix but you're hoping that the duration of therapy will be very short.”

Glomerular sclerosis is extremely unlikely to occur in patients who are treated with cyclosporine for less than 12 months and in whom there is an insignificant rise in creatinine levels. Glomerular sclerosis is much more likely to occur when cyclosporine is used for more than a year.

In addition, long-term cyclosporine A—the main form of this drug—is associated with an increased risk of nonmelanoma skin cancer. However, this risk can be minimized by limiting both dosage and duration of use (no longer than 1–2 years), said Dr. Barker. Cyclosporine use should be minimized in patients who have had significant phototherapy.

▸ Acitretin. It can be used “occasionally in moderate chronic plaque psoriasis, more so in palmo-plantar pustulosis,” said Dr. Barker, who added that he starts with the lowest dosage (25 mg/day) and uses it with narrow-band UVB phototherapy.

However, one should use extreme caution when treating women of child-bearing age with acitretin because it can cause major fetal abnormalities, he cautioned.

In addition, it is very helpful as an adjunctive treatment for patients with severe disease and multiple squamoproliferative lesions who have been on phototherapy in the past.

“This is not an immunosuppressive drug and there is some evidence that it has chemoprotective activity for malignancy,” he said.

Dr. Barker has consulted for several pharmaceutical companies making biologics but noted that none was relevant to his presentation.

PARIS — Nonbiologic systemic drugs can be effective choices for the treatment of psoriasis if they are chosen properly, according to Dr. Jonathan Barker.

“The important message is that standard, traditional systemic drugs work,” said Dr. Barker at the annual congress of the European Academy of Dermatology and Venereology. However, these drugs are not always effective and are often associated with considerable toxicity.

“To optimize systemic therapy, we're talking about maximizing efficacy and minimizing toxicity,” said Dr. Barker, head of the skin inflammation unit at St. John's Institute of Dermatology, King's College, London, who gave an overview of several standard systemic drugs.

▸ Methotrexate. The preferred drug for unrelenting disease that is likely to require long-term therapy, it is also effective for treating psoriatic arthritis said Dr. Barker. The key to avoiding adverse events with the drug is to start with a low dose and increase it slowly.

Dr. Barker said he and his colleagues begin psoriasis patients on 5 mg/week and increase the dose by 5 mg/week up to 15 mg for the first 3 months. The maximum dose they use for psoriasis patients is 25 mg.

It's not commonly recognized that most causes of death that are associated with methotrexate are attributable to bone marrow suppression, not hepatotoxicity. These deaths are usually a result of some confusion over the dosing regimen or folic acid deficiency, he said. Bone marrow suppression is rare when patients are on folic acid supplementation.

Dr. Barker noted that it is possible to monitor liver function without routine liver biopsy by monitoring serum procollagen III aminopeptide (Br. J. Dermatol. 2005;152:444–50). For his psoriasis patients on long-term methotrexate, he checks serum procollagen III aminopeptide every 3 months.

“If this practice were to be widely adopted, then methotrexate would become a more acceptable option for many patients who are dissuaded from considering it because of the threat of repeated liver biopsy,” he said.

▸ Cyclosporine. It is a fast-acting drug that “presents a different set of problems with respect to usage,” Dr. Barker noted. “It's a very good drug for patients with intermittent disease, where they need a quick fix but you're hoping that the duration of therapy will be very short.”

Glomerular sclerosis is extremely unlikely to occur in patients who are treated with cyclosporine for less than 12 months and in whom there is an insignificant rise in creatinine levels. Glomerular sclerosis is much more likely to occur when cyclosporine is used for more than a year.

In addition, long-term cyclosporine A—the main form of this drug—is associated with an increased risk of nonmelanoma skin cancer. However, this risk can be minimized by limiting both dosage and duration of use (no longer than 1–2 years), said Dr. Barker. Cyclosporine use should be minimized in patients who have had significant phototherapy.

▸ Acitretin. It can be used “occasionally in moderate chronic plaque psoriasis, more so in palmo-plantar pustulosis,” said Dr. Barker, who added that he starts with the lowest dosage (25 mg/day) and uses it with narrow-band UVB phototherapy.

However, one should use extreme caution when treating women of child-bearing age with acitretin because it can cause major fetal abnormalities, he cautioned.

In addition, it is very helpful as an adjunctive treatment for patients with severe disease and multiple squamoproliferative lesions who have been on phototherapy in the past.

“This is not an immunosuppressive drug and there is some evidence that it has chemoprotective activity for malignancy,” he said.

Dr. Barker has consulted for several pharmaceutical companies making biologics but noted that none was relevant to his presentation.

BALTIMORE – Medication is not a surefire solution for the symptoms associated with autism spectrum disorders, according to Dr. Kenneth E. Towbin.

“Many people seek medication for children with autism spectrum disorders, imagining that there is a magic bullet that is going to reduce or eliminate the child's symptoms. There are no magic bullets,” said Dr. Towbin, who is chief of clinical child and adolescent psychiatry in the intramural research program at the National Institute of Mental Health.

Still, many children with autism spectrum disorders (ASD) end up on medication, Dr. Towbin said at a conference on autism sponsored by Kennedy Krieger Institute. Several studies estimate that about half of children with ASD have received a prescription medication in the last year.

The primary treatments for autism spectrum disorders are education and behavioral therapies. As a secondary treatment, medication may help reduce some symptoms in ASD, and can be helpful and important, said Dr. Towbin.

Medications should be considered when a child's safety or personal distress is at issue. Drug therapy also can be considered when there is adversity in the child's family life or to sustain educational progress. Lastly, medications can be considered for the treatment of aggression, hyperactivity, perseveration/stereotypy, inattention/distractibility, anxiety, inflexibility, and depression.

Parental collaboration is crucial when choosing drug therapy for ASD symptoms. Parents must understand that medication will not work quickly to improve symptoms, he said.

Be sure to educate parents to assess symptoms, maintain behavioral interventions, and monitor possible side effects. Children with ASD have abnormal sensitivities, which may leave them more vulnerable to medication side effects, Dr. Towbin noted.

Before starting a child with ASD on medication, take the time to understand the nuances within each child's situation. Dr. Towbin told the story of an adolescent patient who was beginning to act out and be disruptive–but only during school–so much so that he was often sent home. Dr. Towbin was approached to start the boy on medication to minimize this behavior.

After talking with the young man, Dr. Towbin learned that teachers had been openly discussing a possible teachers' strike in front of the special education students. As it turned out, the boy was upset about the possibility of a strike and how this would disrupt school–which he liked very much. Optimizing the child's environment and educating others often might prove more helpful than medication. “Medication does not reverse a bad situation,” he said.

Dr. Towbin offered the following guidelines for using pharmacotherapy to treat children with ASD:

▸ Target specific symptoms.

▸ Start at the smallest possible dose.

▸ Increase doses using the smallest possible increments.

▸ Increase doses only after sufficient time has elapsed to gauge the effects of the current dose.

▸ Monitor the effects on the specific target symptoms.

▸ Look for side effects routinely.

▸ Minimize the use of more than one drug at a time.

P Start a second drug only after reaching the maximum feasible dose of the first drug.

P Start a new drug only after sufficient time at the maximum dose has been achieved.

▸ If changing a combination of medications, change only one medication at a time over intervals that are long enough to assess the impact of the change.

The symptom of depression may be a feature that occurs more commonly in higher-functioning autism spectrum individuals, especially in the late-childhood/early-adolescence period, he noted. SSRIs (fluvoxamine [Luvox], fluoxetine, and sertraline [Zoloft]) and the tricyclic agent clomipramine (Anafranil) have been suggested for treating depression in children with ASD. However, Dr. Towbin described the data for using these drugs in this patient population as so-so.

Dr. Towbin offered a few cautionary notes. Children on SSRIs can have interactions with medications they might be taking already. “When you get into polypharmacy, you have to be very careful about how the drugs interact with one another.”

Dr. Towbin reported that he has no financial conflicts of interest.

ELSEVIER GLOBAL MEDICAL NEWS

Questions to Ask Before Treating

What are the frequency, intensity, and duration of symptoms?

What times and locations are associated with symptom onset?

What are the ameliorating and aggravating factors?

How are these symptoms trending over time?

Source: Dr. Towbin

BALTIMORE – Medication is not a surefire solution for the symptoms associated with autism spectrum disorders, according to Dr. Kenneth E. Towbin.

“Many people seek medication for children with autism spectrum disorders, imagining that there is a magic bullet that is going to reduce or eliminate the child's symptoms. There are no magic bullets,” said Dr. Towbin, who is chief of clinical child and adolescent psychiatry in the intramural research program at the National Institute of Mental Health.

Still, many children with autism spectrum disorders (ASD) end up on medication, Dr. Towbin said at a conference on autism sponsored by Kennedy Krieger Institute. Several studies estimate that about half of children with ASD have received a prescription medication in the last year.

The primary treatments for autism spectrum disorders are education and behavioral therapies. As a secondary treatment, medication may help reduce some symptoms in ASD, and can be helpful and important, said Dr. Towbin.

Medications should be considered when a child's safety or personal distress is at issue. Drug therapy also can be considered when there is adversity in the child's family life or to sustain educational progress. Lastly, medications can be considered for the treatment of aggression, hyperactivity, perseveration/stereotypy, inattention/distractibility, anxiety, inflexibility, and depression.

Parental collaboration is crucial when choosing drug therapy for ASD symptoms. Parents must understand that medication will not work quickly to improve symptoms, he said.

Be sure to educate parents to assess symptoms, maintain behavioral interventions, and monitor possible side effects. Children with ASD have abnormal sensitivities, which may leave them more vulnerable to medication side effects, Dr. Towbin noted.

Before starting a child with ASD on medication, take the time to understand the nuances within each child's situation. Dr. Towbin told the story of an adolescent patient who was beginning to act out and be disruptive–but only during school–so much so that he was often sent home. Dr. Towbin was approached to start the boy on medication to minimize this behavior.

After talking with the young man, Dr. Towbin learned that teachers had been openly discussing a possible teachers' strike in front of the special education students. As it turned out, the boy was upset about the possibility of a strike and how this would disrupt school–which he liked very much. Optimizing the child's environment and educating others often might prove more helpful than medication. “Medication does not reverse a bad situation,” he said.

Dr. Towbin offered the following guidelines for using pharmacotherapy to treat children with ASD:

▸ Target specific symptoms.

▸ Start at the smallest possible dose.

▸ Increase doses using the smallest possible increments.

▸ Increase doses only after sufficient time has elapsed to gauge the effects of the current dose.

▸ Monitor the effects on the specific target symptoms.

▸ Look for side effects routinely.

▸ Minimize the use of more than one drug at a time.

P Start a second drug only after reaching the maximum feasible dose of the first drug.

P Start a new drug only after sufficient time at the maximum dose has been achieved.

▸ If changing a combination of medications, change only one medication at a time over intervals that are long enough to assess the impact of the change.

The symptom of depression may be a feature that occurs more commonly in higher-functioning autism spectrum individuals, especially in the late-childhood/early-adolescence period, he noted. SSRIs (fluvoxamine [Luvox], fluoxetine, and sertraline [Zoloft]) and the tricyclic agent clomipramine (Anafranil) have been suggested for treating depression in children with ASD. However, Dr. Towbin described the data for using these drugs in this patient population as so-so.

Dr. Towbin offered a few cautionary notes. Children on SSRIs can have interactions with medications they might be taking already. “When you get into polypharmacy, you have to be very careful about how the drugs interact with one another.”

Dr. Towbin reported that he has no financial conflicts of interest.

ELSEVIER GLOBAL MEDICAL NEWS

Questions to Ask Before Treating

What are the frequency, intensity, and duration of symptoms?

What times and locations are associated with symptom onset?

What are the ameliorating and aggravating factors?

How are these symptoms trending over time?

Source: Dr. Towbin

BALTIMORE – Medication is not a surefire solution for the symptoms associated with autism spectrum disorders, according to Dr. Kenneth E. Towbin.

“Many people seek medication for children with autism spectrum disorders, imagining that there is a magic bullet that is going to reduce or eliminate the child's symptoms. There are no magic bullets,” said Dr. Towbin, who is chief of clinical child and adolescent psychiatry in the intramural research program at the National Institute of Mental Health.

Still, many children with autism spectrum disorders (ASD) end up on medication, Dr. Towbin said at a conference on autism sponsored by Kennedy Krieger Institute. Several studies estimate that about half of children with ASD have received a prescription medication in the last year.

The primary treatments for autism spectrum disorders are education and behavioral therapies. As a secondary treatment, medication may help reduce some symptoms in ASD, and can be helpful and important, said Dr. Towbin.

Medications should be considered when a child's safety or personal distress is at issue. Drug therapy also can be considered when there is adversity in the child's family life or to sustain educational progress. Lastly, medications can be considered for the treatment of aggression, hyperactivity, perseveration/stereotypy, inattention/distractibility, anxiety, inflexibility, and depression.

Parental collaboration is crucial when choosing drug therapy for ASD symptoms. Parents must understand that medication will not work quickly to improve symptoms, he said.

Be sure to educate parents to assess symptoms, maintain behavioral interventions, and monitor possible side effects. Children with ASD have abnormal sensitivities, which may leave them more vulnerable to medication side effects, Dr. Towbin noted.

Before starting a child with ASD on medication, take the time to understand the nuances within each child's situation. Dr. Towbin told the story of an adolescent patient who was beginning to act out and be disruptive–but only during school–so much so that he was often sent home. Dr. Towbin was approached to start the boy on medication to minimize this behavior.

After talking with the young man, Dr. Towbin learned that teachers had been openly discussing a possible teachers' strike in front of the special education students. As it turned out, the boy was upset about the possibility of a strike and how this would disrupt school–which he liked very much. Optimizing the child's environment and educating others often might prove more helpful than medication. “Medication does not reverse a bad situation,” he said.

Dr. Towbin offered the following guidelines for using pharmacotherapy to treat children with ASD:

▸ Target specific symptoms.

▸ Start at the smallest possible dose.

▸ Increase doses using the smallest possible increments.

▸ Increase doses only after sufficient time has elapsed to gauge the effects of the current dose.

▸ Monitor the effects on the specific target symptoms.

▸ Look for side effects routinely.

▸ Minimize the use of more than one drug at a time.

P Start a second drug only after reaching the maximum feasible dose of the first drug.

P Start a new drug only after sufficient time at the maximum dose has been achieved.

▸ If changing a combination of medications, change only one medication at a time over intervals that are long enough to assess the impact of the change.

The symptom of depression may be a feature that occurs more commonly in higher-functioning autism spectrum individuals, especially in the late-childhood/early-adolescence period, he noted. SSRIs (fluvoxamine [Luvox], fluoxetine, and sertraline [Zoloft]) and the tricyclic agent clomipramine (Anafranil) have been suggested for treating depression in children with ASD. However, Dr. Towbin described the data for using these drugs in this patient population as so-so.

Dr. Towbin offered a few cautionary notes. Children on SSRIs can have interactions with medications they might be taking already. “When you get into polypharmacy, you have to be very careful about how the drugs interact with one another.”

Dr. Towbin reported that he has no financial conflicts of interest.

ELSEVIER GLOBAL MEDICAL NEWS

Questions to Ask Before Treating

What are the frequency, intensity, and duration of symptoms?

What times and locations are associated with symptom onset?

What are the ameliorating and aggravating factors?

How are these symptoms trending over time?

Source: Dr. Towbin

WASHINGTON — The novel antibiotic iclaprim appears to be comparable to linezolid in terms of safety and efficacy in the treatment of complicated skin and skin structure infections, based on the results of a study of almost 1,000 patients.

The clinical cure rate for the intent-to-treat (ITT) population was 82% for those on iclaprim, compared with 85% for those on linezolid (Zyvox), Dr. Maria Solonets reported in a poster presented at the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) and the annual meeting of the Infectious Diseases Society of America (IDSA).

"Based on the clinical experience to date, iclaprim appears to be a safe and effective potential alternative for the treatment of complicated skin and skin structure infections, including those caused by MRSA [methicillin-resistant Staphylococcus aureus] and group A streptococcus," Dr. Solonets and her coinvestigators wrote.

Iclaprim is an investigational broad-spectrum diaminopyrimidine that has shown potent in vivo activity against predominantly gram-positive pathogens that are associated with complicated skin and skin structure infections. Dr. Solonets and several of her coinvestigators are employed by Arpida Ltd., Reinach, Switzerland, which is developing the drug.

The data come from the combined results of two Arpida-sponsored phase III clinical trials (ASSIST-1 and ASSIST-2). For both studies, patients (18 years or older) with complicated skin and skin structure infections with a minimum of three local and one systemic sign or symptom of infection were enrolled. Patients were randomized to either 0.8 mg/kg iclaprim infused over a period of 30 minutes every 12 hours or 600 mg linezolid infused over 30 minutes every 12 hours.

Patients were allowed concomitant use of aztreonam and metronidazole for the treatment of gram-negative organisms in mixed infections. However other systemic or topical antibiotics, steroids, or class Ia/III antiarrhythmic drugs were prohibited.

The intent-to-treat population included all randomized patients who received at least one dose of the study medication. The modified intent-to-treat population included all patients in the ITT population who had an infecting gram-positive pathogen isolated at baseline.

Clinical cure was determined by the resolution of signs and symptoms of infection present at baseline or by clinically relevant improvement of local or systemic signs and symptoms of infection. Patients evaluated for clinical cure had to have a minimum of 4 days of treatment and at least seven doses of the study drug. The ITT population included 500 patients randomized to iclaprim and 491 patients randomized to linezolid. Most patients in both groups—92% in the iclaprim and 93% in the linezolid group—were categorized with severe infection.

The most common infection type was deep or extensive cellulitis, followed by wound infections and major abscess. Microbiologic eradication or presumed eradication was based on the absence from any culture, at the test-of-cure assessment, of the causative pathogen isolated at baseline.

S. aureus was the most commonly isolated pathogen at baseline—found in more than 75% in both treatment groups. Approximately 40% of S. aureus isolates were MRSA. MRSA eradication rates for iclaprim were similar to those for linezolid—76% and 79%, respectively.

In terms of safety, the number of adverse events possibly or probably due to the study drug was comparable for iclaprim (113) and linezolid (137). The most common adverse events were gastrointestinal disorders.

Arpida Ltd. announced that it has received notice from the Food and Drug Administration that the agency's Anti-Infective Drugs Advisory Committee will discuss the new drug application (NDA) for intravenous iclaprim in complicated skin and skin structure infections.

WASHINGTON — The novel antibiotic iclaprim appears to be comparable to linezolid in terms of safety and efficacy in the treatment of complicated skin and skin structure infections, based on the results of a study of almost 1,000 patients.

The clinical cure rate for the intent-to-treat (ITT) population was 82% for those on iclaprim, compared with 85% for those on linezolid (Zyvox), Dr. Maria Solonets reported in a poster presented at the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) and the annual meeting of the Infectious Diseases Society of America (IDSA).

"Based on the clinical experience to date, iclaprim appears to be a safe and effective potential alternative for the treatment of complicated skin and skin structure infections, including those caused by MRSA [methicillin-resistant Staphylococcus aureus] and group A streptococcus," Dr. Solonets and her coinvestigators wrote.

Iclaprim is an investigational broad-spectrum diaminopyrimidine that has shown potent in vivo activity against predominantly gram-positive pathogens that are associated with complicated skin and skin structure infections. Dr. Solonets and several of her coinvestigators are employed by Arpida Ltd., Reinach, Switzerland, which is developing the drug.

The data come from the combined results of two Arpida-sponsored phase III clinical trials (ASSIST-1 and ASSIST-2). For both studies, patients (18 years or older) with complicated skin and skin structure infections with a minimum of three local and one systemic sign or symptom of infection were enrolled. Patients were randomized to either 0.8 mg/kg iclaprim infused over a period of 30 minutes every 12 hours or 600 mg linezolid infused over 30 minutes every 12 hours.

Patients were allowed concomitant use of aztreonam and metronidazole for the treatment of gram-negative organisms in mixed infections. However other systemic or topical antibiotics, steroids, or class Ia/III antiarrhythmic drugs were prohibited.

The intent-to-treat population included all randomized patients who received at least one dose of the study medication. The modified intent-to-treat population included all patients in the ITT population who had an infecting gram-positive pathogen isolated at baseline.

Clinical cure was determined by the resolution of signs and symptoms of infection present at baseline or by clinically relevant improvement of local or systemic signs and symptoms of infection. Patients evaluated for clinical cure had to have a minimum of 4 days of treatment and at least seven doses of the study drug. The ITT population included 500 patients randomized to iclaprim and 491 patients randomized to linezolid. Most patients in both groups—92% in the iclaprim and 93% in the linezolid group—were categorized with severe infection.

The most common infection type was deep or extensive cellulitis, followed by wound infections and major abscess. Microbiologic eradication or presumed eradication was based on the absence from any culture, at the test-of-cure assessment, of the causative pathogen isolated at baseline.

S. aureus was the most commonly isolated pathogen at baseline—found in more than 75% in both treatment groups. Approximately 40% of S. aureus isolates were MRSA. MRSA eradication rates for iclaprim were similar to those for linezolid—76% and 79%, respectively.

In terms of safety, the number of adverse events possibly or probably due to the study drug was comparable for iclaprim (113) and linezolid (137). The most common adverse events were gastrointestinal disorders.

Arpida Ltd. announced that it has received notice from the Food and Drug Administration that the agency's Anti-Infective Drugs Advisory Committee will discuss the new drug application (NDA) for intravenous iclaprim in complicated skin and skin structure infections.

WASHINGTON — The novel antibiotic iclaprim appears to be comparable to linezolid in terms of safety and efficacy in the treatment of complicated skin and skin structure infections, based on the results of a study of almost 1,000 patients.

The clinical cure rate for the intent-to-treat (ITT) population was 82% for those on iclaprim, compared with 85% for those on linezolid (Zyvox), Dr. Maria Solonets reported in a poster presented at the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) and the annual meeting of the Infectious Diseases Society of America (IDSA).

"Based on the clinical experience to date, iclaprim appears to be a safe and effective potential alternative for the treatment of complicated skin and skin structure infections, including those caused by MRSA [methicillin-resistant Staphylococcus aureus] and group A streptococcus," Dr. Solonets and her coinvestigators wrote.

Iclaprim is an investigational broad-spectrum diaminopyrimidine that has shown potent in vivo activity against predominantly gram-positive pathogens that are associated with complicated skin and skin structure infections. Dr. Solonets and several of her coinvestigators are employed by Arpida Ltd., Reinach, Switzerland, which is developing the drug.

The data come from the combined results of two Arpida-sponsored phase III clinical trials (ASSIST-1 and ASSIST-2). For both studies, patients (18 years or older) with complicated skin and skin structure infections with a minimum of three local and one systemic sign or symptom of infection were enrolled. Patients were randomized to either 0.8 mg/kg iclaprim infused over a period of 30 minutes every 12 hours or 600 mg linezolid infused over 30 minutes every 12 hours.

Patients were allowed concomitant use of aztreonam and metronidazole for the treatment of gram-negative organisms in mixed infections. However other systemic or topical antibiotics, steroids, or class Ia/III antiarrhythmic drugs were prohibited.

The intent-to-treat population included all randomized patients who received at least one dose of the study medication. The modified intent-to-treat population included all patients in the ITT population who had an infecting gram-positive pathogen isolated at baseline.

Clinical cure was determined by the resolution of signs and symptoms of infection present at baseline or by clinically relevant improvement of local or systemic signs and symptoms of infection. Patients evaluated for clinical cure had to have a minimum of 4 days of treatment and at least seven doses of the study drug. The ITT population included 500 patients randomized to iclaprim and 491 patients randomized to linezolid. Most patients in both groups—92% in the iclaprim and 93% in the linezolid group—were categorized with severe infection.

The most common infection type was deep or extensive cellulitis, followed by wound infections and major abscess. Microbiologic eradication or presumed eradication was based on the absence from any culture, at the test-of-cure assessment, of the causative pathogen isolated at baseline.

S. aureus was the most commonly isolated pathogen at baseline—found in more than 75% in both treatment groups. Approximately 40% of S. aureus isolates were MRSA. MRSA eradication rates for iclaprim were similar to those for linezolid—76% and 79%, respectively.

In terms of safety, the number of adverse events possibly or probably due to the study drug was comparable for iclaprim (113) and linezolid (137). The most common adverse events were gastrointestinal disorders.

Arpida Ltd. announced that it has received notice from the Food and Drug Administration that the agency's Anti-Infective Drugs Advisory Committee will discuss the new drug application (NDA) for intravenous iclaprim in complicated skin and skin structure infections.