Sharon Worcester

Antibiotic Prescribing Reviewed

Appropriate interventions in hospitals and doctors' offices can improve antibiotic prescribing and may reduce drug resistance, according to two new Cochrane reviews.

The first, by Peter Davey, M.D., of the University of Dundee, and his colleagues, looked at 66 studies involving hospitals. Of these, 51 studies showed a significant improvement in at least one antibiotic prescribing outcome. Of 16 that reported microbiological outcomes, 12 showed significant improvement. Interventions such as lectures and seminars to educate and/or persuade staff to change prescribing behaviors were less effective than approaches that involved imposing restrictions via guidelines and orders (Cochrane Database Syst. Rev. 2005;CD003543).

In a review of 39 studies of doctors' offices, attitudes toward prescribing were changed the most by interventions that incorporated information about local circumstances into education of patients and physicians. One-on-one meetings with physicians, small group discussions, and combined approaches had a more powerful effect on prescribing patterns than less complex approaches, such as handing out printed materials or holding lectures without discussion time, Sandra Arnold, M.D., of the University of Tennessee, Memphis, and Sharon E. Straus, M.D., of Mt. Sinai Hospital, Toronto, reported (Cochrane Database Syst. Rev. 2004;CD003539).

Treating Invasive Aspergillosis

Salvage therapies in patients with invasive aspergillosis have little efficacy, so it is imperative to choose an effective initial therapy, a study led by Thomas F. Patterson, M.D., of the University of Texas, suggests.

Of 144 patients treated initially with voriconazole, 36% were switched to another licensed antifungal therapy before completion of the initial therapy, and 48% of those responded. Of 133 patients initially treated with amphotericin B, 80% were switched to another antifungal, and 38% of those responded. Switches were made because of intolerance or insufficient response in 24% of voriconazole patients, compared with 70% of amphotericin B patients (Clin. Infect. Dis. 2005;41:1448–52).

Salvage therapy response rates were poorest with lipid formulations of amphotericin B, particularly when they were used after failed amphotericin B therapy. The overall response rate to such formulations was 30%, but the response rate in those who switched due to poor response to amphotericin B was 12%.

Candidemia Treatment Options

Voriconazole is safer than, and as effective as, the common regimen of amphotericin B followed by fluconazole for treatment of candidemia in non-neutropenic patients, a randomized noninferiority trial suggests.

A total of 422 patients were randomized to receive voriconazole or the amphotericin B and fluconazole regimen, and 41% of those in the intention-to-treat population in both groups had successful outcomes in the primary efficacy analysis. At the last evaluable follow-up, 65% of those in the voriconazole group, and 71% in the amphotericin B group had a successful outcome; the difference was not statistically significant, reported B. J. Kullberg, M.D., of University Nijmegen (the Netherlands) Medical Centre, and colleagues.

Voriconazole cleared blood cultures as quickly as the amphotericin B regimen, but serious adverse events and renal toxicity occurred more frequently in the amphotericin B regimen group, the investigators noted (Lancet 2005;366:1435–42).

The authors concluded that voriconazole, which can be given as an initial intravenous treatment or as an oral step-down agent, is an important treatment option for candidemia as it has a broader spectrum and better safety than amphotericin B.

Gatifloxacin Risk

Gatifloxacin is associated with potentially deadly glucose homeostasis abnormalities, particularly in patients with diabetes, according to Richard Frothingham, M.D., of Duke University, Durham, N.C.

Spontaneous adverse event reports over 6 years show that gatifloxacin was associated with 80% of 568 glucose homeostasis abnormality adverse event reports and 68% of 25 such events involving fatality that were associated with the use of ciprofloxacin, levofloxacin, moxifloxacin, or gatifloxacin. Of all the adverse event reports associated with gatifloxacin, 24% were glucose homeostasis abnormalities, compared with less than 2% of those associated with the other drugs.

Older patients and those being treated for diabetes had the greatest risk of these types of adverse events, Dr. Frothingham noted (Clin. Infect. Dis. 2005;41:1269–76).

Gatifloxacin should be avoided in diabetics, and the dosage in other patients should not exceed 400 mg/day. In patients with creatinine clearance of less than 40 mL/min and probably also in persons over age 65 years, the dosage should be reduced to 200 mg/day, he concluded.

Antibiotic Prescribing Reviewed

Appropriate interventions in hospitals and doctors' offices can improve antibiotic prescribing and may reduce drug resistance, according to two new Cochrane reviews.

The first, by Peter Davey, M.D., of the University of Dundee, and his colleagues, looked at 66 studies involving hospitals. Of these, 51 studies showed a significant improvement in at least one antibiotic prescribing outcome. Of 16 that reported microbiological outcomes, 12 showed significant improvement. Interventions such as lectures and seminars to educate and/or persuade staff to change prescribing behaviors were less effective than approaches that involved imposing restrictions via guidelines and orders (Cochrane Database Syst. Rev. 2005;CD003543).

In a review of 39 studies of doctors' offices, attitudes toward prescribing were changed the most by interventions that incorporated information about local circumstances into education of patients and physicians. One-on-one meetings with physicians, small group discussions, and combined approaches had a more powerful effect on prescribing patterns than less complex approaches, such as handing out printed materials or holding lectures without discussion time, Sandra Arnold, M.D., of the University of Tennessee, Memphis, and Sharon E. Straus, M.D., of Mt. Sinai Hospital, Toronto, reported (Cochrane Database Syst. Rev. 2004;CD003539).

Treating Invasive Aspergillosis

Salvage therapies in patients with invasive aspergillosis have little efficacy, so it is imperative to choose an effective initial therapy, a study led by Thomas F. Patterson, M.D., of the University of Texas, suggests.

Of 144 patients treated initially with voriconazole, 36% were switched to another licensed antifungal therapy before completion of the initial therapy, and 48% of those responded. Of 133 patients initially treated with amphotericin B, 80% were switched to another antifungal, and 38% of those responded. Switches were made because of intolerance or insufficient response in 24% of voriconazole patients, compared with 70% of amphotericin B patients (Clin. Infect. Dis. 2005;41:1448–52).

Salvage therapy response rates were poorest with lipid formulations of amphotericin B, particularly when they were used after failed amphotericin B therapy. The overall response rate to such formulations was 30%, but the response rate in those who switched due to poor response to amphotericin B was 12%.

Candidemia Treatment Options

Voriconazole is safer than, and as effective as, the common regimen of amphotericin B followed by fluconazole for treatment of candidemia in non-neutropenic patients, a randomized noninferiority trial suggests.

A total of 422 patients were randomized to receive voriconazole or the amphotericin B and fluconazole regimen, and 41% of those in the intention-to-treat population in both groups had successful outcomes in the primary efficacy analysis. At the last evaluable follow-up, 65% of those in the voriconazole group, and 71% in the amphotericin B group had a successful outcome; the difference was not statistically significant, reported B. J. Kullberg, M.D., of University Nijmegen (the Netherlands) Medical Centre, and colleagues.

Voriconazole cleared blood cultures as quickly as the amphotericin B regimen, but serious adverse events and renal toxicity occurred more frequently in the amphotericin B regimen group, the investigators noted (Lancet 2005;366:1435–42).

The authors concluded that voriconazole, which can be given as an initial intravenous treatment or as an oral step-down agent, is an important treatment option for candidemia as it has a broader spectrum and better safety than amphotericin B.

Gatifloxacin Risk

Gatifloxacin is associated with potentially deadly glucose homeostasis abnormalities, particularly in patients with diabetes, according to Richard Frothingham, M.D., of Duke University, Durham, N.C.

Spontaneous adverse event reports over 6 years show that gatifloxacin was associated with 80% of 568 glucose homeostasis abnormality adverse event reports and 68% of 25 such events involving fatality that were associated with the use of ciprofloxacin, levofloxacin, moxifloxacin, or gatifloxacin. Of all the adverse event reports associated with gatifloxacin, 24% were glucose homeostasis abnormalities, compared with less than 2% of those associated with the other drugs.

Older patients and those being treated for diabetes had the greatest risk of these types of adverse events, Dr. Frothingham noted (Clin. Infect. Dis. 2005;41:1269–76).

Gatifloxacin should be avoided in diabetics, and the dosage in other patients should not exceed 400 mg/day. In patients with creatinine clearance of less than 40 mL/min and probably also in persons over age 65 years, the dosage should be reduced to 200 mg/day, he concluded.

Antibiotic Prescribing Reviewed

Appropriate interventions in hospitals and doctors' offices can improve antibiotic prescribing and may reduce drug resistance, according to two new Cochrane reviews.

The first, by Peter Davey, M.D., of the University of Dundee, and his colleagues, looked at 66 studies involving hospitals. Of these, 51 studies showed a significant improvement in at least one antibiotic prescribing outcome. Of 16 that reported microbiological outcomes, 12 showed significant improvement. Interventions such as lectures and seminars to educate and/or persuade staff to change prescribing behaviors were less effective than approaches that involved imposing restrictions via guidelines and orders (Cochrane Database Syst. Rev. 2005;CD003543).

In a review of 39 studies of doctors' offices, attitudes toward prescribing were changed the most by interventions that incorporated information about local circumstances into education of patients and physicians. One-on-one meetings with physicians, small group discussions, and combined approaches had a more powerful effect on prescribing patterns than less complex approaches, such as handing out printed materials or holding lectures without discussion time, Sandra Arnold, M.D., of the University of Tennessee, Memphis, and Sharon E. Straus, M.D., of Mt. Sinai Hospital, Toronto, reported (Cochrane Database Syst. Rev. 2004;CD003539).

Treating Invasive Aspergillosis

Salvage therapies in patients with invasive aspergillosis have little efficacy, so it is imperative to choose an effective initial therapy, a study led by Thomas F. Patterson, M.D., of the University of Texas, suggests.

Of 144 patients treated initially with voriconazole, 36% were switched to another licensed antifungal therapy before completion of the initial therapy, and 48% of those responded. Of 133 patients initially treated with amphotericin B, 80% were switched to another antifungal, and 38% of those responded. Switches were made because of intolerance or insufficient response in 24% of voriconazole patients, compared with 70% of amphotericin B patients (Clin. Infect. Dis. 2005;41:1448–52).

Salvage therapy response rates were poorest with lipid formulations of amphotericin B, particularly when they were used after failed amphotericin B therapy. The overall response rate to such formulations was 30%, but the response rate in those who switched due to poor response to amphotericin B was 12%.

Candidemia Treatment Options

Voriconazole is safer than, and as effective as, the common regimen of amphotericin B followed by fluconazole for treatment of candidemia in non-neutropenic patients, a randomized noninferiority trial suggests.

A total of 422 patients were randomized to receive voriconazole or the amphotericin B and fluconazole regimen, and 41% of those in the intention-to-treat population in both groups had successful outcomes in the primary efficacy analysis. At the last evaluable follow-up, 65% of those in the voriconazole group, and 71% in the amphotericin B group had a successful outcome; the difference was not statistically significant, reported B. J. Kullberg, M.D., of University Nijmegen (the Netherlands) Medical Centre, and colleagues.

Voriconazole cleared blood cultures as quickly as the amphotericin B regimen, but serious adverse events and renal toxicity occurred more frequently in the amphotericin B regimen group, the investigators noted (Lancet 2005;366:1435–42).

The authors concluded that voriconazole, which can be given as an initial intravenous treatment or as an oral step-down agent, is an important treatment option for candidemia as it has a broader spectrum and better safety than amphotericin B.

Gatifloxacin Risk

Gatifloxacin is associated with potentially deadly glucose homeostasis abnormalities, particularly in patients with diabetes, according to Richard Frothingham, M.D., of Duke University, Durham, N.C.

Spontaneous adverse event reports over 6 years show that gatifloxacin was associated with 80% of 568 glucose homeostasis abnormality adverse event reports and 68% of 25 such events involving fatality that were associated with the use of ciprofloxacin, levofloxacin, moxifloxacin, or gatifloxacin. Of all the adverse event reports associated with gatifloxacin, 24% were glucose homeostasis abnormalities, compared with less than 2% of those associated with the other drugs.

Older patients and those being treated for diabetes had the greatest risk of these types of adverse events, Dr. Frothingham noted (Clin. Infect. Dis. 2005;41:1269–76).

Gatifloxacin should be avoided in diabetics, and the dosage in other patients should not exceed 400 mg/day. In patients with creatinine clearance of less than 40 mL/min and probably also in persons over age 65 years, the dosage should be reduced to 200 mg/day, he concluded.

ATLANTA — Dermatologic surgeons who shy away from brow lifts are losing about 80% of their blepharoplasty patients, as most blepharoplasty candidates also need a concomitant brow lift. But a fibrin glue technique could change all that, Steven Rotter, M.D., said at the joint annual meeting of the American Society for Dermatologic Surgery and the American College of Mohs Micrographic Surgery and Cutaneous Oncology.

Brow lifts typically should be done before or at the same time as blepharoplasty, but many dermatologic surgeons are uncomfortable with the bone tunnels and fasteners usually used for central fixation during a brow lift. The technique described by Dr. Rotter involves the use of Tisseal—a fibrin glue product—instead of the bony fixation.

The glue is applied following complete release of the periosteum, and the tissue is held in place with even pressure for 2–3 minutes. Because studies have shown that fixation is required for 6–12 weeks in patients undergoing a brow lift, botulinum toxin type A is used to treat all of the depressors and thereby serves as an effective fixator for the needed duration, said Dr. Rotter, a dermatologic surgeon in private practice in Vienna, Va.

The use of the Botox means that muscles don't need to be removed, and the use of the glue means that bone holes don't need to be created. "And any dermatologist can easily do this in an hour or an hour and a half," Dr. Rotter said.

ATLANTA — Dermatologic surgeons who shy away from brow lifts are losing about 80% of their blepharoplasty patients, as most blepharoplasty candidates also need a concomitant brow lift. But a fibrin glue technique could change all that, Steven Rotter, M.D., said at the joint annual meeting of the American Society for Dermatologic Surgery and the American College of Mohs Micrographic Surgery and Cutaneous Oncology.

Brow lifts typically should be done before or at the same time as blepharoplasty, but many dermatologic surgeons are uncomfortable with the bone tunnels and fasteners usually used for central fixation during a brow lift. The technique described by Dr. Rotter involves the use of Tisseal—a fibrin glue product—instead of the bony fixation.

The glue is applied following complete release of the periosteum, and the tissue is held in place with even pressure for 2–3 minutes. Because studies have shown that fixation is required for 6–12 weeks in patients undergoing a brow lift, botulinum toxin type A is used to treat all of the depressors and thereby serves as an effective fixator for the needed duration, said Dr. Rotter, a dermatologic surgeon in private practice in Vienna, Va.

The use of the Botox means that muscles don't need to be removed, and the use of the glue means that bone holes don't need to be created. "And any dermatologist can easily do this in an hour or an hour and a half," Dr. Rotter said.

ATLANTA — Dermatologic surgeons who shy away from brow lifts are losing about 80% of their blepharoplasty patients, as most blepharoplasty candidates also need a concomitant brow lift. But a fibrin glue technique could change all that, Steven Rotter, M.D., said at the joint annual meeting of the American Society for Dermatologic Surgery and the American College of Mohs Micrographic Surgery and Cutaneous Oncology.

Brow lifts typically should be done before or at the same time as blepharoplasty, but many dermatologic surgeons are uncomfortable with the bone tunnels and fasteners usually used for central fixation during a brow lift. The technique described by Dr. Rotter involves the use of Tisseal—a fibrin glue product—instead of the bony fixation.

The glue is applied following complete release of the periosteum, and the tissue is held in place with even pressure for 2–3 minutes. Because studies have shown that fixation is required for 6–12 weeks in patients undergoing a brow lift, botulinum toxin type A is used to treat all of the depressors and thereby serves as an effective fixator for the needed duration, said Dr. Rotter, a dermatologic surgeon in private practice in Vienna, Va.

The use of the Botox means that muscles don't need to be removed, and the use of the glue means that bone holes don't need to be created. "And any dermatologist can easily do this in an hour or an hour and a half," Dr. Rotter said.

ATLANTA — A novel surgical technique for aesthetic remodeling of the navel is proving safe and effective, Betssy C. Hazoury, M.D., reported at the joint annual meeting of the American Society for Dermatologic Surgery and the American College of Mohs Micrographic Surgery and Cutaneous Oncology.

In 42 patients aged 15–40 years, the simple technique—which involves relocation of the umbilical fundus at the lower level of fascia—resulted in aesthetic improvement of congenital or acquired umbilical deformities in all patients, high overall patient satisfaction, and only one complication, said Dr. Hazoury, a dermatologic surgeon in private practice in Santo Domingo, Dominican Republic.

Of all the patients, 20% said they were satisfied with the outcome, and 80% said they were very satisfied. One patient experienced a deep broken suture and required an additional procedure, but no other complications, such as hematoma, infection, or dehiscence occurred, she said.

The ambulatory technique involves a semicircular incision of the skin of the navel, suture fixation to the deep fascia, and posterior cerclage of the skin. It is associated with only minor discomfort and is appropriate for patients with deformities resulting from aging, pregnancy, or weight gain, as well as for those with congenital deformities, Dr. Hazoury noted. Most patients seeking this procedure have a protruding umbilicus and desire "omphaloplasty" for a deeper-looking belly button, she said, noting that umbilical hernia must be ruled out in patients with protrusions.

ATLANTA — A novel surgical technique for aesthetic remodeling of the navel is proving safe and effective, Betssy C. Hazoury, M.D., reported at the joint annual meeting of the American Society for Dermatologic Surgery and the American College of Mohs Micrographic Surgery and Cutaneous Oncology.

In 42 patients aged 15–40 years, the simple technique—which involves relocation of the umbilical fundus at the lower level of fascia—resulted in aesthetic improvement of congenital or acquired umbilical deformities in all patients, high overall patient satisfaction, and only one complication, said Dr. Hazoury, a dermatologic surgeon in private practice in Santo Domingo, Dominican Republic.

Of all the patients, 20% said they were satisfied with the outcome, and 80% said they were very satisfied. One patient experienced a deep broken suture and required an additional procedure, but no other complications, such as hematoma, infection, or dehiscence occurred, she said.

The ambulatory technique involves a semicircular incision of the skin of the navel, suture fixation to the deep fascia, and posterior cerclage of the skin. It is associated with only minor discomfort and is appropriate for patients with deformities resulting from aging, pregnancy, or weight gain, as well as for those with congenital deformities, Dr. Hazoury noted. Most patients seeking this procedure have a protruding umbilicus and desire "omphaloplasty" for a deeper-looking belly button, she said, noting that umbilical hernia must be ruled out in patients with protrusions.

ATLANTA — A novel surgical technique for aesthetic remodeling of the navel is proving safe and effective, Betssy C. Hazoury, M.D., reported at the joint annual meeting of the American Society for Dermatologic Surgery and the American College of Mohs Micrographic Surgery and Cutaneous Oncology.

In 42 patients aged 15–40 years, the simple technique—which involves relocation of the umbilical fundus at the lower level of fascia—resulted in aesthetic improvement of congenital or acquired umbilical deformities in all patients, high overall patient satisfaction, and only one complication, said Dr. Hazoury, a dermatologic surgeon in private practice in Santo Domingo, Dominican Republic.

Of all the patients, 20% said they were satisfied with the outcome, and 80% said they were very satisfied. One patient experienced a deep broken suture and required an additional procedure, but no other complications, such as hematoma, infection, or dehiscence occurred, she said.

The ambulatory technique involves a semicircular incision of the skin of the navel, suture fixation to the deep fascia, and posterior cerclage of the skin. It is associated with only minor discomfort and is appropriate for patients with deformities resulting from aging, pregnancy, or weight gain, as well as for those with congenital deformities, Dr. Hazoury noted. Most patients seeking this procedure have a protruding umbilicus and desire "omphaloplasty" for a deeper-looking belly button, she said, noting that umbilical hernia must be ruled out in patients with protrusions.

ATLANTA — Recently completed phase III data on Reloxin, a botulinum toxin type A formulation known as Dysport in Europe, may hasten the product's availability in the United States, Gary Monheit, M.D., said at the annual meeting of the American Society for Dermatologic Surgery and the American College of Mohs Micrographic Surgery and Cutaneous Oncology.

The new data on this "other Botox" have not been released, but Dr. Monheit described his experience with patients involved in the trial.

In a phase II trial in the United States, Reloxin was shown to be safe and effective at 30 days' follow-up. The phase III trial included 300 patients and tracked safety and efficacy for at least 5 months, he said.

The product had an excellent safety profile in both trials, and in some patients has an early onset of action, compared with Botox (Allergan Inc.), he said, noting that results were often seen in his patients in days rather than weeks.

"There was a very smooth, natural elimination of frown lines, a significant number of responders at 4 months, and action was still noted in a significant number of patients at up to 6 months," explained Dr. Monheit, an investigator for Ipsen Pharmaceuticals Ltd., the product's manufacturer, and Inamed Corp., which will develop and market the product in the United States.

Younger patients with significant frown lines had excellent results with full correction, and with very early onset—many within 24 hours. Furthermore, some had full response well beyond 4 months, he reported. Likewise, forehead and brow response was good at 4 months—and often well beyond that.

Older patients tended to take longer to respond, and some did not achieve the response that was expected. This might have been because of redundant skin, photodamage, or delayed or incomplete muscle response, Dr. Monheit speculated.

In a repeat-dose study that is now underway, investigators are evaluating whether repeat doses are as potent as the initial dose. A total of 1,200 patients are enrolled in the study and will be followed for 1 year, he said, noting that this will be the largest trial to date for the botulinum toxin.

Reloxin is identical to Botox except in its preparation. For example, Reloxin is provided in 500-unit vials, and Botox is provided in 100-unit vials; moreover, Reloxin is suspended in lactose, whereas Botox is suspended is sodium chloride, explained Dr. Monheit, of the department of dermatology at the University of Alabama at Birmingham, and president of the American Association for Dermatologic Surgery.

Given the differences in how Reloxin is prepared and in its onset and duration, it will likely require unique and individualized dosing and injection techniques, Dr. Monheit said.

Patient is shown at baseline in a "maximal frown" pose.

Smoothing is evident after treatment with Reloxin. Photos courtesy Dr. Gary Monheit

ATLANTA — Recently completed phase III data on Reloxin, a botulinum toxin type A formulation known as Dysport in Europe, may hasten the product's availability in the United States, Gary Monheit, M.D., said at the annual meeting of the American Society for Dermatologic Surgery and the American College of Mohs Micrographic Surgery and Cutaneous Oncology.

The new data on this "other Botox" have not been released, but Dr. Monheit described his experience with patients involved in the trial.

In a phase II trial in the United States, Reloxin was shown to be safe and effective at 30 days' follow-up. The phase III trial included 300 patients and tracked safety and efficacy for at least 5 months, he said.

The product had an excellent safety profile in both trials, and in some patients has an early onset of action, compared with Botox (Allergan Inc.), he said, noting that results were often seen in his patients in days rather than weeks.

"There was a very smooth, natural elimination of frown lines, a significant number of responders at 4 months, and action was still noted in a significant number of patients at up to 6 months," explained Dr. Monheit, an investigator for Ipsen Pharmaceuticals Ltd., the product's manufacturer, and Inamed Corp., which will develop and market the product in the United States.

Younger patients with significant frown lines had excellent results with full correction, and with very early onset—many within 24 hours. Furthermore, some had full response well beyond 4 months, he reported. Likewise, forehead and brow response was good at 4 months—and often well beyond that.

Older patients tended to take longer to respond, and some did not achieve the response that was expected. This might have been because of redundant skin, photodamage, or delayed or incomplete muscle response, Dr. Monheit speculated.

In a repeat-dose study that is now underway, investigators are evaluating whether repeat doses are as potent as the initial dose. A total of 1,200 patients are enrolled in the study and will be followed for 1 year, he said, noting that this will be the largest trial to date for the botulinum toxin.

Reloxin is identical to Botox except in its preparation. For example, Reloxin is provided in 500-unit vials, and Botox is provided in 100-unit vials; moreover, Reloxin is suspended in lactose, whereas Botox is suspended is sodium chloride, explained Dr. Monheit, of the department of dermatology at the University of Alabama at Birmingham, and president of the American Association for Dermatologic Surgery.

Given the differences in how Reloxin is prepared and in its onset and duration, it will likely require unique and individualized dosing and injection techniques, Dr. Monheit said.

Patient is shown at baseline in a "maximal frown" pose.

Smoothing is evident after treatment with Reloxin. Photos courtesy Dr. Gary Monheit

ATLANTA — Recently completed phase III data on Reloxin, a botulinum toxin type A formulation known as Dysport in Europe, may hasten the product's availability in the United States, Gary Monheit, M.D., said at the annual meeting of the American Society for Dermatologic Surgery and the American College of Mohs Micrographic Surgery and Cutaneous Oncology.

The new data on this "other Botox" have not been released, but Dr. Monheit described his experience with patients involved in the trial.

In a phase II trial in the United States, Reloxin was shown to be safe and effective at 30 days' follow-up. The phase III trial included 300 patients and tracked safety and efficacy for at least 5 months, he said.

The product had an excellent safety profile in both trials, and in some patients has an early onset of action, compared with Botox (Allergan Inc.), he said, noting that results were often seen in his patients in days rather than weeks.

"There was a very smooth, natural elimination of frown lines, a significant number of responders at 4 months, and action was still noted in a significant number of patients at up to 6 months," explained Dr. Monheit, an investigator for Ipsen Pharmaceuticals Ltd., the product's manufacturer, and Inamed Corp., which will develop and market the product in the United States.

Younger patients with significant frown lines had excellent results with full correction, and with very early onset—many within 24 hours. Furthermore, some had full response well beyond 4 months, he reported. Likewise, forehead and brow response was good at 4 months—and often well beyond that.

Older patients tended to take longer to respond, and some did not achieve the response that was expected. This might have been because of redundant skin, photodamage, or delayed or incomplete muscle response, Dr. Monheit speculated.

In a repeat-dose study that is now underway, investigators are evaluating whether repeat doses are as potent as the initial dose. A total of 1,200 patients are enrolled in the study and will be followed for 1 year, he said, noting that this will be the largest trial to date for the botulinum toxin.

Reloxin is identical to Botox except in its preparation. For example, Reloxin is provided in 500-unit vials, and Botox is provided in 100-unit vials; moreover, Reloxin is suspended in lactose, whereas Botox is suspended is sodium chloride, explained Dr. Monheit, of the department of dermatology at the University of Alabama at Birmingham, and president of the American Association for Dermatologic Surgery.

Given the differences in how Reloxin is prepared and in its onset and duration, it will likely require unique and individualized dosing and injection techniques, Dr. Monheit said.

Patient is shown at baseline in a "maximal frown" pose.

Smoothing is evident after treatment with Reloxin. Photos courtesy Dr. Gary Monheit

CHARLESTON, S.C. — Sexually transmitted diseases and bacterial vaginosis are known to be associated with elevated cervical proinflammatory cytokines in pregnancy, and interim results from an ongoing study suggest that vaginal flora that are opportunistic pathogens also have such an effect.

Candida albicans, Escherichia coli, and group B streptococci all were associated with elevations in specific cytokines in the 244 women enrolled in the study who were available for interim analysis, Marijane A. Krohn, Ph.D., reported at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

“C. albicans, E. coli, and group B streptococci are very frequent colonizers in asymptomatic women—however, these microorganisms appear ready to start an inflammatory process, even when by local vaginal criteria they seem to be nonpathogenic at that time or quiescent,” Dr. Krohn said.

Given that these organisms are pathogenic to immunologically naive fetuses and neonates, and that they also can cause infection in women, it makes sense that they would show some pathogenic potential by being associated with elevated proinflammatory cytokines, she noted.

The women were sampled before 16 weeks' gestation, and some of them also were sampled later in pregnancy.

Cervical proinflammatory cytokines were considered elevated if they were at or above the 75th percentile on any sample, said Dr. Krohn of the University of Pittsburgh.

Of 80 patients who had C. albicans, 47% of them had elevated levels of interleukin (IL)-1α, and 51% of them had elevated levels of IL-1β.

The number of patients with IL-1α and IL-1β at these levels was significantly higher in the participants with C. albicans colonization, compared with those participants without C. albicans colonization. IL-6 was also significantly higher in the colonized group.

Similarly, of the 28 patients with E. coli, 54% had IL-1α at or above the 75th percentile, and significantly more of those with E. coli colonization had elevated IL-1α and IL-1βcompared with those without such colonization.

The researchers said only IL-6 was significantly elevated in the participants who had group B streptococci colonization, compared with the participants of the study without group B streptococci.

CHARLESTON, S.C. — Sexually transmitted diseases and bacterial vaginosis are known to be associated with elevated cervical proinflammatory cytokines in pregnancy, and interim results from an ongoing study suggest that vaginal flora that are opportunistic pathogens also have such an effect.

Candida albicans, Escherichia coli, and group B streptococci all were associated with elevations in specific cytokines in the 244 women enrolled in the study who were available for interim analysis, Marijane A. Krohn, Ph.D., reported at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

“C. albicans, E. coli, and group B streptococci are very frequent colonizers in asymptomatic women—however, these microorganisms appear ready to start an inflammatory process, even when by local vaginal criteria they seem to be nonpathogenic at that time or quiescent,” Dr. Krohn said.

Given that these organisms are pathogenic to immunologically naive fetuses and neonates, and that they also can cause infection in women, it makes sense that they would show some pathogenic potential by being associated with elevated proinflammatory cytokines, she noted.

The women were sampled before 16 weeks' gestation, and some of them also were sampled later in pregnancy.

Cervical proinflammatory cytokines were considered elevated if they were at or above the 75th percentile on any sample, said Dr. Krohn of the University of Pittsburgh.

Of 80 patients who had C. albicans, 47% of them had elevated levels of interleukin (IL)-1α, and 51% of them had elevated levels of IL-1β.

The number of patients with IL-1α and IL-1β at these levels was significantly higher in the participants with C. albicans colonization, compared with those participants without C. albicans colonization. IL-6 was also significantly higher in the colonized group.

Similarly, of the 28 patients with E. coli, 54% had IL-1α at or above the 75th percentile, and significantly more of those with E. coli colonization had elevated IL-1α and IL-1βcompared with those without such colonization.

The researchers said only IL-6 was significantly elevated in the participants who had group B streptococci colonization, compared with the participants of the study without group B streptococci.

CHARLESTON, S.C. — Sexually transmitted diseases and bacterial vaginosis are known to be associated with elevated cervical proinflammatory cytokines in pregnancy, and interim results from an ongoing study suggest that vaginal flora that are opportunistic pathogens also have such an effect.

Candida albicans, Escherichia coli, and group B streptococci all were associated with elevations in specific cytokines in the 244 women enrolled in the study who were available for interim analysis, Marijane A. Krohn, Ph.D., reported at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

“C. albicans, E. coli, and group B streptococci are very frequent colonizers in asymptomatic women—however, these microorganisms appear ready to start an inflammatory process, even when by local vaginal criteria they seem to be nonpathogenic at that time or quiescent,” Dr. Krohn said.

Given that these organisms are pathogenic to immunologically naive fetuses and neonates, and that they also can cause infection in women, it makes sense that they would show some pathogenic potential by being associated with elevated proinflammatory cytokines, she noted.

The women were sampled before 16 weeks' gestation, and some of them also were sampled later in pregnancy.

Cervical proinflammatory cytokines were considered elevated if they were at or above the 75th percentile on any sample, said Dr. Krohn of the University of Pittsburgh.

Of 80 patients who had C. albicans, 47% of them had elevated levels of interleukin (IL)-1α, and 51% of them had elevated levels of IL-1β.

The number of patients with IL-1α and IL-1β at these levels was significantly higher in the participants with C. albicans colonization, compared with those participants without C. albicans colonization. IL-6 was also significantly higher in the colonized group.

Similarly, of the 28 patients with E. coli, 54% had IL-1α at or above the 75th percentile, and significantly more of those with E. coli colonization had elevated IL-1α and IL-1βcompared with those without such colonization.

The researchers said only IL-6 was significantly elevated in the participants who had group B streptococci colonization, compared with the participants of the study without group B streptococci.

The increase in amantadine- and rimantadine-resistant H3N2 influenza A viruses over the past decade is alarming, Rick A. Bright, Ph.D., of the Centers for Disease Control and Prevention, Atlanta, and his colleagues reported.

Between the 1994–1995 and 2003–2004 flu seasons, the proportion of resistant H3N2 viruses increased from 0.4% to 12.3%, a study of more than 7,000 influenza A field isolates showed. Most (84%) of the resistant viruses were isolated since the 2003 flu season, and 61% of those were from people in Asia, the investigators found (Lancet 2005;366:1175–81).

Furthermore, between the 2003–2004 season and the first 6 months of the 2004–2005 season in the United States, resistance among comparable isolates increased from 2% to 15%. The high incidence of drug-resistant H3N2 viruses circulating in regions that also have a high incidence of avian influenza (H5N1)—which is also resistant to amantadine and rimantadine—suggests that these drugs should be used with greater caution.

The increase in amantadine- and rimantadine-resistant H3N2 influenza A viruses over the past decade is alarming, Rick A. Bright, Ph.D., of the Centers for Disease Control and Prevention, Atlanta, and his colleagues reported.

Between the 1994–1995 and 2003–2004 flu seasons, the proportion of resistant H3N2 viruses increased from 0.4% to 12.3%, a study of more than 7,000 influenza A field isolates showed. Most (84%) of the resistant viruses were isolated since the 2003 flu season, and 61% of those were from people in Asia, the investigators found (Lancet 2005;366:1175–81).

Furthermore, between the 2003–2004 season and the first 6 months of the 2004–2005 season in the United States, resistance among comparable isolates increased from 2% to 15%. The high incidence of drug-resistant H3N2 viruses circulating in regions that also have a high incidence of avian influenza (H5N1)—which is also resistant to amantadine and rimantadine—suggests that these drugs should be used with greater caution.

The increase in amantadine- and rimantadine-resistant H3N2 influenza A viruses over the past decade is alarming, Rick A. Bright, Ph.D., of the Centers for Disease Control and Prevention, Atlanta, and his colleagues reported.

Between the 1994–1995 and 2003–2004 flu seasons, the proportion of resistant H3N2 viruses increased from 0.4% to 12.3%, a study of more than 7,000 influenza A field isolates showed. Most (84%) of the resistant viruses were isolated since the 2003 flu season, and 61% of those were from people in Asia, the investigators found (Lancet 2005;366:1175–81).

Furthermore, between the 2003–2004 season and the first 6 months of the 2004–2005 season in the United States, resistance among comparable isolates increased from 2% to 15%. The high incidence of drug-resistant H3N2 viruses circulating in regions that also have a high incidence of avian influenza (H5N1)—which is also resistant to amantadine and rimantadine—suggests that these drugs should be used with greater caution.

Drug-Resistant Flu

The increase in amantadine- and rimantadine-resistant H3N2 influenza A viruses over the past decade is alarming, Rick A. Bright, Ph.D., of the Centers for Disease Control and Prevention, Atlanta, and his colleagues reported.

Between the 1994–1995 and 2003–2004 flu seasons, the proportion of resistant H3N2 viruses increased from 0.4% to 12.3%, a study of more than 7,000 influenza A field isolates showed. Most (84%) of the resistant viruses were isolated since the 2003 flu season, with 61% of those from people in Asia, the investigators found (Lancet 2005;366:1175–81).

Furthermore, between the 2003–2004 season and the first 6 months of the 2004–2005 season in the United States, resistance among comparable isolates increased from 2% to 15%.

The high incidence of drug-resistant H3N2 viruses circulating in regions that also have a high incidence of avian influenza (H5N1)—which is also resistant to amantadine and rimantadine—suggests that these drugs should be used with greater caution.

Pertussis Vaccination

A pertussis vaccine proved safe and effective in adolescents and adults in a recent study, and routine use in these populations might reduce overall disease burden and transmission to children, according to Joel I. Ward, M.D., of the University of California, Los Angeles, and his colleagues.

A total of 2,781 healthy people aged 15–65 years were randomized to receive an acellular pertussis vaccine (GlaxoSmithKline) or a control vaccine. The pertussis-antigen content in the pertussis vaccine was about one-third of that used in children. Primary infection occurred in one person in the pertussis vaccine group, and in nine people in the control vaccine group, for an overall adjusted vaccine efficacy of 92%. No vaccine-associated adverse events occurred (N. Engl. J. Med. 2005;353:1555–63).

Pertussis is difficult to diagnose in adolescents and adults, and the disease burden is underappreciated. The findings of this study suggest that the annual incidence of primary disease in this population in the United States is 370 cases per 100,000 persons aged 15–65 years, or nearly a million cases per year.

Because immunity to pertussis wanes, people immunized as children can become infected later in life. Thus pertussis control may depend on immunization of all adolescents and adults as well as children, the investigators concluded.

Community-Associated MRSA

Certain patient characteristics play a role in the extent of community-associated methicillin-resistant Staphylococcus aureus infection, a study suggests.

The investigators compared 586 patients with CA-MRSA skin and soft tissue infections and 65 patients with invasive disease. Those with invasive disease were significantly more likely to be smokers (odds ratio 2.18) or injection drug users (OR 5.56), or to report a history of underlying illness (OR 2.08), immunosuppressive therapy (OR 9.31), or emphysema or chronic obstructive pulmonary disease (OR 13.9), reported Jessica M. Buck, M.D., and her colleagues at the Minnesota Department of Health, Minneapolis (Emerg. Infect. Dis. 2005;11:1532–8).

Invasive disease isolates were significantly less likely to be susceptible to ciprofloxacin and clindamycin, and significantly more likely to have health care-associated subtypes, compared with the skin and soft tissue isolates. This suggests that patients with invasive disease may have had health care exposures that were not part of the exclusion criteria in the CA-MRSA case definition, and that some of the invasive infections classified as community acquired were actually health care acquired, which are typically resistant to more drugs.

Asthma and Metapneumovirus

The recently discovered human metapneumovirus may play a direct etiologic role in acute asthma exacerbations in adults, a prospective observational study suggests.

Seven of 101 adults hospitalized with an acute asthma exacerbation tested positive for hMPV. One of 75 patients who was also tested at 3-month follow-up had hMPV infection at that time, but none of the 7 who had hMPV infection at admission tested positive at follow-up, reported John V. Williams, M.D., of Vanderbilt University Medical Center, Nashville, and his colleagues (J. Infect. Dis. 2005;192:1149–53).

Previous studies have suggested a link between hMPV infection and acute asthma exacerbations in children, and between other respiratory viruses and exacerbations in children and adults, but this is the first to link hMPV infections with such exacerbations in adults, the investigators noted. Patient characteristics in this study suggest that more severe underlying disease confers greater risk, they added.

Drug-Resistant Flu

The increase in amantadine- and rimantadine-resistant H3N2 influenza A viruses over the past decade is alarming, Rick A. Bright, Ph.D., of the Centers for Disease Control and Prevention, Atlanta, and his colleagues reported.

Between the 1994–1995 and 2003–2004 flu seasons, the proportion of resistant H3N2 viruses increased from 0.4% to 12.3%, a study of more than 7,000 influenza A field isolates showed. Most (84%) of the resistant viruses were isolated since the 2003 flu season, with 61% of those from people in Asia, the investigators found (Lancet 2005;366:1175–81).

Furthermore, between the 2003–2004 season and the first 6 months of the 2004–2005 season in the United States, resistance among comparable isolates increased from 2% to 15%.

The high incidence of drug-resistant H3N2 viruses circulating in regions that also have a high incidence of avian influenza (H5N1)—which is also resistant to amantadine and rimantadine—suggests that these drugs should be used with greater caution.

Pertussis Vaccination

A pertussis vaccine proved safe and effective in adolescents and adults in a recent study, and routine use in these populations might reduce overall disease burden and transmission to children, according to Joel I. Ward, M.D., of the University of California, Los Angeles, and his colleagues.

A total of 2,781 healthy people aged 15–65 years were randomized to receive an acellular pertussis vaccine (GlaxoSmithKline) or a control vaccine. The pertussis-antigen content in the pertussis vaccine was about one-third of that used in children. Primary infection occurred in one person in the pertussis vaccine group, and in nine people in the control vaccine group, for an overall adjusted vaccine efficacy of 92%. No vaccine-associated adverse events occurred (N. Engl. J. Med. 2005;353:1555–63).

Pertussis is difficult to diagnose in adolescents and adults, and the disease burden is underappreciated. The findings of this study suggest that the annual incidence of primary disease in this population in the United States is 370 cases per 100,000 persons aged 15–65 years, or nearly a million cases per year.

Because immunity to pertussis wanes, people immunized as children can become infected later in life. Thus pertussis control may depend on immunization of all adolescents and adults as well as children, the investigators concluded.

Community-Associated MRSA

Certain patient characteristics play a role in the extent of community-associated methicillin-resistant Staphylococcus aureus infection, a study suggests.

The investigators compared 586 patients with CA-MRSA skin and soft tissue infections and 65 patients with invasive disease. Those with invasive disease were significantly more likely to be smokers (odds ratio 2.18) or injection drug users (OR 5.56), or to report a history of underlying illness (OR 2.08), immunosuppressive therapy (OR 9.31), or emphysema or chronic obstructive pulmonary disease (OR 13.9), reported Jessica M. Buck, M.D., and her colleagues at the Minnesota Department of Health, Minneapolis (Emerg. Infect. Dis. 2005;11:1532–8).

Invasive disease isolates were significantly less likely to be susceptible to ciprofloxacin and clindamycin, and significantly more likely to have health care-associated subtypes, compared with the skin and soft tissue isolates. This suggests that patients with invasive disease may have had health care exposures that were not part of the exclusion criteria in the CA-MRSA case definition, and that some of the invasive infections classified as community acquired were actually health care acquired, which are typically resistant to more drugs.

Asthma and Metapneumovirus

The recently discovered human metapneumovirus may play a direct etiologic role in acute asthma exacerbations in adults, a prospective observational study suggests.

Seven of 101 adults hospitalized with an acute asthma exacerbation tested positive for hMPV. One of 75 patients who was also tested at 3-month follow-up had hMPV infection at that time, but none of the 7 who had hMPV infection at admission tested positive at follow-up, reported John V. Williams, M.D., of Vanderbilt University Medical Center, Nashville, and his colleagues (J. Infect. Dis. 2005;192:1149–53).

Previous studies have suggested a link between hMPV infection and acute asthma exacerbations in children, and between other respiratory viruses and exacerbations in children and adults, but this is the first to link hMPV infections with such exacerbations in adults, the investigators noted. Patient characteristics in this study suggest that more severe underlying disease confers greater risk, they added.

Drug-Resistant Flu

The increase in amantadine- and rimantadine-resistant H3N2 influenza A viruses over the past decade is alarming, Rick A. Bright, Ph.D., of the Centers for Disease Control and Prevention, Atlanta, and his colleagues reported.

Between the 1994–1995 and 2003–2004 flu seasons, the proportion of resistant H3N2 viruses increased from 0.4% to 12.3%, a study of more than 7,000 influenza A field isolates showed. Most (84%) of the resistant viruses were isolated since the 2003 flu season, with 61% of those from people in Asia, the investigators found (Lancet 2005;366:1175–81).

Furthermore, between the 2003–2004 season and the first 6 months of the 2004–2005 season in the United States, resistance among comparable isolates increased from 2% to 15%.

The high incidence of drug-resistant H3N2 viruses circulating in regions that also have a high incidence of avian influenza (H5N1)—which is also resistant to amantadine and rimantadine—suggests that these drugs should be used with greater caution.

Pertussis Vaccination

A pertussis vaccine proved safe and effective in adolescents and adults in a recent study, and routine use in these populations might reduce overall disease burden and transmission to children, according to Joel I. Ward, M.D., of the University of California, Los Angeles, and his colleagues.

A total of 2,781 healthy people aged 15–65 years were randomized to receive an acellular pertussis vaccine (GlaxoSmithKline) or a control vaccine. The pertussis-antigen content in the pertussis vaccine was about one-third of that used in children. Primary infection occurred in one person in the pertussis vaccine group, and in nine people in the control vaccine group, for an overall adjusted vaccine efficacy of 92%. No vaccine-associated adverse events occurred (N. Engl. J. Med. 2005;353:1555–63).

Pertussis is difficult to diagnose in adolescents and adults, and the disease burden is underappreciated. The findings of this study suggest that the annual incidence of primary disease in this population in the United States is 370 cases per 100,000 persons aged 15–65 years, or nearly a million cases per year.

Because immunity to pertussis wanes, people immunized as children can become infected later in life. Thus pertussis control may depend on immunization of all adolescents and adults as well as children, the investigators concluded.

Community-Associated MRSA

Certain patient characteristics play a role in the extent of community-associated methicillin-resistant Staphylococcus aureus infection, a study suggests.

The investigators compared 586 patients with CA-MRSA skin and soft tissue infections and 65 patients with invasive disease. Those with invasive disease were significantly more likely to be smokers (odds ratio 2.18) or injection drug users (OR 5.56), or to report a history of underlying illness (OR 2.08), immunosuppressive therapy (OR 9.31), or emphysema or chronic obstructive pulmonary disease (OR 13.9), reported Jessica M. Buck, M.D., and her colleagues at the Minnesota Department of Health, Minneapolis (Emerg. Infect. Dis. 2005;11:1532–8).

Invasive disease isolates were significantly less likely to be susceptible to ciprofloxacin and clindamycin, and significantly more likely to have health care-associated subtypes, compared with the skin and soft tissue isolates. This suggests that patients with invasive disease may have had health care exposures that were not part of the exclusion criteria in the CA-MRSA case definition, and that some of the invasive infections classified as community acquired were actually health care acquired, which are typically resistant to more drugs.

Asthma and Metapneumovirus

The recently discovered human metapneumovirus may play a direct etiologic role in acute asthma exacerbations in adults, a prospective observational study suggests.

Seven of 101 adults hospitalized with an acute asthma exacerbation tested positive for hMPV. One of 75 patients who was also tested at 3-month follow-up had hMPV infection at that time, but none of the 7 who had hMPV infection at admission tested positive at follow-up, reported John V. Williams, M.D., of Vanderbilt University Medical Center, Nashville, and his colleagues (J. Infect. Dis. 2005;192:1149–53).

Previous studies have suggested a link between hMPV infection and acute asthma exacerbations in children, and between other respiratory viruses and exacerbations in children and adults, but this is the first to link hMPV infections with such exacerbations in adults, the investigators noted. Patient characteristics in this study suggest that more severe underlying disease confers greater risk, they added.

CHARLESTON, S.C. — Once-daily treatment with valacyclovir for the suppression of genital herpes caused by herpes simplex virus type 2 was well tolerated for up to 20 months in a recent study.

Previously, data were available only for patients who used daily valacyclovir for up to 12 months, Zane A. Brown, M.D., of the University of Washington, Seattle, and his colleagues reported in a poster at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

For the current study, which was supported by GlaxoSmithKline Inc., 1,484 serodiscordant, heterosexual, monogamous couples were enrolled, and the seropositive partner was randomized to receive either placebo or 500 mg/day of valacyclovir for 8 months. The results of this double-blind phase, which were previously reported by the investigators, showed that the treatment significantly reduced the risk of genital herpes transmission.

Following the double-blind phase, 1,018 of the 1,484 participants treated in the double-blind phase entered an open-label suppression phase of the study, which provided 12 months of suppressive therapy with 500 mg/day of valacyclovir. Patients in this phase were evaluated every 3 months for laboratory values and adverse events.

More than 85% of participants who completed the entire 20 months of treatment were at least 80% compliant with the study medication. During the double-blind and open-label phases, the nature and incidence of adverse events were similar in the 519 participants originally assigned to receive valacyclovir (treatment group) and the 499 originally assigned to receive placebo. Common adverse events included headache, nasopharyngitis, and upper respiratory tract infection.

Serious adverse events were reported infrequently and were similar in frequency in the treatment group (5% incidence rate) and the placebo group (3% incidence rate). Only one serious adverse event (gastritis in one patient) during the 20-month study was considered by the investigators to be possibly attributable to valacyclovir, and it occurred during the open-label portion of the study.

Adverse events leading to treatment discontinuation occurred in fewer than 1% of those in the treatment group, and in 1% of those in the placebo group; clinically significant laboratory abnormalities occurred in 6% of patients in both groups. No deaths occurred during the study periods.

Despite prior lack of data on the safety of valacyclovir for the suppression of genital herpes when used for longer than 12 months, some physicians prescribe such therapy for longer periods, the investigators noted. These findings suggest that the treatment is as safe for up to 20 months as it is with 8–12 months of suppressive therapy, they concluded.

CHARLESTON, S.C. — Once-daily treatment with valacyclovir for the suppression of genital herpes caused by herpes simplex virus type 2 was well tolerated for up to 20 months in a recent study.

Previously, data were available only for patients who used daily valacyclovir for up to 12 months, Zane A. Brown, M.D., of the University of Washington, Seattle, and his colleagues reported in a poster at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

For the current study, which was supported by GlaxoSmithKline Inc., 1,484 serodiscordant, heterosexual, monogamous couples were enrolled, and the seropositive partner was randomized to receive either placebo or 500 mg/day of valacyclovir for 8 months. The results of this double-blind phase, which were previously reported by the investigators, showed that the treatment significantly reduced the risk of genital herpes transmission.

Following the double-blind phase, 1,018 of the 1,484 participants treated in the double-blind phase entered an open-label suppression phase of the study, which provided 12 months of suppressive therapy with 500 mg/day of valacyclovir. Patients in this phase were evaluated every 3 months for laboratory values and adverse events.

More than 85% of participants who completed the entire 20 months of treatment were at least 80% compliant with the study medication. During the double-blind and open-label phases, the nature and incidence of adverse events were similar in the 519 participants originally assigned to receive valacyclovir (treatment group) and the 499 originally assigned to receive placebo. Common adverse events included headache, nasopharyngitis, and upper respiratory tract infection.

Serious adverse events were reported infrequently and were similar in frequency in the treatment group (5% incidence rate) and the placebo group (3% incidence rate). Only one serious adverse event (gastritis in one patient) during the 20-month study was considered by the investigators to be possibly attributable to valacyclovir, and it occurred during the open-label portion of the study.

Adverse events leading to treatment discontinuation occurred in fewer than 1% of those in the treatment group, and in 1% of those in the placebo group; clinically significant laboratory abnormalities occurred in 6% of patients in both groups. No deaths occurred during the study periods.

Despite prior lack of data on the safety of valacyclovir for the suppression of genital herpes when used for longer than 12 months, some physicians prescribe such therapy for longer periods, the investigators noted. These findings suggest that the treatment is as safe for up to 20 months as it is with 8–12 months of suppressive therapy, they concluded.

CHARLESTON, S.C. — Once-daily treatment with valacyclovir for the suppression of genital herpes caused by herpes simplex virus type 2 was well tolerated for up to 20 months in a recent study.

Previously, data were available only for patients who used daily valacyclovir for up to 12 months, Zane A. Brown, M.D., of the University of Washington, Seattle, and his colleagues reported in a poster at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

For the current study, which was supported by GlaxoSmithKline Inc., 1,484 serodiscordant, heterosexual, monogamous couples were enrolled, and the seropositive partner was randomized to receive either placebo or 500 mg/day of valacyclovir for 8 months. The results of this double-blind phase, which were previously reported by the investigators, showed that the treatment significantly reduced the risk of genital herpes transmission.

Following the double-blind phase, 1,018 of the 1,484 participants treated in the double-blind phase entered an open-label suppression phase of the study, which provided 12 months of suppressive therapy with 500 mg/day of valacyclovir. Patients in this phase were evaluated every 3 months for laboratory values and adverse events.

More than 85% of participants who completed the entire 20 months of treatment were at least 80% compliant with the study medication. During the double-blind and open-label phases, the nature and incidence of adverse events were similar in the 519 participants originally assigned to receive valacyclovir (treatment group) and the 499 originally assigned to receive placebo. Common adverse events included headache, nasopharyngitis, and upper respiratory tract infection.

Serious adverse events were reported infrequently and were similar in frequency in the treatment group (5% incidence rate) and the placebo group (3% incidence rate). Only one serious adverse event (gastritis in one patient) during the 20-month study was considered by the investigators to be possibly attributable to valacyclovir, and it occurred during the open-label portion of the study.

Adverse events leading to treatment discontinuation occurred in fewer than 1% of those in the treatment group, and in 1% of those in the placebo group; clinically significant laboratory abnormalities occurred in 6% of patients in both groups. No deaths occurred during the study periods.

Despite prior lack of data on the safety of valacyclovir for the suppression of genital herpes when used for longer than 12 months, some physicians prescribe such therapy for longer periods, the investigators noted. These findings suggest that the treatment is as safe for up to 20 months as it is with 8–12 months of suppressive therapy, they concluded.

CHARLESTON, S.C. — The development of chorioamnionitis in patients with preterm premature rupture of membranes is associated with an increased risk for adverse neonatal outcomes, Natali Aziz, M.D., reported at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

In a retrospective cohort study of 1,153 patients who gave birth between 1980 and 2001 with a diagnosis of preterm premature rupture of membranes (PPROM) made at 24 to 34 weeks' gestation, 29% were diagnosed with chorioamnionitis before delivery. Univariate outcomes on a variety of measures—such as Apgar scores and incidence of respiratory distress syndrome, intracerebral hemorrhage, and pneumonia—were significantly poorer in neonates born to mothers with chorioamnionitis, compared with those born to mothers without chorioamnionitis, said Dr. Aziz of the University of California, San Francisco.

“Management in this setting is better examined prospectively in a randomized, controlled trial, yet given these data, when managing a patient with preterm premature rupture of membranes we must weigh the risks of prematurity against those of expectant management with the ongoing possibility of development of chorioamnionitis,” she said.

Differences were noted in the rates of chorioamnionitis based on gestational age at the time of rupture of membranes (rate of 46% at gestational age of 24–25 weeks vs. 18% at 32 weeks or greater) and duration of latency (higher rates in those with latency greater than 48 hours). Subgroup analyses to adjust for these factors were performed. Many clinical differences remained, but statistical significance was lost due to smaller sample sizes.

In the subgroup analysis based on gestational age at time of rupture of membranes (grouped in 2-week intervals), nonnecrotizing enterocolitis was more common among those with chorioamnionitis in the 24− to 25-week subgroup, intracranial hemorrhage was more common among those with chorioamnionitis in the 30− to 31-week subgroup, and pneumonia was more common among those with chorioamnionitis in the 32-week or greater subgroup.

In a model adjusted for gestational age at the time of ruptured membranes, duration of latency, and use of betamethasone, the chorioamniotic group had significantly higher incidences of intracranial hemorrhage, pneumonia, hyperbilirubinemia, and a neonatal composite variable, including intracranial hemorrhage, pneumonia, and sepsis.

CHARLESTON, S.C. — The development of chorioamnionitis in patients with preterm premature rupture of membranes is associated with an increased risk for adverse neonatal outcomes, Natali Aziz, M.D., reported at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

In a retrospective cohort study of 1,153 patients who gave birth between 1980 and 2001 with a diagnosis of preterm premature rupture of membranes (PPROM) made at 24 to 34 weeks' gestation, 29% were diagnosed with chorioamnionitis before delivery. Univariate outcomes on a variety of measures—such as Apgar scores and incidence of respiratory distress syndrome, intracerebral hemorrhage, and pneumonia—were significantly poorer in neonates born to mothers with chorioamnionitis, compared with those born to mothers without chorioamnionitis, said Dr. Aziz of the University of California, San Francisco.

“Management in this setting is better examined prospectively in a randomized, controlled trial, yet given these data, when managing a patient with preterm premature rupture of membranes we must weigh the risks of prematurity against those of expectant management with the ongoing possibility of development of chorioamnionitis,” she said.

Differences were noted in the rates of chorioamnionitis based on gestational age at the time of rupture of membranes (rate of 46% at gestational age of 24–25 weeks vs. 18% at 32 weeks or greater) and duration of latency (higher rates in those with latency greater than 48 hours). Subgroup analyses to adjust for these factors were performed. Many clinical differences remained, but statistical significance was lost due to smaller sample sizes.

In the subgroup analysis based on gestational age at time of rupture of membranes (grouped in 2-week intervals), nonnecrotizing enterocolitis was more common among those with chorioamnionitis in the 24− to 25-week subgroup, intracranial hemorrhage was more common among those with chorioamnionitis in the 30− to 31-week subgroup, and pneumonia was more common among those with chorioamnionitis in the 32-week or greater subgroup.

In a model adjusted for gestational age at the time of ruptured membranes, duration of latency, and use of betamethasone, the chorioamniotic group had significantly higher incidences of intracranial hemorrhage, pneumonia, hyperbilirubinemia, and a neonatal composite variable, including intracranial hemorrhage, pneumonia, and sepsis.

CHARLESTON, S.C. — The development of chorioamnionitis in patients with preterm premature rupture of membranes is associated with an increased risk for adverse neonatal outcomes, Natali Aziz, M.D., reported at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

In a retrospective cohort study of 1,153 patients who gave birth between 1980 and 2001 with a diagnosis of preterm premature rupture of membranes (PPROM) made at 24 to 34 weeks' gestation, 29% were diagnosed with chorioamnionitis before delivery. Univariate outcomes on a variety of measures—such as Apgar scores and incidence of respiratory distress syndrome, intracerebral hemorrhage, and pneumonia—were significantly poorer in neonates born to mothers with chorioamnionitis, compared with those born to mothers without chorioamnionitis, said Dr. Aziz of the University of California, San Francisco.

“Management in this setting is better examined prospectively in a randomized, controlled trial, yet given these data, when managing a patient with preterm premature rupture of membranes we must weigh the risks of prematurity against those of expectant management with the ongoing possibility of development of chorioamnionitis,” she said.

Differences were noted in the rates of chorioamnionitis based on gestational age at the time of rupture of membranes (rate of 46% at gestational age of 24–25 weeks vs. 18% at 32 weeks or greater) and duration of latency (higher rates in those with latency greater than 48 hours). Subgroup analyses to adjust for these factors were performed. Many clinical differences remained, but statistical significance was lost due to smaller sample sizes.

In the subgroup analysis based on gestational age at time of rupture of membranes (grouped in 2-week intervals), nonnecrotizing enterocolitis was more common among those with chorioamnionitis in the 24− to 25-week subgroup, intracranial hemorrhage was more common among those with chorioamnionitis in the 30− to 31-week subgroup, and pneumonia was more common among those with chorioamnionitis in the 32-week or greater subgroup.

In a model adjusted for gestational age at the time of ruptured membranes, duration of latency, and use of betamethasone, the chorioamniotic group had significantly higher incidences of intracranial hemorrhage, pneumonia, hyperbilirubinemia, and a neonatal composite variable, including intracranial hemorrhage, pneumonia, and sepsis.

CHARLESTON, S.C. — Most clinicians counsel patients appropriately about the cause and prevention of external anogenital warts, but many—including some ob.gyns.—are unaware of the difference between oncogenic and wart-related human papillomavirus types, Zsakeba Henderson, M.D., reported in a poster at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

Of 4,305 clinicians who responded to a 2004 survey, 90% said they have diagnosed anogenital warts in patients. Of the ob.gyns. who responded, 96% have diagnosed anogenital warts in patients, 97% tell patients the warts are sexually transmitted, 97% tell patients that their sex partners can acquire the warts, 96% tell patients they may have been infected long ago, and 86% tell patients not much is known about the duration of human papillomavirus (HPV) infection, said Dr. Henderson of the Centers for Disease Control and Prevention, Atlanta.

Also, 86% of the ob.gyns. said they discuss ways to prevent HPV transmission, and 81% usually or always ask about sexual behaviors to assess risk.

As for recommended methods for preventing transmission, 90% recommend condoms, 79% recommend monogamy, 61% recommend avoiding contact with warts, and 43% recommend abstinence.

Of the respondents, 89% knew that HPV causes anogenital warts, but only 70% knew that HPV types associated with cancer differ from those associated with warts, Dr. Henderson said in an interview.

Although ob.gyns. are doing better than the overall survey population with regard to knowledge about oncogenic vs. wart-related HPV types (48% overall knew cancer- and wart-related types differ), 44% of ob.gyns. (38% overall), knew warts do not increase the risk of cancer at the wart site.

Of particular concern is the relationship between clinician knowledge of how HPV types differ and recommendations for Pap testing. A total of 87% of the ob.gyns. who don't know that oncogenic and wart-related HPV types differ and 78% of those who do know they differ recommend prompt Pap smears in patients presenting with warts. And 57% of those who don't know, and 47% of those who do know recommend more frequent Pap smears.

“It really didn't matter what their knowledge was—about half are recommending more frequent Pap smears in patients with warts, which is not in accordance with current clinical guidelines,” Dr. Henderson said.

Anecdotally speaking, some respondents recommend Pap smears because of concerns about increased risk for HPV exposure, but there is no evidence that prompt or more frequent Pap testing is warranted in patients with anogenital warts, she added.

Also of concern based on the survey responses is that while most ob.gyns. are counseling patients appropriately about the cause and prevention of anogenital warts, they also reported many barriers to counseling, including difficulty dealing with patients' emotional and relationship issues, inadequate reimbursement for patient counseling, difficulty motivating patients to adopt prevention measures, and lack of time for patient counseling. Such barriers were reported by more than half of the respondents.

The findings of this survey, which are still being analyzed, will be used to develop training materials to promote appropriate counseling methods, Dr. Henderson noted.

CHARLESTON, S.C. — Most clinicians counsel patients appropriately about the cause and prevention of external anogenital warts, but many—including some ob.gyns.—are unaware of the difference between oncogenic and wart-related human papillomavirus types, Zsakeba Henderson, M.D., reported in a poster at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

Of 4,305 clinicians who responded to a 2004 survey, 90% said they have diagnosed anogenital warts in patients. Of the ob.gyns. who responded, 96% have diagnosed anogenital warts in patients, 97% tell patients the warts are sexually transmitted, 97% tell patients that their sex partners can acquire the warts, 96% tell patients they may have been infected long ago, and 86% tell patients not much is known about the duration of human papillomavirus (HPV) infection, said Dr. Henderson of the Centers for Disease Control and Prevention, Atlanta.

Also, 86% of the ob.gyns. said they discuss ways to prevent HPV transmission, and 81% usually or always ask about sexual behaviors to assess risk.

As for recommended methods for preventing transmission, 90% recommend condoms, 79% recommend monogamy, 61% recommend avoiding contact with warts, and 43% recommend abstinence.

Of the respondents, 89% knew that HPV causes anogenital warts, but only 70% knew that HPV types associated with cancer differ from those associated with warts, Dr. Henderson said in an interview.

Although ob.gyns. are doing better than the overall survey population with regard to knowledge about oncogenic vs. wart-related HPV types (48% overall knew cancer- and wart-related types differ), 44% of ob.gyns. (38% overall), knew warts do not increase the risk of cancer at the wart site.

Of particular concern is the relationship between clinician knowledge of how HPV types differ and recommendations for Pap testing. A total of 87% of the ob.gyns. who don't know that oncogenic and wart-related HPV types differ and 78% of those who do know they differ recommend prompt Pap smears in patients presenting with warts. And 57% of those who don't know, and 47% of those who do know recommend more frequent Pap smears.

“It really didn't matter what their knowledge was—about half are recommending more frequent Pap smears in patients with warts, which is not in accordance with current clinical guidelines,” Dr. Henderson said.

Anecdotally speaking, some respondents recommend Pap smears because of concerns about increased risk for HPV exposure, but there is no evidence that prompt or more frequent Pap testing is warranted in patients with anogenital warts, she added.

Also of concern based on the survey responses is that while most ob.gyns. are counseling patients appropriately about the cause and prevention of anogenital warts, they also reported many barriers to counseling, including difficulty dealing with patients' emotional and relationship issues, inadequate reimbursement for patient counseling, difficulty motivating patients to adopt prevention measures, and lack of time for patient counseling. Such barriers were reported by more than half of the respondents.

The findings of this survey, which are still being analyzed, will be used to develop training materials to promote appropriate counseling methods, Dr. Henderson noted.

CHARLESTON, S.C. — Most clinicians counsel patients appropriately about the cause and prevention of external anogenital warts, but many—including some ob.gyns.—are unaware of the difference between oncogenic and wart-related human papillomavirus types, Zsakeba Henderson, M.D., reported in a poster at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

Of 4,305 clinicians who responded to a 2004 survey, 90% said they have diagnosed anogenital warts in patients. Of the ob.gyns. who responded, 96% have diagnosed anogenital warts in patients, 97% tell patients the warts are sexually transmitted, 97% tell patients that their sex partners can acquire the warts, 96% tell patients they may have been infected long ago, and 86% tell patients not much is known about the duration of human papillomavirus (HPV) infection, said Dr. Henderson of the Centers for Disease Control and Prevention, Atlanta.

Also, 86% of the ob.gyns. said they discuss ways to prevent HPV transmission, and 81% usually or always ask about sexual behaviors to assess risk.

As for recommended methods for preventing transmission, 90% recommend condoms, 79% recommend monogamy, 61% recommend avoiding contact with warts, and 43% recommend abstinence.

Of the respondents, 89% knew that HPV causes anogenital warts, but only 70% knew that HPV types associated with cancer differ from those associated with warts, Dr. Henderson said in an interview.

Although ob.gyns. are doing better than the overall survey population with regard to knowledge about oncogenic vs. wart-related HPV types (48% overall knew cancer- and wart-related types differ), 44% of ob.gyns. (38% overall), knew warts do not increase the risk of cancer at the wart site.

Of particular concern is the relationship between clinician knowledge of how HPV types differ and recommendations for Pap testing. A total of 87% of the ob.gyns. who don't know that oncogenic and wart-related HPV types differ and 78% of those who do know they differ recommend prompt Pap smears in patients presenting with warts. And 57% of those who don't know, and 47% of those who do know recommend more frequent Pap smears.

“It really didn't matter what their knowledge was—about half are recommending more frequent Pap smears in patients with warts, which is not in accordance with current clinical guidelines,” Dr. Henderson said.

Anecdotally speaking, some respondents recommend Pap smears because of concerns about increased risk for HPV exposure, but there is no evidence that prompt or more frequent Pap testing is warranted in patients with anogenital warts, she added.

Also of concern based on the survey responses is that while most ob.gyns. are counseling patients appropriately about the cause and prevention of anogenital warts, they also reported many barriers to counseling, including difficulty dealing with patients' emotional and relationship issues, inadequate reimbursement for patient counseling, difficulty motivating patients to adopt prevention measures, and lack of time for patient counseling. Such barriers were reported by more than half of the respondents.

The findings of this survey, which are still being analyzed, will be used to develop training materials to promote appropriate counseling methods, Dr. Henderson noted.