Sharon Worcester

Resistance to Fluoroquinolones

Fluoroquinolone resistance was an independent risk factor for death in a study of patients with nosocomial Escherichia coli and Klebsiella pneumoniae infections.

Sixteen (13%) of 123 patients with resistant infection in the retrospective cohort study died, compared with 4 (6%) of 70 patients with susceptible infection. After multivariate analysis, fluoroquinolone (FQ)-resistant infection remained independently and significantly associated with mortality (odds ratio 4.41), reported Ebbing Lautenbach, M.D., of the University of Pennsylvania, Philadelphia, and his colleagues. However, FQ-resistant patients were significantly less likely to be treated with an antimicrobial active against the infection in the first 24–48 hours after samples were obtained for culture. After adjusting for time to effective therapy, the association between FQ resistance and mortality lost significance (adjusted odds ratio 2.53), the investigators noted (Clin. Infect. Dis. 2005;41:923–9).

The findings underscore the need for early, appropriate antimicrobial therapy in patients with FQ-resistant infections, but also highlight the problem of such resistance and the need for ongoing efforts to halt its increasing prevalence, they concluded.

Emphysematous Pyelonephritis

Host and bacterial virulence factors each play a role in the pathogenesis of emphysematous pyelonephritis, a study suggests.

Forty-seven patients with the rare but deadly gas-forming infection of the kidney known as emphysematous pyelonephritis (EPN) were compared with 79 patients with non-EPN kidney disease in terms of virulence factors. Diabetes with poor glycemic control was the only host factor independently associated with EPN (odds ratio 4.9), but urinary tract obstruction with impaired renal circulation also was more prevalent in EPN patients (32% vs. 11%), reported Chin-Chung Tseng, M.D., and colleagues at the National Cheng Kung University, Tainan, Taiwan (Am. J. Kidney Dis. 2005;46:432–9).

Furthermore, in causative strains of Escherichia coli (the causative agent in 16 of 47 of the EPN cases, and in 60%–70% of cases in general), the papG II adhesin gene was identified significantly less often than in non-EPN E. coli strains (odds ratio 0.2), and the genetic determinant of uropathogenic-specific protein was identified more often in causative strains than in non-EPN E. coli strains, the investigators found.

Cartilage-Piercing Infections

An outbreak of severe infections following upper ear piercings has been linked to contaminated antiseptic solution.

Fifteen people became infected with Pseudomonas aeruginosa following upper ear piercing at a single body-art parlor. Nine of the patients required hospitalization and treatment with intravenous antibiotics and surgery, reported Caroline G. Fisher of the Monroe County Department of Public Health in Rochester, N.Y., and her colleagues.

A case-control study involving the 15 patients and 61 controls showed that compared with noncartilage piercings, cartilage piercing at the helix, combined with the use of an antiseptic solution provided by the parlor, was associated with a 1,000-fold increase in infection risk (Am. J. Prev. Med. 2005;29:204–9).

It was determined that the solution, which is not effective against Pseudomonas, was contaminated during mixing. The findings underscore the risks associated with cartilage piercing and the need for safe and appropriate procedures.

Chemotherapy-Related Infections

Levofloxacin prevented infections following chemotherapy for cancer in two recent studies, but concerns remain about emerging resistance.

In one randomized study of 760 patients with chemotherapy-induced neutropenia, Giampaolo Bucaneve, M.D., of Hospital Policlinico Monteluce, Perugia, Italy, and his colleagues found that levofloxacin reduced the risk of fever by 20%, lowered documented infections by 17%, and reduced bacteremias by up to 16% (N. Engl. J. Med. 2005;353:977–87).

In another randomized study of 1,565 chemotherapy patients, Michael Cullen, M.D., of the University of Birmingham (England) and colleagues found that levofloxacin reduced the incidence of fever, compared with placebo: 4% of treatment patients vs. 8% on placebo had at least one fever during the first chemotherapy course. Levofloxacin reduced infection, severe infection, and hospitalization for infection rates (N. Engl. J. Med. 2005;353:988–98).

In an editorial, Lindsey R. Baden, M.D., wrote that patients at greatest risk, the period of increased risk, and the likelihood of the emergence of resistant organisms need to be defined. Improvement in risk stratification will minimize unnecessary use of antimicrobials and preserve the benefits described in the two studies (N. Engl. J. Med. 2005;353:1052–4).

Resistance to Fluoroquinolones

Fluoroquinolone resistance was an independent risk factor for death in a study of patients with nosocomial Escherichia coli and Klebsiella pneumoniae infections.

Sixteen (13%) of 123 patients with resistant infection in the retrospective cohort study died, compared with 4 (6%) of 70 patients with susceptible infection. After multivariate analysis, fluoroquinolone (FQ)-resistant infection remained independently and significantly associated with mortality (odds ratio 4.41), reported Ebbing Lautenbach, M.D., of the University of Pennsylvania, Philadelphia, and his colleagues. However, FQ-resistant patients were significantly less likely to be treated with an antimicrobial active against the infection in the first 24–48 hours after samples were obtained for culture. After adjusting for time to effective therapy, the association between FQ resistance and mortality lost significance (adjusted odds ratio 2.53), the investigators noted (Clin. Infect. Dis. 2005;41:923–9).

The findings underscore the need for early, appropriate antimicrobial therapy in patients with FQ-resistant infections, but also highlight the problem of such resistance and the need for ongoing efforts to halt its increasing prevalence, they concluded.

Emphysematous Pyelonephritis

Host and bacterial virulence factors each play a role in the pathogenesis of emphysematous pyelonephritis, a study suggests.

Forty-seven patients with the rare but deadly gas-forming infection of the kidney known as emphysematous pyelonephritis (EPN) were compared with 79 patients with non-EPN kidney disease in terms of virulence factors. Diabetes with poor glycemic control was the only host factor independently associated with EPN (odds ratio 4.9), but urinary tract obstruction with impaired renal circulation also was more prevalent in EPN patients (32% vs. 11%), reported Chin-Chung Tseng, M.D., and colleagues at the National Cheng Kung University, Tainan, Taiwan (Am. J. Kidney Dis. 2005;46:432–9).

Furthermore, in causative strains of Escherichia coli (the causative agent in 16 of 47 of the EPN cases, and in 60%–70% of cases in general), the papG II adhesin gene was identified significantly less often than in non-EPN E. coli strains (odds ratio 0.2), and the genetic determinant of uropathogenic-specific protein was identified more often in causative strains than in non-EPN E. coli strains, the investigators found.

Cartilage-Piercing Infections

An outbreak of severe infections following upper ear piercings has been linked to contaminated antiseptic solution.

Fifteen people became infected with Pseudomonas aeruginosa following upper ear piercing at a single body-art parlor. Nine of the patients required hospitalization and treatment with intravenous antibiotics and surgery, reported Caroline G. Fisher of the Monroe County Department of Public Health in Rochester, N.Y., and her colleagues.

A case-control study involving the 15 patients and 61 controls showed that compared with noncartilage piercings, cartilage piercing at the helix, combined with the use of an antiseptic solution provided by the parlor, was associated with a 1,000-fold increase in infection risk (Am. J. Prev. Med. 2005;29:204–9).

It was determined that the solution, which is not effective against Pseudomonas, was contaminated during mixing. The findings underscore the risks associated with cartilage piercing and the need for safe and appropriate procedures.

Chemotherapy-Related Infections

Levofloxacin prevented infections following chemotherapy for cancer in two recent studies, but concerns remain about emerging resistance.

In one randomized study of 760 patients with chemotherapy-induced neutropenia, Giampaolo Bucaneve, M.D., of Hospital Policlinico Monteluce, Perugia, Italy, and his colleagues found that levofloxacin reduced the risk of fever by 20%, lowered documented infections by 17%, and reduced bacteremias by up to 16% (N. Engl. J. Med. 2005;353:977–87).

In another randomized study of 1,565 chemotherapy patients, Michael Cullen, M.D., of the University of Birmingham (England) and colleagues found that levofloxacin reduced the incidence of fever, compared with placebo: 4% of treatment patients vs. 8% on placebo had at least one fever during the first chemotherapy course. Levofloxacin reduced infection, severe infection, and hospitalization for infection rates (N. Engl. J. Med. 2005;353:988–98).

In an editorial, Lindsey R. Baden, M.D., wrote that patients at greatest risk, the period of increased risk, and the likelihood of the emergence of resistant organisms need to be defined. Improvement in risk stratification will minimize unnecessary use of antimicrobials and preserve the benefits described in the two studies (N. Engl. J. Med. 2005;353:1052–4).

Resistance to Fluoroquinolones

Fluoroquinolone resistance was an independent risk factor for death in a study of patients with nosocomial Escherichia coli and Klebsiella pneumoniae infections.

Sixteen (13%) of 123 patients with resistant infection in the retrospective cohort study died, compared with 4 (6%) of 70 patients with susceptible infection. After multivariate analysis, fluoroquinolone (FQ)-resistant infection remained independently and significantly associated with mortality (odds ratio 4.41), reported Ebbing Lautenbach, M.D., of the University of Pennsylvania, Philadelphia, and his colleagues. However, FQ-resistant patients were significantly less likely to be treated with an antimicrobial active against the infection in the first 24–48 hours after samples were obtained for culture. After adjusting for time to effective therapy, the association between FQ resistance and mortality lost significance (adjusted odds ratio 2.53), the investigators noted (Clin. Infect. Dis. 2005;41:923–9).

The findings underscore the need for early, appropriate antimicrobial therapy in patients with FQ-resistant infections, but also highlight the problem of such resistance and the need for ongoing efforts to halt its increasing prevalence, they concluded.

Emphysematous Pyelonephritis

Host and bacterial virulence factors each play a role in the pathogenesis of emphysematous pyelonephritis, a study suggests.

Forty-seven patients with the rare but deadly gas-forming infection of the kidney known as emphysematous pyelonephritis (EPN) were compared with 79 patients with non-EPN kidney disease in terms of virulence factors. Diabetes with poor glycemic control was the only host factor independently associated with EPN (odds ratio 4.9), but urinary tract obstruction with impaired renal circulation also was more prevalent in EPN patients (32% vs. 11%), reported Chin-Chung Tseng, M.D., and colleagues at the National Cheng Kung University, Tainan, Taiwan (Am. J. Kidney Dis. 2005;46:432–9).

Furthermore, in causative strains of Escherichia coli (the causative agent in 16 of 47 of the EPN cases, and in 60%–70% of cases in general), the papG II adhesin gene was identified significantly less often than in non-EPN E. coli strains (odds ratio 0.2), and the genetic determinant of uropathogenic-specific protein was identified more often in causative strains than in non-EPN E. coli strains, the investigators found.

Cartilage-Piercing Infections

An outbreak of severe infections following upper ear piercings has been linked to contaminated antiseptic solution.

Fifteen people became infected with Pseudomonas aeruginosa following upper ear piercing at a single body-art parlor. Nine of the patients required hospitalization and treatment with intravenous antibiotics and surgery, reported Caroline G. Fisher of the Monroe County Department of Public Health in Rochester, N.Y., and her colleagues.

A case-control study involving the 15 patients and 61 controls showed that compared with noncartilage piercings, cartilage piercing at the helix, combined with the use of an antiseptic solution provided by the parlor, was associated with a 1,000-fold increase in infection risk (Am. J. Prev. Med. 2005;29:204–9).

It was determined that the solution, which is not effective against Pseudomonas, was contaminated during mixing. The findings underscore the risks associated with cartilage piercing and the need for safe and appropriate procedures.

Chemotherapy-Related Infections

Levofloxacin prevented infections following chemotherapy for cancer in two recent studies, but concerns remain about emerging resistance.

In one randomized study of 760 patients with chemotherapy-induced neutropenia, Giampaolo Bucaneve, M.D., of Hospital Policlinico Monteluce, Perugia, Italy, and his colleagues found that levofloxacin reduced the risk of fever by 20%, lowered documented infections by 17%, and reduced bacteremias by up to 16% (N. Engl. J. Med. 2005;353:977–87).

In another randomized study of 1,565 chemotherapy patients, Michael Cullen, M.D., of the University of Birmingham (England) and colleagues found that levofloxacin reduced the incidence of fever, compared with placebo: 4% of treatment patients vs. 8% on placebo had at least one fever during the first chemotherapy course. Levofloxacin reduced infection, severe infection, and hospitalization for infection rates (N. Engl. J. Med. 2005;353:988–98).

In an editorial, Lindsey R. Baden, M.D., wrote that patients at greatest risk, the period of increased risk, and the likelihood of the emergence of resistant organisms need to be defined. Improvement in risk stratification will minimize unnecessary use of antimicrobials and preserve the benefits described in the two studies (N. Engl. J. Med. 2005;353:1052–4).

CHARLESTON, S.C. — Smoking has been linked with the occurrence of bacterial vaginosis, but a recent study further elucidating its effects on microvaginal flora suggests that smoking is particularly associated with heavy growth of Gardnerella vaginalis and Mycoplasma hominis.

“I think at this point, investigations are needed to determine if smoking should be considered a modifiable risk factor for bacterial vaginosis,” Harold C. Wiesenfeld, M.D., said at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

In the prospective cross-sectional study of 749 nonpregnant women, 56% were smokers, and most of them were daily smokers. Bacterial vaginosis was identified in 66% of the overall study population, compared with 69% of the smokers.

Heavy colonization with G. vaginalis was present in 72% of smokers vs. 64% of nonsmokers, and heavy colonization with M. hominis was present in 43% of smokers vs. 32% of nonsmokers.

Colonization with H₂O₂-producing lactobacilli was present in 33% of smokers vs. 41% of nonsmokers, said Dr. Wiesenfeld of the department of ob.gyn. and reproductive sciences at the University of Pittsburgh.

The women studied were recruited from an STD clinic, family planning clinics, and ambulatory gynecology clinics. All underwent a standardized interview and physical examination that included a Gram's stain, Trichomonas vaginalis culture, and semiquantitative cultures of vaginal fluid for aerobic and anaerobic organisms.

Additionally, cervical samples were cultured for Neisseria gonorrhoeae and tested by polymerase chain reaction for Chlamydia trachomatis.

Smoking in this study was not associated with gonorrhea, C. trachomatis, or T. vaginalis infection.

CHARLESTON, S.C. — Smoking has been linked with the occurrence of bacterial vaginosis, but a recent study further elucidating its effects on microvaginal flora suggests that smoking is particularly associated with heavy growth of Gardnerella vaginalis and Mycoplasma hominis.

“I think at this point, investigations are needed to determine if smoking should be considered a modifiable risk factor for bacterial vaginosis,” Harold C. Wiesenfeld, M.D., said at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

In the prospective cross-sectional study of 749 nonpregnant women, 56% were smokers, and most of them were daily smokers. Bacterial vaginosis was identified in 66% of the overall study population, compared with 69% of the smokers.

Heavy colonization with G. vaginalis was present in 72% of smokers vs. 64% of nonsmokers, and heavy colonization with M. hominis was present in 43% of smokers vs. 32% of nonsmokers.

Colonization with H₂O₂-producing lactobacilli was present in 33% of smokers vs. 41% of nonsmokers, said Dr. Wiesenfeld of the department of ob.gyn. and reproductive sciences at the University of Pittsburgh.

The women studied were recruited from an STD clinic, family planning clinics, and ambulatory gynecology clinics. All underwent a standardized interview and physical examination that included a Gram's stain, Trichomonas vaginalis culture, and semiquantitative cultures of vaginal fluid for aerobic and anaerobic organisms.

Additionally, cervical samples were cultured for Neisseria gonorrhoeae and tested by polymerase chain reaction for Chlamydia trachomatis.

Smoking in this study was not associated with gonorrhea, C. trachomatis, or T. vaginalis infection.

CHARLESTON, S.C. — Smoking has been linked with the occurrence of bacterial vaginosis, but a recent study further elucidating its effects on microvaginal flora suggests that smoking is particularly associated with heavy growth of Gardnerella vaginalis and Mycoplasma hominis.

“I think at this point, investigations are needed to determine if smoking should be considered a modifiable risk factor for bacterial vaginosis,” Harold C. Wiesenfeld, M.D., said at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

In the prospective cross-sectional study of 749 nonpregnant women, 56% were smokers, and most of them were daily smokers. Bacterial vaginosis was identified in 66% of the overall study population, compared with 69% of the smokers.

Heavy colonization with G. vaginalis was present in 72% of smokers vs. 64% of nonsmokers, and heavy colonization with M. hominis was present in 43% of smokers vs. 32% of nonsmokers.

Colonization with H₂O₂-producing lactobacilli was present in 33% of smokers vs. 41% of nonsmokers, said Dr. Wiesenfeld of the department of ob.gyn. and reproductive sciences at the University of Pittsburgh.

The women studied were recruited from an STD clinic, family planning clinics, and ambulatory gynecology clinics. All underwent a standardized interview and physical examination that included a Gram's stain, Trichomonas vaginalis culture, and semiquantitative cultures of vaginal fluid for aerobic and anaerobic organisms.

Additionally, cervical samples were cultured for Neisseria gonorrhoeae and tested by polymerase chain reaction for Chlamydia trachomatis.

Smoking in this study was not associated with gonorrhea, C. trachomatis, or T. vaginalis infection.

CHARLESTON, S.C. — Certain vaginal isolates affect the quantity of HIV RNA in cervicovaginal lavage, a study suggests.

Hydrogen peroxide-producing lactobacilli, for example, were associated with a significant decrease in cervicovaginal lavage (CVL) HIV RNA concentrations, and Trichomonas vaginalis, Prevotella bivia, and Mycoplasma hominis. Other anaerobes were associated with increases in CVL HIV RNA concentrations, Jane Hitti, M.D., reported at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

Factors affecting the HIV RNA concentrations are important, because genital viral load is an important determinant of sexual and perinatal HIV transmission, she noted.

For the study, 38 HIV-positive women completed 163 study visits. Vaginal cultures, CVL, and plasma were collected at each visit for HIV RNA quantitation. Of 163 CVL samples, 95 had detectable HIV RNA, and the levels correlated significantly with plasma HIV RNA levels, said Dr. Hitti of the University of Washington, Seattle.

After adjustment for log plasma HIV RNA, the log difference in CVL HIV RNA was significant for H₂O₂ lactobacillus and T. vaginalis. Increased CVL HIV RNA concentrations were associated, although not significantly, with M. hominis, P. bivia, black gram negative rods, Candida albicans, and bacterial vaginosis or indeterminate flora.

Also, CVL HIV RNA concentrations were increased with higher vaginal concentrations of IL-8 in this study.

Several vaginal isolates appear to directly influence CVL viral load, and the effects appear to be independent of plasma viral load, she concluded, noting that an antibiotic treatment trial is underway to determine whether treatment for bacterial vaginosis and associated infections will decrease genital viral load.

“A very logical next step would be looking at ways to augment endogenous lactobacilli and looking at what effects that has,” she said.

The prevalence of H₂0₂-producing lactobacilli is lower than what has been reported among HIV-negative women, even in the presence of bacterial vaginosis, she explained.

CHARLESTON, S.C. — Certain vaginal isolates affect the quantity of HIV RNA in cervicovaginal lavage, a study suggests.

Hydrogen peroxide-producing lactobacilli, for example, were associated with a significant decrease in cervicovaginal lavage (CVL) HIV RNA concentrations, and Trichomonas vaginalis, Prevotella bivia, and Mycoplasma hominis. Other anaerobes were associated with increases in CVL HIV RNA concentrations, Jane Hitti, M.D., reported at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

Factors affecting the HIV RNA concentrations are important, because genital viral load is an important determinant of sexual and perinatal HIV transmission, she noted.

For the study, 38 HIV-positive women completed 163 study visits. Vaginal cultures, CVL, and plasma were collected at each visit for HIV RNA quantitation. Of 163 CVL samples, 95 had detectable HIV RNA, and the levels correlated significantly with plasma HIV RNA levels, said Dr. Hitti of the University of Washington, Seattle.

After adjustment for log plasma HIV RNA, the log difference in CVL HIV RNA was significant for H₂O₂ lactobacillus and T. vaginalis. Increased CVL HIV RNA concentrations were associated, although not significantly, with M. hominis, P. bivia, black gram negative rods, Candida albicans, and bacterial vaginosis or indeterminate flora.

Also, CVL HIV RNA concentrations were increased with higher vaginal concentrations of IL-8 in this study.

Several vaginal isolates appear to directly influence CVL viral load, and the effects appear to be independent of plasma viral load, she concluded, noting that an antibiotic treatment trial is underway to determine whether treatment for bacterial vaginosis and associated infections will decrease genital viral load.

“A very logical next step would be looking at ways to augment endogenous lactobacilli and looking at what effects that has,” she said.

The prevalence of H₂0₂-producing lactobacilli is lower than what has been reported among HIV-negative women, even in the presence of bacterial vaginosis, she explained.

CHARLESTON, S.C. — Certain vaginal isolates affect the quantity of HIV RNA in cervicovaginal lavage, a study suggests.

Hydrogen peroxide-producing lactobacilli, for example, were associated with a significant decrease in cervicovaginal lavage (CVL) HIV RNA concentrations, and Trichomonas vaginalis, Prevotella bivia, and Mycoplasma hominis. Other anaerobes were associated with increases in CVL HIV RNA concentrations, Jane Hitti, M.D., reported at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

Factors affecting the HIV RNA concentrations are important, because genital viral load is an important determinant of sexual and perinatal HIV transmission, she noted.

For the study, 38 HIV-positive women completed 163 study visits. Vaginal cultures, CVL, and plasma were collected at each visit for HIV RNA quantitation. Of 163 CVL samples, 95 had detectable HIV RNA, and the levels correlated significantly with plasma HIV RNA levels, said Dr. Hitti of the University of Washington, Seattle.

After adjustment for log plasma HIV RNA, the log difference in CVL HIV RNA was significant for H₂O₂ lactobacillus and T. vaginalis. Increased CVL HIV RNA concentrations were associated, although not significantly, with M. hominis, P. bivia, black gram negative rods, Candida albicans, and bacterial vaginosis or indeterminate flora.

Also, CVL HIV RNA concentrations were increased with higher vaginal concentrations of IL-8 in this study.

Several vaginal isolates appear to directly influence CVL viral load, and the effects appear to be independent of plasma viral load, she concluded, noting that an antibiotic treatment trial is underway to determine whether treatment for bacterial vaginosis and associated infections will decrease genital viral load.

“A very logical next step would be looking at ways to augment endogenous lactobacilli and looking at what effects that has,” she said.

The prevalence of H₂0₂-producing lactobacilli is lower than what has been reported among HIV-negative women, even in the presence of bacterial vaginosis, she explained.

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 up to 12 months of daily valacyclovir use, 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 three 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 entire 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, the investigators reported.

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 up to 12 months of daily valacyclovir use, 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 three 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 entire 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, the investigators reported.

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 up to 12 months of daily valacyclovir use, 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 three 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 entire 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, the investigators reported.

CHARLESTON, S.C. — Chlamydia trachomatis may play more of a role in abnormal uterine bleeding than previously recognized, Miklos Toth, M.D., reported at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

Although many women with abnormal uterine bleeding have endometritis that is associated with silent pelvic inflammatory disease (PID), and C. trachomatis is the most important pathogen in the etiology of silent PID, the histologic features of chlamydia endometritis and the relationship between C. trachomatis and abnormal uterine bleeding have not been well described, said Dr. Toth of Lenox Hill Hospital, New York.

To better define these factors, he studied 92 archived endometrial biopsy specimens from premenopausal women with abnormal uterine bleeding and/or endometritis. Of these, 48% tested positive for C. trachomatis by species-specific monoclonal antibody against the major outer membrane protein (MOMP).

The specimens also were tested for histopathology associated with inflammation, and associations were noted between C. trachomatis (defined as a positive MOMP-specific stain) and higher counts of plasma cells, macrophages, and lymphocytic foci, Dr. Toth said.

The strongest predictor of C. trachomatis, as indicated by the receiver operating characteristic curve (area under the curve = 0.88), was macrophage count. The mean number of macrophages in the C. trachomatis-positive specimens was 619, which was significantly greater than the macrophage count of 11 in the negative specimens.

The currently accepted histologic definition of silent PID (five or fewer polymorphonuclear leukocytes and one or fewer plasma cells per 40×) was not indicative of C. trachomatis in this study.

These findings suggest that C. trachomatis is underestimated in women with abnormal uterine bleeding and that currently used histologic criteria for silent PID will miss many cases of C. trachomatis infection. Women with missed infection who become pregnant may have increased risk for miscarriage, Dr. Toth said.

The findings also suggest that macrophage counts are a very promising tool for detecting C. trachomatis in the endometrium, he noted.

CHARLESTON, S.C. — Chlamydia trachomatis may play more of a role in abnormal uterine bleeding than previously recognized, Miklos Toth, M.D., reported at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

Although many women with abnormal uterine bleeding have endometritis that is associated with silent pelvic inflammatory disease (PID), and C. trachomatis is the most important pathogen in the etiology of silent PID, the histologic features of chlamydia endometritis and the relationship between C. trachomatis and abnormal uterine bleeding have not been well described, said Dr. Toth of Lenox Hill Hospital, New York.

To better define these factors, he studied 92 archived endometrial biopsy specimens from premenopausal women with abnormal uterine bleeding and/or endometritis. Of these, 48% tested positive for C. trachomatis by species-specific monoclonal antibody against the major outer membrane protein (MOMP).

The specimens also were tested for histopathology associated with inflammation, and associations were noted between C. trachomatis (defined as a positive MOMP-specific stain) and higher counts of plasma cells, macrophages, and lymphocytic foci, Dr. Toth said.

The strongest predictor of C. trachomatis, as indicated by the receiver operating characteristic curve (area under the curve = 0.88), was macrophage count. The mean number of macrophages in the C. trachomatis-positive specimens was 619, which was significantly greater than the macrophage count of 11 in the negative specimens.

The currently accepted histologic definition of silent PID (five or fewer polymorphonuclear leukocytes and one or fewer plasma cells per 40×) was not indicative of C. trachomatis in this study.

These findings suggest that C. trachomatis is underestimated in women with abnormal uterine bleeding and that currently used histologic criteria for silent PID will miss many cases of C. trachomatis infection. Women with missed infection who become pregnant may have increased risk for miscarriage, Dr. Toth said.

The findings also suggest that macrophage counts are a very promising tool for detecting C. trachomatis in the endometrium, he noted.

CHARLESTON, S.C. — Chlamydia trachomatis may play more of a role in abnormal uterine bleeding than previously recognized, Miklos Toth, M.D., reported at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

Although many women with abnormal uterine bleeding have endometritis that is associated with silent pelvic inflammatory disease (PID), and C. trachomatis is the most important pathogen in the etiology of silent PID, the histologic features of chlamydia endometritis and the relationship between C. trachomatis and abnormal uterine bleeding have not been well described, said Dr. Toth of Lenox Hill Hospital, New York.

To better define these factors, he studied 92 archived endometrial biopsy specimens from premenopausal women with abnormal uterine bleeding and/or endometritis. Of these, 48% tested positive for C. trachomatis by species-specific monoclonal antibody against the major outer membrane protein (MOMP).

The specimens also were tested for histopathology associated with inflammation, and associations were noted between C. trachomatis (defined as a positive MOMP-specific stain) and higher counts of plasma cells, macrophages, and lymphocytic foci, Dr. Toth said.

The strongest predictor of C. trachomatis, as indicated by the receiver operating characteristic curve (area under the curve = 0.88), was macrophage count. The mean number of macrophages in the C. trachomatis-positive specimens was 619, which was significantly greater than the macrophage count of 11 in the negative specimens.

The currently accepted histologic definition of silent PID (five or fewer polymorphonuclear leukocytes and one or fewer plasma cells per 40×) was not indicative of C. trachomatis in this study.

These findings suggest that C. trachomatis is underestimated in women with abnormal uterine bleeding and that currently used histologic criteria for silent PID will miss many cases of C. trachomatis infection. Women with missed infection who become pregnant may have increased risk for miscarriage, Dr. Toth said.

The findings also suggest that macrophage counts are a very promising tool for detecting C. trachomatis in the endometrium, he noted.

CHARLESTON, S.C. — HIV-infected women were at no greater risk for postpartum depression than were their HIV-negative counterparts in a recent study, Nyota A. Peace, M.D., reported at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

The retrospective case-control study included 26 HIV-infected pregnant women. There were also 52 uninfected controls who were divided into two groups—those with a high-risk pregnancy and those with a low-risk pregnancy.

The case patients and controls were matched for age, race, and study period, and did not differ in regard to education levels, substance abuse, and history of depression, according to Dr. Peace of New Jersey Medical School, Newark.

High-risk control patients had the highest mean depression scores (8 out of a possible 30 on the Edinburgh Postnatal Depression Scale), but the scores did not differ significantly between these patients, the HIV patients (mean score of 5), or the low-risk control women (mean score of 5).

Compared with the women with low depression scores (under 11), those with high depression scores (greater than 11) did not differ in regard to the presence of typical risk factors for postpartum depression, such as young age, pregnancy-induced anxiety, life stressors, and lack of social support.

Although a high prevalence of depression in the HIV-positive population has been reported, data on the association between HIV and postpartum depression are limited.

The findings suggest that high-risk conditions other than HIV infection are linked with higher depression scores, and that factors typically associated with higher risk for postpartum depression are no more prevalent in patients with high depression scores than in those with low depression scores, Dr. Peace said at the meeting.

CHARLESTON, S.C. — HIV-infected women were at no greater risk for postpartum depression than were their HIV-negative counterparts in a recent study, Nyota A. Peace, M.D., reported at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

The retrospective case-control study included 26 HIV-infected pregnant women. There were also 52 uninfected controls who were divided into two groups—those with a high-risk pregnancy and those with a low-risk pregnancy.

The case patients and controls were matched for age, race, and study period, and did not differ in regard to education levels, substance abuse, and history of depression, according to Dr. Peace of New Jersey Medical School, Newark.

High-risk control patients had the highest mean depression scores (8 out of a possible 30 on the Edinburgh Postnatal Depression Scale), but the scores did not differ significantly between these patients, the HIV patients (mean score of 5), or the low-risk control women (mean score of 5).

Compared with the women with low depression scores (under 11), those with high depression scores (greater than 11) did not differ in regard to the presence of typical risk factors for postpartum depression, such as young age, pregnancy-induced anxiety, life stressors, and lack of social support.

Although a high prevalence of depression in the HIV-positive population has been reported, data on the association between HIV and postpartum depression are limited.

The findings suggest that high-risk conditions other than HIV infection are linked with higher depression scores, and that factors typically associated with higher risk for postpartum depression are no more prevalent in patients with high depression scores than in those with low depression scores, Dr. Peace said at the meeting.

CHARLESTON, S.C. — HIV-infected women were at no greater risk for postpartum depression than were their HIV-negative counterparts in a recent study, Nyota A. Peace, M.D., reported at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

The retrospective case-control study included 26 HIV-infected pregnant women. There were also 52 uninfected controls who were divided into two groups—those with a high-risk pregnancy and those with a low-risk pregnancy.

The case patients and controls were matched for age, race, and study period, and did not differ in regard to education levels, substance abuse, and history of depression, according to Dr. Peace of New Jersey Medical School, Newark.

High-risk control patients had the highest mean depression scores (8 out of a possible 30 on the Edinburgh Postnatal Depression Scale), but the scores did not differ significantly between these patients, the HIV patients (mean score of 5), or the low-risk control women (mean score of 5).

Compared with the women with low depression scores (under 11), those with high depression scores (greater than 11) did not differ in regard to the presence of typical risk factors for postpartum depression, such as young age, pregnancy-induced anxiety, life stressors, and lack of social support.

Although a high prevalence of depression in the HIV-positive population has been reported, data on the association between HIV and postpartum depression are limited.

The findings suggest that high-risk conditions other than HIV infection are linked with higher depression scores, and that factors typically associated with higher risk for postpartum depression are no more prevalent in patients with high depression scores than in those with low depression scores, Dr. Peace said at the meeting.

CHARLESTON, S.C. — Asymptomatic trichomoniasis during pregnancy appears to elicit a maternal inflammatory response, and should not be ignored, Brenna L. Anderson, M.D., said during the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

In a nested case-control study of 199 serum samples from women enrolled in the Vaginal Infections and Prematurity Study between 23 and 26 weeks' gestation and followed until delivery, median concentrations of granulocyte-macrophage colony-stimulating factor (GM-CSF) were significantly higher in samples from women with asymptomatic trichomoniasis than in those without the infection, indicating a systemic inflammatory response.

Also, those with trichomoniasis were significantly more likely to have a GM-CSF concentration in the highest quartile.

The association between infection and GM-CSF concentrations persisted even after the investigators controlled for center, tobacco use, and bacterial vaginosis, said Dr. Anderson of the University of Pittsburgh.

She noted that both the case and control samples were matched for race and sexually transmitted disease coinfection.

The two groups did not differ in regard to maternal age, gestational age at delivery, and rate of chlamydia or gonorrhea, she reported.

The inflammatory response appears to be exacerbated by coinfection with other sexually transmitted infections. There was a significant test for trend in those coinfected with gonorrhea or chlamydia, compared with those infected with only trichomoniasis and those with no sexually transmitted infection, she said.

In addition to GM-CSF, Dr. Anderson compared concentrations of five other cytokines, interleukin-β (IL-β, IL-6, IL-8, macrophage inflammatory protein-1α, and regulated on activation, normal T-cell expressed and secreted, in the serum samples.

The concentrations of these cytokines were uniformly unchanged between the groups, Dr. Anderson said during the meeting.

The cytokines IL-2, IL-4, IL-10, interferon-γ, and IL-12p40 were not measured, because a pilot analysis of 40 serum samples showed they did not have reliably detectable concentrations.

The local host response to a number of sexually transmitted infections has been well studied, providing evidence of a local host inflammatory response to organisms including Trichomonas vaginalis, Neisseria gonorrhoeae, and Chlamydia trachomatis.

In addition, there is a long-established association between lower genital tract infection and preterm birth and premature rupture of membranes. Furthermore, inflammatory mediators of local host response have been found in cervicovaginal fluid.

But the current study is one of few that attempt to characterize systemic inflammatory response to such infections, Dr. Anderson said.

Although one large multicenter trial showed a link between preterm birth and treatment of trichomoniasis in pregnancy, the study had several limitations, and failed to explain the mechanism for preterm birth in treated patients. Therefore, the option of not treating patients with asymptomatic trichomoniasis remains unattractive due to medical and public health concerns, Dr. Anderson said.

“We believe that GM-CSF represents a biologically plausible link between a local infection and a systemic response,” Dr. Anderson said at the meeting, explaining that serum GM-CSF has been shown to be elevated in other systemic response syndromes, and has been shown to be an important mediator of local infection in animal models of trichomoniasis.

The cytokine may be an important growth factor in placental implantation, she added.

“We therefore conclude that trichomoniasis in pregnancy should not be regarded as a benign condition,” Dr. Anderson said.

Further study to “more fully characterize the inflammatory response” to trichomoniasis and other sexually transmitted infections in pregnancy will be planned, Dr. Anderson noted at the meeting.

CHARLESTON, S.C. — Asymptomatic trichomoniasis during pregnancy appears to elicit a maternal inflammatory response, and should not be ignored, Brenna L. Anderson, M.D., said during the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

In a nested case-control study of 199 serum samples from women enrolled in the Vaginal Infections and Prematurity Study between 23 and 26 weeks' gestation and followed until delivery, median concentrations of granulocyte-macrophage colony-stimulating factor (GM-CSF) were significantly higher in samples from women with asymptomatic trichomoniasis than in those without the infection, indicating a systemic inflammatory response.

Also, those with trichomoniasis were significantly more likely to have a GM-CSF concentration in the highest quartile.

The association between infection and GM-CSF concentrations persisted even after the investigators controlled for center, tobacco use, and bacterial vaginosis, said Dr. Anderson of the University of Pittsburgh.

She noted that both the case and control samples were matched for race and sexually transmitted disease coinfection.

The two groups did not differ in regard to maternal age, gestational age at delivery, and rate of chlamydia or gonorrhea, she reported.

The inflammatory response appears to be exacerbated by coinfection with other sexually transmitted infections. There was a significant test for trend in those coinfected with gonorrhea or chlamydia, compared with those infected with only trichomoniasis and those with no sexually transmitted infection, she said.

In addition to GM-CSF, Dr. Anderson compared concentrations of five other cytokines, interleukin-β (IL-β, IL-6, IL-8, macrophage inflammatory protein-1α, and regulated on activation, normal T-cell expressed and secreted, in the serum samples.

The concentrations of these cytokines were uniformly unchanged between the groups, Dr. Anderson said during the meeting.

The cytokines IL-2, IL-4, IL-10, interferon-γ, and IL-12p40 were not measured, because a pilot analysis of 40 serum samples showed they did not have reliably detectable concentrations.

The local host response to a number of sexually transmitted infections has been well studied, providing evidence of a local host inflammatory response to organisms including Trichomonas vaginalis, Neisseria gonorrhoeae, and Chlamydia trachomatis.

In addition, there is a long-established association between lower genital tract infection and preterm birth and premature rupture of membranes. Furthermore, inflammatory mediators of local host response have been found in cervicovaginal fluid.

But the current study is one of few that attempt to characterize systemic inflammatory response to such infections, Dr. Anderson said.

Although one large multicenter trial showed a link between preterm birth and treatment of trichomoniasis in pregnancy, the study had several limitations, and failed to explain the mechanism for preterm birth in treated patients. Therefore, the option of not treating patients with asymptomatic trichomoniasis remains unattractive due to medical and public health concerns, Dr. Anderson said.

“We believe that GM-CSF represents a biologically plausible link between a local infection and a systemic response,” Dr. Anderson said at the meeting, explaining that serum GM-CSF has been shown to be elevated in other systemic response syndromes, and has been shown to be an important mediator of local infection in animal models of trichomoniasis.

The cytokine may be an important growth factor in placental implantation, she added.

“We therefore conclude that trichomoniasis in pregnancy should not be regarded as a benign condition,” Dr. Anderson said.

Further study to “more fully characterize the inflammatory response” to trichomoniasis and other sexually transmitted infections in pregnancy will be planned, Dr. Anderson noted at the meeting.

CHARLESTON, S.C. — Asymptomatic trichomoniasis during pregnancy appears to elicit a maternal inflammatory response, and should not be ignored, Brenna L. Anderson, M.D., said during the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

In a nested case-control study of 199 serum samples from women enrolled in the Vaginal Infections and Prematurity Study between 23 and 26 weeks' gestation and followed until delivery, median concentrations of granulocyte-macrophage colony-stimulating factor (GM-CSF) were significantly higher in samples from women with asymptomatic trichomoniasis than in those without the infection, indicating a systemic inflammatory response.

Also, those with trichomoniasis were significantly more likely to have a GM-CSF concentration in the highest quartile.

The association between infection and GM-CSF concentrations persisted even after the investigators controlled for center, tobacco use, and bacterial vaginosis, said Dr. Anderson of the University of Pittsburgh.

She noted that both the case and control samples were matched for race and sexually transmitted disease coinfection.

The two groups did not differ in regard to maternal age, gestational age at delivery, and rate of chlamydia or gonorrhea, she reported.

The inflammatory response appears to be exacerbated by coinfection with other sexually transmitted infections. There was a significant test for trend in those coinfected with gonorrhea or chlamydia, compared with those infected with only trichomoniasis and those with no sexually transmitted infection, she said.

In addition to GM-CSF, Dr. Anderson compared concentrations of five other cytokines, interleukin-β (IL-β, IL-6, IL-8, macrophage inflammatory protein-1α, and regulated on activation, normal T-cell expressed and secreted, in the serum samples.

The concentrations of these cytokines were uniformly unchanged between the groups, Dr. Anderson said during the meeting.

The cytokines IL-2, IL-4, IL-10, interferon-γ, and IL-12p40 were not measured, because a pilot analysis of 40 serum samples showed they did not have reliably detectable concentrations.

The local host response to a number of sexually transmitted infections has been well studied, providing evidence of a local host inflammatory response to organisms including Trichomonas vaginalis, Neisseria gonorrhoeae, and Chlamydia trachomatis.

In addition, there is a long-established association between lower genital tract infection and preterm birth and premature rupture of membranes. Furthermore, inflammatory mediators of local host response have been found in cervicovaginal fluid.

But the current study is one of few that attempt to characterize systemic inflammatory response to such infections, Dr. Anderson said.

Although one large multicenter trial showed a link between preterm birth and treatment of trichomoniasis in pregnancy, the study had several limitations, and failed to explain the mechanism for preterm birth in treated patients. Therefore, the option of not treating patients with asymptomatic trichomoniasis remains unattractive due to medical and public health concerns, Dr. Anderson said.

“We believe that GM-CSF represents a biologically plausible link between a local infection and a systemic response,” Dr. Anderson said at the meeting, explaining that serum GM-CSF has been shown to be elevated in other systemic response syndromes, and has been shown to be an important mediator of local infection in animal models of trichomoniasis.

The cytokine may be an important growth factor in placental implantation, she added.

“We therefore conclude that trichomoniasis in pregnancy should not be regarded as a benign condition,” Dr. Anderson said.

Further study to “more fully characterize the inflammatory response” to trichomoniasis and other sexually transmitted infections in pregnancy will be planned, Dr. Anderson noted at the meeting.

CHARLESTON, S.C. — Oral and vaginal metronidazole appear to have comparable efficacy for the treatment of bacterial vaginosis in low-risk pregnant women, but neither is optimal for prevention of infectious complications at delivery, Jane Hitti, M.D., reported during the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

In a double-blind, placebo-controlled study of 126 women with bacterial vaginosis who were randomized at or before 20 weeks' gestation to receive either oral or vaginal metronidazole, the treatment failure rate was similar for both groups (29% for oral administration vs. 35% for vaginal administration), Dr. Hitti of the University of Washington, Seattle, reported in a poster presentation at the meeting.

The oral administration group received 250 mg of metronidazole three times daily for 1 week; the vaginal administration group was treated with 5 g of 0.75% gel twice daily for 5 days. Treatment failure was defined as persistent BV at 4 weeks after treatment, she noted.

Although treatment outcomes in regard to bacterial vaginosis persistence were statistically similar for the two groups, the rate of certain infectious complications at delivery was of concern.

For example, the cesarean wound infection rate was 33% in the oral metronidazole group, compared with 18% in the vaginal metronidazole group, 0% in a group of 47 women with intermediate Gram stain results, and 6% in a group of 190 women with normal Gram stain results.

The difference between the oral treatment group and the normal controls reached statistical significance.

Furthermore, the rate of chorioamnionitis was 20% in the vaginal treatment group, compared with 9% in the oral treatment group, 7% in the intermediate Gram stain group, and 10% in the controls. These differences did not reach statistical significance, but the findings suggest that infectious complications remain a concern in patients with bacterial vaginosis, regardless of metronidazole treatment delivery method.

CHARLESTON, S.C. — Oral and vaginal metronidazole appear to have comparable efficacy for the treatment of bacterial vaginosis in low-risk pregnant women, but neither is optimal for prevention of infectious complications at delivery, Jane Hitti, M.D., reported during the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

In a double-blind, placebo-controlled study of 126 women with bacterial vaginosis who were randomized at or before 20 weeks' gestation to receive either oral or vaginal metronidazole, the treatment failure rate was similar for both groups (29% for oral administration vs. 35% for vaginal administration), Dr. Hitti of the University of Washington, Seattle, reported in a poster presentation at the meeting.

The oral administration group received 250 mg of metronidazole three times daily for 1 week; the vaginal administration group was treated with 5 g of 0.75% gel twice daily for 5 days. Treatment failure was defined as persistent BV at 4 weeks after treatment, she noted.

Although treatment outcomes in regard to bacterial vaginosis persistence were statistically similar for the two groups, the rate of certain infectious complications at delivery was of concern.

For example, the cesarean wound infection rate was 33% in the oral metronidazole group, compared with 18% in the vaginal metronidazole group, 0% in a group of 47 women with intermediate Gram stain results, and 6% in a group of 190 women with normal Gram stain results.

The difference between the oral treatment group and the normal controls reached statistical significance.

Furthermore, the rate of chorioamnionitis was 20% in the vaginal treatment group, compared with 9% in the oral treatment group, 7% in the intermediate Gram stain group, and 10% in the controls. These differences did not reach statistical significance, but the findings suggest that infectious complications remain a concern in patients with bacterial vaginosis, regardless of metronidazole treatment delivery method.

CHARLESTON, S.C. — Oral and vaginal metronidazole appear to have comparable efficacy for the treatment of bacterial vaginosis in low-risk pregnant women, but neither is optimal for prevention of infectious complications at delivery, Jane Hitti, M.D., reported during the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

In a double-blind, placebo-controlled study of 126 women with bacterial vaginosis who were randomized at or before 20 weeks' gestation to receive either oral or vaginal metronidazole, the treatment failure rate was similar for both groups (29% for oral administration vs. 35% for vaginal administration), Dr. Hitti of the University of Washington, Seattle, reported in a poster presentation at the meeting.

The oral administration group received 250 mg of metronidazole three times daily for 1 week; the vaginal administration group was treated with 5 g of 0.75% gel twice daily for 5 days. Treatment failure was defined as persistent BV at 4 weeks after treatment, she noted.

Although treatment outcomes in regard to bacterial vaginosis persistence were statistically similar for the two groups, the rate of certain infectious complications at delivery was of concern.

For example, the cesarean wound infection rate was 33% in the oral metronidazole group, compared with 18% in the vaginal metronidazole group, 0% in a group of 47 women with intermediate Gram stain results, and 6% in a group of 190 women with normal Gram stain results.

The difference between the oral treatment group and the normal controls reached statistical significance.

Furthermore, the rate of chorioamnionitis was 20% in the vaginal treatment group, compared with 9% in the oral treatment group, 7% in the intermediate Gram stain group, and 10% in the controls. These differences did not reach statistical significance, but the findings suggest that infectious complications remain a concern in patients with bacterial vaginosis, regardless of metronidazole treatment delivery method.

CHARLESTON, S.C. — Oral valacyclovir was the most economically favorable treatment choice for the prevention of intrapartum herpes transmission in a recent analysis.

The clinical outcomes and costs of the three strategies, including oral valacyclovir, oral acyclovir, and no prophylaxis, were compared using a decision analysis model in a hypothetical cohort of 1 million women with recurrent herpes infection. All strategies included cesarean section for patients with active lesions during labor, Monique G. Lin, M.D., of the University of Alabama, Birmingham, and her colleagues reported in a poster at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

The valacyclovir model included 500 mg given twice daily beginning at 36 weeks' gestation; the oral acyclovir model included 200 mg given four times daily beginning at 36 weeks' gestation.

The investigators used the literature and “local sources” to determine baseline costs, and based their analysis on current treatment strategies that employ polymerase chain reaction, viral culture, and high-dose intravenous acyclovir for treatment of affected neonates. Using this model, the researchers showed that the total costs in the hypothetical cohort were $9.94 billion for valacyclovir, $9.93 billion for acyclovir, and $13.7 billion for no prophylaxis.

The number of cases of neonatal death or moderate-to-severe neonatal morbidity associated with each treatment in this model was 1,911 with valacyclovir, 2,111 with acyclovir, and 8,240 with no prophylaxis.

The number of cases prevented by using valacyclovir prophylaxis was 6,239, and the number prevented by using acyclovir prophylaxis was 6,129.

The cost per case prevented was $1.57 million for valacyclovir and $1.62 million for acyclovir, the investigators reported at the meeting.

CHARLESTON, S.C. — Oral valacyclovir was the most economically favorable treatment choice for the prevention of intrapartum herpes transmission in a recent analysis.

The clinical outcomes and costs of the three strategies, including oral valacyclovir, oral acyclovir, and no prophylaxis, were compared using a decision analysis model in a hypothetical cohort of 1 million women with recurrent herpes infection. All strategies included cesarean section for patients with active lesions during labor, Monique G. Lin, M.D., of the University of Alabama, Birmingham, and her colleagues reported in a poster at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

The valacyclovir model included 500 mg given twice daily beginning at 36 weeks' gestation; the oral acyclovir model included 200 mg given four times daily beginning at 36 weeks' gestation.

The investigators used the literature and “local sources” to determine baseline costs, and based their analysis on current treatment strategies that employ polymerase chain reaction, viral culture, and high-dose intravenous acyclovir for treatment of affected neonates. Using this model, the researchers showed that the total costs in the hypothetical cohort were $9.94 billion for valacyclovir, $9.93 billion for acyclovir, and $13.7 billion for no prophylaxis.

The number of cases of neonatal death or moderate-to-severe neonatal morbidity associated with each treatment in this model was 1,911 with valacyclovir, 2,111 with acyclovir, and 8,240 with no prophylaxis.

The number of cases prevented by using valacyclovir prophylaxis was 6,239, and the number prevented by using acyclovir prophylaxis was 6,129.

The cost per case prevented was $1.57 million for valacyclovir and $1.62 million for acyclovir, the investigators reported at the meeting.

CHARLESTON, S.C. — Oral valacyclovir was the most economically favorable treatment choice for the prevention of intrapartum herpes transmission in a recent analysis.

The clinical outcomes and costs of the three strategies, including oral valacyclovir, oral acyclovir, and no prophylaxis, were compared using a decision analysis model in a hypothetical cohort of 1 million women with recurrent herpes infection. All strategies included cesarean section for patients with active lesions during labor, Monique G. Lin, M.D., of the University of Alabama, Birmingham, and her colleagues reported in a poster at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

The valacyclovir model included 500 mg given twice daily beginning at 36 weeks' gestation; the oral acyclovir model included 200 mg given four times daily beginning at 36 weeks' gestation.

The investigators used the literature and “local sources” to determine baseline costs, and based their analysis on current treatment strategies that employ polymerase chain reaction, viral culture, and high-dose intravenous acyclovir for treatment of affected neonates. Using this model, the researchers showed that the total costs in the hypothetical cohort were $9.94 billion for valacyclovir, $9.93 billion for acyclovir, and $13.7 billion for no prophylaxis.

The number of cases of neonatal death or moderate-to-severe neonatal morbidity associated with each treatment in this model was 1,911 with valacyclovir, 2,111 with acyclovir, and 8,240 with no prophylaxis.

The number of cases prevented by using valacyclovir prophylaxis was 6,239, and the number prevented by using acyclovir prophylaxis was 6,129.

The cost per case prevented was $1.57 million for valacyclovir and $1.62 million for acyclovir, the investigators reported at the meeting.

CHARLESTON, S.C. — Recent deaths due to sepsis following medical abortion may be the result of an interaction between factors specific to mifepristone—one of the drugs used in the abortions—and Clostridium sordellii, the cause of infection in at least three of the five patients who died, James A. McGregor, M.D., said at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

Five deaths linked with the use of mifepristone (Mifeprex) for medical abortion have been reported and have prompted revisions to the product's package insert. The Food and Drug Administration and the drug's maker, Danco Laboratories LLC, announced the most recent change in July. The insert will now advise physicians to tell patients to seek care if they develop diarrhea, nausea, or vomiting with or without abdominal pain in the days after using the drug.

The first of the five deaths that prompted the warnings occurred in Canada in 2001 during a clinical trial of mifepristone. That case and two others that occurred in California since 2003 were associated with C. sordellii infection. The cause of infection in the two other deaths, which also occurred in California, has not been identified, but all five patients died after using oral mifepristone followed by vaginal misoprostol, rather than the FDA-approved regimen, which consists of oral mifepristone followed by oral misoprostol.

In a poster presented at the meeting, Dr. McGregor of the University of Southern California, Los Angeles, described case findings in the two California patients with confirmed C. sordellii infection and associated toxic shock-like syndrome.

Both were previously healthy, young (aged 18 and 22), primiparous women treated with the modified mifepristone/misoprostol medical abortion protocol, including 200-mg mifepristone orally followed by 800-mcg misoprostol inserted vaginally by the patient the next day. The patients reported to local emergency departments within 6 days complaining of abdominal pain, nausea, and light-headedness or faintness. Both were afebrile, tachycardic, tachypneic, and hypotensive.

Laboratory findings demonstrated hemoconcentration and dramatic leukocytosis, and both patients suffered refractory shock and cardiopulmonary arrest, Dr. McGregor noted.

“Mifepristone has multiple pharmacologic properties that may interfere with innate immune responses to infection, toxin exposures, and inflammatory stimuli,” he explained in an interview.

The drug is long-lasting, and it blocks steroid stress responses and the inflammation-dampening effects of cortisol, he explained.

And C. sordellii, which is present in the vagina in approximately 5% of all women and in up to 29% of women after pregnancy loss, can be toxigenic, he added.

Based on the findings from the two cases he presented, Dr. McGregor proposes that the following five factors comprise a case definition of C. sordellii-associated toxic shock-like syndrome after pregnancy termination:

▸ Previously well woman with early pregnancy.

▸ Onset of nonspecific complaints of flulike illness, such as abdominal/pelvic pain, faintness, and/or light-headedness, within 2 weeks of pregnancy termination.

▸ Physical findings of hypotension, tachycardia, tachypnea, and fever or hypothermia.

▸ Laboratory findings of elevated hematocrit and hemoglobin levels, dramatic leukocytosis left shift with increased band forms greater than 10%, and positive culture or nucleic acid-based microbial testing for C. sordellii.

▸ Exclusion of other toxic shock syndrome or other toxic shock-like syndrome, including sepsis syndrome caused by other bacteria, viruses, fungi, or parasites.

Research on host-environment susceptibility factors might further elucidate the mechanisms of this syndrome and contribute to primary prevention, he added.

Dr. McGregor speculated that infection recognized early could possibly be treated successfully with combined approaches including appropriate antibiotics, a protein C inhibitor (a new treatment for shock), high-dose steroids, and surgical removal of infected tissues.

However, factors associated with these deaths raise unanswered questions about the clustering of cases in California, the role of mifepristone in removing cortisol's suppression of inflammation, and the importance of vaginal self-administration of the drug on vaginal microflora.

Danco Laboratories has noted that more than 460,000 prescriptions for mifepristone have been written since it was approved in 2000, making the fatal sepsis rate about 1 in 100,000.

CHARLESTON, S.C. — Recent deaths due to sepsis following medical abortion may be the result of an interaction between factors specific to mifepristone—one of the drugs used in the abortions—and Clostridium sordellii, the cause of infection in at least three of the five patients who died, James A. McGregor, M.D., said at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

Five deaths linked with the use of mifepristone (Mifeprex) for medical abortion have been reported and have prompted revisions to the product's package insert. The Food and Drug Administration and the drug's maker, Danco Laboratories LLC, announced the most recent change in July. The insert will now advise physicians to tell patients to seek care if they develop diarrhea, nausea, or vomiting with or without abdominal pain in the days after using the drug.

The first of the five deaths that prompted the warnings occurred in Canada in 2001 during a clinical trial of mifepristone. That case and two others that occurred in California since 2003 were associated with C. sordellii infection. The cause of infection in the two other deaths, which also occurred in California, has not been identified, but all five patients died after using oral mifepristone followed by vaginal misoprostol, rather than the FDA-approved regimen, which consists of oral mifepristone followed by oral misoprostol.

In a poster presented at the meeting, Dr. McGregor of the University of Southern California, Los Angeles, described case findings in the two California patients with confirmed C. sordellii infection and associated toxic shock-like syndrome.

Both were previously healthy, young (aged 18 and 22), primiparous women treated with the modified mifepristone/misoprostol medical abortion protocol, including 200-mg mifepristone orally followed by 800-mcg misoprostol inserted vaginally by the patient the next day. The patients reported to local emergency departments within 6 days complaining of abdominal pain, nausea, and light-headedness or faintness. Both were afebrile, tachycardic, tachypneic, and hypotensive.

Laboratory findings demonstrated hemoconcentration and dramatic leukocytosis, and both patients suffered refractory shock and cardiopulmonary arrest, Dr. McGregor noted.

“Mifepristone has multiple pharmacologic properties that may interfere with innate immune responses to infection, toxin exposures, and inflammatory stimuli,” he explained in an interview.

The drug is long-lasting, and it blocks steroid stress responses and the inflammation-dampening effects of cortisol, he explained.

And C. sordellii, which is present in the vagina in approximately 5% of all women and in up to 29% of women after pregnancy loss, can be toxigenic, he added.

Based on the findings from the two cases he presented, Dr. McGregor proposes that the following five factors comprise a case definition of C. sordellii-associated toxic shock-like syndrome after pregnancy termination:

▸ Previously well woman with early pregnancy.

▸ Onset of nonspecific complaints of flulike illness, such as abdominal/pelvic pain, faintness, and/or light-headedness, within 2 weeks of pregnancy termination.

▸ Physical findings of hypotension, tachycardia, tachypnea, and fever or hypothermia.

▸ Laboratory findings of elevated hematocrit and hemoglobin levels, dramatic leukocytosis left shift with increased band forms greater than 10%, and positive culture or nucleic acid-based microbial testing for C. sordellii.

▸ Exclusion of other toxic shock syndrome or other toxic shock-like syndrome, including sepsis syndrome caused by other bacteria, viruses, fungi, or parasites.

Research on host-environment susceptibility factors might further elucidate the mechanisms of this syndrome and contribute to primary prevention, he added.

Dr. McGregor speculated that infection recognized early could possibly be treated successfully with combined approaches including appropriate antibiotics, a protein C inhibitor (a new treatment for shock), high-dose steroids, and surgical removal of infected tissues.

However, factors associated with these deaths raise unanswered questions about the clustering of cases in California, the role of mifepristone in removing cortisol's suppression of inflammation, and the importance of vaginal self-administration of the drug on vaginal microflora.

Danco Laboratories has noted that more than 460,000 prescriptions for mifepristone have been written since it was approved in 2000, making the fatal sepsis rate about 1 in 100,000.

CHARLESTON, S.C. — Recent deaths due to sepsis following medical abortion may be the result of an interaction between factors specific to mifepristone—one of the drugs used in the abortions—and Clostridium sordellii, the cause of infection in at least three of the five patients who died, James A. McGregor, M.D., said at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

Five deaths linked with the use of mifepristone (Mifeprex) for medical abortion have been reported and have prompted revisions to the product's package insert. The Food and Drug Administration and the drug's maker, Danco Laboratories LLC, announced the most recent change in July. The insert will now advise physicians to tell patients to seek care if they develop diarrhea, nausea, or vomiting with or without abdominal pain in the days after using the drug.

The first of the five deaths that prompted the warnings occurred in Canada in 2001 during a clinical trial of mifepristone. That case and two others that occurred in California since 2003 were associated with C. sordellii infection. The cause of infection in the two other deaths, which also occurred in California, has not been identified, but all five patients died after using oral mifepristone followed by vaginal misoprostol, rather than the FDA-approved regimen, which consists of oral mifepristone followed by oral misoprostol.

In a poster presented at the meeting, Dr. McGregor of the University of Southern California, Los Angeles, described case findings in the two California patients with confirmed C. sordellii infection and associated toxic shock-like syndrome.

Both were previously healthy, young (aged 18 and 22), primiparous women treated with the modified mifepristone/misoprostol medical abortion protocol, including 200-mg mifepristone orally followed by 800-mcg misoprostol inserted vaginally by the patient the next day. The patients reported to local emergency departments within 6 days complaining of abdominal pain, nausea, and light-headedness or faintness. Both were afebrile, tachycardic, tachypneic, and hypotensive.

Laboratory findings demonstrated hemoconcentration and dramatic leukocytosis, and both patients suffered refractory shock and cardiopulmonary arrest, Dr. McGregor noted.

“Mifepristone has multiple pharmacologic properties that may interfere with innate immune responses to infection, toxin exposures, and inflammatory stimuli,” he explained in an interview.

The drug is long-lasting, and it blocks steroid stress responses and the inflammation-dampening effects of cortisol, he explained.

And C. sordellii, which is present in the vagina in approximately 5% of all women and in up to 29% of women after pregnancy loss, can be toxigenic, he added.

Based on the findings from the two cases he presented, Dr. McGregor proposes that the following five factors comprise a case definition of C. sordellii-associated toxic shock-like syndrome after pregnancy termination:

▸ Previously well woman with early pregnancy.

▸ Onset of nonspecific complaints of flulike illness, such as abdominal/pelvic pain, faintness, and/or light-headedness, within 2 weeks of pregnancy termination.

▸ Physical findings of hypotension, tachycardia, tachypnea, and fever or hypothermia.

▸ Laboratory findings of elevated hematocrit and hemoglobin levels, dramatic leukocytosis left shift with increased band forms greater than 10%, and positive culture or nucleic acid-based microbial testing for C. sordellii.

▸ Exclusion of other toxic shock syndrome or other toxic shock-like syndrome, including sepsis syndrome caused by other bacteria, viruses, fungi, or parasites.

Research on host-environment susceptibility factors might further elucidate the mechanisms of this syndrome and contribute to primary prevention, he added.

Dr. McGregor speculated that infection recognized early could possibly be treated successfully with combined approaches including appropriate antibiotics, a protein C inhibitor (a new treatment for shock), high-dose steroids, and surgical removal of infected tissues.

However, factors associated with these deaths raise unanswered questions about the clustering of cases in California, the role of mifepristone in removing cortisol's suppression of inflammation, and the importance of vaginal self-administration of the drug on vaginal microflora.

Danco Laboratories has noted that more than 460,000 prescriptions for mifepristone have been written since it was approved in 2000, making the fatal sepsis rate about 1 in 100,000.