FDA Public Meeting Report on "Drug Interactions With Hormonal Contraceptives: Public Health and Drug Development Implications".

Potential drug interactions with hormonal contraceptives are an important public health concern. A public meeting on "Drug Interactions With Hormonal Contraceptives: Public Health and Drug Development Implication" was hosted by the United States Food and Drug Administration (FDA). The meeting endeavored to provide an opportunity for the FDA to seek input from experts on the public health concerns associated with the use of hormonal contraceptives and interacting drugs that might affect efficacy and safety, including pharmacokinetic/pharmacodynamic considerations, in the design of drug interaction studies of hormonal contraceptives for drug development and approaches to translating the results of drug interaction information into informative labeling and communication. The input received could be used to refine FDA's thinking on hormonal contraceptives drug interaction study design and interpretation and labeling communication of drug interaction risk. This meeting benefited from strong and diverse participation from the Center for Drug Evaluation and Research at the FDA, Centers for Disease Control and Prevention, National Institutes of Health, Swedish Medical Products Agency, pharmaceutical industry, and representatives of academia. This report provides a summary of the key discussion based on the presentations and panel discussion.

Effects of Depot Medroxyprogesterone Acetate Injection Timing on Medical Abortion Efficacy and Repeat Pregnancy: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effects of timing of depot medroxyprogesterone acetate injection on medical abortion outcome and risk of repeat pregnancy within the subsequent 6 months. METHODS: In a multinational randomized trial, we assigned women undergoing medical abortion who wanted depot medroxyprogesterone acetate to administration either with mifepristone (Quickstart group) or after the abortion (Afterstart group). We ascertained abortion outcome, pregnancies, and contraception use over 7 months. RESULTS: From August 2013 to March 2015, we enrolled 461 participants with pregnancy durations of 75 days or less. Of participants included in the abortion outcome analyses, 14 of 220 (6.4%) and 12 of 226 (5.3%) in the Quickstart and Afterstart groups, respectively, had surgery to complete the abortion; the upper 90% confidence limit on this difference was 4.9%, within our prestipulated 5% noninferiority margin. Ongoing pregnancy after initial abortion treatment was significantly more common in the Quickstart group (8/220 [3.6%]) than in the Afterstart group (2/226 [0.9%]); the difference was 2.7% (90% confidence interval 0.4-5.6%). By 6 months, 5 of 213 (2.3%) and 7 of 217 (3.2%) in the Quickstart and Afterstart groups, respectively, became pregnant (exact log-rank test, P=.64). Use of highly effective contraceptives was significantly more common in the Quickstart group at 31 days (P<.001), but no difference was apparent at 6 months. The Quickstart group was significantly more satisfied with group assignment. CONCLUSION: Depot medroxyprogesterone acetate administration with mifepristone did not appreciably increase the risk of surgery after medical abortion but did increase the risk of ongoing pregnancy. It enhanced patient satisfaction, but we found no evidence that it decreased 6-month risk of repeat pregnancy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT01902485.

Assessment of the vaginal residence time of biomarkers of semen exposure.

OBJECTIVE: The primary objective of this pilot study is to determine and compare the residence time in the vagina of biomarkers of semen exposure for up to 15 days post exposure. The biomarkers are prostate-specific antigen (PSA), Y chromosome DNA, the sex determining region of the Y chromosome (SRY) and testis-specific protein Y-encoded 4 (TSPY4). The secondary objectives are to determine if biomarker concentrations differed between intercourse and inoculation groups, to establish whether the sampling frequency post exposure affected biomarker concentrations and decay profile and to determine if biomarker concentrations in vaginal swabs obtained by the participant at home were similar to swabs obtained by the nurse in the clinic. STUDY DESIGN: We randomized healthy women to unprotected intercourse (n=17) versus vaginal inoculation with the male partner's semen in the clinic (n=16). Women were then further randomized to have vaginal swabs obtained at either 7 or 4 time points after semen exposure, up to 15 days post exposure, either obtained at home by the participant or in the clinic by the research nurse. RESULTS: PSA and SRY were markers of recent semen exposure. TSPY4 was detectable in approximately 50% of participants at 15 days post exposure. Unprotected intercourse resulted in significantly higher concentrations of select biomarkers. Sampling frequency and home versus clinic sampling had no significant effect on biomarker concentrations. CONCLUSIONS: Objective biomarkers of recent or distant semen exposure may have great utility for verifying protocol compliance in a variety of clinical trials.

Effect of Immediate Compared With Delayed Insertion of Etonogestrel Implants on Medical Abortion Efficacy and Repeat Pregnancy: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect of insertion of etonogestrel implants with mifepristone compared with after the abortion on the risks of medical abortion failure and repeat pregnancy over the subsequent 6 months. METHODS: In a randomized trial, we assigned patients undergoing medical abortion to receive etonogestrel implants either with the mifepristone (Quickstart group) or after the abortion (Afterstart group). We followed them for 7 months to ascertain abortion outcome, pregnancies, and contraception use. RESULTS: Between September 2013 and August 2014, we enrolled 236 participants in the Quickstart group and 240 in the Afterstart group. To examine abortion failure, we conducted a noninferiority analysis from which we excluded nine participants who had missing outcome data and four with specified protocol violations. Of the rest, 9 of 229 (3.9%) and 9 of 234 (3.8%) in the Quickstart and Afterstart groups, respectively, had surgery to complete the abortion; the difference of 0.08% (90% confidence interval -3.1% to 3.3%) excluded our prestipulated noninferiority margin of 5 percentage points. Among participants with pregnancy follow-up through 6 months, 1 of 213 (0.5%) and 3 of 208 (1.4%) in the Quickstart and Afterstart groups, respectively, became pregnant within that time; 6-month pregnancy rates did not differ significantly by group (exact log-rank test, P=.28). At enrollment, significantly more participants in the Quickstart group than in the Afterstart group were satisfied with their group assignments (187/236 [79%] compared with 129/240 [54%], respectively; P<.001). CONCLUSION: Insertion of etonogestrel implants with mifepristone did not appreciably increase medical abortion failure risk and it enhanced patient satisfaction, but we found no evidence that it decreased repeat pregnancy rates. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01902485.

Six-month and 1-year continuation rates following postpartum insertion of implants and intrauterine devices.

OBJECTIVE: Studies show immediate postpartum (PP) insertion increases use of contraceptive implants and intrauterine devices (IUDs). Our objective was to compare the satisfaction and continuation rates of the two types of devices at 6 months and 1 year following PP insertion. STUDY DESIGN: We enrolled 133 women in a prospective cohort study following immediate PP insertion of an implant or IUD at two academic hospitals during 8 months of 2011. Subjects completed an enrollment survey during hospital admission and a follow-up phone survey 6 months and 1 year PP. RESULTS: At 6 months PP, 72% of subjects provided follow-up information. Implant users were more likely to be using the originally-placed device (40/41, 98% vs. 45/55, 82%, p=0.02); nine women reported IUD expulsions. When accounting for replacement of expelled IUDs, IUD continuation at 6 months was 89% yielding similar continuation rates between groups (p=0.12). At 1 year PP, 51% provided follow-up. Of those, 82% still had a LARC method in place with similar continuation by device type (84% for implants, 81% for IUDs, p=0.96). Overall, satisfaction was similarly high in both groups. CONCLUSION: Due to IUD expulsion, implants had a higher continuation rate than IUDs six months following immediate PP insertion. After replacement of expelled IUDs, continuation and satisfaction were similar for both devices at 6 months and 1 year. IMPLICATIONS: Placement of implants and IUDs immediately PP can lead to high satisfaction. Despite early IUD expulsions, continuation rates were similar to those placed outside of the immediate PP period.

Timing of postpartum intrauterine device placement: a cost-effectiveness analysis.

OBJECTIVE: To determine if immediate postpartum (PP) intrauterine device (IUD) placement prevents pregnancy and is cost-effective compared with routine placement. DESIGN: We developed a decision-analysis model to determine the number of pregnancies prevented and the cost-effectiveness of immediate PP IUD placement defined as within the first 10 minutes of placental expulsion compared with routine placement at the PP visit. Associated costs and probability estimates for adherence to PP follow-up, IUD placement, expulsion, and pregnancy were determined from the literature. SETTING: Hospital and outpatient facility. PATIENT(S): Women desiring PP IUDs. INTERVENTION(S): IUD placement. MAIN OUTCOME MEASURE(S): The main outcome measure was the number of pregnancies prevented per 1,000 women. The secondary outcome was an incremental cost-effectiveness ratio (ICER) defined as the marginal cost per quality-adjusted life-year (QALY) gained. An ICER of <$50,000/QALY gained was considered to be cost-effective. RESULT(S): Immediate PP IUD placement prevented 88 unintended pregnancies per 1,000 women over a 2-year time horizon. Immediate PP IUD placement was the dominant strategy. For every 1,000 women who desired a PP IUD, attempted immediate PP placement resulted in a cost savings of $282,540 and a gain of 10 QALYs. The model is most sensitive to the cost of an undesired pregnancy. When the cost of a live birth is <$6,000, immediate placement is no longer cost-saving but remains cost-effective. Monte Carlo simulation demonstrates that immediate PP IUD placement is cost-effective in 99% of simulations. CONCLUSION(S): Immediate PP IUD placement is a dominant strategy that prevents unintended pregnancy.

Detection of two biological markers of intercourse: prostate-specific antigen and Y-chromosomal DNA.

BACKGROUND: Although biological markers of women's exposure to semen from vaginal intercourse have been developed as surrogates for risk of infection or probability of pregnancy, data on their persistence time and clearance are limited. STUDY DESIGN: During 2006-2008, 52 couples were enrolled for three 14-day cycles of abstinence from vaginal sex during which women were exposed in the clinic to a specific quantity (10, 100 or 1000 µL) of their partner's semen. Vaginal swabs were collected before and at 1, 6, 12, 24, 48, 72 and 144 h after exposure for testing for prostate-specific antigen (PSA) and Y-chromosome DNA (Yc DNA). RESULTS: Immediately after exposure to 1000 µL of semen, the predicted sensitivity of being PSA positive was 0.96; this decreased to 0.65, 0.44, 0.21 and 0.07 at 6, 12, 24 and 48 h, respectively. Corresponding predicted sensitivity of being Yc DNA positive was 0.72 immediately postexposure; this increased to 0.76 at 1 h postexposure and then decreased to 0.60 (at 6 h), 0.63 (at 12 h), 0.49 (at 24 h), 0.21 (at 48 h), 0.17 (at 72 h) and 0.12 (at 144 h). CONCLUSIONS: Overall findings suggest that PSA may be more consistent as a marker of very recent exposure and that Yc DNA is more likely to be detected in the vagina after 12 h postexposure compared to PSA.

Contraception for the HIV-positive woman: a review of interactions between hormonal contraception and antiretroviral therapy.

BACKGROUND: Preventing unintended pregnancy in HIV-positive women can significantly reduce maternal-to-child HIV transmission as well as improve the woman's overall health. Hormonal contraceptives are safe and effective means to avoid unintended pregnancy, but there is concern that coadministration of antiretroviral drugs may alter contraceptive efficacy. MATERIALS AND METHODS: We performed a literature search of PubMed and Ovid databases of articles published between January 1980 and February 2012 to identify English-language reports of drug-drug interactions between hormonal contraceptives (HCs) and antiretroviral drugs (ARVs). We also reviewed the FDA prescribing information of contraceptive hormone preparations and antiretrovirals for additional data and recommendations. RESULTS: Twenty peer-reviewed publications and 42 pharmaceutical package labels were reviewed. Several studies of combined oral contraceptive pills (COCs) identified decreased serum estrogen and progestin levels when coadministered with certain ARVs. The contraceptive efficacy of injectable depot medroxyprogesterone acetate (DMPA) and the levonorgestrel intrauterine system (LNG-IUS) were largely unaffected by ARVs, while data on the contraceptive patch, ring, and implant were lacking. CONCLUSIONS: HIV-positive women should be offered a full range of hormonal contraceptive options, with conscientious counseling about possible reduced efficacy of COCs and the contraceptive implant when taken with ARVs. DMPA and the LNG-IUS maintain their contraceptive efficacy when taken with ARVs.

Immediate placement of intrauterine devices after first and second trimester pregnancy termination.

BACKGROUND: We reviewed our experience with intrauterine device (IUD) placement after surgical abortion up to 20 weeks' gestation. STUDY DESIGN: Women presenting for elective abortion between January 2004 and March 2009 who requested an IUD were included in this retrospective review. RESULTS: Of 308 women requesting postabortion IUD placement, 221 (72%) planned insertion at the time of abortion (immediate group) and 87 (28%) planned insertion at their postoperative visit (interval group). IUDs were placed in 96% of the immediate group and in 23% of the interval group (212/221 vs. 20/87; p<.0001). Failure to return for placement was the most common reason for noninsertion in the interval group (60/87=69%). Follow-up information was obtained for 56% of patients and was documented a median of 137 days postabortion (range 3-1594 days). There was no difference in complication rates between groups. Expulsion rates were 3% and 0% in the immediate and interval groups, respectively (6/212 vs. 0/20; p=.4). Considering only those with documented follow-up after immediate insertion (119), there was a nonsignificant trend towards increased expulsion with placement after second vs. first trimester abortion (4/54=7% vs. 2/65=2%; p=.3). When analyzing the 172 subjects with documented follow-up, those planning immediate insertion were more likely to have an IUD in situ at the last contact than those planning later insertion (84/124=68% vs. 20/48=42%; p=.002). CONCLUSION: Immediate postabortion IUD insertion is safe and effective. Given the low rate of return for interval insertion, immediate placement may be preferable.

Reduced incidence of gestational diabetes with bariatric surgery.

BACKGROUND: Obesity is a risk factor for gestational diabetes mellitus (GDM), and bariatric surgery is an effective treatment for obesity. Our objective was to determine the association of bariatric surgery with the incidence of GDM and related complications. STUDY DESIGN: We performed a retrospective study comparing rates of GDM and related outcomes (including cesarean section, large-for-gestational-age infant, shoulder dystocia, and infection) between a group of women with a delivery before bariatric surgery and a group with a delivery after bariatric surgery. We used a private insurance claims database with information on 23,594 women who had bariatric surgery between 2002 and 2006. The dataset was searched to identify women with codes for bariatric surgery and a pregnancy resulting in a delivery at greater than 22 weeks gestation. Incidences of GDM and selected delivery complications for delivery before versus after bariatric surgery were compared using Fisher exact test and logistic regression. RESULTS: There were 346 women who had a delivery before bariatric surgery, and 354 had a delivery after bariatric surgery. Women with delivery after bariatric surgery had lower incidences of GDM (8% vs 27%, odds ratio (OR) 0.23, (95% CI 0.15 to 0.36) and cesarean section (28% vs 43%, OR0.53, 95% CI 0.39 to 0.72) than those with delivery before bariatric surgery. CONCLUSIONS: Bariatric surgery is associated with a decreased incidence of GDM and cesarean section in subsequent pregnancies. This potential effect of bariatric surgery should be considered in the management of obese women of childbearing age. Prospective studies are needed to confirm these findings.

Impact of bariatric surgery on hypertensive disorders in pregnancy: retrospective analysis of insurance claims data.

OBJECTIVE: To determine whether women who had a delivery after bariatric surgery have lower rates of hypertensive disorders in pregnancy compared with women who had a delivery before bariatric surgery. DESIGN: Retrospective cohort study. SETTING: Claims data for 2002-6 from seven insurance plans in the United States. PARTICIPANTS: 585 women aged 16-45 who had undergone bariatric surgery, had at least one pregnancy and delivery, and had continuous insurance coverage during pregnancy plus two weeks after delivery. MAIN OUTCOME MEASURE: Hypertensive disorders in pregnancy defined with ICD-9 codes. The independent variable was the timing of delivery in relation to bariatric surgery, classified as deliveries before and after surgery. We used logistic regression to calculate odds ratios and confidence intervals for each type of hypertensive disorder in pregnancy. RESULTS: Among the 585 women who had undergone bariatric surgery and had a delivery, 269 delivered before surgery and 316 delivered after surgery. Gastric bypass was the surgery in 82% (477) of all women. Women who delivered before surgery were younger at the time of delivery (mean age 31.3 v 32.5) but had higher rates of pre-existing diabetes and gestational diabetes mellitus. Compared with women who delivered before surgery, women who delivered after surgery had substantially lower rates of pre-eclampsia and eclampsia (odds ratio 0.20, 95% confidence interval 0.09 to 0.44), chronic hypertension complicating pregnancy (0.39, 0.20 to 0.74), and gestational hypertension (0.16, 0.07 to 0.37), even after adjustment for age at delivery, multiple pregnancy (that is, twins or more), surgical procedure, pre-existing diabetes, and insurance plan. CONCLUSION: In this retrospective analysis of US women, bariatric surgery was associated with lower rates of hypertensive disorders in subsequent pregnancy.

The contraceptive vaginal ring.

The contraceptive vaginal ring offers effective contraception that is self-administered, requires less frequent dosing than many other forms of contraception, and provides low doses of hormones. NuvaRing (Organon, Oss, The Netherlands), the only contraceptive vaginal ring approved for use in the United States, contains etonogestrel and ethinyl estradiol. It is inserted into the vagina for 3 weeks, followed by a 1-week ring-free period, and works by inhibiting ovulation. Most women note a beneficial effect on bleeding profiles and are satisfied with NuvaRing. Commonly reported adverse events include vaginitis, leukorrhea, headaches, and device-related events such as discomfort. Serious adverse events are rare. In Chile and Peru, progesterone-only vaginal contraceptive rings are available for nursing women. Studies are ongoing examining new formulations of vaginal contraceptive rings.

Paracervical block with combined ketorolac and lidocaine in first-trimester surgical abortion: a randomized controlled trial.

OBJECTIVE: To study the effects of a paracervical block with combined ketorolac and lidocaine on perceived pain during first-trimester surgical abortion. METHODS: A double-masked, placebo-controlled, randomized clinical trial of 50 women undergoing first-trimester surgical abortions (before 11 weeks of gestation) received either oral ibuprofen with a lidocaine-alone paracervical block or an oral placebo and paracervical block with combined ketorolac and lidocaine. Women completed a series of 100-mm visual analog scales (anchors: 0=none, 100 mm=worst imaginable) to measure their perceived pain (anticipated pain, pain during and after surgical abortion, and total satisfaction). RESULTS: Twenty-five women received preoperative oral ibuprofen followed by paracervical block with lidocaine alone, and 25 received oral placebo followed by paracervical block with combined ketorolac and lidocaine. Groups were similar with respect to sociodemographic variables. Women who received paracervical block with combined ketorolac and lidocaine reported significantly less pain after cervical dilation (59.8 compared with 74.8 mm, P<.05). The groups did not differ in perceived procedure-related or postoperative pain. There was no difference in overall satisfaction with pain control between the two groups (63.6 compared with 62.9 mm, P=.93). CONCLUSION: Paracervical block with combined ketorolac and lidocaine significantly decreases perceived pain associated with cervical dilation during first-trimester surgical abortion. This analgesic mixture may be offered as an alternative pain regimen to women seeking first-trimester surgical abortion. It may also offer improved pain control in other gynecologic procedures necessitating cervical dilation. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00617097. LEVEL OF EVIDENCE: I.

Findings associated with recurrence of bacterial vaginosis among adolescents attending sexually transmitted diseases clinics.

STUDY OBJECTIVE: Bacterial vaginosis (BV) is a common infection and has been associated with adverse health outcomes, including preterm birth, pelvic inflammatory disease (PID), and acquisition of HIV. There are limited data on recurrent BV in adolescents. A relationship between the frequency of BV recurrence and specific risk factors might shed light on the pathophysiology of BV and lead to targeted interventions. DESIGN: Record-based historical clinic study. SETTING: Adolescent visits to two sexually transmitted disease (STD) clinics between 1990 and 2002. PARTICIPANTS: 254 girls who had >/= 2 episodes of BV and at least 3 clinical visits, matched on clinic attendance frequency to 254 girls with only 1 documented BV episode and 254 girls with no history of BV. MAIN OUTCOME MEASURE: Risk factor differences between groups. ANALYSIS: Multinomial logistic regression with robust estimator of the standard errors, accounting for repeated measures. RESULTS: 5,977 adolescent girls visited the clinics. 1509 (25%) had at least one episode of BV; of those, 303 (19.9%) had 2 or more BV episodes. Girls with a history of 1 BV episode and girls with a history of 2 or more BV episodes were more likely to be infected with Trichomonas vaginalis [OR 1.77, 95% CI: 1.17-2.67, OR 1.56, 95% CI: 1.05-2.34] and be diagnosed with PID [OR 1.50, 95% CI: 1.02-2.22, OR 2.05, 95% CI: 1.41-2.98] compared to girls with no BV history, respectively. Girls with a history of BV were also more likely to report active oral sex and lack of contraceptive use. CONCLUSION: Adolescent girls who attend STD clinics have a high prevalence of BV. Although the association between BV and PID is not clearly causal, when one condition is diagnosed, evaluation and counseling for the other may reduce recurrence and sequelae.

Factors associated with increased charges for hysterectomy.

OBJECTIVE: To evaluate factors associated with increased hospital charges for hysterectomy with specific attention to differences based on surgical approach. METHODS: We performed a retrospective cohort study of 686 patients who underwent hysterectomy between January 1997 and September 1997 using medical chart review and hospital financial information. Demographic information, surgical approach (abdominal, vaginal, or laparoscopic), and surgical and postoperative factors were extracted from the medical record. Hospital charges were obtained from the hospital billing database. Relationships between charges and various clinical and demographic variables were examined using chi(2), Fisher exact test, t tests, or analysis of variance, where appropriate. Logistic regression was used to estimate odds ratios while controlling for important confounding variables. RESULTS: In our logistic regression model, blood loss greater than 1,000 mL (odds ratio [OR] 11.8, 95% confidence interval [CI] 4.2-33.2) and operative time 105 minutes or more (OR 14.2, CI 5.8-34.5) were strongly associated with higher charges for hysterectomy. Other factors associated with higher charges included: postoperative fever (OR 2.2, CI 1.1-4.5), increasing length of hospitalization (OR 5.3, CI 3.7-7.7), the use of prophylactic antibiotics (OR 3.0, CI 1.3-6.6), and the laparoscopic surgical approach compared with vaginal hysterectomy (OR 2.7, CI 1.0-7.0). CONCLUSION: Surgical factors such as operative time and blood loss were strongly associated with increased hospital charges for hysterectomy.

Diagnosis and management of oncogenic cervical human papillomavirus infection.

Cervical HPV infection should be managed less as a typical STI and more as a strong risk factor predisposing to cervical cancer development. HPV infection is undeniably transmitted predominately through sexual contact.However, the fact that more than 80% of women followed over time will acquire at least one HR-HPV infection reflects the ubiquitous nature of the infection and the ease of transmission. Although the behavioral profiles typically associated with an increased risk for STI (including lifetime partner number, age at first intercourse, and so forth) will certainly lead to an increased risk for HPV detection, there is a high absolute prevalence of HPV even among women who have few lifetime sex partners. It could be argued that to counsel patients for an HPV infection as an STI would be counterproductive, as short of absolute abstinence, the prevention of infection is difficult and treatment options, short of excisional procedures for neoplasia, are limited. The real promise held in this area is the availability of an apparently highly effective prophylactic HPV vaccine, targeting at least HPV 16, 18, 6, and 11[33,34]. This vaccine cocktail, if it achieved 100% coverage, could theoretically prevent 50% to 70% of invasive cervical cancers and most genital warts. Vaccination will be required among women before initiation of sexual contact, presumably among girls 10 to 13 years of age. Many programmatic issues remain regarding the implementation of HPV vaccine programs, including the marketing of the vaccine as STI or cancer prevention,as reviewed in detail by Gravitt and Shah [72]. Even in the era of potentially effective vaccines, screening for cervical cancer is likely to remain a priority in cervical cancer prevention programs for at least several decades. Vaccine trials have proven high short-term efficacy; however, these effects were clearly type-specific and antibody titers gradually decrease postvaccination. It is unclear whether the protection will remain over an individual's lifetime without vaccine booster, and oncogenic HPV infections not targeted by vaccination will continue to contribute to risk for development of cervical intraepithelial neoplasia and cancer. Therefore, although the public health success of HPV vaccination is undoubtedly promising, the role of cervical cancer screening as a secondary prevention effort should not be trivialized. In fact, the nature of screening programs should continue to be reevaluated in the context of effective but limited spectrum vaccines.

Prophylactic antibiotic administration prior to hysterectomy: a quality improvement initiative.

OBJECTIVE: To determine whether institution of a preoperative antibiotic policy could increase the use of prophylactic antibiotics prior to hysterectomy. STUDY DESIGN: A retrospective cohort study of 400 women who underwent abdominal, vaginal or laparoscopic hysterectomy for benign indications at Women and Infants Hospital was performed. Rates and timing of prophylactic preoperative antibiotic administration were determined, as were the rates of postoperative febrile morbidity. These data were compared to data collected in a medical record review of 686 hysterectomies performed prior to institution of the antibiotic policy. RESULTS: Prior to the institution of the antibiotic policy, 50% of patients (342/686, 95% CI 46.0, 53.7) received prophylactic preoperative antibiotics. After introduction of the antibiotic policy, 91.2% (95% CI 88.0, 93.8) of patients received prophylactic preoperative antibiotics. Approximately 66% of the antibiotics were administered within the 60 minutes preceding the surgical incision. Postoperative febrile morbidity was noted in 14% of patients prior to the antibiotic policy as compared to 11% of patients after the policy was instituted. Abdominal surgical approach was found to be a clinically and statistically significant risk factor for febrile morbidity (OR = 7.0; 95% CI 2.3, 20.9). CONCLUSION: Rates of prophylactic preoperative antibiotic administration significantly increased after institution of a hospital policy advocating routine antibiotic prophylaxis prior to hysterectomy. Additional steps must be taken to ensure more routine and appropriately timed administration of antibiotics prior to hysterectomy and to continuously monitor the use of prophylactic antibiotics.