Brenna L. Hughes

Cefazolin prophylaxis in obese women undergoing cesarean delivery: a randomized controlled trial.

OBJECTIVE: To compare adipose tissue concentration among obese women receiving 2 g compared with 3 g of precesarean cefazolin prophylaxis. METHODS: This was a double-blind randomized controlled trial of women with singleton gestations and body mass indexes (BMIs) of 30 or greater at their first prenatal visit undergoing cesarean delivery at term. Women were randomly allocated, stratified by BMI, to receive 2 g or 3 g of cefazolin. Subcutaneous adipose tissue was harvested twice: before (opening) fascial incision and after (closing) fascial closure. The primary outcome was opening adipose tissue cefazolin concentration, measured by high-pressure liquid chromatography. RESULTS: From April 2013 to July 2014, 58 women were enrolled, 57 included in the analysis: 28 in the 2-g group and 29 in the 3-g group. Baseline characteristics were similar between groups. Median opening adipose tissue concentration was similar between the 2-g and 3-g groups (9.4 [interquartile range 5.1–13.4] compared with 11.7 [interquartile range 7–18.3] micrograms/g, P=.12). The percentage of women with opening concentrations above 8 micrograms/g, the minimally inhibitory concentration of cefazolin for Staphylococcus species, was similar (61% compared with 72%, P=.35). All samples were above 2 micrograms/g, the minimally inhibitory concentration for Enterobacteriaceae. Closing adipose tissue concentrations and stratified analyses were consistent with the overall analysis. CONCLUSION: In obese women undergoing cesarean delivery, prophylaxis with 3 g of cefazolin did not significantly increase adipose tissue concentration. Thus, our data do not support recommendations for 3-g dosing. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01810354. LEVEL OF EVIDENCE: I

Diagnosis and antenatal management of congenital cytomegalovirus infection

Congenital cytomegalovirus (CMV) is the most common viral infection, affecting nearly 40,000 infants each year in the United States. Of seronegative women, 1-4% will acquire a primary infection during pregnancy, and the majority of these women will be asymptomatic. Prior maternal exposure to CMV does not preclude neonatal infection. The purpose of this document is to review diagnosis of primary maternal CMV infection, diagnosis of fetal CMV infection, and whether antenatal therapy is warranted. We recommend the following: (1) that women with a diagnosis of primary CMV infection in pregnancy be advised that the risk of congenital infection is 30-50%, on average, and that the severity of infection varies widely (Best Practice); (2) for women suspected of having primary CMV infection in pregnancy, we recommend that diagnosis should be either by IgG seroconversion or with positive CMV IgM, positive IgG, and low IgG avidity (grade 1B); (3) amniocentesis is the best option as a prenatal diagnostic tool to detect fetal congenital CMV infection, performed >21 weeks of gestation and >6 weeks from maternal infection (grade 1C); (4) we do not recommend routine screening of all pregnant women for evidence of primary CMV infection at this time (grade 1B); and (5) we do not recommend antenatal treatment with ganciclovir or valacyclovir; and we recommend that any antenatal therapy, either with antivirals or CMV hyperimmune globulin, should only be offered as part of a research protocol (Best Practice).

Third-Trimester Prenatal Syphilis Screening: A Cost-Effectiveness Analysis.

OBJECTIVE: To estimate the cost to prevent one case of congenital syphilis or fetal or neonatal death with universal third-trimester syphilis rescreening in the United States and to estimate the incidence of syphilis seroconversion at which rescreening becomes cost-effective. METHODS: We created a decision model comparing universal third-trimester syphilis rescreening in women who screened negative in the first trimester with no rescreening. The assumed base case incidence of seroconversion was 0.012%. The primary outcome was the cost to prevent one case of congenital syphilis. Secondary outcomes included the cost to prevent one fetal or neonatal death and the number needed to rescreen to prevent one adverse outcome. A strategy was considered cost-effective if it cost less than

Whither oxygen for intrauterine resuscitation

285,000 to prevent one case of congenital syphilis (the estimated long-term care cost). RESULTS: Under our assumptions, universal third-trimester rescreening would cost an additional

Population Pharmacokinetics of Cefazolin in Serum and Adipose Tissue From Overweight and Obese Women Undergoing Cesarean Delivery

419,842 for each case of congenital syphilis prevented and

Use of Cefazolin for Group B Streptococci Prophylaxis in Women Reporting a Penicillin Allergy Without Anaphylaxis

3,621,144 and

Geographic Disparities in Cytomegalovirus Infection During Pregnancy

6,052,534, respectively, for each fetal and neonatal death prevented. Rescreening 4,000,000 women would prevent 60 cases of congenital syphilis and seven fetal and four neonatal deaths. Prevention of one case of congenital syphilis would require 65,790 women be rescreened. Seroconversion incidence of 0.017% would make third-trimester rescreening cost-effective. CONCLUSION: Universal third-trimester syphilis rescreening requires a large number of women be rescreened at a high health care cost to prevent one adverse outcome from maternal syphilis. Seroconversion incidence must be 19-fold higher than the national average of primary and secondary syphilis in women for universal third-trimester rescreening to be cost-effective.

Sepsis in Pregnancy: Identification and Management.

Oxygen is frequently administered to women in labor in the hope of improving fetal status. However, there is a paucity of outcome data to support this practice. Although maternal oxygen administration may make physiological sense, unwarranted faith in maternal oxygen therapy may delay the indicated intervention or result in continued labor stimulation when neither is in the best interests of the fetus. A properly designed clinical trial would help answer whether maternal oxygen supplementation in labor should be considered an indicated intervention for nonreassuring fetal status.

Group B Streptococci Screening Before Repeat Cesarean Delivery: A Cost-Effectiveness Analysis.

The optimal antibiotic prophylaxis dosing regimen of cefazolin for cesarean delivery (CD) in overweight and obese women is unknown. This study was done to compare the duration that cefazolin concentrations remain above the minimum inhibitory concentration (MIC) in adipose tissue (AT). Serum and AT concentrations from 3 previous studies in CD patients were comodeled using the nonparametric adaptive grid algorithm in Pmetrics. AT concentrations for 5000 overweight and obese patients receiving 1‐, 2‐, and 3‐g cefazolin regimens were simulated to calculate the probability that free drug concentrations remained above an MIC of 2 μg/mL at 1, 1.5, and 2 hours after administration. Sixty‐seven patients (mean body mass index 38.7 kg/m2; range 25.5‐55.8 kg/m2) provided data. A 2‐compartment model with 1 of the compartments representing AT fit the data best. Final model parameters were clearance 7.38 ± 5.34 L/h, volume of central compartment 11.8±9.36 L, and AT volume of distribution 80.12 ± 55.47 L. The mean±SD (median) penetration ratio of cefazolin into AT was 0.81 ± 2.06 (0.62). At 1.5 and 2 hours, 1‐, 2‐, and 3‐g regimens achieved AT concentrations above the MIC in 71.2%, 92.4%, and 94.7%, and 55.7%, 86.8%, and 91.7%, respectively, of simulated patients. Cefazolin achieved good penetration into AT. Because CD duration is commonly less than 1.5 hours, a 2‐g dose has a high probability of providing AT concentrations above the target pathogens’ MIC for overweight and obese females. A second dose may be considered for longer surgeries.

Comprehensive review and update of cytomegalovirus infection in pregnancy

OBJECTIVE: To estimate the proportion of group B streptococci (GBS)-colonized women with a reported penicillin allergy without anaphylaxis receiving appropriate intrapartum antibiotic prophylaxis. METHODS: We performed a retrospective cohort study of GBS-colonized, penicillin-allergic women delivering at term receiving intrapartum antibiotic prophylaxis during labor. Scheduled cesarean deliveries were excluded. The primary outcome was the proportion of women who received appropriate antibiotic coverage, defined as penicillin or cefazolin. Secondary outcomes included neonatal outcomes such as Apgar score, blood draws, antibiotic use, length of hospital stay, and composite morbidity. RESULTS: Of 165 women reporting a penicillin allergy without anaphylaxis, 73 (44.2%) received an appropriate antibiotic and 92 (55.8%) received an inappropriate antibiotic. Of those receiving an inappropriate antibiotic, 56 (60.9%) were given clindamycin, 1 (1.1%) erythromycin, and 35 (38.0%) vancomycin. Women reporting rash as a penicillin reaction were more likely to receive cefazolin than another antibiotic (44 [60.3%] compared with 24 [26.1%], respectively; P<.001), whereas women whose reaction was not documented were less likely to receive cefazolin (18 [24.7%] compared with 63 [68.5%], respectively; P<.001). Among neonates whose mothers received appropriate compared with inappropriate antibiotics, there were no differences in Apgar score, number of blood draws, antibiotic use, length of hospital stay, or composite morbidity. CONCLUSION: More than half of women allergic to penicillin without anaphylaxis received an antibiotic other than penicillin or cefazolin as prophylaxis, indicating poor adherence to national guidelines.