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Limited Course of Antibiotic Treatment for Chorioamnionitis

Black, Lauren Page BA; Hinson, Lindsay MD; Duff, Patrick MD

doi: 10.1097/AOG.0b013e31824b2e29
Original Research
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OBJECTIVE: We sought to estimate the effectiveness of a limited course of antibiotics in treating patients with chorioamnionitis.

METHODS: We conducted a retrospective review of patients treated for chorioamnionitis at our medical center from 2005 to 2009. Patients received ampicillin plus gentamicin as soon as the diagnosis was made. Postpartum they received only the next scheduled dose of each antibiotic. Patients who underwent a cesarean delivery received either metronidazole or clindamycin immediately after cord clamping. The primary outcome was treatment failure, defined as persistent fever requiring continuation of antibiotics, surgical intervention, or administration of heparin.

RESULTS: Of the 423 patients, 282 delivered vaginally, and 141 delivered by cesarean. Overall, 399 (94%; 95% confidence interval [CI], 92–96%) were treated successfully and 24 (6%; 95% CI 3.7–8.3%) failed short-course treatment. Of the 282 patients who delivered vaginally, 279 (99%; 95% CI 98–100%) were cured with short-term therapy. Of the 141 who delivered by cesarean, 120 (85%; 95% CI 79–91%) were cured (P<.001). Seventeen of the patients with total treatment failure had endometritis and responded to continuation of antibiotics. Seven patients had more serious complications: wound infection (n=4) and septic thrombophlebitis (n=3). All of the serious complications occurred after cesarean delivery, and all of the affected patients either were obese or had prolonged labor or prolonged rupture of membranes.

CONCLUSION: A limited course of antibiotics was sufficient for virtually all patients (99%) with chorioamnionitis who had a vaginal delivery. However, a subset of patients who delivered by cesarean may have benefited from a more extended course of antibiotic therapy.

LEVEL OF EVIDENCE: III

A short course of antibiotics is 99% effective in treating chorioamnionitis in women who deliver vaginally and 85% effective in women who deliver by cesarean.

From the Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, University of Florida College of Medicine, Gainesville, Florida.

Presented as a poster at the American College of Obstetricians and Gynecologists Annual Clinical Meeting, May 5–9, 2012, San Diego, California.

Corresponding author: Patrick Duff, MD, University of Florida College of Medicine, Gainesville, FL 32610-0294; e-mail: duffp@ufl.edu.

Financial Disclosure The authors did not report any potential conflicts of interest.

Chorioamnionitis is a common obstetric complication, occurring in 1–5% of term pregnancies and in up to 25% of patients who undergo preterm delivery.1,2 If chorioamnionitis is treated promptly, serious sequelae are rare. Intrapartum treatment of chorioamnionitis reduces neonatal morbidity; thus, prompt and effective treatment is critically important for both the mother and the fetus.36 The most tested antibiotic regimen for chorioamnionitis is a combination of ampicillin, 2 g intravenously every 6 hours, plus gentamicin, 1.5 mg/kg every 8 hours.7,8 Metronidazole or clindamycin should be added to this regimen to enhance coverage of anaerobic organisms if the patient requires cesarean delivery. Failure to add anaerobic coverage in patients who undergo a cesarean delivery will result in treatment failure in up to 25% of patients.2,7

In most published reports of patients with chorioamnionitis, antibiotic treatment was continued until the patient was asymptomatic and afebrile for 24–48 hours, but this treatment approach was based largely on expert opinion.9 In 2003, Edwards and Duff10 published a study that compared single-dose postpartum antibiotic therapy with extended treatment in patients with chorioamnionitis. This randomized controlled trial demonstrated that there was no statistically significant difference in adverse outcomes (2.9% compared with 4.3%; P=.749) between patients who had only a single dose of postpartum antibiotics compared with those who received an extended course of medications (ie, treatment until they had been afebrile and asymptomatic for a minimum of 24 hours). As a result of this study, an extended course of antibiotics for chorioamnionitis has no longer been used at our institution.

The purpose of the present study was to estimate the adequacy and safety of this limited course of treatment for chorioamnionitis in a larger series of patients treated over a multiyear period. We wanted to assess whether limited-course therapy had waned in effectiveness as a result of changes in patient demographics or microbial susceptibility to our chosen antibiotics.

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MATERIALS AND METHODS

With approval from the University of Florida Health Center Institutional Review Board, under a protocol exempted from informed consent, we reviewed all records in our department's electronic database coded for a diagnosis of chorioamnionitis from January 1, 2005, through December 31, 2009. The diagnosis of clinical chorioamnionitis was defined by an intrapartum temperature of 38°C or more and one or more of the following findings: maternal heart rate greater than 100 beats per minute (bpm), baseline fetal heart rate greater than 160 bpm, uterine tenderness, or foul-smelling amniotic fluid. In addition, patients had no other obvious localizing sign of infection.2 This stringent definition excluded patients who may have had transient mild temperature elevations secondary to epidural anesthesia or misoprostol administration.

At the time the diagnosis of chorioamnionitis was made, patients were treated with our standard regimen of ampicillin 2 g intravenously every 6 hours plus gentamicin 1.5 mg/kg every 8 hours, until delivery, followed by a single postpartum dose at the appropriate drug-specific time interval.10 This treatment regimen was specified in a set of standing orders to ensure consistent compliance with recommended treatment. In patients who had a cesarean delivery, a single intravenous dose of metronidazole (500 mg) was administered after the neonate's umbilical cord was clamped to provide specific coverage against anaerobic organisms. Patients who were allergic to penicillin were treated intrapartum with clindamycin (900 mg intravenously every 8 hours) plus gentamicin (1.5 mg/kg intravenously every 8 hours) once the diagnosis of chorioamnionitis was established. If these patients had a cesarean delivery, metronidazole was not administered because clindamycin also has excellent antianaerobic coverage. Fewer than 10% of patients received clindamycin in lieu of metronidazole. Patients were followed after delivery by a team consisting of four residents and an attending physician.

We used descriptive statistics to assess the key outcome measure, which was therapeutic failure, defined as persistent postpartum fever requiring continuation of antibiotics, surgical intervention (to drain a pelvic abscess or incisional abscess), or administration of heparin (for septic pelvic vein thrombophlebitis). Persistent fever was defined as a single temperature of 39°C or higher after the first postpartum dose of antibiotics or two or more temperatures of 38.4°C or higher at least 4 hours apart. Patients identified as having therapeutic failures were divided into those with endometritis and those with the more serious complications of wound infection, pelvic abscess, and septic pelvic thrombophlebitis. The treatment failure group was analyzed for commonalities that may have contributed to the development of postpartum complications. Differences in the primary outcome in patients who had a vaginal delivery compared with a cesarean delivery were assessed using the uncorrected χ2 test. P<.05 was considered significant; 95% confidence intervals (CIs) were determined, as appropriate.

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RESULTS

Our medical center serves a predominantly indigent, rural population. Most patients are insured under the Florida Medicaid Insurance Program or are self-pay. The entire group of patients from whom we derived our study population is presented in Figure 1. As noted in the figure, our final sample included 423 patients, which represented 3.9% of the laboring patients during this time period.

Fig. 1

Fig. 1

Of the 423 patients reviewed, 282 delivered vaginally and 141 delivered by cesarean. Seventy-six percent of patients received epidural anesthesia. Overall, 399 (94%; 95% CI 92–96%) were treated successfully and 24 (6%; 95% CI 3.7–8.3) failed treatment. Of the 282 patients who delivered vaginally, 279 (99%; 95% CI 98–100%) were cured with short-course therapy. Of the 141 who delivered by cesarean, 120 (85%; 95% CI 79–91%) were cured (P<.001). Of those patients who failed therapy, 17 had endometritis. The remaining treatment failures included four patients with wound infections and three patients with septic vein thrombophlebitis. These seven patients were categorized as having “serious complications” (Fig. 2).

Fig. 2

Fig. 2

Of the 17 patients with endometritis, 14 underwent a cesarean delivery. The average hospital stay for these patients was 4 days (range 3–6 days). All except one had received antianaerobic therapy during cesarean delivery as per our protocol. All subsequently received gentamicin 7 mg/kg intravenously every 24 hours and clindamycin 900 mg intravenously every 8 hours until they were afebrile for 24 hours. None of these individuals required surgical intervention.

Four patients had wound infections, all after cesarean delivery. Their average hospital stay was 4 days (range 3–20 days). Three of these patients had had misoprostol inductions of labor, with lengths of labor of 27 hours, 28 hours, and 34 hours, and they subsequently required cesarean delivery for an arrest of dilation. Their body mass indexes (BMIs, calculated as weight (kg)/[height (m)]2) were 44.8, 31.1, and 48.5, respectively. The remaining patient had a cesarean delivery at 29 weeks for preterm premature rupture of membranes, chorioamnionitis, and malpresentation. All patients were discharged home on oral antibiotics; none developed fascial dehiscences.

Three patients, all of whom delivered by cesarean, had septic pelvic vein thrombophlebitis (ovarian vein thrombosis) confirmed by computed tomographic scan. All received additional antianaerobic therapy immediately after the umbilical cord was clamped. The average hospital stay for these patients was 13 days. All patients eventually responded to antibiotics plus intravenous heparin. Two had had misoprostol inductions of labor, with lengths of labor of 27 hours and 20 hours. Their BMIs were 29.2 and 31.1, respectively. The remaining patient was delivered secondary to preterm premature rupture of membranes, chorioamnionitis, and malpresentation. Her BMI was 40.3.

The average BMI of the seven patients who developed serious complications was 37. Five of the seven women were obese, defined as a BMI between 30 and 39, or extremely obese, defined as a BMI higher than 40. One was overweight, defined as a BMI of 25 to 29. One was of normal weight.

Overall, of the 21 treatment failures in the cesarean delivery group, 16 women had either prolonged rupture of membranes (n=6) or a BMI greater than 30 (n=10). Six women had both prolonged rupture of membranes and were obese. In the 120 women who had a cesarean delivery and were successfully treated, 42 had either prolonged rupture of membranes (n=3) or a BMI higher than 30 (n=39). None had both prolonged rupture of membranes and a BMI higher than 30. The difference in frequency of either prolonged rupture of membranes or a BMI higher than 30 in treatment failures compared with treatment successes was highly significant (P<.01).

All patients with treatment failure were identified while they were still hospitalized. A search of our electronic database demonstrated that none of the patients with an initially uncomplicated hospital course required readmission to our medical center with a delayed complication of chorioamnionitis.

We did not do routine microbiologic studies in patients with endometritis, wound infection, or septic pelvic vein thrombophlebitis. No patient had drainage of an intra-abdominal abscess for isolation of microorganisms.

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DISCUSSION

Several authors have recommended shorter courses of antibiotic treatment for chorioamnionitis. In 1997 Chapman and Owen11 studied 109 women who had been treated for chorioamnionitis in the intrapartum period and delivered vaginally. Of these, 55 women were given a single dose of antibiotics postpartum and 54 women were given multiple doses; women in both treatment groups had a similar incidence of failure. For women who delivered vaginally, a single postpartum dose of antibiotics reduced the cost and average length of hospital stay compared with women who were treated with multiple doses of antibiotics. The socioeconomic characteristics of the patients in this study were similar to those of our patients.

In a prospective, randomized, placebo-controlled, double-blinded trial of 36 women who delivered vaginally, LaBella et al12 found that postpartum antibiotics added little therapeutic benefit. In both the long and short arms of the trial, the incidence of persistent infection was less than 5% (P=not significant).

Our study supports the conclusions of these reports and the previous report from our institution10 that a limited course of antibiotics is sufficient postpartum therapy for most patients with chorioamnionitis, particularly those who deliver vaginally. In the original report by Edwards and Duff,10 the overall treatment failure rate was 4.6% in the short-term treatment group and 3.5% in the extended treatment group (P=.639). In the vaginal delivery group, the failure rate was 3.4% in the short-term group compared with 4.5% in the long-term group (P=.999). In the cesarean delivery group, the failure rates were 6.3% and 1.9%, respectively (P=.375).

The present study includes a larger sample size than the original investigation (n=423 compared with n=292) and confirms the effectiveness of the treatment regimen over a longer period of time (5 compared with 3 years). Our study shows that a limited course of antibiotics, overall, is effective in treating 94% (95% CI 92–96) of patients with chorioamnionitis. Only 1% of patients who delivered vaginally failed therapy compared with 15% of patients who delivered by cesarean (P<.001). Of the latter group, the women who failed therapy were likely either to be obese or to have had an extended duration of labor, ruptured membranes or both. We believe that the higher failure rate in the cesarean delivery group in the present study compared with our previous study is most likely due to the larger sample size, longer time period of observation, and the steadily increasing prevalence of obesity in our patient population.

With rising rates of obesity in the United States, it is important to address complications that uniquely affect this subset of the population. Obesity (BMI higher than 30) is clearly a major risk factor for wound infection.13 A recent large series reported by Robinson et al14 confirmed that obese women have an increased risk of preeclampsia, antepartum venous thromboembolism, gestational diabetes, premature induction of labor, cesarean delivery, and wound infection, as well as a higher prevalence of antibiotic use in labor and postpartum. The strong correlation between increased postpartum morbidity and obesity is also reflected in our treatment failure group. Of the seven patients in our analysis who developed serious complications, five were obese and one was severely overweight.

All our cases of serious complications occurred after cesarean delivery. Six of these deliveries were in patients who not only were obese, but also had a prolonged period of rupture of membranes. The remaining patient had prolonged preterm premature rupture of membranes. These findings indicate that, whereas single-dose postpartum antibiotic therapy is sufficient for essentially all patients having a vaginal delivery and for the majority of patients having a cesarean delivery, a distinct subset of patients, namely obese patients and those who are delivered by cesarean after a long period of labor and ruptured membranes, may benefit from a more extended course of antibiotic therapy.

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© 2012 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.