ro13-9904 and Chorioamnionitis

This review aimed to examine the existing evidence about interventions proposed for the treatment of clinical chorioamnionitis, with the goal of developing an evidence-based contemporary approach for the management of this condition. Most trials that assessed the use of antibiotics in clinical chorioamnionitis included patients with a gestational age of ≥34 weeks and in labor. The first-line antimicrobial regimen for the treatment of clinical chorioamnionitis is ampicillin combined with gentamicin, which should be initiated during the intrapartum period. In the event of a cesarean delivery, patients should receive clindamycin at the time of umbilical cord clamping. The administration of additional antibiotic therapy does not appear to be necessary after vaginal or cesarean delivery. However, if postdelivery antibiotics are prescribed, there is support for the administration of an additional dose. Patients can receive antipyretic agents, mainly acetaminophen, even though there is no clear evidence of their benefits. Current evidence suggests that the administration of antenatal corticosteroids for fetal lung maturation and of magnesium sulfate for fetal neuroprotection to patients with clinical chorioamnionitis between 24 0/7 and 33 6/7 weeks of gestation, and possibly between 23 0/7 and 23 6/7 weeks of gestation, has an overall beneficial effect on the infant. However, delivery should not be delayed to complete the full course of corticosteroids and magnesium sulfate. Once the diagnosis of clinical chorioamnionitis has been established, delivery should be considered, regardless of the gestational age. Vaginal delivery is the safer option and cesarean delivery should be reserved for standard obstetrical indications. The time interval between the diagnosis of clinical chorioamnionitis and delivery is not related to most adverse maternal and neonatal outcomes. Patients may require a higher dose of oxytocin to achieve adequate uterine activity or greater uterine activity to effect a given change in cervical dilation. The benefit of using continuous electronic fetal heart rate monitoring in these patients is unclear. We identified the following promising interventions for the management of clinical chorioamnionitis: (1) an antibiotic regimen including ceftriaxone, clarithromycin, and metronidazole that provides coverage against the most commonly identified microorganisms in patients with clinical chorioamnionitis; (2) vaginal cleansing with antiseptic solution

Topics: Acetylcysteine; Adrenal Cortex Hormones; Ampicillin; Anti-Bacterial Agents; Anti-Infective Agents, Local; Antioxidants; Antipyretics; Ceftriaxone; Cesarean Section; Chorioamnionitis; Clarithromycin; Clindamycin; Delivery, Obstetric; Endometritis; Evidence-Based Medicine; Female; Gentamicins; Gestational Age; Humans; Magnesium Sulfate; Metronidazole; Practice Guidelines as Topic; Pregnancy; Puerperal Infection; Tocolytic Agents

Topics: Abortion, Septic; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Ceftriaxone; Chorioamnionitis; Female; Humans; Pregnancy; Pregnancy Complications, Infectious; Salmonella enteritidis; Salmonella Infections; Young Adult

The disposition of ornidazole and its two major hydroxylated metabolites was studied in five pregnant women (gestational ages 25 5/7 to 38 4/7 weeks) with either chorioamnionitis or pyelonephritis treated with ceftriaxone 2 g, tobramycin 3 mg/kg body weight and ornidazole 1 g all administered once-daily. Two series of blood samples were obtained, the first on the first day of treatment and the second at steady-state on day 5. Local and systemic tolerability of ornidazole was excellent and patients showed complete remission without premature delivery. There was no evidence of ornidazole accumulation, and the pharmacokinetic parameters were very similar to those seen in healthy subjects. The dosage regimen of ornidazole therefore requires no adjustment during pregnancy. Trough concentrations of ornidazole measured at 24 h post dose were above the MIC of sensitive organisms. Children born to the trial patients showed normal initial development and their growth was normal.

Topics: Adult; Ceftriaxone; Chorioamnionitis; Drug Therapy, Combination; Escherichia coli Infections; Female; Humans; Infant, Newborn; Ornidazole; Pregnancy; Pregnancy Complications, Infectious; Proteus Infections; Pyelonephritis; Tobramycin

Cervical insufficiency is a risk factor for spontaneous midtrimester abortion or early preterm birth. Intra-amniotic infection has been reported in 8-52% of such patients and intra-amniotic inflammation in 81%. Some professional organizations have recommended perioperative antibiotic treatment when emergency cervical cerclage is performed. The use of prophylactic antibiotics is predicated largely on the basis that they reduce the rate of complications during the course of vaginal surgery. However, it is possible that antibiotic administration can also eradicate intra-amniotic infection/inflammation and improve pregnancy outcome.. To describe the outcome of antibiotic treatment in patients with cervical insufficiency and intra-amniotic infection/inflammation.. Of 22 patients with cervical insufficiency and intra-amniotic infection/inflammation, 3 (14%) had microorganisms in the amniotic fluid. Of the 22 patients, 6 (27%) delivered within 1 week of amniocentesis and the remaining 16 (73%) delivered more than 1 week after the diagnostic procedure. Among these, 12 had a repeat amniocentesis to assess the microbial and inflammatory status of the amniotic cavity; in 75% (9/12), there was objective evidence of resolution of intra-amniotic inflammation or intra-amniotic infection demonstrated by analysis of amniotic fluid at the time of the repeat amniocentesis. Of the 4 patients who did not have a follow-up amniocentesis, all delivered ≥34 weeks, 2 of them at term; thus, treatment success occurred in 59% (13/22) of cases.. In patients with cervical insufficiency and intra-amniotic infection/inflammation, administration of antibiotics (ceftriaxone, clarithromycin, and metronidazole) was followed by resolution of the intra-amniotic inflammatory process or intra-amniotic infection in 75% of patients and was associated with treatment success in about 60% of cases.

Topics: Adult; Amniocentesis; Amniotic Fluid; Anti-Bacterial Agents; Biomarkers; Candida albicans; Ceftriaxone; Cerclage, Cervical; Chorioamnionitis; Clarithromycin; Delivery, Obstetric; Female; Humans; Interleukin-6; Leukocytes; Matrix Metalloproteinase 8; Metronidazole; Pregnancy; Retrospective Studies; Streptococcus anginosus; Ureaplasma; Uterine Cervical Incompetence

Intra-amniotic infection is present in 10% of patients with an episode of preterm labor, and is a risk factor for impending preterm delivery and neonatal morbidity/mortality. Intra-amniotic inflammation is often associated with intra-amniotic infection, but is sometimes present in the absence of detectable microorganisms. Antibiotic treatment of intra-amniotic infection has traditionally been considered to be ineffective. Intra-amniotic inflammation without microorganisms has a prognosis similar to that of intra-amniotic infection.. To determine whether antibiotics can eradicate intra-amniotic infection or intra-amniotic inflammation in a subset of patients with preterm labor and intact membranes.. The study population consisted of women who met the following criteria: 1) singleton gestation between 20 and 34 weeks; 2) preterm labor and intact membranes; 3) transabdominal amniocentesis performed for the evaluation of the microbiologic/inflammatory status of the amniotic cavity; 4) intra-amniotic infection and/or intra-amniotic inflammation; and 5) received antibiotic treatment that consisted of ceftriaxone, clarithromycin, and metronidazole. Follow-up amniocentesis was performed in a subset of patients. Amniotic fluid was cultured for aerobic and anaerobic bacteria and genital mycoplasmas, and polymerase chain reaction was performed for Ureaplasma spp. Intra-amniotic infection was defined as a positive amniotic fluid culture or positive polymerase chain reaction, and intra-amniotic inflammation was suspected when there was an elevated amniotic fluid white blood cell count or a positive result of a rapid test for matrix metalloproteinase-8. For this study, the final diagnosis of intra-amniotic inflammation was made by measuring the interleukin-6 concentration in stored amniotic fluid (>2.6 ng/mL). These results were not available to managing clinicians. Treatment success was defined as eradication of intra-amniotic infection and/or intra-amniotic inflammation or delivery ≥37 weeks.. Of 62 patients with intra-amniotic infection and/or intra-amniotic inflammation, 50 received the antibiotic regimen. Of those patients, 29 were undelivered for ≥7 days and 19 underwent a follow-up amniocentesis. Microorganisms were identified by culture or polymerase chain reaction of amniotic fluid obtained at admission in 21% of patients (4/19) who had a follow-up amniocentesis, and were eradicated in 3 of the 4 patients. Resolution of intra-amniotic infection/inflammation was confirmed in 79% of patients (15/19), and 1 other patient delivered at term, although resolution of intra-amniotic inflammation could not be confirmed after a follow-up amniocentesis. Thus, resolution of intra-amniotic inflammation/infection or term delivery (treatment success) occurred in 84% of patients (16/19) who had a follow-up amniocentesis. Treatment success occurred in 32% of patients (16/50) with intra-amniotic infection/inflammation who received antibiotics. The median amniocentesis-to-delivery interval was significantly longer among women who received the combination of antibiotics than among those who did not (11.4 days vs 3.1 days: P = .04).. Eradication of intra-amniotic infection/inflammation after treatment with antibiotics was confirmed in 79% of patients with preterm labor, intact membranes, and intra-amniotic infection/inflammation who had a follow-up amniocentesis. Treatment success occurred in 84% of patients who underwent a follow-up amniocentesis and in 32% of women who received the antibiotic regimen.

Topics: Adult; Amniocentesis; Amniotic Fluid; Anti-Bacterial Agents; Biomarkers; Ceftriaxone; Chorioamnionitis; Clarithromycin; Delivery, Obstetric; Female; Humans; Interleukin-6; Leukocyte Count; Matrix Metalloproteinase 8; Metronidazole; Obstetric Labor, Premature; Pregnancy; Pregnancy Complications, Infectious; Retrospective Studies

Antibiotic administration is a standard practice in preterm premature rupture of membranes (PROM). Specific anti-microbial agents often include ampicillin and/or erythromycin. Anaerobes and genital mycoplasmas are frequently involved in preterm PROM, but are not adequately covered by antibiotics routinely used in clinical practice. Our objective was to compare outcomes of PROM treated with standard antibiotic administration versus a new combination more effective against these bacteria.. A retrospective study compared perinatal outcomes in 314 patients with PROM <34 weeks receiving anti-microbial regimen 1 (ampicillin and/or cephalosporins; n = 195, 1993-2003) versus regimen 2 (ceftriaxone, clarithromycin and metronidazole; n = 119, 2003-2012). Intra-amniotic infection/inflammation was assessed by positive amniotic fluid culture and/or an elevated amniotic fluid MMP-8 concentration (>23 ng/mL).. (1) Patients treated with regimen 2 had a longer median antibiotic-to-delivery interval than those with regimen 1 [median (interquartile range) 23 d (10-51 d) versus 12 d (5-52 d), p < 0.01]; (2) patients who received regimen 2 had lower rates of acute histologic chorioamnionitis (50.5% versus 66.7%, p < 0.05) and funisitis (13.9% versus 42.9%, p < 0.001) than those who had received regimen 1; (3) the rates of intra-ventricular hemorrhage (IVH) and cerebral palsy (CP) were significantly lower in patients allocated to regimen 2 than regimen 1 (IVH: 2.1% versus 19.0%, p < 0.001 and CP: 0% versus 5.7%, p < 0.05); and (4) subgroup analysis showed that regimen 2 improved perinatal outcomes in pregnancies with intra-amniotic infection/inflammation, but not in those without intra-amniotic infection/inflammation (after adjusting for gestational age and antenatal corticosteroid administration).. A new antibiotic combination consisting of ceftriaxone, clarithromycin, and metronidazole prolonged the latency period, reduced acute histologic chorioamnionitis/funisitis, and improved neonatal outcomes in patients with preterm PROM. These findings suggest that the combination of anti-microbial agents (ceftriaxone, clarithromycin, and metronidazole) may improve perinatal outcome in preterm PROM.

Topics: Adult; Anti-Bacterial Agents; Ceftriaxone; Chorioamnionitis; Clarithromycin; Drug Therapy, Combination; Female; Fetal Membranes, Premature Rupture; Humans; Infant, Newborn; Metronidazole; Obstetric Labor, Premature; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Retrospective Studies; Time Factors

To determine whether a new antibiotic regimen could reduce the frequency of intra-amniotic inflammation/infection in patients with preterm PROM.. This retrospective cohort study was conducted to evaluate the effect of antibiotics on the frequency of intra-amniotic inflammation/infection based on the results of follow-up transabdominal amniocenteses from 89 patients diagnosed with preterm PROM who underwent serial amniocenteses. From 1993-2003, ampicillin and/or cephalosporins or a combination was used ("regimen 1"). A new regimen (ceftriaxone, clarithromycin and metronidazole) was used from 2003-2012 ("regimen 2"). Amniotic fluid was cultured and matrix metalloproteinase-8 (MMP-8) concentrations were measured.. (1) The rates of intra-amniotic inflammation and intra-amniotic inflammation/infection in patients who received regimen 2 decreased during treatment from 68.8% to 52.1% and from 75% to 54.2%, respectively. In contrast, in patients who received regimen 1, the frequency of intra-amniotic inflammation and infection/inflammation increased during treatment (31.7% to 55% and 34.1% to 58.5%, respectively); and (2) intra-amniotic inflammation/infection was eradicated in 33.3% of patients who received regimen 2, but in none who received regimen 1.. The administration of ceftriaxone, clarithromycin and metronidazole was associated with a more successful eradication of intra-amniotic inflammation/infection and prevented secondary intra-amniotic inflammation/infection more frequently than an antibiotic regimen which included ampicillin and/or cephalosporins in patients with preterm PROM.

Topics: Adult; Anti-Bacterial Agents; Antibiotic Prophylaxis; Ceftriaxone; Chorioamnionitis; Clarithromycin; Drug Therapy, Combination; Female; Fetal Membranes, Premature Rupture; Humans; Metronidazole; Pregnancy; Retrospective Studies; Young Adult

Topics: Adult; Anaphylaxis; Anti-Bacterial Agents; Ceftriaxone; Cesarean Section; Chorioamnionitis; Female; Fetal Membranes, Premature Rupture; Gestational Age; Humans; Obstetric Labor Complications; Pregnancy; Streptococcal Infections

Topics: Adult; Anti-Bacterial Agents; Ceftriaxone; Chorioamnionitis; Fatal Outcome; Female; Fetal Death; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Recurrence; Streptococcal Infections; Streptococcus agalactiae

The purpose of this study was to determine ceftriaxone (CTX) pharmacokinetics during pregnancy. Six women (26 to 34 years of age) admitted for chorioamnionitis (n = 4) or pyelonephritis (n = 2) were included. Gestational age ranged from 29 1/7 to 40 5/7 weeks. Initial intravenous treatment was ceftriaxone (CTX) (2 g/d), tobramycin (3 mg/kd/d) and ornidazole (1 g/d). Blood specimens were collected during the first treatment day (D1) to determine the primary pharmacokinetic profile of CTX then at steady-state (D7) to look for systemic accumulation. In two patients, transplacental passage of CTX was evaluated by determining the ratio of fetal and maternal concentrations (F/M) at delivery. Plasma CTX levels were determined using high-performance liquid chromatography. A noncompartmental method was used for pharmacokinetic analysis. Each patient served as her own control. Data obtained on D1 and D7 were compared using Wilcoxon's test (values of p < or = 0.05 were considered significant). A group of healthy controls given a similar regimen was also used. 1) Tolerance was outstanding, recovery was achieved in every case, and there were no premature deliveries. 2) No evidence of accumulation of CTX was found and kinetic profiles on D1 and D7 were not significantly different. 3) Mean kinetic parameter values were closely similar to those found in healthy volunteers. 4) Residual levels of total CTX and free CTX determined after 24 hours were greater than the minimal inhibitory concentration (MICs) of susceptible organisms. 5) The usual recommended dosage of CTX (2 g/d) proved adequate during the third trimester of pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Ceftriaxone; Chorioamnionitis; Drug Therapy, Combination; Escherichia coli Infections; Female; Humans; Placenta; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Trimester, Third; Proteus Infections; Pseudomonas Infections

The pharmacokinetics of ceftriaxone (CTRX) and its clinical efficacy in perinatal infections were studied. The obtained results are summarized as follows. 1. Concentrations of CTRX in maternal serum, umbilical cord serum and amniotic fluid were determined following intravenous injection with 1 g of CTRX. Maternal serum levels were not lower than 100 micrograms/ml immediately after administration, and gradually decreased to about 10 micrograms/ml in 12 hours, and to 4 micrograms/ml in 24 hours. The half-life of CTRX in maternal serum was 5.6 hours. CTRX levels in umbilical cord serum were about 7 micrograms/ml at 10 minutes after injection, increasing to 12 to 13 micrograms/ml in 12 hours and decreasing to 5 micrograms/ml in 24 hours. CTRX levels in amniotic fluid were slightly lower than those in the umbilical cord serum, and about 2 micrograms/ml at 10 minutes after injection, and they remained at 4 to 8 micrograms/ml thereafter for 28 hours. 2. CTRX (1 g) was intravenously administered twice daily to 9 patients with perinatal infections for 3 to 7 days. Clinical efficacies of CTRX were judged excellent in 2 cases and good in 7, suggesting that CTRX was effective in all cases. No side effects or laboratory abnormalities were observed in any case. As a result of these findings, CTRX may be considered a very useful antibiotic in perinatal infections.

Topics: Amniotic Fluid; Ceftriaxone; Cesarean Section; Chorioamnionitis; Endometritis; Female; Fetal Blood; Humans; Injections, Intravenous; Pregnancy; Premedication; Puerperal Infection