zithromax and Chorioamnionitis

This study aimed to estimate the effect of erythromycin vs azithromycin on the duration of latency and the rate of clinical chorioamnionitis in women with preterm prelabor rupture of membranes by performing a systematic review and meta-analysis of the existing literature.. From inception to October 2021, we explored MEDLINE, Scopus, Embase, CINAHL, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials.. Studies comparing the duration of latency and the rate of clinical chorioamnionitis between women with preterm prelabor rupture of membranes who were treated with erythromycin and those who were treated with azithromycin at the time of diagnosis were included.. Here, 2 reviewers separately ascertained studies, obtained data, and gauged study quality. The mean length of latency and the rate of clinical chorioamnionitis were compared and mean differences and odds ratios with 95% confidence intervals were estimated.. A total of 5 studies with 1289 women were identified. The mean length of latency in women with preterm prelabor rupture of membranes was similar between individuals treated with erythromycin and those treated with azithromycin: 6.6 days vs 6.7 days (mean difference, 0.07 days; 95% confidence interval, -0.45 to 0.60; I. The administration of azithromycin in women with preterm prelabor rupture of membranes was associated with a similar latency period but a lower rate of clinical chorioamnionitis than the administration of erythromycin.

Topics: Azithromycin; Chorioamnionitis; Erythromycin; Female; Fetal Membranes, Premature Rupture; Humans; Infant, Newborn; Pregnancy

Considerable evidence has shown that intra-amniotic infection with Ureaplasma spp. increases the risk of chorioamnionitis and preterm labor. Ureaplasma spp. are among the smallest organisms, and their isolation is uncommon in routine clinical practice because of their size and high auxotrophy. Although Ureaplasma spp. have been reported as causative agents of preterm birth, they also have a high incidence in vaginal swabs collected from healthy reproductive-age women; this has led to questions on the virulence of Ureaplasma spp. and to them being considered as harmless commensal bacteria. Therefore, many efforts have been made to clarify the pathogenicity of Ureaplasma spp. at the molecular level. Ureaplasma spp. are surrounded by lipoproteins, including multiple-banded antigen. Both multiple-banded antigen and its derivative, that is, the synthetic lipopeptide, UPM-1, induce an inflammatory response in a preterm mice model, which was adequate to cause preterm birth or stillbirth. In this review, we present an overview of the virulence mechanisms of Ureaplasma spp. and treatment of ureaplasma infection during pregnancy to prevent possible serious sequelae in infants. In addition, relevant mechanisms underlying antibiotic resistance in Ureaplasma spp. are discussed. Ureaplasma spp. are naturally resistant against β-lactam antibiotics because of the lack of a cell wall. Azithromycin is one of the effective agents that can control intrauterine ureaplasma infection. In fact, macrolide- and fluoroquinolone-resistant isolates of Ureaplasma spp. have already been observed in perinatal practice in Japan.

Topics: Adult; Amniotic Fluid; Anti-Bacterial Agents; Azithromycin; Chorioamnionitis; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Pregnancy; Pregnancy Complications, Infectious; Premature Birth; Ureaplasma; Ureaplasma Infections; Virulence

To compare the effectiveness of single-dose azithromycin, with or without amoxicillin, with placebo to prevent peripartum infection in laboring women.. We conducted a multicenter, three-group, double-blind randomized controlled trial of women with viable term nonanomalous pregnancies with either prolonged labor of 18 hours or longer or rupture of membranes for 8 hours or longer in Cameroon. Women with chorioamnionitis before randomization, study drug contraindications, or planned cesarean births were excluded. Women were randomized to oral azithromycin 1 g-placebo (group 1), oral azithromycin 1 g-oral amoxicillin 2 g (group 2), or placebo-placebo (group 3). All groups received usual care, including antibiotics given at the health care professional's discretion. The primary outcome was a composite of maternal peripartum infection or death from any cause up to 6 weeks postpartum. Two primary comparisons (group 1 vs group 3 and group 2 vs group 3) were planned. We estimated that 241 women per group (planning for 750 total) would provide 80% power at two-sided α=0.05 (0.025 per comparison) to detect a 50% effect size assuming 20% baseline composite infection rate.. From January 6, 2018, to May 15, 2020, 6,531 women were screened, and 756 (253 in group 1, 253 in group 2, and 250 in group 3) were randomized. Baseline characteristics (including body mass index, duration of rupture of membranes or labor, and parity) were balanced across groups, except for maternal age. More than 60% of women in each group received usual-care antibiotics: more than 90% penicillin and approximately 50% for prolonged rupture of membranes across all study groups. Composite outcome incidences were similar in antibiotic groups 1 (6%) and 2 (7%) compared with placebo group 3 (10%) (RR 0.6, 95% CI 0.3-1.2; 0.7, 95% CI 0.4-1.3, respectively). Chorioamnionitis and wound infection were significantly lower in group 2 (3.2% vs 0.4% and 4% vs 0.8% respectively, both P=.02) compared with group 3. There were no differences in other maternal or neonatal outcomes including neonatal infection.. A single dose of oral azithromycin with or without amoxicillin for prolonged labor or rupture of membranes at term did not reduce maternal peripartum or neonatal infection. Observed lower than expected infection rates and frequent usual-care antibiotic use may have contributed to these findings.. ClinicalTrials.gov, NCT03248297.. Merck for Mothers Investigator Studies Program grant.

Topics: Abscess; Administration, Oral; Adult; Amoxicillin; Anti-Bacterial Agents; Antibiotic Prophylaxis; Azithromycin; Bacterial Infections; Cameroon; Cesarean Section; Chorioamnionitis; Double-Blind Method; Endometritis; Female; Humans; Infant, Newborn; Infection Control; Labor, Obstetric; Peripartum Period; Pregnancy; Pregnancy Complications, Infectious; Sepsis; Treatment Outcome; Wound Infection

In the group of 35 patients with cerclage, intermediate fetal mortality was reduced from 37.1% to 0 (p < 0.001); late fetal mortality rate from 8.5% to 2.8% (p = 0.606); prematurity from 65.7% to 5.7% (p < 0.001); newborn underweight from 11.4% to 5.7% (p = 0.671); newborns with very low weight from 34.2% to 0 (p < 0.001) and the abortion rate from 8.5% to 0 ( p  < 0.001). In the group of 19 patients without buckling, intermediate fetal mortality was reduced from 26.3% to 10.5% (p = 402); late fetal mortality from 63.1% to 0 (p < 0.001); prematurity 78.9% to 31.5% (p < 0.009); the newborn of low weight from 31.5% to 10.5% (p = 0.234); newborns with very low weight from 68.4% to 15.7% (p < 0.003) and the abortion rate from 36.8 to 0 (p < 0.001). In conclusion, we believe the results of this study demonstrate the effectiveness of therapeutic and prophylactic cervical cerclage associated with prolonged antibiotic therapy.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Cerclage, Cervical; Chorioamnionitis; Drug Administration Schedule; Female; Fetal Death; Humans; Pregnancy; Premature Birth; Prospective Studies; Risk Factors; Treatment Outcome

To determine if maternal serum interleukin-6 (IL-6) levels remain predictive of funisitis after completion of antibiotic administration in preterm premature rupture of membranes (PPROM).. A secondary analysis of a prospective cohort study. Daily blood samples obtained from PPROM subjects were analyzed for IL-6 by enzyme-linked immunosorbent assay. Subjects (N = 39) delivered >7 days post admission and were divided into those with and without funisitis. Data were analyzed using Mann-Whitney U test.. Maternal serum IL-6 levels obtained 24-48 hours and 48-72 hours before delivery are elevated in PPROM subjects with funisitis compared to those without funisitis (6.3 vs. 2.7 pg/ml, P < 0.03; 6.1 vs. 1.7 pg/ml, P < 0.02). Receiver operator characteristic curve revealed an IL-6 level of 1.98 pg/ml had sensitivity of 86.7%, specificity of 46.7%, positive predictive value of 61.9% and negative predictive value of 77.8%.. This data suggests that maternal serum IL-6 levels continue to be predictive of PPROM subjects destined to develop funisitis after completion of antibiotics.

Topics: Ampicillin; Anti-Bacterial Agents; Azithromycin; Chorioamnionitis; Delivery, Obstetric; Female; Fetal Membranes, Premature Rupture; Humans; Interleukin-6; Mothers; Pregnancy; Prognosis; Time Factors; Treatment Failure

Preterm birth (PTB) is one of the leading causes of neonatal mortality and morbidity worldwide. A shortened cervix is a recognised risk factor for PTB, and amniotic fluid sludge (AFS) diagnosed on ultrasound may be suggestive of underlying inflammation or infection.. The aim is to determine if azithromycin, administered in cases of a shortened cervix, results in prolongation of gestation with improvements in neonatal outcomes.. We performed a retrospective cohort study at three tertiary maternity services in Melbourne, Australia, between 2015 and 2020. Women with a singleton pregnancy were included if they had a cervical length of 15 mm or less at 13-24 weeks' gestation, with or without AFS. Exclusion criteria comprised multiple pregnancy, major fetal congenital anomaly, placenta praevia, prelabour premature rupture of membranes, vaginal bleeding and/or clinical signs suggestive of chorioamnionitis at the time of diagnosis of the short cervix. The results of antibiotic treatment with azithromycin were compared to those of no antibiotic treatment. The outcomes of interest were PTB, prelabour premature rupture of membranes (PPROM), chorioamnionitis and neonatal morbidity.. A total of 374 women were included in the study, of whom 129 received azithromycin and 245 received no antibiotics. When adjusting for potential confounders, the adjusted risk of PTB overall was higher in the treatment group (adjusted hazard ratio 1.36 (95% confidence interval 1.04-1.77) P = 0.023) with no differences found for PPROM, chorioamnionitis or neonatal morbidity.. These data do not support the routine use of azithromycin in women with a short cervix, including those with AFS detected on ultrasound.

Topics: Amniotic Fluid; Anti-Bacterial Agents; Azithromycin; Cervix Uteri; Chorioamnionitis; Cohort Studies; Female; Fetal Membranes, Premature Rupture; Humans; Infant, Newborn; Pregnancy; Premature Birth; Retrospective Studies; Sewage

Ureaplasma parvum infection is a prevalent cause of intrauterine infection associated with preterm birth, preterm premature rupture of membranes, fetal inflammatory response syndrome, and adverse postnatal sequelae. Elucidation of diagnostic and treatment strategies for infection-associated preterm labor may improve perinatal and long-term outcomes for these cases.. This study assessed the effect of intraamniotic Ureaplasma infection on fetal hemodynamic and cardiac function and the effect of maternal antibiotic treatment on these outcomes.. Umbilical and fetal pulmonary artery vascular impedances were significantly increased in animals from the intraamniotic inoculation with Ureaplasma parvum group (P<.05). Azithromycin treatment restored values to control levels. Amniotic fluid prostaglandin F2 alpha levels were significantly higher in animals with abnormal umbilical artery pulsatility index (>1.1) than in those with normal blood flow (P<.05; Spearman ρ=0.6, P<.05). In the intraamniotic inoculation with Ureaplasma parvum group, left ventricular cardiac output was significantly decreased (P<.001), and more animals had abnormal right-to-left ventricular cardiac output ratios (defined as >1.6, P<.05). Amniotic fluid interleukin-6 concentrations were elevated in cases of abnormal right-to-left ventricular cardiac output ratios compared with those in normal cases (P<.05).. Fetal hemodynamic alterations were associated with intraamniotic Ureaplasma infection and ameliorated after maternal antibiotic treatment. Doppler ultrasonographic measurements merit continuing investigation as a diagnostic method to identify fetal cardiovascular and hemodynamic compromise associated with intrauterine infection or inflammation and in the evaluation of therapeutic interventions or clinical management of preterm labor.

Topics: Administration, Intravenous; Amnion; Amniotic Fluid; Animals; Anti-Bacterial Agents; Aorta; Azithromycin; Blood Flow Velocity; Cardiac Output; Chorioamnionitis; Disease Models, Animal; Ductus Arteriosus; Echocardiography, Doppler; Female; Fetal Heart; Hemodynamics; Injections; Interleukin-6; Macaca mulatta; Middle Cerebral Artery; Pregnancy; Pregnancy Complications, Infectious; Pulmonary Artery; Pulsatile Flow; Ultrasonography, Doppler; Ultrasonography, Prenatal; Umbilical Arteries; Ureaplasma; Ureaplasma Infections

To determine if antibiotic regimens including azithromycin versus erythromycin has an impact on pregnancy latency and development of clinical chorioamnionitis in the context of preterm prelabor rupture of membranes.. This study included 310 patients, with 142 receiving the azithromycin regimen and 168 receiving the erythromycin regimen. Patients receiving the azithromycin regimen had a statistically significant advantage in overall rates of clinical chorioamnionitis (13.4% versus 25%,. Our study suggests that latency antibiotic regimens substituting azithromycin for erythromycin have lower rates and decreased risk of clinical chorioamnionitis, neonatal sepsis, and postpartum endometritis with no difference in pregnancy latency.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Antibiotic Prophylaxis; Azithromycin; Cesarean Section; Chorioamnionitis; Drug Administration Schedule; Endometritis; Erythromycin; Female; Fetal Membranes, Premature Rupture; Humans; Middle Aged; Neonatal Sepsis; Postpartum Period; Pregnancy; Prospective Studies; Young Adult

Preterm premature rupture of membranes complicates 2-3% of pregnancies. Many institutions have advocated for the use of azithromycin instead of erythromycin. This is secondary to national shortages of erythromycin, ease of administration, better side effect profile, and decreased cost of azithromycin as compared with erythromycin.. The objective of the study was to evaluate whether there are differences in the latency from preterm premature rupture of membranes to delivery in patients treated with different dosing regimens of azithromycin vs erythromycin.. Four hundred fifty-three patients who met inclusion criteria were identified. Seventy-eight patients received azithromycin for 1 day, 191 patients received azithromycin for 5 days, 52 patients received azithromycin for 7 days, and 132 patients received erythromycin. Women who received the 5 day regimen were younger and less likely to be non-African American, have hypertension, have sexually transmitted infection, or experienced substance abuse. There was no statistical difference in median latency time of azithromycin 1 day (4.9 days, 95% confidence interval, 3.3-6.4), azithromycin 5 days (5.0, 95% confidence interval, 3.9-6.1), or azithromycin 7 days (4.9 days, 95% confidence interval, 2.8-7.0) when compared with erythromycin (5.1 days, 95% confidence interval, 3.9-6.4) after adjusting for demographic variables (P = .99). Clinical chorioamnionitis was not different between groups in the adjusted model. Respiratory distress syndrome was increased in the azithromycin 5 day group vs azithromycin 1 day vs erythromycin (44% vs. 29% and 29%, P = .005, respectively).. There was no difference in latency to delivery, incidence of chorioamnionitis, or neonatal outcomes when comparing different dosing regimens of the azithromycin with erythromycin, with the exception of respiratory distress syndrome being more common in the 5 day azithromycin group. Azithromycin could be considered as an alternative to erythromycin in the expectant management of preterm premature rupture of membranes if erythromycin is unavailable or contraindicated. There appears to be no additional benefit to an extended course of azithromycin beyond the single-day dosing, but final recommendations on dosing strategies should rely on clinical trials.

Topics: Adult; Amoxicillin; Ampicillin; Anti-Bacterial Agents; Azithromycin; Chorioamnionitis; Cohort Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Erythromycin; Female; Fetal Membranes, Premature Rupture; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Length of Stay; Pregnancy; Respiratory Distress Syndrome, Newborn; Retrospective Studies

Prophylactic antibiotics to prolong latency and reduce the risk of neonatal and maternal infections are used for preterm premature rupture of membranes. This study compared outcomes between two macrolides: roxithromycin given twice a day for a week and azithromycin, given as a single dose, which is more convenient.. Two local protocols were retrospectively compared: roxithromycin and ampicillin from July 2005 to May 2016, and azithromycin and ampicillin from May 2016 to May 2018. Inclusion criteria were singleton pregnancy, at 24-34 weeks of gestation upon admission with preterm premature rupture of membranes. Primary outcome was length of the latency period, defined as time from first antibiotic dose to 34 + 0 weeks, or spontaneous or indicated delivery prior to 34 + 0 weeks. Secondary outcomes were rates of chorioamnionitis, delivery mode, birth weight and Apgar scores.. A total of 207 women met inclusion criteria, of whom, 173 received penicillin and roxithromycin and 34 received penicillin and azithromycin. Baseline characteristics were similar between groups. The latent period was longer in the azithromycin group than in the roxithromycin group (14.09 ± 14.2 days and 7.87 ± 10.2 days, respectively, P = 0.003). Rates of chorioamnionitis, cesarean deliveries, Apgar scores and birth weights were similar between the groups.. Azithromycin compared to roxithromycin results in a longer latency period in the setting of preterm premature rupture of membranes at 24-34 weeks of gestation. Given its more convenient regimen and our results, it seems justified to use azithromycin as the first-line treatment for patients with preterm premature rupture of membranes.

Topics: Adult; Ampicillin; Anti-Bacterial Agents; Antibiotic Prophylaxis; Apgar Score; Azithromycin; Birth Weight; Cesarean Section; Chorioamnionitis; Comparative Effectiveness Research; Drug Administration Schedule; Female; Fetal Membranes, Premature Rupture; Humans; Infant, Newborn; Obstetric Labor Complications; Pregnancy; Pregnancy Outcome; Retrospective Studies; Roxithromycin; Treatment Outcome

First, to determinate the frequency of chorioamnionitis and funisitis in cases of intramniotic detection of Ureaplasma urealyticum. Second, to assess the predictive capability of some biological markers in the amniotic fluid of these women to predict histological inflammation.. We prospectively studied 20 cases of women with premature rupture of membranes or preterm labour (PROM) or preterm labour and intraamniotic detection of Ureaplasma urealyticum. Gestational age at admission was 26.74 ± 2.53 weeks. Amniotic fluid concentrations of IL18, IL 2, IL4, IL6, IL10, IL12, TNF-alpha, IFN-g, and MMP-8 were measured by the Multiplex method. Amniotic fluid glucose and leukocyte count were also measured by standard methods. Placental detailed histological studies were performed. Student's t-test, forward stepwise conditional binary logistic regression analysis and ROC curves were used.. Histological chorioamnionitis was present in 45% of cases (9/20) and funisitis just in 15% (3/20). Interleukins 6, 8, 12, MMP-8, and leukocyte count were significantly elevated in cases of histological inflammation, defined as choriamnionitis or chorioamniotis + funisitis (p = .007, .03, .01, .03, .03, respectively) while glucose was decreased (p = .04). Binary logistic regression for the prediction of inflammation showed a high predictive value (R. A significant percentage of cases with intraamniotic detection of Ureaplasma urealyticum shows no pathological signs of histological inflammation. Concentration of Interleukin 6 in amniotic fluid can be useful for the diagnosis of subclinical chorioamnionitis in these cases.

Topics: Adult; Amniotic Fluid; Anti-Bacterial Agents; Azithromycin; Biomarkers; Chorioamnionitis; Female; Humans; Pregnancy; Prospective Studies; Spain; Ureaplasma Infections; Ureaplasma urealyticum

Our goals were to describe azithromycin (AZI) pharmacokinetics in maternal plasma (MP), fetal plasma (FP), and amniotic fluid (AF) following intra-amniotic infection (IAI) with Ureaplasma in pregnant rhesus monkeys and to explore concentration-response relationships.. Following intra-amniotic inoculation of Ureaplasma parvum, rhesus monkeys received AZI (12.5 mg/kg every 12 hours intravenously for 10 days; n = 10). Intensive pharmacokinetic sampling of MP, FP, and AF was scheduled following the first (ie, single) dose and the last (ie, multiple) dose. Noncompartmental and pharmacokinetic modeling methods were used.. The AF area under the concentration-time curve at 12 hours was 0.22 µg×h/mL following a single dose and 6.3 µg×h/mL at day 10. MP and AF accumulation indices were 8.4 and 19, respectively. AZI AF half-life following the single dose and multiple dose were 156 and 129 hours, respectively. The median MP:FP ratio in concomitantly drawn samples was 3.2 (range, 1.3-9.6; n = 9). Eradication of U. parvum occurred at 6.6 days, with a 95% effective concentration (EC95) of 39 ng/mL for the maximum AZI AF concentration.. Our study demonstrates that a maternal multiple-dose AZI regimen is effective in eradicating U. parvum IAI by virtue of intra-amniotic accumulation and suggests that antenatal therapy has the potential to mitigate complications associated with U. parvum infection in pregnancy, such as preterm labor and fetal sequelae.

Topics: Administration, Intravenous; Amniotic Fluid; Animals; Anti-Bacterial Agents; Azithromycin; Chorioamnionitis; Disease Models, Animal; Female; Fetal Blood; Macaca mulatta; Pregnancy; Pregnancy Complications, Infectious; Ureaplasma Infections

We assessed the efficacy of a maternal multidose azithromycin (AZI) regimen, with and without antiinflammatory agents to delay preterm birth and to mitigate fetal lung injury associated with Ureaplasma parvum intraamniotic infection.. Long-term catheterized rhesus monkeys (n = 16) received intraamniotic inoculation of U parvum (10(7) colony-forming U/mL, serovar 1). After contraction onset, rhesus monkeys received no treatment (n = 6); AZI (12.5 mg/kg, every 12 h, intravenous for 10 days; n = 5); or AZI plus dexamethasone and indomethacin (n = 5). Outcomes included amniotic fluid proinflammatory mediators, U parvum cultures and polymerase chain reaction, AZI pharmacokinetics, and the extent of fetal lung inflammation.. Maternal AZI therapy eradicated U parvum intraamniotic infection from the amniotic fluid within 4 days. Placenta and fetal tissues were 90% culture negative at delivery. AZI therapy significantly delayed preterm delivery and prevented advanced fetal lung injury, although residual acute chorioamnionitis persisted.. Specific maternal antibiotic therapy can eradicate U parvum from the amniotic fluid and key fetal organs, with subsequent prolongation of pregnancy, which provides a therapeutic window of opportunity to effectively reduce the severity of fetal lung injury.

Topics: Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Azithromycin; Chorioamnionitis; Dexamethasone; Drug Therapy, Combination; Female; Fetal Diseases; Indomethacin; Lung Injury; Macaca mulatta; Polymerase Chain Reaction; Pregnancy; Premature Birth; Treatment Outcome; Ureaplasma; Ureaplasma Infections