Towers, C. V., Carr, M. H., Padilla, G., & Asrat, T. (1998). Potential consequences of widespread antepartal use of ampicillin. American journal of obstetrics and gynecology, 179(4), 879-883. https://doi.org/10.1016/s0002-9378(98)70182-6
Towers CV, Carr MH, Padilla G, Asrat T. Potential consequences of widespread antepartal use of ampicillin. Am J Obstet Gynecol. 1998;179(4):879-883. doi:10.1016/s0002-9378(98)70182-6
Towers, Craig V., et al. "Potential consequences of widespread antepartal use of ampicillin." American journal of obstetrics and gynecology, vol. 179, no. 4, 1998, pp. 879-883.
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Recommendations for the use of antenatal antibiotics in obstetrics have increased in the past few years, especially for prophylaxis against group B streptococci, for prolongation of the latency time in patients with preterm premature rupture of the membranes, and as an adjuvant treatment in preterm labor. Our objective was to determine whether the use of antenatal ampicillin affects the incidence of and resistance of early-onset neonatal sepsis with organisms other than group B streptococci.
Study Design
A prospective cohort study was performed between January 1, 1991, and December 31, 1996. Every case of blood culture-proven neonatal sepsis was prospectively surveyed. The type of bacteria isolated, drug resistance, antenatal antibiotic use and treatment indication, gestational age at delivery, and other antenatal and outcome variables were gathered. Early-onset neonatal sepsis was defined as disease onset within 7 days after birth.
Results
A total of 42 cases of early-onset neonatal sepsis among 29,897 neonates delivered were found during the 6-year period. Of these, 15 cases were due to group B streptococci and 27 were the result of non-group B streptococcal organisms (21 gram-negative rods and 6 gram-positive cocci). Among the 27 non-group B streptococcal cases, 15 mothers had received antenatal ampicillin and 13 of the 15 bacterial isolates from these neonates (87%) were resistant to ampicillin, versus only 2 ampicillin-resistant isolates (17%) among the 12 cases in which no antenatal antibiotics were administered (P = .0004). Of the 15 mothers who were treated with ampicillin, 13 received more than 1 dose. In evaluating each year of the study, the overall administration of antibiotics to pregnant women in the antenatal period increased from <10% in 1991 to 16.9% in 1996. The incidence of early-onset neonatal sepsis with group B streptococci decreased during this time, whereas the incidence of early-onset sepsis with non-group B streptococcal organisms, especially Escherichia coli, increased.
Conclusions
The increased administration of antenatal ampicillin to pregnant women may be responsible for the increased incidence of early-onset neonatal sepsis with non-group B streptococcal organisms that are resistant to ampicillin. At this time penicillin G, rather than ampicillin, is therefore recommended for prophylaxis against group B streptococci. In addition, future studies are needed to determine whether alternate approaches, such as immunotherapy or vaginal washing, could be of benefit.
We sought to evaluate the effect of antepartum and intrapartum antibiotic use on antimicrobial-resistant neonatal sepsis. We analyzed perinatal outcomes for 8474 pregnancies (8593 live births) delivered at 6 hospitals. Data were collected regarding maternal antibiotic use and perinatal course, neonatal cultures, and outcomes. The diagnosis of confirmed neonatal sepsis required at least one positive blood or cerebrospinal fluid culture. Neonatal cultures were evaluated on the basis of the occurrence and timing of maternal antibiotic exposure. There were 96 neonates with confirmed sepsis (11.2/1000 live births). Sepsis was 19.3-fold more common after preterm birth (57 vs 3. 1/1000; P <.001), with 76% of septic infants being delivered preterm. Forty-five percent of pathogens were ampicillin resistant. Ampicillin resistance increased with preterm birth (50% vs 26%; P =. 04), antepartum antibiotics (57% vs 34%; P =.03), intrapartum antibiotics (55% vs 28%; P <.01), and any prenatal antibiotic exposure (52% vs 22%; P =.01). Infection with an organism resistant to at least one maternal antibiotic was more common with intrapartum antibiotic exposure than with antepartum exposure only (57% vs 17%; P =.01). Regarding early-onset sepsis (n = 55), ampicillin resistance was more common with intrapartum antibiotics (50% vs 16%; P <.01), and resistance to at least one maternally administered antibiotic was more frequent with intrapartum exposure (56.7% vs 0%; P <.01). Maternal antibiotic treatment is associated with neonatal sepsis by organisms resistant to ampicillin and to maternally administered antibiotics.
Anti-Infective and Anti-Inflammatory Agents · Antibiotics in Reproductive Care
To compare ampicillin with and without sulbactam with respect to the effect on the latency period after preterm premature rupture of membranes (PROM). Patients with PROM at 25-35 weeks' gestation were offered participation in a randomized blinded trial comparing ampicillin-sulbactam with ampicillin. Evaluations for cervical pathogens were performed on admission and patients were followed-up with daily maternal and fetal evaluation. Maternal and neonatal outcomes were analyzed using indicated techniques. Fifty-three women were studied, with 25 receiving ampicillin-sulbactam and 28 receiving ampicillin. The ampicillin-sulbactam group had a significantly longer latency period (433 +/- 625 versus 143 +/- 165 hours, P = .03) and significantly fewer neonatal complications (five versus 20, P < .001). Although no neonatal infectious complications were observed in sulbactam-treated cases, there were four cases of neonatal sepsis and two of neonatal pneumonia in the ampicillin group. Also, significantly more neonates in the ampicillin group required prolonged oxygen and ventilatory support. There was no significant difference in maternal morbidity. In our population with preterm PROM, a broad-spectrum antibiotic that provides anaerobic coverage appears to extend latency and decrease neonatal morbidity without increasing adverse maternal outcome.
Progesterone metabolites and estriol were determined in urine and faeces collected daily from three pregnant women (33–37 weeks) before and during ampicillin administration (2 g/day orally).
Two of the three subjects showed marked changes in their faecal steroid excretion during ampicillin administration: the faecal progesterone-metabolite pattern changed from containing 69–79% unconjugated metabolites and 19–26% glucuronides under control conditions, to high steroid sulphate content (28–44%); the faecal elimination of 3β-hydroxy-5α-pregnan-20-one and 5α-pregnane-3β,20α-diol glucuronide all but ceased; two 16α-hydroxylated progesterone metabolites were detected in significant amounts in faeces during ampicillin administration but not under normal conditions. Steroid sulphate hydrolysis, epimerization of 3α,5αto 3β,5α-steroids and 16α-dehydroxylation are all well known actions of intestinal bacteria on biliary steroids. It thus seems clear that the changes found in the faecal progesterone metabolite pattern are due to the reduction of the intestinal flora by ampicillin.
Under control conditions the bulk of the faecal estriol was unconjugated. During ampicillin administration this excretion remained unchanged but in addition large quantities of conjugated estriol appeared in the faeces, apparently as a result of inhibition of bacterial deconjugation.
Ampicillin administration also caused decreased urinary excretion of estriol and pregnanediol glucuronide. It seems likely that these well documented effects of ampicillin on urinary steroid excretion are caused by an interruption of the enterohepatic circulation of steroids which results from the inhibition of intestinal steroid metabolism described above.
Preterm birth complicates 8-10% of all pregnancies in the United States and is the leading cause of infant morbidity and mortality. Neonatal morbidity and mortality is concentrated among very low-birthweight and extremely premature infants, particularly those delivered prior to 30 weeks' gestational age. In addition to the contribution of preterm birth to neonatal morbidity and mortality, the economic costs associated with this pregnancy complication are staggering. Efforts to reduce the preterm birth rate have been largely focused on prevention and early intervention with treatment for preterm labor. Mixed results regarding the success of prematurity prevention programs have been reported, and controversy continues to surround the efficacy of tocolytic therapy in the treatment of preterm labor. Although neonatal survival for infants born at early gestational ages has steadily improved in recent years, survival of infants delivered prior to 24 weeks' gestation remains very poor. Additionally, despite this decline in neonatal mortality, the United States still lags behind most industrialized nations in infant mortality, and no change in the rate of low birthweight has occurred in recent decades. Multiple lines of evidence support a role for infection as an etiologic factor in preterm labor. Although this association has been well known for many years, a wealth of new data is emerging, linking subclinical genital tract infection with spontaneous preterm birth, particularly among pregnancies that result in birth prior to 30 weeks' gestational age as a result of spontaneous preterm labor or preterm, premature rupture of membranes. Conversely, preterm birth that occurs closer to term is less likely to be associated with genital tract infection. Improved understanding of the link between genital tract infection and preterm birth now provides an exciting potential for the development of sensitive new markers to identify women at risk and effective interventions to prevent preterm birth. A review and comment on this growing literature is provided.
Therapeutics › Anti-Infective and Anti-Inflammatory Agents › Antibiotics in Reproductive Care · Pregnancy › Neonatal Outcomes › Neonatal Morbidity
PMID 9790363 9790363 DOI 10.1016/s0002-9378(98)70182-6 10.1016/s0002-9378(98)70182-6 Towers et al. 1998, Towers 1998
Cite this article
Towers, C. V., Carr, M. H., Padilla, G., & Asrat, T. (1998). Potential consequences of widespread antepartal use of ampicillin. American journal of obstetrics and gynecology, 179(4), 879-883. https://doi.org/10.1016/s0002-9378(98)70182-6
Towers CV, Carr MH, Padilla G, Asrat T. Potential consequences of widespread antepartal use of ampicillin. Am J Obstet Gynecol. 1998;179(4):879-883. doi:10.1016/s0002-9378(98)70182-6
Towers, Craig V., et al. "Potential consequences of widespread antepartal use of ampicillin." American journal of obstetrics and gynecology, vol. 179, no. 4, 1998, pp. 879-883.
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