The effect of timing of single-dose transplacental ampicillin-sulbactam therapy for prevention of neonatal group B streptococcal colonization and bacteremia in a rabbit model.

OBJECTIVE: Our purpose was to evaluate the effect of maternal administration of ampicillin-sulbactam on group B streptococcal colonization and bacteremia in newborn rabbits. STUDY DESIGN: Before induction of labor, timed pregnant New Zealand White rabbits on day 29 of a 31-day gestation received no therapy or ampicillin-sulbactam 50 mg/kg intramuscularly as a single dose 2 to 8 hours before delivery. Labor was induced with oxytocin. After delivery, the oropharynx of each pup was inoculated with 10(9) cfu of type la group B Streptococcus. Cultures of each pup were taken from the oropharynx and anorectum daily and from the heart at death or after 96 hours. Ampicillin-sulbactam concentrations were determined at delivery in both mothers and pups. RESULTS: Thirteen animals were assigned to no therapy and 14 animals to ampicillin-sulbactam. Untreated pups had 100% oropharyngeal colonization at 24 hours. Pups treated with antibiotic were significantly less likely to have positive oropharyngeal cultures at 24 and 48 hours after birth than did untreated pups (24 hours 47% vs 100%, p < 0.0001; 48 hours 68% vs 91%, p = 0.0006). For anorectal cultures treated pups were significantly less likely to have positive culture results. Heart cultures were also less likely to have positive results for treated animals at 48 and 72 hours than for untreated animals (48 hours 30% vs 96%, p = 0.0001; 72 hours 31% vs 71%, p = 0.03). Treated pups had higher rates of survival at 48 hours (89% vs 62%, p < 0.0001). When neonatal oropharyngeal colonization at 24 hours after birth was compared with length of time from maternal antibiotic injection to delivery, there was a significant polynomial relationship (r = 0.78, p < 0.05). Ampicillin-sulbactam serum concentrations were highest 3 to 5 hours after injection. An inverse relationship existed between the rate of neonatal oropharyngeal colonization with group B streptococci at 24 hours after birth and neonatal ampicillin serum concentrations near birth (r = 0.733). CONCLUSION: Transplacental treatment with a single intramuscular dose of ampicillin-sulbactam significantly decreased neonatal colonization and bacteremia after oral inoculation with type la group B Streptococcus. An effect of ampicillin-sulbactam was evident as early as 2 hours but maximal 3 to 5 hours after injection.

A comparison of aztreonam and two regimens of gentamicin in a rabbit model of intra-amniotic infection and sepsis.

OBJECTIVE: To compare aztreonam in a standard dose with two gentamicin doses in the early treatment of experimental intra-amniotic infection in rabbits induced by intracervical inoculation with Escherichia coli. METHODS: Timed pregnant rabbits on day 21 (70% of gestation) were inoculated intracervically with 10(4)-10(5) colony-forming units of E coli. After inoculation, the animals were treated with one of three regimens: 1) aztreonam at 90 mg/kg/day ("standard" dose in humans), 2) gentamicin at 4.5 mg/kg/day ("standard" dose in humans), or 3) higher-dose gentamicin at 6.0 mg/kg/day, each given in three divided doses daily. Outcomes included fever, delivery, and presence of a live fetus. At necropsy, cultures were taken from endometrium, amniotic fluid, and blood. Data were analyzed by Fisher exact test because the expected cell size was fewer than five. RESULTS: Compared with rabbits treated with aztreonam, those treated with gentamicin 4.5 mg/kg/day delivered significantly more often (P = .002), had more positive cultures (P < .001), and had significantly fewer live fetuses (P < .001). Compared with rabbits treated with gentamicin 6.0 mg/kg/day, those treated with gentamicin 4.5 mg/kg/day delivered more often (P = .003), had fewer live fetuses (P = .02), and had more positive cultures (P = .02). There were no significant differences between the aztreonam and gentamicin 6.0 mg/kg/day groups. CONCLUSIONS: This study demonstrates in an animal model that aztreonam and gentamicin at 6.0 mg/kg/day are more effective than gentamicin at 4.5 mg/kg/day (a dose that is widely used empirically in humans) in the early treatment of experimental intra-amniotic infection in rabbits. Aztreonam was as effective as gentamicin at 6.0 mg/kg/day. In this rabbit model, in which intra-amniotic infection is accompanied by maternal sepsis, 4.5 mg/kg/day of gentamicin was not adequate for the treatment of severe maternal infection.

A rabbit model for bacterially induced preterm pregnancy loss: intervention studies with ampicillin-sulbactam.

We conducted experiments with a previously described rabbit model of Escherichia coli-induced preterm pregnancy loss. Does at 70% gestation were inoculated hysteroscopically with 0.2 ml of Escherichia coli (10(5) colony-forming units per milliliter) or saline solution. Animals were randomly assigned to either receive treatment with ampicillin-sulbactam (begun 1 to 2 hours before inoculation and continued for up to 7 days) or to receive no therapy. Animals were killed after delivery or after 7 days. Saline solution-inoculated animals had no pregnancy loss. Of the Escherichia coli-inoculated animals, those treated with ampicillin-sulbactam had significantly fewer deliveries, fewer positive cultures, and more live fetuses than the untreated animals (p less than or equal to 0.001). Cultures from multiple sites, amniotic fluid prostaglandin levels, and maternal progesterone levels were obtained, and the placenta, uterus, and fetal lung were histologically evaluated. In the second phase of the study, the Escherichia coli-inoculated animals were treated with ampicillin-sulbactam at one of three times: at inoculation or 2 or 4 hours after inoculation. The Escherichia coli-inoculated does treated with ampicillin-sulbactam at or before inoculation had significantly fewer deliveries, fewer positive cultures, and more live fetuses than the Escherichia coli-inoculated does in which treatment was delayed 4 hours (p less than or equal to 0.01).

Heterofermentative carbohydrate metabolism of lactose-impaired mutants of Streptococcus lactis.

Two mutants of Streptococcus lactis ATCC 11454 have been isolated which possess an impaired lactose-fermenting capacity; galactose utilization is also affected, but to a lesser extent. Although the Embden-Meyerhof-Parnas pathway is the major, if not the sole, pathway of carbohydrate metabolism in the three strains, the fermentation end products of the mutants are dramatically different from the typical homolactic pattern of the wild type. Under conditions of low oxygen tension and growth-limiting lactose concentrations, mutant strain T-1 produces largely formic acid, acetic acid (2:1), and ethanol rather than lactic acid. Aerated cultures produce acetic acid, CO(2) (1:1), acetyl-methylcarbinol, and diacetyl. When the mutants use galactose as an energy source, lactic acid is the major end product, but significant heterofermentative activity is observed. The aberrations responsible for the mutant phenotypes reside in the proteins which catalyze the transport and hydrolysis of galactosides. It is hypothesized that the impaired transport system of the mutants reduces the intracellular pool of glycolytic intermediates below that of the wild type. Since fructose-1, 6-diphosphate is an activator of lactic dehydrogenase in S. lactis, lactic acid production is reduced, and pathways leading to the formation of other products are expressed.