Rapid death of infant rhesus monkeys injected with Clostridium difficile toxins A and B: physiologic and pathologic basis

Clostridium botulinum can colonize and produce botulinal toxin in the human infant intestine, which the toxin then permeates to cause generalized flaccid paralysis, and occasionally, sudden death. This study was undertaken to test the hypothesis that toxins produced by other intestinal clostridia, e.g., C. difficile, might also cause systemic illness and sometimes death in infants (J Pediatr 100:568, 1982). Because this hypothesis could not be evaluated clinically until the systemic manifestations of C. difficile toxins in primates were known, infant rhesus monkeys were given 6 to 11 micrograms/kg of the recently purified C. difficile toxins A or B, either intravenously or intraperitoneally. The animals showed no abnormalities for several hours, but then developed lethargy, hypotonia, hypothermia, and, shortly before death, sudden elevation of serum concentrations of potassium, magnesium, and phosphorus and of enzymes that derived mainly from skeletal muscle, heart and brain. Five of six animals died quietly 3.5 to 8.0 hours after onset of symptoms. Death appeared to result from cessation of breathing, after which the sinus tachycardia then deteriorated to a flat ECG. Necropsy findings were insufficient to explain the cause of death. It appears that in infant monkeys microgram amounts of C. difficile toxins A and B can produce a rapid quiet death, the cause of which is undetectable at necropsy, a situation pathologically reminiscent of crib death in human infants, although the possible clinical identity of these two conditions has yet to be established.     

Potentiation of neuromuscular weakness in infant botulism by aminoglycosides.

A retrospective study of ten patients with infant botulism who received gentamicin or kanamycin suggests that aminoglycoside antibiotics potentiate muscular weakness and precipitate respiratory failure as late as 27 days after onset of the disease. Although it is difficult to separate progression of the disease from the effects of antibiotics, the rapidity of deterioration following aminoglycoside treatment and the rapidity of recovery following cessation of aminoglycoside therapy is highly suggestive. A review of five patients who received only penicillin or a semisynthetic derivative of penicillin did not reveal any temporal deterioration with onset of penicillin therapy or improvement with cessation of penicillin therapy.     

Prolactin in umbilical cord blood and the respiratory distress syndrome.

Prolactin was measured in umbilical cord serum obtained from 77 newborn infants of gestational age 28 to 40 weeks. A positive correlation with gestational age was demonstrated. Between 30 and 36 weeks of gestation the elevation of the regression line of the concentration of cord PRL versus gestation age was significantly lower (P less than 0.05) for those infants who developed respiratory distress syndrome compared to the regression line for infants who did not develop RDS. Between 32 and 33.5 weeks, the mean +/- SEM cord PRL concentration in infants who developed RDS (101.7 +/- 9.5 ng/ml) was significantly less (P less than 0.025) than the PRL concentration in those who did not develop RDS (161.8 +/- 18.9 ng/ml). Cord PRL did not correlate with cord cortisol or dehydroepiandrosterone sulfate concentrations. Cord growth hormone concentrations did not show any relationship to the occurrence of RDS. Serum PRL was not suppressed in a further 114 infants whose mothers were treated prenatally with betamethasone. These findings raise the possibility of a role of PRL in fetal lung maturation.     

Use of the serum bactericidal titer to assess the adequacy of oral antibiotic therapy in the treatment of acute hematogenous osteomyelitis.

Serum bactericidal titers against Staphylococcus aureus were measured in 63 children who were receiving mafcillin or methicillin intravenously, or dicloxacillin, penicillin, or cephalexin orally. The SBTs obtained following unit does of 25 mg/kg of dicloxacillin, 35 mg/kg of penicillin, or 25 mg/kg of cephalexin with probenecid were comparable to those seen following intravenous doses of 40 mg/kg nafcillin or methicillin. Twenty-two children with acute hematogenous osteomyelitis proven or presumed to be due to S. aureus were treated intravenously until point tenderness and fever had resolved, and then with oral therapy. The mean duration of intravenous therapy was 14 days. Oral doses were adjusted so that a peak SBT of greater than or equal to 1:16 and a trough SBT of greater than or equal to 1:2 were obtained in most children. No recurrences occurred. The SBT proved to be a practical means of assessing the adequacy of oral therapy in children with infections due to S. aureus.     

Choanal atresia and associated multiple anomalies.

Seventeen unrelated patients with multiple anomalies of unknown etiology were identified by the presence of choanal atresia. A regularly recurring pattern of associated features involving mental retardation, postnatal growth deficiency, hypogenitalism (males), small ears, cardiac defects, micrognathia, postnatal microcephaly, and ocular coloboma was identified. Choanal atresia when accompanied by multiple anomalies of unknown etiology has a serious prognosis with a predictable pattern of associated defects.     

Pulmonary excretion of carbon monoxide in the human infant as an index of bilirubin production. I. Effects of gestational and postnatal age and some common neonatal abnormalities.

Using a single pass, flow-through system, the pulmonary excretion rate of endogenously produced carbon monoxide was measured as an index of bilirubin production in human infants with varying gestational and postnatal ages and with a variety of clinical abnormalities. No significant difference in VECO was found related to sex or gestational age. The mean VECO for a small group of Oriental infants was significantly increased. VECO decreased with increasing postnatal age. As expected, infants with hemolytic disease of the newborn had a markedly increased mean VECO. Infants with jaundice of unknown etiology also had an elevated mean VECO, implying that increased bilirubin production may be a factor contributing to the "nonphysiologic" bilirubinemias of these infants.     

Epidemiology of the group B streptococcus: maternal and nosocomial sources for infant acquisitions.

Repeated bacteriologic observations were made in 462 newborn infants and correlated with similar data from their mothers to evaluate the relative contributions of the birth canal and the hospital environment to acquisition of group B streptococci in the first few days of life. Fifty-eight percent of infants whose mothers were intrapartum carriers acquired streptococci in comparison with 12% of those whose mothers were noncarriers. Acquisitions from the birth canal were not influenced by the route of delivery or the time between membrane rupture and birth, but could be related to the quantity of streptococci in maternal cultures. Observations in ten cohorts of infants, including serotyping and bacteriophage susceptibility of group B isolates, demonstrated clear-cut streptococcal spread among infants in two cohorts. Infants appeared to harbor larger numbers of streptococci at more body sites following acquisition from the birth canal than after acquisition from the hospital environment.