Developmental pharmacokinetics of mezlocillin in newborn infants

Single-dose pharmacokinetics of mezlocillin were studied in 53 newborn infants (72% less than or equal to 36 weeks' gestation) given ampicillin and an aminoglycoside for suspected or proved sepsis. Mezlocillin (75 mg/kg IV or IM) was substituted for ampicillin, serum was assayed microbiologically, and noncompartmental pharmacokinetic parameters were calculated. Analysis of covariance showed that dose/area under the serum concentration-time curve for mezlocillin was influenced by body weight, intramuscular administration, and treatment with gentamicin. A dual intravenous/intramuscular nonlinear regression model yielded an apparent intramuscular bioavailability of 84%. Clearance was proportional to body weight (WT) (r2 = 0.70). Mean CL/WT (0.078 L/hr/kg) was one-half adult values and influenced by gestational age. Steady-state volume of distribution varied linearly with weight (r2 = 0.80), the mean value (0.38 L/kg) being twice that in adults. Mezlocillin half-life (mean 3.71 hours) exceeded adult values and did not correlate with weight. Twenty-four newborn infants received 75 mg/kg mezlocillin every 6 or every 8 hours, along with gentamicin, during the first 7 to 10 days of life. Peak (1.5 hours) and trough (6 or 8 hours) concentrations were determined; the latter decreased from day 3 to days 7 to 10, suggesting a possible postnatal age-dependent change in mezlocillin elimination. Although mezlocillin disposition is affected by age and therapeutic factors, weight alone may adequately predict dosing requirements.     

Technetium 99m-methylene diphosphonate bone scans in children with reflex neurovascular dystrophy

Eleven children with reflex neurovascular dystrophy were investigated by technetium-labeled methylene diphosphonate bone scanning. Eight of 12 scans demonstrated abnormal findings, four showing diffusely decreased uptake and four diffusely increased uptake of the radionuclide in the affected site. Three scans showed normal findings initially, as did one previously abnormal scan when repeated in the asymptomatic patient 6 months later. Diffusely abnormal findings can be helpful in the diagnosis of childhood reflex neurovascular dystrophy, but a normal scan does not exclude the diagnosis.     

Hepatic microsomal drug oxidation and electron transport in newborn infants

Many drugs require oxidative metabolism for termination of action and/or for elimination from the body. Many oxidative reactions are catalyzed by hepatic microsomal enzymes. The activities of various drug-metabolizing enzymes, namely, NADPH cytochrome c reductase, NADPH oxidase, aminopyrine-N-demethylase, and analine P-hydroxylase, and the content of cytochrome P-450, were measured in hepatic microsomes obtained from seven newborn infants and four adult patients. The results in the newborn infant show increasing activities of these enzymes (except aminopyrine-N-demethylase) related to advancing age. Good correlation between three components of the hepatic microsomal mixed function oxidase system and aniline p-hydroxylase was established, whereas only NADPH oxidation correlated with aminopyrine N-demethylation. The rate of substrate or drug oxidation and the activities of the components of the microsomal electron transport pathway were lower than comparable values in the adult. The data demonstrate a possible biochemical basis for the transient deficiency in drug metabolism seen in newborn infants.     

Broviac catheter-related Malassezia furfur sepsis in five infants receiving intravenous fat emulsions

Malassezia furfur, a lipophilic fungus commonly found on the skin of healthy adult, was isolated from Broviac catheter blood cultures in five sick infants who were receiving fat emulsions intravenously. The most common manifestations of sepsis included apnea and bradycardia, low-grade fever, interstitial pneumonia, elevated neutrophil band counts, and thrombocytopenia. All infants recovered without antifungal therapy after removal of the Broviac catheters. Early onset of fungemia after catheter placement in these five infants and the recovery of M. furfur from the skin of nearly 33% of hospitalized premature neonates indicate that contamination of the Broviac catheter at time of placement may be the most likely origin of infection.     

Short-term clinical, nutritional, and functional effects of continuous elemental enteral alimentation in children with cystic fibrosis

Ten children with cystic fibrosis, aged 3.5 to 12 years, whose weights were lower than 90% of the expected weight for height, received high-calorie elemental enteral alimentation for four weeks. Clinical, anthropometric, and biochemical evaluations as well as blood gas analyses and chest radiograph scoring were performed in all. Pulmonary function tests were performed in the five older children, and progressive exercise tests in three. These evaluations were done before, immediately after, and two months after termination of therapy. Nutritional therapy resulted in an increase of caloric intake and in dramatic weight gain, which persisted only for a short time and was mainly related to adipose tissue accretion. No functional improvement accompanied the amelioration in nutritional status. This short-term nutritional therapy in malnourished children with cystic fibrosis was effective in increasing relative weight and energy stores, but there was no evidence of any long-term functional benefit.     

Efficacy of topical antibiotic therapy in acute conjunctivitis in children

We studied 102 children aged 1 month to 18 years in a randomized, double-blind trial designed to determine both the natural history of bacterial conjunctivitis and whether topical antibiotic therapy is beneficial. Affected eyes were treated four times a day for 7 days with drug (polymyxin-bacitracin ophthalmic ointment) or placebo. Eighty-four patients had proved bacterial conjunctivitis (Haemophilus influenzae 61, Streptococcus pneumoniae 22, both one); 66 of these received only topical therapy. By 3 to 5 days, 21 of 34 (62%) patients receiving topical antibiotic were clinically cured, whereas only nine of 32 (28%) patients given placebo were cured (P less than 0.02). By 8 to 10 days, 31 (91%) of the patients given antibiotic and 23 (72%) of the placebo group were cured (P = NS). The bacterial pathogen was eradicated by day 3 to 5 in 71% and by day 8 to 10 in 79% of patients given antibiotic, compared to 19% and 31% of the placebo group (P less than 0.001). Acute bacterial conjunctivitis is a self-limited disease, but topical antibiotic therapy with polymyxin-bacitracin shortens the duration of clinical disease and enhances eradication of the causative organism from the conjunctiva.     

Controlled trial of furosemide therapy in infants with chronic lung disease

To study the effects of furosemide therapy in infants with chronic lung disease (CLD), a double-blind controlled trial was designed. Seventeen infants with evidence of CLD (oxygen requirements greater than 30% at greater than 3 weeks of age and chest radiographic findings consistent with CLD) were studied. Pulmonary function was measured immediately before, and after 48 hours and 7 days of treatment with furosemide (1 mg/kg/12 hr intravenously or 2 mg/kg/12 hr orally) or placebo. Clinical status improved in six of seven infants who received furosemide and in two of 10 infants who received placebo (P less than 0.002). In the furosemide group, ventilator and oxygen requirements decreased (P less than 0.003); minute ventilation, alveolar ventilation, and dynamic compliance increased; and venous admixture decreased (P less than 0.05). There were no significant changes in the placebo group. Our findings suggest that furosemide significantly improves lung function during therapy in infants with CLD and allows earlier weaning from ventilatory support and supplemental oxygen.     

Apnea associated with regurgitation in infants

To determine whether regurgitation might be a factor in the pathogenesis of apnea in certain infants, we compared the frequency of short and prolonged apnea immediately following regurgitation to that during control periods. Ten infants (nine preterm and one term) with histories of frequent regurgitation and also apneic spells were studied for 2 to 3 hours by monitoring nasal airflow, abdominal respiratory movements, electrocardiogram, pharyngeal pH, and pharyngeal pressure. In six of these infants additional observations were made without the intrapharyngeal recording devices. Fourty-four episodes of regurgitation were observed. Both prolonged apnea (P less than 0.05) and short apnea (P less than 0.01) occurred much more frequently during regurgitation than during the control period; however, the majority of prolonged apneic spells observed were unassociated with regurgitation. The increased frequency of apnea during regurgitation was not related to the presence of intrapharyngeal recording devices. Although nasal regurgitation was frequently associated with short apnea, no prolonged apnea was observed during the seven episodes of nasal regurgitation observed. The 14-fold increase in prolonged apnea frequency immediately following regurgitation supports the hypothesis for a causal relationship between apnea and regurgitation.