Thomas Rubio

Comparison of a β-lactam alone versus β-lactam and an aminoglycoside for pulmonary exacerbation in cystic fibrosis

We determined whether a β-lactam and an aminoglycoside have efficacy greater than a β-lactam alone in the management of a pulmonary exacerbation in patients with cystic fibrosis. Study design: Azlocillin and placebo or azlocillin and tobramycin were administered to 76 patients with a pulmonary exacerbation caused by Pseudomonas aeruginosa in a randomized double-blind, third-party monitored protocol. Improvement was assessed by standardized clinical evaluation, pulmonary function testing, sputum bacterial density, sputum DNA content, and time to the next pulmonary exacerbation requiring hospitalization. Results: No significant difference was seen between the 2 treatment groups in clinical evaluation, sputum DNA concentration, forced vital capacity, forced expiratory volume in second 1, or peak expiratory flow rate at the end of treatment (33 receiving azlocillin alone and 43 both antibiotics); adverse reactions were equivalent in each group. Sputum P. aeruginosa density decreased more with combination therapy (P = .034). On follow-up evaluation, an average of 26 days after the end of treatment, all outcome indicators had worsened in both groups. Time to readmission for a new pulmonary exacerbation was significantly longer in the group receiving azlocillin plus tobramycin (P < .001). Treatment-emergent tobramycin resistance occurred in both groups and was more frequent with combination therapy. Conclusion: We conclude that the combination of a β-lactam and an aminoglycoside produces a longer clinical remission than a β-lactam alone and slightly better initial improvement. (J Pediatr 1999;134:413-21)

Intravenous immune globulin therapy for early-onset sepsis in premature neonates*

Newborn infants may have IgG deficiencies that increase their susceptibility to bacterial infection. To determine whether intravenous immune globulin (IVIG) therapy improves survival rates in early-onset sepsis, we prospectively entered 753 neonates (birth weight 500 to 2000 gm, gestation less than or equal to 34 weeks, age less than or equal to 12 hours) into a multicenter, double-blind, controlled trial. Blood culture specimens were obtained and infants randomly assigned to receive 10 ml (per kilogram) intravenously of a selected IVIG (500 mg/kg) or albumin (5 mg/kg) preparation. Maternal and neonatal risk factors were not different between groups. Thirty-one babies (4.2%) had early-onset sepsis; the causative organisms were group B streptococcus (12 babies), Escherichia coli (6), and others (13). Of these 31 neonates, 7 (23%) died. Total serum IgG was higher for 7 days after IVIG therapy than after albumin treatment (p less than 0.05). During these 7 days, 5 (30%) of 17 albumin-treated and none of 14 IVIG-treated patients died (p less than 0.05). The survival rate at 56 days of age, however, was not significantly improved. Group B streptococcus type-specific IgG antibody was significantly increased after IVIG treatment and appeared to be related to the amount of IVIG specific antibody. Infusion-related adverse reactions were less frequent in patients receiving IVIG therapy (0.5%) than in those receiving albumin. The IVIG therapy in neonates with early-onset sepsis, while reducing the early mortality rate, did not significantly affect the overall survival rate. Further studies are necessary to confirm these findings and to determine more effective therapeutic regimens.

Familial third-fourth pharyngeal pouch syndrome with apparent autosomal dominant transmission

A family is presented in which both siblings and their father had evidence of third-fourth pharyngeal pouch syndrome (DiGeorge syndrome). All three individuals had hypocalcemia and unusual facies. Both infants had truncus arteriosus. One infant had evidence of impaired cell-mediated immunity; the father had a relatively decreased number of T-lymphocytes. The syndrome is uncommon, most cases being isolated, and familial presentations are even rarer. Two recent reports described several affected individuals who also had partial deletions of chromosome 22. Chromosome banding studies in our family were normal. Thus our family demonstrates an autosomal dominant pattern of inheritance, although it cannot be proved that this is a single gene defect. We propose that inasmuch as the presentation of the syndrome is quite varied, thorough family investigation including high-resolution cytogenetic analysis is necessary. Familial cases may be more common and require genetic counseling.

Intravenous immune globulin prophylaxis of late-onset sepsis in premature neonates.

To determine whether a single dose of intravenously administered immune globulin (IVIG) decreases late-onset sepsis in premature infants, we prospectively entered 753 neonates with birth weight 500 to 2000 gm, gestation < or = 34 weeks, and age < or = 12 hours into a multicenter, double-blind, controlled trial. Infants were randomly selected to receive a single intravenous infusion, 10 ml/kg, of either IVIG (500 mg/kg) or albumin (5 mg/kg) and were observed for 8 weeks for infection. Maternal and neonatal risk factors for infection did not differ between groups. Although serum IgG values before infusion were related to gestation (R = 0.62), the change in serum IgG or half-life of IgG after IVIG infusion was not (R < or = 0.09). The serum IgG concentration was increased (p < 0.05) in IVIG-treated patients for 8 weeks. There were 88 episodes of late-onset sepsis in 79 neonates (10.5%). Causative organisms included the following: Staphylococcus epidermidis (37 episodes), Enterococcus (9), Staphylococcus aureus (7), Candida (6), Escherichia coli (6), and multiple organisms (11). Sepsis, death, and death as a result of infection were unaffected by treatment. We conclude that a single infusion of IVIG, 500 mg/kg, shortly after birth was not effective prophylaxis for late-onset infection in premature neonates. Future studies of late-onset sepsis prophylaxis should consider IVIG with known pathogen-specific antibody concentrations against organisms causing these infections, in particular S. epidermidis.

Developmental pharmacokinetics of mezlocillin in 4 newborn infants

The disposition of mezlocillin was evaluated in 4 newborn infants in a sequential two-phase study at postnatal ages of 1 day and 8 or 10 days. Renal function was estimated by creatinine clearance (CLCR) and pharmacokinetic parameters of mezlocillin was were determined from serum concentrations and urinary excretion rates. All weight-normalized mezlocillin clearances (total, renal, and nonrenal) and CLCR were less than adult values, but increased after 8 or 10 days of mezlocillin therapy and postnatal development. The volume of distribution at steady state did not significantly change throughout this period, and approximated the expanded extracellular fluid volume typically found in neonates. The elimination half-lives were substantially shorter by phase II of the study. Both renal and nonrenal elimination processes were enhanced by 1 week of postnatal development even though body weight did not increase. Mezlocillin disposition in neonates is thus affected by body weight, gestational age, and postnatal age.

1561 MEZLOCILLIN (MEZ) VS. CONVENTIONAL BINATION ANTI-MICROBIAL THERAPY FOR PREMATURE INFANTS ADMITTED TO AN INTENSIVE CARE NURSERY (ICN)

The combination of ampicillin with an aminoglycoside is the conventional antimicrobial therapy for premature infants admitted to an ICN. If MEZ alone is at least as effective as the combined use of ampicillin and amikacin (AMI), it should be preferentially used because it is cheaper and less toxic. Criteria for proven or suspect infections, and for the clinical response to therapy were used to evaluate each infants response to the selected therapy. This evaluation was done without the knowledge of which antibiotic was used. One-half of 172 premature infants studied were randomly selected to be treated with MEZ. The efficacy of therapy for proven or suspect infections as well as the incidences of apnea, hypotension, and nephrotoxicity in this group were compared to the other group of 86 patients who received the conventional combination therapy. There were no differences between the two patient groups in their birth weights (1.39 kilo vs. 1.42 kilo), gestational ages (30 wks vs. 31 wks), nor in the incidences of apnea or hypotension. The clinical response in patients with suspect (42 patients) or proven (30 patients) infections were no different between the two therapies. AMI therapy was more nephrotoxic as demonstrated by a diminished postnatal rise in creatinine clearance in the patients receiving this drug. (42% vs. 23% rise in creatinine clearance) These data support the use of MEZ in premature infants with the diagnosis of infection.