Marcia A. Miller

Prospective comparative trial of ceftriaxone vs. conventional therapy for treatment of bacterial meningitis in children

Fifty children with bacterial meningitis were prospectively evaluated in a randomized comparative trial of twice daily ceftriaxone with conventional ampicillin and chloramphenicol therapy. The groups were comparable in age, sex, days of illness before admission, severity of illness at admission, etiology and admission cerebrospinal fluid (CSF) parameters and bacterial colony counts. The pathogens were Haemophilus influenzae type b (34 beta-Iactamasenegative, 8 beta-lactamase-positive); Streptococcus pneumoniae (4); Neisseria meningitidis (3); and Streptococcus agalactiae (1). Initial CSF colony counts ranged from 2.5 x 102 to 1 x 1010 colony-forming units/ml. In 44 children a lumbar puncture was repeated 10.5 to 18 hours after starting treatment; 16 to 21 (67%) ceftriaxone patients and 12 of 20 (60%) conventional therapy patients had sterile cultures. The reduction in the CSF bacterial colony counts (6.3 log10 colony-forming units/ml) was similar in both groups. Ceftriaxone CSF levels ranged from 1.0 to 8.0

Malassezia furfur skin colonization of infants hospitalized in intensive care units

mU/ml, representing a mean CSF penetration of 11.3% (range, 3.0 to 24.5%) of the simultaneous serum concentration. The median ceftriaxone bactericidal titer in CSF was 1:1024 compared with 1:4 achieved with conventional therapy. There were no significant differences in clinical responses or in frequency of complications, except for diarrhea which occurred in 59% of the ceftriaxone group and in 22% of the other (P < 0.01). Despite one H. influenzae type b relapse occurring in the ceftriaxone group, ceftriaxone appears to be safe and as effective as conventional therapy for bacterial meningitis in children older than 2 months of age.

In vitro activity of cefamandole, cefoxitin, cefuroxime, and carbenicillin, alone and in combination with aminoglycosides against Serratia marcescens.

We studied the prevalence of Malassezia furfur skin colonization of infants hospitalized in our neonatal and infant cardiac and surgical intensive care units by culturing at monthly intervals. Of 361 infants studied over 1 year, 133 (36.8%) had at least one positive culture for M. furfur. Colonized infants, compared with noncolonized infants, had younger mean gestational age (32.4 vs 35.2 weeks, P less than 0.01), lower mean birth weight (1.76 vs 2.31 kg, P less than 0.01), a longer stay in hospital (Wilcoxon P less than 0.01), and more mean days use of an incubator (12.7 vs 7.6 days, P less than 0.01), lamb wool (12.9 vs 8.2 days, P less than 0.01), paper tape (10.8 vs 8.2 days, P less than 0.01), and Op-Site tape (14.1 vs 10.1 days, P less than 0.01). These data suggest that hospitalization in an infant intensive care unit often leads to M. furfur colonization. Although frequent adult handling may be a source, other aspects of intensive care will require careful scrutiny to define more completely the risk factors leading to M. furfur colonization of ill infants.

Intrapatient variation in tobramycin kinetics in low birth weight infants during first postnatal week

Synergistic antibiotic studies were undertaken to compare the effectiveness of two new β‐lactamase resistant cephalosporins, cefamandole, and carbenicillin, with four aminoglycosides against clinical strains of Serratia marcescens. The strains demonstrated various combinations of resistance and/or susceptibility to the antibiotics tested. Tobramycin was the most effective aminoglycoside when used in combination with β‐lactam antibiotics. Carbenicillin and cefamandole demonstrated similar activity with aminoglycosides in synergy experiments.

Tobramycin pharmacokinetics in premature identical twins during newborn period.

SummaryNineteen newborn infants receiving tobramycin, 2.5 mg/kg every 12 h were studied on two occasions at steady-state during the first week of postnatal age. The two studies were separated by two to four days. Total body clearance of tobramycin averaged 1.15 and 1.14 ml/min/kg (p>0.05), apparent volume of distribution averaged 0.82 and 0.68 l/kg (p>0.05), and elimination half-life averaged 8.6 and 7.1 h (p>0.05), during the first and second study, respectively. When the data were further analyzed based on the birth weight, tobramycin kinetics changed during the second study compared to the first study in very low birth weight infants. In eight infants ⩽1.5 kg birth weight, although total clearance of tobramycin was similar, the average apparent volume of distribution decreased from 1.04 l/kg during the first study to 0.73 l/kg during the second study (p<0.05) and elimination half-life from 11.1 h during the first study to 8.7 h during the second study (p<0.05). These data indicate that these infants may require a change in dosing interval with continued tobramycin therapy during the first week of postnatal age. Intrapatient variation in tobramycin kinetics should be considered, in addition to the interpatient variation reported previously, when monitoring the serum concentration to individualize tobramycin therapy in newborn infants ⩽1.5 kg birth weight.

402 TOBRAMYCIN PHARMACOKINETICS IN IDENTICAL TWINS DURING NEWBORN PERIOD

Tobramycin is frequently used in premature infants but little is known about its pharmacokinetics in identical twins during the newborn period. We studied 6 twin infants (gestational age 29-31 weeks; postnatal age 3-4 days; birth weight 1.0-1.3 kg) receiving tobramycin 2.5 mg/kg i.v. over 20 min every 12-18 h. Steady-state peak and trough serum concentrations of tobramycin were in the range of 5.3-8.4 and 1.2-2.0 micrograms/ml, respectively. Total clearance (ClT) ranged from 0.74 to 1.19 ml/min/kg, distribution volume (V) from 0.74 to 0.94 liter/kg, and elimination half-life (t1/2) from 8.2 to 12.8 h. Comparison of data between infants in three identical twin pairs showed that despite a similar infusion method: (a) the time to achieve peak serum concentration ranged from 0.5 to 2.0 h; (b) the peak and trough concentrations normalized for dose varied from 0 to 50%, and (c) the ClT, V and t1/2 varied from 3 to 20%. These data should be considered in therapeutic drug monitoring of tobramycin in premature, identical twins during the newborn period.

1063 CEFUROXIME (CXM) THERAPY OF POTENTIALLY BACTEREMIC SOFT TISSUE INFECTIONS IN CHILDREN

Tobramycin is commonly used in newborn infants but little is known about its pharmacokinetics in identical twins. We studied six infants (gestational age 29-31 weeks; postnatal age 3-4 days; birth weight 1.0-1.3 kg) receiving tobramycin 2.5 mg/kg IV over 20 minutes every 12-18 hours. On third day of therapy, blood samples were collected at 0, 0.5, 1, 2, 4, 8, 12 and 18 hours after starting the infusion and analyzed by EMIT. Peak and trough serum concentrations of tobramycin ranged from 5.3-8.4 μg/ml and 1.2-2.0 μg/ml, respectively. Total clearance (clT) ranged from 0.74-1.19 ml/min/kg, distribution volume (V) from 0.74-0.94 L/kg, and elimination half-life (t½) from 8.2-12.8 hours. Comparison of data between infants in three identical twin pairs showed that despite a similar infusion method: (a) the time to achieve peak serum concentration ranged from 0.5-2.0 hours; (b) the peak and trough concentrations varied from 0-50%; and (c) the clT;, V and t½ varied from 3-20%. These data indicate that peak and trough serum concentrations may be more variable than the kinetic parameters in identical twins. This information should be considered in therapeutic drug monitoring of tobramycin in identical twins during the newborn period.

COMPARATIVE TRIAL OF CEFTRIAXONE |[lpar]|CTX|[rpar]| VS|[period]| AMPICILLIN/CHLORAMPHENICOL |[lpar]|A|[sol]|C|[rpar]| THERAPY |[lpar]|Rx|[rpar]| FOR BACTERIAL MENINGITIS IN CHILDREN

Although used extensively in Europe, there is limited pediatric clinical experience with CXM in the United States. Thirty children, 4-43 mo in age received CXM, 25 mg/kg IV every 8 hr for potentially bacteremic soft tissue infections of the face, or epiglottitis. Infections treated included pre-septal (16) and buccal (12) cellulitis and epiglottitis (2). Blood cultures were positive in 18 patients: H. influenzae type b-13 (2 β-lactamase positive); S. pneumoniae-4; and β-lactamase positive, nontypable H. influenzae-1. An additional 5 patients with buccal cellulitis had negative cultures but H. influenzae type b antigenuria. All isolates were susceptible to CXM. The median MBC for the blood culture isolates was 0.5 μg/ml (range 0.008-2.0 μg/ml). A good clinical response was noted in all patients and repeat blood cultures performed on initially bacteremic patients were sterile. The mean duration of CXM therapy was 4.6±1.2 days. All patients were discharged on an appropriate oral antibiotic to complete a 10 day course of therapy. There were no clinical adverse effects or breakthrough meningitis experienced during therapy with CXM. Lab abnormalitis encountered included absolute granulocytopenia (4); thrombocytosis (3); and elevated liver functions (2). CXM appears to be a safe and effective therapy of pediatric soft tissue infections due to H. influenzae and S. pneumoniae.

Acetaminophen accumulation in pediatric patients after repeated therapeutic doses

Forty-five patients, 3 mo-5 yr in age, were randomly assigned Rx with CTX (23 pts) - loading dose of 75 mg/kg followed by 50 mg/kg q 12 hr or A/C (22 pts) - 50/25 mg/kg q 6 hr. The groups were comparable in age, sex, race, days and severity of illness before admission, etiology and admission CSF bacterial colony counts. The pathogens were H. flu type b (31 β-lactamase neg, 7 β-lactamase pos), S. pneumoniae (4), and N. meningitidis (3). Initial CSF colony counts ranged from 2.5×102 - 1×1010 CFU/ml. In 39 pts, an LP was repeated 10.5-18 hrs after starting Rx: 13/20 CTX and 11/19 A/C pts had sterile cultures. Mean falls in the CSF bacterial colony counts were 6.4 and 6.2 log10 CFU/ml, respectively. CTX MICs for the H. flu isolates ranged from 0.0004-0.006 μg/ml. CTX CSF levels ranged from 1.0-8.0 μg/ml, representing a mean CSF penetration of 9.4% (range 1.2-24.5%) of the simultaneous serum concentration. Median CSF bactericidal titers were ≥1:1024 for CTX and 1:8 for A/C. There was no difference in the clinical course as to the time of defervescence, seizures or hearing loss. However, one relapse occurred in the CTX group. Adverse reactions in the CTX/A/C groups included neutropenia-2/5, eosinophilia-6/8, thrombocytosis-15/17, elevated SGOT/SGPT-2/2, hyperbilirubinemia-3/0, prolonged prothrombin time-1/1, rash-0/1 and diarrhea-11/4. CXT appears to be safe and as effective as A/C therapy for bacterial meningitis in children.