Abdul J Khan

Pharmacokinetics of cefoperazone in full-term and premature neonates.

The pharmacokinetics of cefoperazone were evaluated in 28 newborn infants who were being treated for sepsis. A dose of 50 mg/kg was administered intravenously on days 0 to 2 in all, with a second dose administered on days 5 to 7 in 14 infants. Cerebrospinal fluid penetration was also studied in seven neonates. The mean peak concentration of cefoperazone in the serum of premature infants less than 33 weeks of gestational age, 159 (standard deviation, +/- 22) micrograms/ml, was higher than concentrations in premature infants 33 to 36 weeks of age and full-term infants (110 +/- 41 and 109 +/- 29 micrograms/ml, respectively). The mean concentrations 24 h after dosage were similar in all three groups, 13 to 17 micrograms/ml. The mean serum half-lives were similar in the three subgroups and ranged from 7 to 9 h. After the dose at 5 to 7 days, mean blood levels in the subgroups at 0.5 h were 149, 112, and 112 micrograms/ml; 24-h levels ranged from 9 to 12 micrograms/ml. The mean serum half-lives ranged from 5 to 7 h. Cerebrospinal fluid levels in patients with meningitis ranged from 2.8 to 9.5 micrograms/ml and in patients without meningitis from 1 to 7 micrograms/ml. Peak blood levels were 15 to 1,000 times higher than the 90% minimal inhibitory concentration of common pathogens found in newborns. These observations support the potential efficacy of cefoperazone in treatment of infections, including meningitis, in newborn infants.

Pharmacokinetics and Safety of Cefamandole in Infants and Children

Cefamandole, a new cephalosporin antibiotic, has greater activity against common pathogens, including Escherichia coli, Haemophilus influenzae, and Proteus (including indole-positive strains), than available cephalosporin drugs. We have evaluated the safety and pharmacokinetics of this drug in 30 infants and children. Blood levels and urinary excretion of the drug were similar to those previously found in adults. The only side effects were mild and transient elevation of serum glutamic oxalacetic transaminase in 12 patients and of blood urea nitrogen in 1 patient in whom serum creatinine remained normal and unchanged.

Pharmacokinetic evaluation of cefoperazone in infants.

The pharmacokinetics of cefoperazone were evaluated in 25 infants (mean age, 26 days) after intramuscular and intravenous routes of administration. The levels in blood that were achieved were severalfold higher than those required to inhibit common pathogens. The mean half-life of 240 min was one-half of that observed in 1- to 2-day-old infants but about twice that seen in adults. Further evaluation is needed to study the efficacy of the drug in infants and children.

CORRECTION OF DEFECTIVE NEUTROPHIL CHEMOTAXIS BY SYSTEMIC VITAMIN C (VC) THERAPY IN NEWBORN INFANTS (NB)

Vitamin C has been shown to improve defective chemotaxis in Chediak - Higashi Syndrome. We evaluated its effect on NBs whose predisposition to sepsis is partly attributable to defective chemotaxis. Ten term NBs were treated with 4 doses of 100 mgs of VC q6 hrs starting on day 2 of life. Blood was obtained for study immediately before and after VC treatment. Chemotactic index (CI) and random migration index (RM) were determined by a modified Boydens chamber technique. PMNs were deposited on a 3 μ millipore filter which divided the chamber into an upper compartment filled with Hanks solution (HS), and lower filled with a mixture containing AB serum, endotoxin and HS. Following incubation and staining a ratio of migrated cells to total cells was determined and termed CI. In a parallel run with HS on either side the ratio was termed RM. The result (table) indicates that CI and RM increased about 64% followingVC therapy, a difference significant at P<0.02. We conclude that Vitamin C by improving the PMN qualitatively may be a useful adjunct to the treatment of sepsis in NB infants in general and in leukopenic infants in particular.

Metabolic Screening via Heel Stick versus Umbilical Arterial Catheter— A Comparison

The results presented in Table 1 show that, with the exception of hemoglobin and hypothyroidism screening, the UAC specimen concurred with HS specimen in 100% of cases. In one case, positive for sickle cell disease, UAC revealed a false-negative result i.e., normal hemoglobin results. This patient had been transfused with Hgb AA blood just prior to the UAC blood sampling. In addition, 2 cases of hypothyroidism tested as false positive with UAC specimen. These two patients could not be followed up. Result of thyroid screening on sample of 58

THE NATELSON-TYPE TUBE FOR THE ERYTHROCYTE SEDIMENTATION RATE (ESR) : A METHOD TO REDUCE BLOOD SAMPLE SIZE. 1034

THE NATELSON-TYPE TUBE FOR THE ERYTHROCYTE SEDIMENTATION RATE (ESR) : A METHOD TO REDUCE BLOOD SAMPLE SIZE. 1034

HIGH INCIDENCE OF HYPERTENSION (HTN) DURING STATUS ASTHMATICUS (SA) IN CHILDREN. 2287

Incidence of HTN, a potential morbidity factor, among Asthmatics is unknown. An occasional observation of Systolic (SYS) HTN led us to evaluate the BP of 61 pts with SA (mean age 6.0 yrs) and 42 control (mean age of 5.0 yrs) hospitalized in PICU patients for 3 days. Value of 95% tile was used to define in HTN. All patients with SA received steriods B agonists inhalation and theophyllin. Number (%) with HTN in the 2 groups are compared(Table).

EVALUATION OF UPPER RESPIRATORY TRACT (URT) COLONIZATION (CCL) IN HUMAN IMMUNODEFICIENCY VIRUS (HIV) INFECTED (INF) CHILDREN: 997

HIV-INF children may be predisposed to alteration of normal flora and COL with opportunistic pathogens (PATH), because they are on long term prophylactic and therapeutic antibiotics and under-lying immunodeficiency states. In order to evaluate the frequency and pattern of URT COL, we studied 21 children (mean age 72 mos) for aerobes and fungi by oropharyngeal cultures and correlated with virologic (HIV RNA by PCR), immunologic (quantitative T cells by flow cytometry), and clinical parameters (CDC classification). Unusual PATH were isolated from 15 (71%) cases; 7 (33%) being Pathic BACT, 11(52%) candida, and 3 (14%) mixed; only 2 cases had > 2 isolates. PATH included S. marcescens, P. aeruginosa,Acinetobacter. baumanii, H. influenzae, GABHS, Enterobacter group, and K. pneumoniae and Candida species (C. albicans andtropicalis); S. marcescens and P. aeruginosa were resistant to TMP-SMZ (same patient;CDC class C3; viral load 242400 RNA/ml; CD4 count 6/mm3). BACT COL had significant clinical disease progression (table) than those with neg cultures(P=0.03) and with Nonbact col (P=0.02). Non-colonizers had higher age-adjusted CD4 & CD8 counts and lower viral load compared to colonizers, but insignificantly.

NEUTROPHIL (PMN) MIGRATION IN RESPONSE TO CHEMOTACTIC FACTORS GENERATED BY THE INVADING PATHOGENS IN ACUTE BACTERIAL ENTERITIS (ABE)

The role of chemotactic and random migration(RM) in ABE is not known. They were determined in 9 pts with ABE due to shigella or salmonella between days 3&5 of admission and 9 controls. One day prior to study each isolate was grown in medium 199 to generate specific chemotactic factors (SCF). Leukocytes were harvested from heparinized blood and 1.0×106PMNS were deposited on to 3 u millipore filter which was placed in the Boydens chamber. The upper compartment of the chamber was filled with Hanks solution (HS) and the lower with SCF 100uL/mL of HS. Three simultaneous chambers were also set up with endotoxin activated serum (EAS), E. coli generated factors (ECF) and HS alone in the lower compartments. After 3hrs incubation filters were stained and cells which migrated to lower surface were counted. A ratio of migrated to total cells with SCE, EAS & ECF was termed as chemotactic index(CI) and RM with HS alone. In 4 pts studies were repeated after therapy. Mean (±1SD) values are presented (table): Mean CIs of patients with all the 3 factors were significantly lower than those of controls and significantly increased after therapy. RM was similar. Supression PMN chemotaxis may be one step in the pathogenesis of ABE. Counteracting it with drug/agents may improve the outcome.

421 EFFECT OF IN VITRO AND SYSTEMIC VITAMIN C (VC) ON THE NEUTROPHIL FUNCTION IN SICK NEWBORNS (NBs)

VC has been shown to improve chemotaxis in normal newborns. We evaluated its effect in vitro on 11 sick term NBs, including 8 on antibiotics for undocumented sepsis, on day 2-3 of life. WBCs, separated from the blood, were divided into 2 aliquots. One was incubated for 30 min with Hanks solution (HS) containing 20 μg/ml VC and the other with HS alone.In a separate study 10 different term NBs with suspected sepsis were treated with 4 doses of lOOmgs of VC q6h starting on day 2 of life. Blood was drawn before and after VC treatment. Chemotaxis was determined by a modified Boydens chamber technique. PMNs were deposited on a 3μ millipore filter which divided the chamber into an upper compartment filled with Hanks solution (HS), and lower filled with a mixture containing AB serum, endotoxin and HS. Following incubation and staining a ratio of migrated cells to total cells was determined (CI). In a parallel run with HS on either side the ratio was termed RM.Mean CI increased 64% following VC incubation and VC therapy. RM remained unchanged in both studies. VC may be a useful adjunct to therapy of NBs with sepsis but more studies are needed.