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Biomedical subjects

E O Mason

Publications and source records attributed to E O Mason.

At least 91 records · Page 5Linked to original sources

Frequency and properties of naturally occurring adherent piliated strains of Haemophilus influenzae type b.

We found that 41 of 75 (55%) children with Haemophilus influenzae type b disease (70 cases of meningitis, 2 of cellulitis, 2 of septic arthritis, and 1 of epiglottitis) and 2 of 120 (1.7%) children with upper respiratory infection were colonized with H. influenzae type b in the nasopharynx (NP). Of these 43 NP strains from children with systemic H. influenzae type b disease, 7 (16%) adhered to human buccal epithelial cells. The strains isolated from the systemic site of all children, including children from whose NP adherent bacteria were isolated, did not adhere to buccal epithelial cells in vitro. Each adherent NP strain had biotype (I), serotype (b), and antibiotic susceptibility (sensitive) similar to that of the corresponding nonadherent systemic isolate. With one exception, all NP-systemic pairs had similar major outer membrane proteins. Six of the seven NP strains had a protein band in the whole cell lysate preparation with a molecular weight between 22,000 and 23,000, which could not be seen in the nonadherent cerebrospinal fluid strains. Electron micrographs of all adherent strains showed that more than 95% of the organisms examined were highly piliated, whereas the nonadherent strains were not piliated. All piliated strains agglutinated human erythrocytes. Adherence to buccal epithelial cells and agglutination of erythrocytes could not be blocked by mannose or alpha-methyl-D-mannoside. We speculate that piliation is not important for NP colonization by H. influenzae type b and that the loss of pili may be required for host invasion.

Adhesiveness↗

Vancomycin pharmacokinetics in premature infants.

Vancomycin pharmacokinetics were studied in nine premature infants. Infants weighing less than 1,000 gm had significantly larger volumes of drug distribution and consequently longer drug half-lives than larger premature infants, regardless of postconceptual or actual age. These differences alter the vancomycin dosing recommendations in these two groups of premature infants. We recommend initial dosage regimens consisting of a loading dose of vancomycin of 25 mg/kg followed by doses of 15 mg/kg every 12 hours for infants with weights less than 1,000 gm. Infants weighing over 1,000 gm should receive 10 mg/kg every 12 hours, with a loading dose of 12.5 mg/kg. Serum vancomycin concentration should be monitored, however, for final optimization of therapy.

Birth Weight↗

Prospective comparative trial of moxalactam versus ampicillin or chloramphenicol for treatment of Haemophilus influenzae type b meningitis in children.

In a prospective, randomized study, moxalactam in 44 children was compared with ampicillin or chloramphenicol in 47 children for the treatment of Haemophilus influenzae type b meningitis. Both groups were comparable in terms of clinical and laboratory findings at admission. The hospital course, neurologic sequelae including deafness, and number of deaths were the same for both groups. The incidence of adverse reactions also was the same except that diarrhea and thrombocytosis occurred significantly (P less than or equal to 0.04) more frequently in children given moxalactam. Moxalactam was equivalent to ampicillin or chloramphenicol in the treatment of H. influenzae type b meningitis in children.

Ampicillin↗

Generation of chemotactic activity in serum by Haemophilus influenzae type b.

Studies were performed to characterize chemotactic activity generated by Haemophilus influenzae type b (HiTb) in serum or elaborated independent of serum. Neutrophil aggregometry, Sephadex G-75 gel chromatography, and anti-C5 neutralization studies were used to demonstrate that the complement fragment C5a represented the major chemotactic moiety derived from HiTb-serum interactions. HiTb elaborated minimal chemotactic activity independently. Maximal C5a generation by HiTb as measured by neutrophil response in chemotaxis, shape change, and aggregation assays required specific antibody to the capsular polysaccharide, polyribosyl ribitol phosphate (PRP). Significantly more C5a was generated in pooled normal human serum containing high titers of anti-PRP (determined by an enzyme-linked immunosorbent assay) than in hypogammaglobulinemic serum. Furthermore, C5a generated in hypogammaglobulinemic serum reconstituted with purified high-titer immunoglobulin G, hyperimmune rabbit serum or heat-inactivated normal human serum was comparable to that generated in normal human serum. Absorption of antibody with PRP versus whole HiTb showed a contribution by non-PRP-directed antibody. As shown with the use of C4-deficient guinea pig serum, C5a generation occurred via the alternative complement pathway in nonimmune serum, and activation of the alternative complement pathway was facilitated by specific anti-PRP. C5a generation in test sera was proportional to its opsonic activity for HiTb as assessed by a luminol-chemiluminescence assay. Overall low levels of C5a activity were observed in 13 pediatric patient serum samples obtained during the acute phase of HiTb meningitis, and no pulmonary symptoms or radiographic abnormalities consistent with a leukocyte aggregation syndrome were observed in these patients.

Antibodies, Bacterial↗

Role of adherence in the pathogenesis of Haemophilus influenzae type b infection in infant rats.

We evaluated the role of pili in the pathogenesis of disease due to Haemophilus influenzae type b (HiTb), using the infant rat model. Piliated and nonpiliated HiTb strains were isolated from the nasopharynx and cerebrospinal fluid, respectively, of three children. Infant rats inoculated intranasally with nonadherent HiTb developed bacteremia and meningitis more frequently (P = 0.005) than animals inoculated with companion adherent HiTb strains. When analyzed separately, only one HiTb pair (884/880) demonstrated significant differences in the incidence of bacteremia and meningitis between the adherent and nonadherent strains. Blood or cerebrospinal isolates recovered from infant rats inoculated with piliated adherent HiTb strains were not piliated and were not adherent in vitro. Adherent and nonadherent HiTb colonized the nasopharynx of infant rats equally. The piliated strains of HiTb were not adherent in vivo or in vitro to rat nasal or buccal epithelial cells, respectively. Piliated strains of HiTb have no apparent advantage over nonpiliated HiTb strains for colonization or invasion of infant rats. Furthermore, the loss of piliation is noted for cerebrospinal fluid, blood, and nasal isolates of HiTb cultured from infant rats inoculated with an adherent piliated HiTb strain. Thus, the loss or suppression of pili may be an important prerequisite for the invasion of the host by HiTb strains that are highly piliated.

Animals↗

Enzyme-linked immunosorbent assay for detection of capsular antibodies against Haemophilus influenzae type b: comparison with radioimmunoassay.

An enzyme-linked immunosorbent assay (ELISA) is described for detection of anti-capsular antibodies against Haemophilus influenzae type b. Polyribosephosphate was covalently bonded to poly-L-lysine before adsorption to microtiter plates. ELISA immunoglobulin G and immunoglobulin M anti-polyribosephosphate antibody titers were comparable to total anti-polyribosephosphate antibody concentration determined by radioimmunoassay. The ELISA technique will be useful for further investigations of host response to infections due to H. influenzae type b but is not intended to be used as a serological method for documenting H. influenzae type b infections.

Adsorption↗

Moxalactam treatment of serious infections primarily due to Haemophilus influenzae type b in children.

Thirty-eight children completed therapy with moxalactam for a variety of non-CNS infections. Haemophilus influenzae type b (seven ampicillin-resistant strains) was the etiologic agent for 32 children. Doses of moxalactam ranged from 113 to 200 mg/kg/d in three or four divided doses administered parenterally. All children with infections due to H influenzae type b had excellent responses to moxalactam therapy. Children treated for infections due to other agents also responded satisfactorily to moxalactam therapy. Moxalactam concentrations in joint and pleural fluids greatly exceeded the minimal bactericidal concentrations of moxalactam for H influenzae type b. Adverse reactions included neutropenia, eosinophilia, thrombocytosis, and transient elevation of transaminase levels. Moxalactam administered parenterally, at a dose of 113 to 150 mg/kg/d in three or four divided doses is effective therapy for serious infections in children due to H influenzae type b and selected other organisms.

Bacterial Infections↗

Pharmacokinetics of moxalactam in anuric children and during hemodialysis.

Pharmacokinetics of moxalactam were determined in children with chronic renal failure during a 4-hour hemodialysis or an interdialytic period following a 50 mg/kg dose. Mean elimination half-life during dialysis was 3.9 hours compared to 12.9 hours during the interdialytic period. Mean clearance of moxalactam was 86 ml/minute during hemodialysis and 25 ml/minute between dialysis. Mean dialyzer clearance of moxalactam was 45 ml/minute. The mean fraction of moxalactam removed during a 4-hour hemodialysis was 18% in nine children. In anuric children, a 50 mg/kg dose of moxalactam should be given every 48 hours in an interdialytic period and a 25 mg/kg dose given after each dialysis.

Adolescent↗

Clindamycin versus nafcillin or methicillin in the treatment of Staphylococcus aureus osteomyelitis in children.

The treatment of osteomyelitis due to Staphylococcus aureus was evaluated by randomized trial in 12 children who received clindamycin and 13 children who received nafcillin or methicillin. In the nafcillin/methicillin group, the mean duration of intravenous (IV) therapy was 27 days (range 14 to 38 days) plus 3.7 weeks (range 0 to 8 weeks) of oral therapy with dicloxacillin. In the clindamycin group, the mean duration of IV therapy was 5.8 days (range three to ten days) plus 4.7 weeks (range three to nine weeks) of oral therapy with clindamycin. The geometric means (GMs) of peak serum bactericidal titers for IV therapy were 45 (range 16 to 256) and seven (2 to 256) for nafcillin/methicillin and clindamycin respectively. The GMs of peak serum inhibitory and bactericidal titers for oral therapy with clindamycin were 99 (range 16 to 512) and four (range 1 to 128) and were generally within one dilution of the IV titer. The outcome of therapy was excellent for ten children in the nafcillin/methicillin group and for 11 children in the clindamycin group. In the clindamycin group, the outcome did not correlate with achieving a peak bactericidal titer of greater than 1:8. Clindamycin administered IV until the patient is afebrile for three consecutive days and then orally for approximately four weeks is an alternative to nafcillin/methicillin in the therapy of S aureus osteomyelitis in children.

Administration, Oral↗

Pharmacology of kanamycin in the newborn.

We studied the pharmacologic effects of kanamycin in three groups of newborn infants: group 1--birth weight (BW) less than or equal to 2,000 gm, chronologic age (CA) less than 7 days; group 2--BW greater than 2,000 gm, CA less than 7 days; and group 3--BW greater than 2,000 gm, CA 7 to 28 days. The dose of kanamycin was 15 mg/kg/day, administered in two intramuscular doses. Serum kanamycin levels were measured 15 minutes before the dose and 1/2, 1, 6, and 8 hours after the dose. Infants in group 1 had a mean peak concentration of 18.7 micrograms/ml, those in group 2, 19.6 micrograms/ml, and those in group 3, 15.6 micrograms/ml. The mean peak concentrations varied inversely with chronologic age but were not influenced by birth weight. Mean serum half-life varied inversely with birth weight, gestational age, and chronologic age. We recommend a standard dose of 15 mg/kg/day for newborn infants. Modification of this dose may be required for individual infants.

Age Factors↗

Successful moxalactam therapy for gram-negative bacillary meningitis in neonates.

Three neonates with gram-negative bacillary meningitis were treated with moxalactam after therapy with ampicillin plus aminoglycoside, trimethoprim-sulfamethoxazole, or chloramphenicol failed to sterilize the CSF. Clinical improvement and CSF sterility occurred after therapy with moxalactam was initiated. Moxalactam concentrations in CSF exceeded MICs of each organism. All three patients were cured of their infection. Moxalactam appears to be an effective antibiotic for the treatment of neonatal gram-negative bacillary meningitis.

Bacterial Infections↗

Adherence of Haemophilus influenzae to buccal epithelial cells.

The role of adherence of Haemophilus influenzae to epithelial surfaces in the pathogenesis of infection is unknown. Fluorescent-antibody and radiolabeled adherence methods were adapted to study H. influenzae adherence to human buccal epithelial cells. By the fluorescent-antibody method, 19 of 21 (90%) nontypable H. influenzae strains were found to be adherent compared with 2 of 42 (5%) type b strains (P less than 0.0001). Using a radiolabeled adherence method, we found that 9 of 12 (75%) nontypable H. influenzae strains were adherent to buccal epithelial cells whereas only 3 of 32 (9%) type b strains were adherent (P = 0.001). Results of H. influenzae adherence examined by both methods correlated significantly (P = 0.01). H. influenzae adherence to adult pharyngeal, nasal, and buccal epithelial cells was comparable. Type b H. influenzae did not adhere to the buccal epithelial cells of well children, children with H. influenzae type b disease, or children with upper respiratory infections. In contrast, nontypable H. influenzae did adhere to the buccal epithelial cells of well children and children with upper respiratory infections. These observed in vitro differences in adherence between nontypable and type b H. influenzae strains may explain differences in colonization, pathogenesis, and types of infection due to nontypable and type b H. influenzae.

Adhesiveness↗

Serotype and ampicillin susceptibility of Haemophilus influenzae causing systemic infections in children: 3 years of experience.

Over a 3-year period, 96% of systemic infections in children caused by Haemophilus influenzae were of serotype b. Of 346 invasive infections, 15 (4%) were caused by non-type b H. influenzae. The monthly prevalence of ampicillin resistance in all isolates was highly variable (0 to 63%). Ampicillin resistance in H. influenzae causing invasive disease occurred in 13% of non-type b and 21.8% of type b isolates. There was no significant difference (x2 - 0.21; p greater than 0.10) in the rate of ampicillin resistance between type b and non-type b H. influenzae causing systemic illness in children over a 3-year period.

Adolescent↗

Pharmacokinetics and cerebrospinal fluid penetration of moxalactam in children with bacterial meningitis.

The serum pharmacokinetics and CSF penetration of moxalactam were determined in 39 children with bacterial meningitis. The mean serum concentrations 30 minutes after a 37.5 or 50 mg/kg dose were 66.7 and 113 micrograms/ml, respectively. The t 1/2 beta was between 1.8 and 2.0 hours. The mean +/- 1 SD CSF/serum percentage was 18.5 +/- 16.0% (range 2.0 to 61%) for all children on any day of therapy or hour, after the last of three 50 mg/kg doses. Cerebrospinal fluid bactericidal titers were greater than or equal to 1:32 in 13 of 14 CSF specimens. Moxalactam adequately penetrates into the CSF of children with bacterial meningitis after repetitive 50 mg/kg doses.

Blood-Brain Barrier↗

Antagonism of ampicillin and chloramphenicol for meningeal isolates of group B streptococci.

The increasing prevalence of ampicillin-resistant Haemophilus influenzae type b has led to the recommendation that ampicillin and chloramphenicol be given as the initial therapy for suspected bacterial meningitis in infants and children. However, during the first 2 months of life, H. influenzae type b is a rare cause of meningitis, whereas group B streptococcus is the most frequently isolated agent. Since ampicillin and chloramphenicol have been shown to be antagonistic for other streptococci, an in vitro study of their effect on group B streptococci was performed. The effect of ampicillin and chloramphenicol, alone and in combination, on 18 meningeal isolates was determined for 2 different inocula of group B streptococci, using microtiter broth dilution and growth kinetic assays. Isoboles, fractional lethal concentration indices, or both indicated antagonism for all strains. Growth kinetic assays for two representative strains demonstrated inhibition of the early bactericidal activity of ampicillin by chloramphenicol. These findings of in vitro antagonism suggest that this combination may be contraindicated for the treatment of infants with group B streptococcal meningitis.

Ampicillin↗