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Biomedical subjects

G D Overturf

Publications and source records attributed to G D Overturf.

At least 19 recordsLinked to original sources

Infection caused by Streptococcus pneumoniae in children with sickle cell disease: epidemiology, immunologic mechanisms, prophylaxis, and vaccination.

The incidence of invasive infection due to Streptococcus pneumoniae is 6.9 infections per 100 patient-years among children with sickle cell anemia (SS genotype) who are less than 5 years of age; this rate is 30-100 times that which would be expected in a healthy population of this age. Splenic dysfunction is the major contributor to the increased risk. Postulated abnormalities of immunologic defense mechanisms, including synthesis of polyclonal IgG and IgM, the alternative complement pathway, opsonic activity, and T and B cell interaction, may also enhance risk. Preceding or concomitant viral infection is suspected of predisposing to pneumococcal infection, but no definitive data are available. The most prevalent pneumococcal serotypes causing disease in this setting include types 6, 14, 18, 19, and 23; these same serotypes are most frequently involved in "vaccine failure." Current evidence demonstrates only modest protective efficacy for contemporary pneumococcal vaccines in young patients with sickle cell anemia; thus alternative vaccines are required. Convincing evidence for a protective effect of antibiotic prophylaxis has been obtained in limited time trials. However, presently used prophylactic regimens pose problems related to compliance and provide imperfect protection; moreover, their optimal duration remains unknown.

Anemia, Sickle Cell

Antibiotic treatment of community acquired bacterial meningitis.

Community acquired meningitis is predominantly caused by three agents: Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis Four physical properties of available drugs--molecular size, protein binding, lipid solubility and ionization--affect drug entry to the central nervous system (CNS). These factors, coupled with acute changes in blood-brain barriers and intrinsic bactericidal activity, have a bearing on the success of treatment with all agents. Third generation cephalosporins have largely supplanted older regimens due to their intrinsic qualities of greater bactericidal activity, optimal cerebrospinal fluid pharmacokinetics, and low toxicity. The pharmacological principles of treatment of CNS bacterial infections, pharmacology of available drugs, and current treatment recommendations are reviewed.

Anti-Bacterial Agents

Antibacterial activity of crotalid venoms against oral snake flora and other clinical bacteria.

Despite heavy oral and fang contamination of crotalid species with a wide variety of potentially pathogenic bacteria, crotalid envenomation is associated with a low incidence of bacterial infection. Minimal inhibitory and bactericidal concentrations of venoms from three crotalid species were determined against six aerobic and eight anaerobic reference and oral crotalid microorganisms. All anaerobic isolates were resistant to greater than 20,480 micrograms/ml, whereas variable activity (range, 5-20,480 micrograms/ml) was observed for aerobic strains. Further studies against other aerobic clinical isolates demonstrated that venom had the greatest activity (MIC, less than or equal to 80 micrograms/ml) against staphylococci, Pseudomonas aeruginosa, and Enterobacter, Citrobacter, Proteus, and Morganella species. Inhibitory activity was lost with prolonged incubation for many gram-negative species. Crotalid venoms are broadly active against aerobic gram-negative and -positive bacteria. This activity may play a role in the low incidence of infection after envenomation injuries.

Animals

Phage typing of Staphylococcus intermedius.

Staphylococcus intermedius, a coagulase-positive staphylococcal species, is a common canine pathogen and a rare human wound pathogen. A total of 145 strains of S. intermedius (ATCC 29663, 4 reference strains, 4 human isolates, 44 canine infection isolates, and 92 isolates from canine gingiva) were screened for lysogenic phage by a modified Fisk method. Nineteen phage preparations were prepared for preliminary typing experiments. Lytic activity was observed on 93 of 145 (64.1%) isolates, yielding 44 lytic patterns with individual strains susceptible to one or more phages. Five phages lysed only a single strain, but lytic patterns varied from 1 to 11 lytic phages per isolate. A distinct lytic pattern did not separate canine or human wound isolates from canine gingival isolates. All human wound isolates fell into the two most common canine gingival or wound patterns; the single human nasopharyngeal isolate was not lysed by any phage. Twenty-two of 44 (55%) canine wound isolates and 65 of 92 (71%) gingival isolates yielded lytic patterns. Lysogenic phages are common in S. intermedius. This preliminary study suggests that phage typing may be a useful tool in distinguishing epidemiologically related strains.

Animals

Ampicillin dosage in bacterial meningitis with special reference to Haemophilus influenzae.

Ampicillin remains the preferred drug for most cases of bacterial meningitis, including those due to Haemophilus influenzae type b. A prospective study was performed comparing high (400 mg/kg per day)- and low (150 mg/kg per day)-dosage regimens of ampicillin in the treatment of 172 patients with bacterial meningitis. Response to both regimens was equivalent in terms of average hospital stay, duration of ampicillin therapy, microbiological response, and death and residua. Patients with H. influenzae infections treated with low-dosage regimens had slightly prolonged febrile courses. This study suggests that high-dosage regimens of ampicillin offer no benefit over low-dosage regimens in the treatment of bacterial meningitis.

Ampicillin

Use and efficacy of pneumococcal vaccine in patients with Hodgkin disease.

Fulminant bacterial sepsis has been described in patients with Hodgkin disease who have undergone splenectomy for staging purposes. The organisms commonly associated with sepsis in this setting include Streptococcus pneumoniae and Haemophilus influenzae. Polyvalent pneumococcal vaccine (Merck) has recently been licensed and has been suggested for use in patients with Hodgkin disease who are at risk for postsplenectomy sepsis. We administered 14-valent pneumococcal vaccine to 24 patients with Hodgkin disease and 24 normal controls, and measured antibody response to 13 antigens at time of immunization and at 3 wk and 3 mo following immunization. Our results indicate that patients who have been previously treated for Hodgkin disease, with chemotherapy, radiotherapy, or both, have severe impairment of antibody response. Untreated patients, however, respond in a manner similar to normal controls.

Antibodies, Bacterial

Measurement of lactic acid in cerebrospinal fluid of patients with infections of the central nervous system.

The concentration of lactic acid in cerebrospinal fluid (CSF) was determined by gas-liquid chromatography in 205 samples of CSF from 97 patients with or without infections of the central nervous system. Patients without infection or those with nonbacterial (presumably viral) meningitis consistently had low concentrations of lactic acid in CSF (i.e., less than or equal to 35 mg/100 ml), whereas patients with bacterial or tuberculosis meningitis consistently had concentrations of lactic acid in CSF of greater than 35 mg/100 ml. There was no overlap in concentrations of lactic acid between these two groups. Further, lactic acid concentrations in CSF from patients partially treated for meningitis were generally greater than 35 mg/100 ml through the third day of therapy and, thereafter, progressively declined to less than 20 mg/100 ml by the seventh to 10th day of therapy. Relapse of bacterial infection was consistently documented by a recurrence of an increased concentration of lactic acid in CSF. Preliminary experience with determination of the concentration of lactic acid in CSF suggests that it may be useful in distinguishing bacterial (with or without positive cultures) and tuberculous meningitis from meningitis due to nonbacterial causes.

Adolescent

Differential inactivation of cephapirin vs. cephalothin by penicillin-resistant strains of Staphylococcus aureus: a preliminary study.

The bactericidal effectiveness of cephapirin and cephalothin against small (approximately 10(5)) and large (approximately 10(8)) inocula of penicillin-resistant Staphylococcus aureus was evaluated. With the smaller inoculum, no differences in bactericidal activity between the two drugs (tested at 2 and 40 microgram/ml) were seen after incubation for 2, 4, 6, or 24 hr. Neither cephalosporin effectively killed a larger inoculum in a concentration of 250 times the minimal bactericidal concentration for selected strains. Total inactivation of cephapirin (40 microgram/ml) by eight of 13 strains was demonstrated with the larger inoculum. These preliminary studies indicate that inactivation of cephapirin is pH-dependent. No strain inactivated cephapirin in less than or equal to 4 hr. Inactivation was independent of temperature at 37 C and 42 C. Although cephalothin was resistant to inactivation under the same conditions, the inoculum required to inactivate cephapirin was not killed by 100 microgram of cephalothin/ml. Although strains of S. aureus that slowly inactivate cephapirin appear to be prevalent, no strain that rapidly inactivates this cephalosporin was identified.

Cephalosporins

Failure of cefamandole in treatment of meningitis due to Haemophilus influenzae type b.

The in vitro activity of cefamandole was determined against 58 isolates of Haemophilus influenzae type b; 47 were beta-lactamase-negative (ampicillin-susceptible), and 11 produced beta-lactamase (ampicillin-resistant). Ampicillin-susceptible strains were susceptible to cefamandole with a median minimal bactericidal concentration (MBC) of 0.4 microgram/ml. Ampicillin-resistant strains had a median MBC of 0.8 microgram/ml. Prior studies have documented these concentrations of cefamandole in cerebrospinal fluid in the presence of inflamed meninges. Three children with meningitis due to H. influenzae type b were treated with cefamandole (200 mg/kg per day), including one child with disease due to an ampicillin-resistant strain. All patients showed clinical improvement during therapy. However, sterility of the cerebrospinal fluid was never achieved in two patients during 72--96 hr of therapy with cefamandole. The third patient relapsed with a recurrence of positive cultures during the seventh day of cefamandole therapy. Therefore, cefamandole does not appear to be a useful agent for treatment of meningitis due to H. influenzae type b irrespective of in vitro susceptibility or evidence of penetration into the cerebrospinal fluid.

Ampicillin

Human rabies.

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Adolescent

Meningococcal disease in California. Epidemiology and management.

Between 1969 and 1975 in California, 1,953 cases of meningococcal disease were reported. For cases reported in 1973, 1974 and 1975, detailed information about chemoprophylaxis of cases and contacts was obtained in addition to demographic and laboratory data. A review of data for the seven years showed a reduction in the case rate from 2.6 to 0.6 per 100,000 population, but this drop was due primarily to a very substantial decline in the military rate from 35.7 to 1.8 per 100,000 population. No reduction was apparent in the case fatality rate. Five groups of associated meningococcal disease cases were identified for a total of nine secondary or coprimary cases among 862 household contacts. Associated cases occurred in 10.4 per 1,000 household contacts-a rate several hundred times greater than that for the general population. THE STUDY FINDINGS INDICATE THAT MANY PHYSICIANS ARE UNAWARE OF THE FOLLOWING: (1) nonhousehold contacts are at little or no risk of contracting meningococcal disease; (2) prophylaxis should be offered only to household or intimate contacts immediately upon identification of an index case without waiting for test results for meningococcal carriage; (3) valid medical and epidemiologic indications exist for administering prophylaxis to household contacts who are culture negative as well as those who are culture positive; (4) the current drug of choice for prophylaxis is rifampin, but since no drug is completely effective, close medical observation remains the most important factor in the management of household or intimate contacts to meningococcal disease.

Adolescent

Bacterial meningitis and septicemia in sickle cell disease.

A total of 422 patients with sickle cell disorders have been observed for 3,442 patient years. During this period, 53 episodes of septicemia or meningitis occurred, indicating a risk of 12.5% from these infections for each individual. If only patients with SS hemoglobinopathy (sickle cell anemia) (323 patients) are considered, the risk was 15.2%. The case fatality ratios for sepsis and meningitis were 35% and 10%, respectively. Disease due to Streptococcus pneumoniae occurred, almost exclusively, among children with SS hemoglobinopathy who were less than 5 years of age. After the first decade, illnesses among patients with all types of sickle cell disorders were frequently associated with an identifiable source of infection, a chronic course, and frequent involvement of Gram-negative organisms.

Adolescent