Biomedical subjects
J M Leedom
Publications and source records attributed to J M Leedom.
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.
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.
Comparative trial of carbenicillin and ampicillin therapy for purulent meningitis.
A randomized therapeutic trial of carbenicillin (CB) or ampicillin (AMP) in purulent meningitis was performed in 86 pediatric and adult patients (41 Haemophilus influenzae, 22 Streptococcus pneumoniae, 13 Neisseria meningitidis, and 10 of unknown etiology). All isolates, incuding H. influenzae, were susceptible to CB and AMP. Median cerebrospinal fluid (CSF) antibiotic concentrations were 0.85 and 1.60 mug/ml for CB and AMP, respectively, during administration of daily doses of 400 mg/kg and 0.65 and 0.45 mug/ml, respectively, on daily doses of 200 mg/kg. Higher CSF concentrations, up to a median concentration of 4.5 mug/ml, were observed in patients with CSF protein concentrations >/=75 mg/100 ml. Clinical responses were equivalent on either antibiotic regimen. Among AMP patients (45), 8 had significant residua and 3 died; among CB patients (41), 5 had residua and none died. However, 38% of H. influenzae patients treated with CB had positive CSF cultures on day 1 follow-up lumbar punctures, compared with only 5.8% of AMP patients with H. influenzae. The significance of a delay of CSF sterilization among CB-treated patients is unknown, since there was no correlation between persistence of hemophilus organisms and the frequency of adverse outcome. AMP and CB are equivalent for the treatment of bacterial meningitis due to susceptible organisms.
Susceptibility of Hemophilus influenzae, type b, to ampicillin at Los Angeles County/University of Southern California Medical Center. A reappraisal after ten years.
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Epidemiological implications of rubella "vaccine failures".
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Clinical rubella with arthritis resulting from reinfection.
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Responses of previously reinfected rubella vaccinees to challenge with Brown strain rubella virus.
The responses of seven hpv-77 rubella vaccinees to initial challenge with "wild" rubella virus have been compared with their responses to rechallenge with Brown strain rubella virus and to the responses of five "natural" immunes to initial Brown strain challenge. Previous exposure to "wild" rubella virus 220 days post vaccine-induced immunity had resulted in six of the seven vaccinees experiencing asymptomatic reinfection. On "rechallenge" none of the previously "reinfected vaccine immunes" demonstrated clinical, virologic or serologic evidence of reinfection. These data are consistent with the conclusion that persons with vaccine-induced immunity may be assured of more prolonged and solid immunity to rubella without having to suffer the clinical disease if they are reinfected with nonattenuated rubella virus. Rigidly controlled experiments, designed to study the practicality and safety of immunization with live rubella vaccine(s), followed by deliberate challenge of vaccinees with "wild" or low tissue culture passage rubella virus, seem warranted. In addition, these data indicate that it is imperative that a distinction should be made between "vaccine immunes" and previously "reinfected vaccine immunes" in any evaluation of long term rubella vaccine(s) efficacy and vaccine-induced antibody decay.
Meningitis due to Listeria monocytogenes. A review of 25 cases.
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Gentamicin in the treatment of meningitis.
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Transmission of rubella vaccine virus from vaccinees to contacts.
The report presents evidence of the transmission of hpv-77 derived rubella vaccine virus from vaccinees to two susceptible contacts. The first instance of transmission was to a child who served as a transmission control on a "closed" study ward, and the second was to an antibody-negative mother in an "open" family study. Neither of these persons had any clinical evidence of rubella. Both had significant increases in rubella hemagglutination inhibiting (hai) antibody titers, but detectable complement fixing (cf) antibodies did not develop in either. With the kind of antigen used in our rubella cf test, this pattern of serologic response is characteristic of, but not diagnostic of, infection with the rubella vaccine virus. The serological evidence which was compatible with rubella vaccine virus infection, the complete absence of serologic or clinical evidence of "wild" rubella virus infections among the other four rubella susceptible transmission control children and the security precautions employed to ensure isolation on the "closed" ward, make "wild" rubella virus infection extremely unlikely. The evidence for rubella vaccine virus infection in the other susceptible contact is not as conclusive, because "wild" rubella virus infection is difficult to rule out in any person living in an "open" family situation. Nevertheless the need for more data is emphasized by the virtual certainty that rubella vaccine virus transmission did occur in the subject on the isolation ward, plus the high probability that the infection observed in the family group setting also represented transmission of rubella vaccine virus. Such data can only come from close surveillance of recipients of live rubella virus vaccines and their contacts in the future.
Important assumptions, extrapolations, and established facts which underlie the use of live rubella virus vaccines.
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Reinfection with rubella virus despite live vaccine induced immunity. Trials of HPV-77 and HPV-80 live rubella virus vaccines and subsequent artificial and natural challenge studies.
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The critically ill child: management of acute bacterial meningitis.
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In vitro susceptibility of Neisseria meningitidis to rifampin.
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Variable results of cephalothin therapy for meningococcal meningitis.
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Viremia in a recipient of HPV-77 Rubella virus vaccine.
A live rubella virus vaccine, HPV-77 (High Passage Virus - 77 tissue culture passages) was administered subcutaneously to eight rubella-susceptible children housed in an isolation ward. One blood specimen, taken on the tenth day after vaccination, from one of the eight vaccines, yielded a rubella virus. This virus had laboratory markers which were "vaccine-like." To our knowledge, this represents the first isolation of rubella virus from the blood of a recipient of HPV-77 vaccine. However, the consistent antibody responses among vaccinees and the regular presence of rubella virus in their pharynges argue that viremia occurs in almost every susceptible recipient. The most logical explanation for the failure to document viremia in other recipients of HPV-77 vaccine is that the viremia is ordinarily low grade or transient or both.