Pneumococcal vaccination in recipients of renal allografts.
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Biomedical subjects
Publications and source records attributed to G D Overturf.
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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.
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.
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.
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.
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.
A 59-year-old man is presented who had immunoblastic lymphadenopathy which evolved over a three-year period into immunoblastic sarcoma. His course was complicated by vaccinia necrosum, which necessitated prolonged therapy with Marboran and vaccinia-immune globulin. The persistence of virus was documented at autopsy by positive viral culture and ultra-structural examination. This case illustrates the potential hazards of administration of live viral vaccines to an immune compromised host presumed to be in remission and suggests that the continued activity of viral infection may signal the unsuspected persistence of underlying disease.
A 5-year-old child developed acute lymphoblastic leukemia during convalescence from an episode of Reye's syndrome that was treated with multiple exchange transfusions. Routine laboratory, histology, and viral serology were unable to establish a common etiology for the 2 illnesses. Cultural and immunologic methods to search for evidence of infection with type-C viruses or viral genes in lymphoblasts from the buffy coat and bone marrow failed to reveal these agents. Although no common infectious etiology was defined for the close temporal occurrence of 2 rare diseases, the possibility of an iatrogenically induced malignancy was considered.
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.
Twelve patients, aged 6 months to 62 years, with proven bacterial meningitis, were given a single intravenous dose of cefamandole (33 mg/kg) 75 to 140 min before a routine lumbar puncture. Infecting organisms included Haemophilus influenzae (eight cases), Streptococcus pneumoniae (two cases), and Neisseria meningitidis and beta-hemolytic streptococcus (one each). Cerebrospinal fluid (CSF) was analyzed by microbiological assay for cefamandole. The median concentration was 0.60 mug/ml, ranging from undetectable to 7.4 mug/ml. CSF cefamandole concentrations correlated with CSF protein: in six patients with CSF protein less than 100 mug/dl, the range of drug concentration was 0 to 0.62 mug/ml; and in six patients with CSF protein above 100 mg/dl, the range was 0.57 to 7.4 mug/ml. No significant correlation was noted between severity of illness, type of organism involved, or patient age and concentration of drug achieved.
Infectious complications of ventriculo- and lumboperitoneal shunts in two patients are presented. Cerebrospinal fluid infection due to aerobic and anaerobic enteric flora was characteristic of each case. Both infections occurred several months after shunt surgery and were associated with colonic perforation by the distal limb of the peritoneal catheter. These cases emphasize this unusual hazard of peritoneal shunts and demonstrate methods for diagnosis and effective therapy.
The bactericidal activity of penicillin-aminoglycoside combinations was studied in 16 strains of Group B streptococci. Minimal inhibitory concentrations (MIC) against kanamycin or gentamicin were greater than 50 microgram/ml, whereas ampicillin or penicillin inhibitory concentrations were uniformly less than 0.1 microgram/ml. Although all strains had bactericidal concentrations (MBC) less than 0.1 microgram penicillin/ml, penicillin at a concentration equal to each strains respective MBC reduced inoculum colony forming units (CFU) 2 logs in only 6 of 16 strains in bactericidal kinetic studies. However, the addition of gentamicin in concentrations of 5.0 or 10.0 microgram/ml to penicillin markedly enhanced bactericidal activity in all strains tested. The addition of lower concentrations of gentamicin (1.0 microgram/ml) had minimal advantage over penicillin alone. No distinct advantage was noted for combinations including either ampicillin or kanamycin. The theoretical advantage of penicillin-aminoglycoside combinations in experimental conditions, suggests that the use of antibiotic combinations in clinical infections due to Group B streptococci, may result in a more rapid eradication of these organisms.
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Amikacin has been used to treat Providencia stuarii infections on the Burn Service at Los Angeles County/University of Southern California Medical Center since March, 1973. The median minimal inhibitory concentration (MIC) of strains collected on this service prior to the introduction of amikacin was 3.13 mug. per milliliter, whereas the median MIC of strains collected during the last 4 months of the study was 12.5 mug per milliliter. High bactericidal concentrations (MBC) noted at the time of initial studies predicted the emergence of resistant clones, with MBV values rising to as great as 100 mu per milliliter. Further, isolates from burn patients during the initial 5 days of treatment with amikacin had a median MIC of 6925 mug per milliliter, in contrast to values of 25 mug per milliliter in strains isolated after 5 days of treatment. The epidemiologic significance of intensive treatment of gram-negative infections occurring in a close population with selected antibiotics is discussed. The performance of susceptibility tests which included determination of bactericidal concentrations was a major tool in the recognition of the potential for selection of resistant micro-organisms.
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