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Biomedical subjects

R S Daum

Publications and source records attributed to R S Daum.

At least 19 recordsLinked to original sources
PubMed1997

Infant immunization with pneumococcal CRM197 vaccines: effect of saccharide size on immunogenicity and interactions with simultaneously administered vaccines.

Six pentavalent pneumococcal conjugate vaccines (Pn-CRM197) were evaluated among 400 infants. The vaccines differed in saccharide chain length (oligosaccharide [OS] or polysaccharide [PS]) and saccharide quantity (0.5, 2, or 5 microg). Subjects were randomized into groups 1-6 (Pn-CRM197 recipients) or 7 (controls) for immunization at 2, 4, and 6 months of age. Pn-CRM197 were well tolerated and elicited mean antibody concentrations that exceeded those in controls for all 5 capsular serotypes. PS formulations were generally more immunogenic than their OS counterparts. For PS vaccines, a dose-response was documented (5 microg > 2 microg > 0.5 microg), but the differences between the 5- and 2-microg formulations were insignificant. The mean anti-PRP antibody concentration was significantly higher among Pn-CRM197 recipients. It is concluded that PS vaccines are more immunogenic than OS vaccines. The improved immunogenicity from Haemophilus type b oligosaccharide conjugate (HbOC) vaccine when given with Pn-CRM197 suggests that a decreased dose of HbOC vaccine may be sufficient to elicit protection.

Antibodies, Bacterial↗
PubMed1997

Increased production of penicillin-binding protein 2, increased detection of other penicillin-binding proteins, and decreased coagulase activity associated with glycopeptide resistance in Staphylococcus aureus.

The mechanism of glycopeptide resistance in the genus Staphylococcus is unknown. Since these antimicrobial compounds act by binding the peptidoglycan precursor terminus, the target of transglycosylase and transpeptidase enzymes, it was hypothesized that resistance might be mediated in Staphylococcus aureus by increased production or activity of these enzymes, commonly called penicillin-binding proteins (PBPs). To evaluate this possibility, glycopeptide-resistant mutants were prepared by passage of several clinical isolates of this species in nutrient broth containing successively increasing concentrations of the glycopeptide vancomycin or teicoplanin. Decreased coagulase activity and increased resistance to lysostaphin were uniformly present in the vancomycin-resistant mutants. Peptidoglycan cross-linking increased in one resistant isolate and decreased in two resistant isolates. The amounts of radioactive penicillin that bound to each PBP in susceptible and resistant strains were compared; PBP2 production was also evaluated by Western blotting. Increased penicillin labeling and production of PBP2 were found in all resistant derivatives selected by either vancomycin or teicoplanin. Moreover, the increase in PBP2 penicillin labeling occurred early in a series of vancomycin-selected derivatives and was strongly correlated (r > 0.9) with the increase in vancomycin and teicoplanin MIC. An increase in penicillin labeling also occurred, variably, in PBP1, PBP3, and/or PBP4. These data demonstrate a strong correlation between resistance to glycopeptides and increased PBP activity and/or production in S. aureus. Such an increase could allow PBPs to better compete with glycopeptides for the peptidoglycan precursor.

Bacterial Proteins↗
PubMed1996

The effect of epidemic measles on immunization rates.

OBJECTIVE: To evaluate whether immunization against a vaccine-preventable disease is sought to avoid the naturally occurring disease itself, we hypothesized that the rate of "on-time" measles immunization would increase during an epidemic of that disease. If such an effect occurred, we wondered whether it would have an impact on on-time administration of other recommended immunizations. DESIGN: Retrospective evaluation of immunization rates of children at their second birthday with the use of computerized health records of children entering kindergarten in an 8-year interval spanning the onset of epidemic measles in Chicago, Ill, in 1989 and 1990. SETTING: Children entering Chicago public schools. MAIN OUTCOME MEASURES: Rates of receipt of measles-containing vaccine (MCV), 1 to 4 doses of a diptheria toxoid-tetanus toxoid-pertussis (DTP) or diphtheria toxoid-tetanus toxoid (DT) vaccine, 1 to 3 doses of oral or inactivated polio vaccine (OPV/IPV), and the full series of these vaccines (4:3:1) that are required to be "up-to-date" by the second birthday. RESULTS: The rate of on-time MCV receipt increased from 56% to 58% in the years prior to 70% during the epidemic (1989 and 1990). A similar increase did not occur to DTP/DT 4 or OPV/IPV 3. Moreover, among older children delayed in MCV receipt, evidence of catch-up immunization also occurred during the epidemic years; similar catch-up for delayed DTP/DT 4 or OPV/IPV 3 immunization did not occur. CONCLUSIONS: Dramatic increases in one-time and catch-up MCV receipt occurred during the Chicago measles epidemic of 1989 and 1990. The lack of similar increases in DTP/DT 4 and OPV/IPV 3 suggests MCV receipt was not associated with receipt of other recommended immunizations during that time.

Bacterial Proteins↗
PubMed1996

Overproduction of a 37-kilodalton cytoplasmic protein homologous to NAD+-linked D-lactate dehydrogenase associated with vancomycin resistance in Staphylococcus aureus.

We previously reported the isolation of a laboratory-derived Staphylococcus aureus mutant, 523k, that has constitutive low-level resistance to vancomycin (MIC = 5 micrograms/ml) and teicoplanin (MIC = 5 micrograms/ml) and elaborates a ca. 39-kDa cytoplasmic protein that was not detected in the parent strain 523 (MIC = 1 micrograms/ml). We have now detected the protein in strain 523 by immunoblotting with antiserum raised against the protein. Consistent with our initial observations, densitometric analysis of the immunoblots revealed an increased production of the protein in 523k compared with that of the susceptible parent 523. The 5' region of the gene encoding the protein of interest was identified by nucleotide sequencing a PCR product amplified from the genome of 523k with degenerate primers designed to encode the amino acid sequence of proteolytic peptides obtained from the protein. The remainder of the gene was identified by library screening, PCR, and nucleotide sequencing. The gene encodes a 36.7-kDa protein with homology to a family of bacterial NAD+-dependent, D-specific 2-hydroxyacid dehydrogenases which includes both D-lactate dehydrogenase and the enterococcal vancomycin resistance protein VanH and is therefore designated ddh. Increased production of the product of ddh, Ddh, was associated with increased D-lactate dehydrogenase activity in 523k, a finding which suggested that Ddh is likely to be the D-lactate dehydrogenase previously identified in S. aureus. The increased D-lactate dehydrogenase activity in strain 523k and the structural similarities among Ddh, D-lactate dehydrogenase, and VanH suggest that overproduction of Ddh might play a role in vancomycin resistance in this strain.

Alcohol Oxidoreductases↗
PubMed1996

Interchangeability of Haemophilus influenzae type b vaccines in the primary series: evaluation of a two-dose mixed regimen.

OBJECTIVE: To evaluate two- or three-dose "mixed" regimens of Haemophilus influenzae type b conjugate vaccines in the priming series. DESIGN: Two randomized clinical trials with 140 and 181 infants, respectively. SETTING: Private practices in New Orleans and Chicago. METHODS: In trial I, infants received one of four regimens. Two were recommended regimens for polyribosylribitol phosphate (PRP)-meningococcal protein conjugate (M) and PRP-tetanus toxoid conjugate (T). Two mixed regimens consisted of M at 2 months followed by two doses of T or PRP-diphtheria toxoid conjugate (D) at 4 and 6 months. Trial II consisted of three groups. Two were recommended regimens for M and T. The third was a two-dose mixed regimen consisting of M at 2 months and T at 4 months. Parents were interviewed and instructed to record side effects after each vaccination. Serum was assayed for H influenzae type b anticapsular antibody (anti-PRP). RESULTS: Minor differences in safety profiles likely reflected alpha error. In trial I, M (lot 0884T, one of several known to have had decreased immunogenicity), probably primed for substantial increase in serum antibody when D or T was given at 4 and 6 months. In trial II, infants who received the two-dose mixed regimen (M from immunogenic lot 0116W at 2 months and T at 4 months) had a significantly higher mean area under the curve than recipients of the three-dose TTT regimen when antibody concentration was plotted against age, although the geometric mean anti-PRP antibody concentration for the MT-recipients was significantly lower at 7 months. CONCLUSIONS: M used in trial I may have primed infants despite poor immunogenicity. The two-dose mixed regimen (MT-) in trial II produced a mean anti-PRP antibody concentration with higher sustained anti-PRP concentrations from 2 to 7 months, as judged by the area under the curve, but a lower mean anti-PRP antibody concentration at 7 months.

Antibodies, Bacterial↗
PubMed1995

Antimicrobial resistance in staphylococci.

Staphylococci have developed a variety of strategies for dealing with the presence of antibiotics encountered in clinical environments. Resistance to beta-lactams and other antimicrobial agents has been accomplished by a diverse array of molecular mechanisms. Options available to treat infections caused by staphylococci resistant to methicillin are limited, and the next generation of antibiotics to be introduced, should glycopeptide resistance become an important clinical problem, is not yet on the horizon.

Anti-Bacterial Agents↗
PubMed1995

The V-region repertoire of Haemophilus influenzae type b polysaccharide antibodies induced by immunization of infants.

Haemophilus influenzae type b (Hib) is a significant pathogen for young children, and three Hib vaccines (named PRP-OMPC, HbOC, and PRP-T) are currently available for young children. Extensive studies of anti-Hib polysaccharide (PS) antibodies (Abs) have shown that the V regions of Abs against the Hib PS comprise a VH gene in the VH3 gene family and a VL gene from various K kappa and V lambda subgroups. To study immunogenic properties of the three vaccines in young children, we determined the VL subgroups and avidities of anti-Hib-PS Abs induced by the three clinically available conjugate vaccines. Ab avidity was measured by determining the concentration of a Hib-PS oligomer that abrogates half of the binding of immunoglobulin G anti-Hib-PS Abs to microwells. The PRP-OMPC vaccine induced lower-avidity Abs than the prelicensure HbOC vaccine (P = 0.05). When we compared anti-Hib-PS Abs expressing V kappa Ia, V kappa II, and V lambda subgroups, a greater Ab response was induced by the prelicensure HbOC vaccine than other vaccines (P < 0.05). When anti-Hib-PS Abs with the V kappa III subgroup were compared, however, both PRP-T and prelicensure HbOC vaccines induced a comparable response, which in turn was greater than those induced by the PRP-OMPC or the postlicensure HbOC vaccine (P < 0.001). The VL repertoire of Abs induced with the prelicensure HbOC or PRP-T vaccine in young children is dominated (about 80%) by anti-Hib-PS Abs using subgroup V kappa II. However, anti-Hib-PS using V kappa II VL accounts for only about 40% of the total anti-Hib-PS Abs induced with the PRP-OMPC vaccine or the postlicensure HbOC. Our data suggest that immunogenic properties of Hib vaccines in young children vary depending on the vaccine preparations as well as the vaccine types.

Antibodies, Bacterial↗
PubMed1995

Safety and immunogenicity of PRP-T combined with DTP: excretion of capsular polysaccharide and antibody response in the immediate post-vaccination period.

OBJECTIVE: To evaluate whether combining Haemophilus influenzae type b capsular polysaccharide covalently linked to tetanus toxoid (PRP-T) and diphtheria-tetanus-pertussis (DTP) in one syringe produced a vaccine that was safe and immunogenic. DESIGN: Randomized clinical trial. SETTING: Suburban New Orleans pediatric population. PARTICIPANTS: Convenience sample of 150 healthy infants. METHODS: Enrollees were randomized to receive DTP and PRP-T in one injection (Group 1), DTP and PRP-T separately (Group 2), or DTP and H influenzae type b capsular saccharide coupled to a nontoxic variant of diphtheria toxin, CRM197 (HbOC) separately (Group 3) at 2, 4, and 6 months of age. All infants received oral polio vaccine at 2 and 4 months of age. Parents were instructed to record side effects on a standardized form after each vaccine administration. Blood was drawn before each immunization and at 7 months of age; an additional blood and a urine specimen was obtained 2 to 3 days after one of the vaccination visits. Serum was assayed for H influenzae anticapsular antibody (anti-PRP), anti-pertussis toxoid, anti-fimbrial hemagglutinins, anti-diphtheria and anti-tetanus toxoid antibodies, and antibody to polio viruses. Urine was assayed for H influenzae type b capsular polysaccharide. RESULTS: The rate of occurrence of fever did not differ significantly between groups. Local swelling and erythema occurred more often at the administration site in Group 1 infants than at the DTP administration sites of infants in Groups 2 and 3 after the first and second vaccinations. The mean concentration of all antibodies we assayed did not differ significantly when Group 1 and 2 infants were compared. HbOC recipients (Group 3) had lower mean anti-H influenzae anticapsular antibody and higher mean anti-diphtheria and anti-tetanus antibody concentrations after two and three doses compared with Group 1 and Group 2 infants. No group had a significant change in mean anti-PRP antibody concentration 2 to 3 days after vaccination with any dose. After vaccination, antigenuria occurred less frequently in Group 1 infants (54%, 78%, and 72% in Groups 1, 2, and 3, respectively, P < .01). CONCLUSIONS: Combining PRP-T and DTP produced a combination vaccine associated with a slight increase in the rate of erythema and swelling but with similar immunogenicity of the vaccine components and oral polio vaccine.

Antibodies, Bacterial↗
PubMed1994

Nosocomial epiglottitis associated with penicillin- and cephalosporin-resistant Streptococcus pneumoniae bacteremia.

We cared for a 4-year-old male with nosocomially acquired epiglottitis caused by Streptococcus pneumoniae. He had been receiving ceftazidime therapy when this infection was recognized. The S. pneumoniae isolate was of serotype 15B and was resistant to beta-lactam antibiotics, cephalosporins (including those with extended spectra), and trimethoprim-sulfamethoxazole. Clinicians and clinical microbiologists must be aware that cephalosporin susceptibility may no longer be assumed for penicillin-resistant S. pneumoniae isolates and that susceptibility testing for the extended-spectrum cephalosporins should be performed whenever this species is isolated from a normally sterile body fluid.

Bacteremia↗
PubMed1993

Accuracy of immunization histories provided by adults accompanying preschool children to a pediatric emergency department.

OBJECTIVE: Because some have advocated the use of emergency departments to administer delayed childhood immunizations, we evaluated the accuracy of immunization histories obtained in this setting by comparison with medical records of inner-city health care facilities. DESIGN: Questionnaires were orally administered to adults accompanying children to the emergency department. Individual medical records were reviewed. SETTING: Pediatric emergency department at Wyler Children's Hospital, University of Chicago and 68 inner-city primary care clinics. PATIENTS: Children aged 3 to 65 months registering for medical care. Of the sample, 98% were African American; 75% were Medicaid recipients. MAIN OUTCOME MEASURES: Adults' knowledge of immunization histories, immunization cards, and medical records compared with American Academy of Pediatrics/Immunization Practices Advisory Committee recommendations. RESULTS: Of the accompanying adults, 64% stated that their child's general immunization status was "up-to-date"; 65% of these had clinic records confirming that status. Only 8% of specific regimens stated by these adults accurately matched those found in clinic records. Moreover, 45% of adults accompanying children at least 16 months and older provided inaccurate information regarding previous receipt of measles immunization. CONCLUSION: Information provided by accompanying adults (from recall or from immunization cards) is inadequate to determine accurately which preschoolers in the pediatric emergency department are delayed in immunizations.

Chicago↗
PubMed1993

Anti-PRP antibody levels after a primary series of PRP-OMPC and persistence of antibody titres following primary and booster doses.

The Haemophilus influenzae capsular polysaccharide-outer membrane protein conjugate, PRP-OMPC (PedvaxHIB) elicits very good antibody responses in infants > or = 2 months of age after the first dose. Increasing age at time of first vaccination correlates with higher antibody responses. Anti-PRP responses are consistently high with the first injection among all population groups studied. Booster doses stimulate anamnestic antibody responses after one year of age. Among US children (excluding Navajo and Apache children) given a primary injection at 14-18 months of age, the geometric mean titre (GMT) after 2 to 3 years was > 1 micrograms/ml. US children (excluding Navajo and Apache children) given a primary series at 2 and 4 months of age and a booster at 18 months of age also had an anti-PRP GMT > 1 micrograms/ml 2.5 years later. Navajo and Apache children given a primary series at 2 and 4 months of age and a booster at 12-15 months had antibody levels of 1.50 micrograms/ml one year later. Antibody persistence data suggest there will be long-term protection against Haemophilus influenzae b disease following immunization with PRP-OMPC.

Antibodies, Bacterial↗
PubMed1992

Severe measles in immunocompromised patients.

OBJECTIVE: To describe the severity of measles in immunocompromised hosts and to assess preventive and therapeutic modalities. DATA SOURCES: Patients admitted to two academic medical centers between September 1989 and December 1990 and English language references obtained by MEDLINE from 1963 to 1991. Bibliographies were used to identify reports prior to 1963. STUDY SELECTION: We identified nine immunocompromised patients with measles. Further analysis was based on 35 patients from two cohort studies of measles in oncology patients and 24 reported cases of measles in human immunodeficiency virus (HIV)-infected patients. DATA EXTRACTION: Clinical data are presented from the nine patients we treated. Information concerning measles complications, presence of rash, use of prophylactic immunoglobulin, and therapeutic measures was extracted from the literature. DATA SYNTHESIS: Of our nine patients, eight developed severe complications and two died. Two patients had no rash. In combining our patients with those from the literature, severe complications occurred in about 80%. The case fatality rate for severe measles was about 70% for oncology patients and about 40% for HIV-infected patients. Rash was absent in about 30%. The efficacy of prophylactic or therapeutic measures could not be assessed due to the small number of patients. However, we observed a rapid defervescence following administration of ribavirin. Vaccinated, HIV-infected patients had a lower mortality rate than those not previously vaccinated (P = .06). CONCLUSIONS: Measles is a severe illness in immunocompromised patients, and the absence of rash is frequent. While treatment is supportive, ribavirin requires further study. Measles vaccine may be efficacious in HIV-infected patients. Vaccination of oncology patients should be reassessed.

Adolescent↗
PubMed1992

Characterization of Staphylococcus aureus isolates with decreased susceptibility to vancomycin and teicoplanin: isolation and purification of a constitutively produced protein associated with decreased susceptibility.

"Derivative isolates" with 4- to 8-fold and 8- to 16-fold increases in MICs of vancomycin and teicoplanin, respectively, were selected from 2 susceptible clinical isolates of Staphylococcus aureus by serial incubation in low-level vancomycin. A protein of approximately 39 kDa was demonstrable in the cytoplasmic fraction and occasionally in the membrane fraction by SDS-PAGE of both derivatives. This protein was purified by DEAE chromatography, preparative SDS-PAGE, and electroelution. Derivative bacteria were larger on transmission electron microscopy, had thicker cell walls, and had changes in colony morphology on solid media. Further evidence for cell wall reorganization included loss of phage and capsular typing, decreased susceptibility to lysostaphin/lysozyme killing, and changes in condition for detection of optimal coagulase activity. The mechanism of decreased susceptibility to glycopeptide antibiotics among S. aureus derivative isolates is uncertain. The production of the approximately 39-kDa cytoplasmic protein and cell wall reorganization may mediate changed affinity of glycopeptide-peptidoglycan binding or impairment of glycopeptide access to its cell wall target.

Bacterial Proteins↗
PubMed1992

IgG1, IgG2 and IgM responses to two Haemophilus influenzae type b conjugate vaccines in young infants.

PRP-meningococcal outer membrane protein complex (PRP-OMPC) and oligosaccharide linked to variant diphtheria toxin (HbOC) Haemophilus influenzae type b (HIB) conjugate vaccines have both been licensed for United States infants at 2 months of age. Differences in serologic responses for these vaccines have been noted with PRP-OMPC producing an early response at 2 months of age and HbOC producing a higher response after a third dose at 6 months of age. To further characterize the nature of these distinct responses, we measured the IgG1, IgG2 and IgM anti-HIB concentrations by enzyme-linked immunosorbent assay after administration of both vaccines. PRP-OMPC produced an IgM and IgG1 anti-HIB response following the initial dose at 2 months of age. After two doses of HbOC an increase in IgG1 and IgM were noted and after a third dose at 6 months of age an IgG2 anti-HIB response occurred. In addition 33 study subjects were boosted with PRP-OMPC at age 18 months and compared with 34 subjects who received only a primary dose. The anti-HIB IgG1 and IgG2 concentrations following the booster dose were both significantly higher for the primed group (P = 0.0001 and P = 0.001, respectively). Both HIB conjugate vaccines produce predominantly IgG1 anti-HIB antibody responses. The early response to PRP-OMPC vaccine at 2 months of age may result from adjuvant characteristics of the OMPC.

Antibodies, Bacterial↗