Biomedical subjects
Robert S Daum
Publications and source records attributed to Robert S Daum.
VraSR two-component regulatory system and its role in induction of pbp2 and vraSR expression by cell wall antimicrobials in Staphylococcus aureus.
The VraS/VraR two-component system (VraSR) regulates transcriptional induction of penicillin-binding protein 2 (encoded by pbp2) by vancomycin in Staphylococcus aureus. We have now defined the vraSR operon and determined that its induction by beta-lactams as well as by vancomycin is autoregulated. Induction of the pbp2 and vraSR operons by beta-lactams and related compounds within 1 hour after exposure to the antimicrobials was dependent on vraS. However, when a disk diffusion assay that can detect induction of genes over an extended time period was used, induction of the pbp2 operon was mediated by some beta-lactams, including oxacillin; this induction was independent of vraS.
Staphylococcus aureus sepsis and the Waterhouse-Friderichsen syndrome in children.
Staphylococcus aureus has increasingly been recognized as a cause of severe invasive illness. We describe three children who died at our institution after rapidly progressive clinical deterioration from this infection, with necrotizing pneumonia and multiple-organ-system involvement. The identification of bilateral adrenal hemorrhage at autopsy was characteristic of the Waterhouse-Friderichsen syndrome, a constellation of findings usually associated with fulminant meningococcemia. The close genetic relationship among the three responsible isolates of S. aureus, one susceptible to methicillin and two resistant to methicillin, underscores the close relationship between virulent methicillin-susceptible S. aureus and methicillin-resistant S. aureus isolates now circulating in the community.
Impact of community-associated, methicillin-resistant Staphylococcus aureus on management of the skin and soft tissue infections in children.
Skin and soft tissue infections (SSTIs) are common illnesses that have a significant impact on health care management. Community-associated, methicillin-resistant Staphylococcus aureus (CA-MRSA) infections have been documented among healthy individuals without predisposing risk factors. The appearance and spread of CA-MRSA represent a new challenge in pediatric medicine and have important clinical implications for therapy of infections caused by S. aureus. This article provides a review of recent changes in the epidemiology of CA-MRSA, pathogenic potential, and therapeutic considerations in the management of SSTIs in children.
Epidemic community-associated methicillin-resistant Staphylococcus aureus: modern times for an ancient pathogen.
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Successful multiresistant community-associated methicillin-resistant Staphylococcus aureus lineage from Taipei, Taiwan, that carries either the novel Staphylococcal chromosome cassette mec (SCCmec) type VT or SCCmec type IV.
Methicillin-resistant Staphylococcus aureus (MRSA) isolates carry the methicillin resistance gene (mecA) on a horizontally transferred genetic element called the staphylococcal chromosome cassette mec (SCCmec). Community-acquired MRSA (CAMRSA) isolates usually carry SCCmec type IV. We previously reported that 76% of 17 CAMRSA isolates (multilocus sequence type 59) obtained from pediatric patients with skin and soft tissue infections (SSTI) from Taipei did not carry SCCmec types I to IV. We used DNA sequence analysis to determine that the element harbored by these nontypeable isolates is a novel subtype of SCCmec V called SCCmec V(T.) It contains a ccrC recombinase gene variant (ccrC2) and mec complex C2. One SSTI isolate contained molecular features of SCCmec IV but also contained ccrC2 (a feature of SCCmec V(T)), suggesting that it may harbor a composite SCCmec element. The genes lukS-PV and lukF-PV encoding the Panton-Valentine leukocidin (PVL) were present in all CAMRSA SSTI isolates whether they contained SCCmec type IV or V(T). SCCmec V(T) was also present in 5 of 34 (14.7%) CAMRSA colonization isolates collected from healthy children from Taipei who lacked MRSA risk factors. Four (80%) of the these isolates contained lukS-PV and lukF-PV, as did 1 of 27 (3.7%) SCCmec IV-containing colonization isolates. A total of 63% (10 of 16) of the SSTI isolates and 61.7% (21 of 34) of the colonization isolates tested were resistant to at least four classes of non-beta-lactam antimicrobials. SCCmec V(T) is a novel SCCmec variant that is found in multiply resistant CAMRSA strains with sequence type 59 in Taipei in association with the PVL leukotoxin genes.
Novel non-mecA-containing staphylococcal chromosomal cassette composite island containing pbp4 and tagF genes in a commensal staphylococcal species: a possible reservoir for antibiotic resistance islands in Staphylococcus aureus.
Among methicillin-resistant Staphylococcus aureus isolates, a staphylococcal chromosomal cassette containing the mecA gene (SCCmec) is integrated into the chromosome at a unique site. SCCmec also contains unique ccrAB recombinase genes mediating its integration and excision from the genome and is flanked by characteristic left and right direct- and inverted-repeat sequences. A few non-mecA-containing SCC elements that have the other molecular features described above have recently been described. The origin of these cassettes is not clear. We have identified two new members of the SCC family integrated within orfX in Staphylococcus epidermidis strain ATCC 12228, neither of which carries mecA. One is a 57-kb element flanked by a unique 28-bp SCC direct repeat. It was called the SCC composite island (SCC-CI) because it carries a 19-kb SCC element (SCCpbp4) nested within it. SCCpbp4 contains pbp4 and tagF genes, as well as one pair of ccrAB genes (allotype 2) flanked by classical SCC-specific terminal repeats. External to SCCpbp4, SCC-CI contains a second pair of ccrAB genes (allotype 4), three IS431 elements, and genes mediating resistance to heavy metals. Genes mediating restriction-modification that may facilitate horizontal transfer are also present within SCC-CI, both within and outside SCCpbp4. Several novel arrangements of the SCC direct and inverted repeats were identified. Several long stretches of homology with other SCCs were found within and outside SCCpbp4. In view of the fact that SCC-CI was found in a commensal species, it may represent a reservoir for sequences involved in genetic shuffling between staphylococci and may contribute to the diversity found in SCC elements.
On-time immunization rates among children who enter Chicago public schools.
OBJECTIVE: A primary objective of the Healthy People 2010 initiatives is to increase on-time immunization rates during the first 2 years of life and to decrease racial disparities in coverage. The objective of this study was to determine on-time immunization coverage rates among infants and toddlers stratified by race/ethnicity in a large metropolitan center. METHODS: A retrospective cohort study that was based on immunization records in the Chicago Public Schools computerized database was conducted using all 67376 children who completed kindergarten in 2001 and 2002. RESULTS: On-time immunization rates in Chicago public school children are low (31% at 7 months, 32% at 19 months, 59% at 36 months). At 19 months of age and thereafter, Hispanic children had the highest rate of on-time immunization coverage. Among children <48 months old, black children had the lowest rates of up-to-date immunization status. At 48 months of age, the up-to-date rate for black children improved to a rate similar to white children (58%) and by school entry surpassed the up-to-date rate for white children (71%). Compared with the recommended 2, 4, 6, and 15 to 18 months schedule, black children received 4 doses of diphtheria/tetanus/acellular pertussis at a mean age of 10.0, 14.6, 20.4, and 34.5 months of age. In contrast, Hispanic children received the same doses at a mean of 4.5, 7.4, 11.0, and 25.1 month of age. In addition, approximately 25% of black children received the majority of their vaccinations >12 months later than the recommended time intervals. CONCLUSIONS: Striking immunization delay still exists during the infant and toddler years. Targeted efforts are needed to increase on-time immunization rates and to decrease racial disparity in immunization coverage.
Toward global Haemophilus influenzae type b immunization.
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Severe Staphylococcus aureus infections caused by clonally related community-acquired methicillin-susceptible and methicillin-resistant isolates.
We investigated the genetic relatedness of 5 community-acquired (CA) Staphylococcus aureus isolates obtained from 4 consecutive pediatric patients presenting with sepsis syndrome and severe pneumonia during a 3-week period in 2000. Two patients were infected with methicillin-susceptible S. aureus (MSSA), and 2 were infected with methicillin-resistant S. aureus (MRSA). The pulsed-field gel electrophoresis patterns for the 2 CA-MRSA isolates were identical to each other, as were the patterns for the 3 CA-MSSA isolates. A 2-band difference reflecting the presence of a staphylococcal cassette chromosome mec (SCCmec) element distinguished the CA-MRSA isolates from the CA-MSSA isolates. The small, mobile type IV SCCmec element was present in the CA-MRSA isolates. These data suggest that an insertion or, less likely, a deletion of the SCCmec type IV element occurred in a highly virulent S. aureus background. Staphylococcal toxin genes sea, seh, lukS-PV, and lukF-PV were detected in all isolates. Also, in all isolates, was a partial homolog of seo (seo'). The relationship among these patient isolates strengthens the assumption that CA-MRSA infections may be caused by isolates closely related to MSSA isolates.
Antimicrobial resistance in Staphylococcus aureus at the University of Chicago Hospitals: a 15-year longitudinal assessment in a large university-based hospital.
OBJECTIVES: To describe a longitudinal profile of resistance to beta-lactam antimicrobials among isolates of Staphylococcus aureus at a large university teaching hospital and to evaluate the impact of the methicillin resistance phenotype on resistance trends for non-beta-lactam antimicrobials. DESIGN: Retrospective evaluation of antimicrobial susceptibility data for all 17,287 S. aureus isolates obtained from January 1986 through December 2000. SETTING: The University of Chicago Hospitals, a family of tertiary-care, university-affiliated hospitals in Chicago, Illinois, consisting of 547 adult and pediatric beds. RESULTS: The annual rate of resistance to methicillin increased from 13% in 1986 to 28% in 2000 (P < .001) and has not plateaued. For each non-beta-lactam antimicrobial tested, the annual rates of resistance were far higher among methicillin-resistant S. aureus (MRSA) isolates than among methicillin-susceptible S. aureus (MSSA) isolates. The annual rates of resistance to the macrolide, lincosamide, and streptogramin (MLS) antimicrobials erythromycin and clindamycin increased among MSSA isolates (P < .01), but remained lower than 20%. Resistance to the MLS antimicrobials was higher among MRSA isolates (higher than 60%), but the annual rate decreased significantly during the study (P < .01). CONCLUSION: The prevalence of methicillin resistance among S. aureus isolates has continued to increase; resistance to non-beta-lactam antimicrobials is far more common among MRSA isolates. Recent decreases in the proportion of MRSA isolates resistant to non-beta-lactam antimicrobials suggest important changes in the epidemiology of this pathogen.
Disseminated vaccinia false alarm.
We report the case of a 6-year-old girl who presented in December 2002 with fever and a vesicular rash. Initially she was diagnosed with Stevens-Johnson syndrome. The differential diagnosis was expanded, however, when an exposure to a person who was believed to be vaccinated recently against smallpox was revealed. We describe the sequence of events that ensued and the workup for a possible case of disseminated virus.
Transcriptional induction of the penicillin-binding protein 2 gene in Staphylococcus aureus by cell wall-active antibiotics oxacillin and vancomycin.
We found an increased abundance of pbpB-specific transcripts in vancomycin intermediate-resistant Staphylococcus aureus (VISA) isolates compared with that found in paired, genetically identical, susceptible isolates. This difference in expression cannot be explained by differences in the pbpB promoter sequence. Since the factors controlling pbpB gene expression have remained largely unexplored, various conditions that might affect pbpB transcript abundance were examined. In both vancomycin-susceptible and VISA strains, pbpB expression varied with the growth phase, with the highest abundance of pbpB-specific transcripts detected during mid-log phase. Interestingly, both vancomycin and oxacillin were able to induce pbpB transcription above a constitutive level. When vancomycin was absent, one of the three pbpB-specific transcripts that were usually faintly detected in non-VISA strains was more readily detected in VISA strains during mid-log but not stationary phase. This transcript was enhanced in non-VISA strains by vancomycin induction. Gel shift assays indicated that an increased amount of the putative transcription factor that binds to both P1 and P1' promoter regions is present in the cytosol of vancomycin-induced cells. Neither the SigB sigma factor nor the quorum-sensing agr locus was required for growth phase-variable pbpB expression or transcriptional induction of pbpB by vancomycin or oxacillin. Also, MecI, MecR1, BlaI, and BlaR1, regulatory proteins that mediate beta-lactam-inducible expression of mecA and beta-lactamase, were not required for antibiotic induction of pbpB transcription. These data support the idea that pbpB expression is modulated by a trans-acting factor in response to the presence of the cell wall-active antibiotics vancomycin and oxacillin.
Resistance to autolysis in vancomycin-selected Staphylococcus aureus isolates precedes vancomycin-intermediate resistance.
Four clinical U.S. glycopeptide intermediate resistant Staphylococcus aureus (GISA) isolates were resistant to Triton X-100-induced autolysis. Similar resistance was demonstrated in an isolate obtained after a single passage of a susceptible clinical isolate in low-level vancomycin. Strains with the vancomycin-induced Triton X-100 resistance phenotype produced active murein hydrolases but were resistant to lysis by murein hydrolases.
Physician knowledge of catch-up regimens and contraindications for childhood immunizations.
OBJECTIVES: To determine physician success at designing catch-up regimens for children delayed in immunizations and physician knowledge regarding contraindications to immunization. METHODS: A self-administered survey was completed by pediatricians, general practitioners, and family practitioners in Cook County, Illinois. Surveys included 6 open-ended vignettes describing hypothetical children delayed in immunization for whom participants were asked to design catch-up regimens. Bivariate and multivariate logistic regression were used to determine predictors of correct response. The surveys also inquired about management of scenarios that might be perceived as contraindications to immunize with the Haemophilus influenzae type b or measles-mumps-rubella vaccines. RESULTS: The mean score of correct responses was 1.83 of a possible 6.0. Almost one third of respondents answered all 6 vignettes incorrectly. The proportion of incorrect responses was high for all 6 vignettes (39%-86%), but higher for questions that addressed the immunization of children older than 12 months. Errors in vaccine administration were most commonly attributed to omitted vaccines, with varicella-zoster vaccine and pneumococcal conjugate vaccine omitted most frequently. Pediatricians were >4 times more likely to answer correctly than were family practitioners. Participants in the Vaccines for Children (VFC) program were more than twice as likely to answer correctly than were non-VFC providers. Knowledge of contraindications was inconsistent, particularly for measles-mumps-rubella vaccine. CONCLUSIONS: Childhood vaccine providers have substantial knowledge deficits of recommended immunization schedules and vaccine contraindications that may contribute to missed opportunities to immunize. Pediatricians and participants in the VFC program were more successful at designing catch-up regimens for children with immunization delay.
Obstacles to the elimination of Haemophilus influenzae type b disease: three illustrative cases.
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A novel methicillin-resistance cassette in community-acquired methicillin-resistant Staphylococcus aureus isolates of diverse genetic backgrounds.
Until recently, it has been unclear whether community-acquired (CA) methicillin-resistant Staphylococcus aureus (MRSA) isolates represent the spread of hospital MRSA isolates into the community. In 2 CA-MRSA isolates, a novel genetic element, designated staphylococcal cassette chromosome mec (SCCmec) type IV, was found; it differs from SCCmec types I-III in its small size and absence of non-beta-lactam genetic-resistance determinants. To study the prevalence of type IV SCCmec, polymerase chain reaction characterization of SCCmec was performed on DNA from 12 CA-MRSA isolates. The 12 CA-MRSA isolates were from diverse genetic backgrounds, as evidenced by their stratification into 5 pulsed-field gel electrophoresis types, 4 coagulase types, and 2 ribotypes. Eleven of the 12 isolates contained the novel SCCmec type IV element. Ten were resistant only to beta-lactam antibiotics. SCCmec type IV is present on the genome of CA-MRSA isolates. Its relatively small size and presence in isolates of diverse genetic backgrounds suggest that it may spread among S. aureus isolates.