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Bernard Beall

Publications and source records attributed to Bernard Beall.

At least 19 recordsLinked to original sources

Whole-genome sequencing-based pathogen characterization for streptococcal infection directly from positive blood culture samples.

Clinical laboratories are increasingly using diagnostic tests directly on positive blood cultures, which may lead to fewer attempts to recover bacterial isolates. Consequently, public health laboratories can benefit from assays that directly process blood culture samples without requiring submission of clinical isolates to determine additional pathogen features not identified by clinical tests, such as vaccine serotype and bacterial genomic relatedness, for surveillance and outbreak response purposes. In partnership with the Minnesota Active Bacterial Core surveillance (ABCs) site, we identified blood culture samples positive for ABCs streptococcal pathogens and characterized them by a direct whole-genome sequencing from blood culture (dWGS) assay. The dWGS results were compared with the results of a reference method (WGS of isolates from the same cultures) to evaluate concordance in pathogen features and genome assemblies. Of the 97 eligible blood culture samples, 83 (86%) passed dWGS quality control criteria and were subjected to a total of 655 dWGS-based tests, which yielded 651 (99.3%) evaluable results. The percent agreement with reference results was 100% (83/83) for M protein gene (emm)/capsular types and 100% (81/81) for multilocus sequencing types. For genotypic antimicrobial susceptibility testing prediction, the percent prediction agreement was 100% (487/487), false resistant prediction rate was 0% (0/417), and the false susceptible prediction rate was 0% (0/66). Assemblies of pathogen genomes from the same patient differed by 1.08 ± 1.68 (mean ± SD) sites per genome. The dWGS assay can extract high-quality, important streptococcal strain characteristics directly from positive blood culture samples to support evolving public health needs.IMPORTANCEWhole-genome sequencing (WGS) technologies have emerged as a transformative toolkit used by public health microbiology laboratories to detect and characterize pathogens. The surveillance of bacterial diseases often relies on clinical laboratories to submit pathogen isolates to regional or national public health laboratories, which have the capacity to routinely conduct WGS-based strain characterization. Clinical laboratories are increasingly using diagnostic tests directly on positive blood cultures, which may lead to fewer attempts to recover bacterial isolates. The study evaluated a direct whole-genome sequencing from blood culture (dWGS) assay that directly processes blood culture samples. The dWGS assay recovered high quality, important streptococcal strain characteristics, including vaccine serotypes and whole-genome assemblies, without requiring submission of clinical isolates. Thus, the dWGS assay represents a promising tool for addressing the evolving needs of public health laboratories in the metagenomics era.

Humans↗

Nursing home outbreak of invasive group a streptococcal infections caused by 2 distinct strains.

OBJECTIVE: To identify factors contributing to a cluster of deaths from invasive group A streptococcus (GAS) infection in a nursing home facility and to prevent additional cases. DESIGN: Outbreak investigation. SETTING: A 146-bed nursing home facility in northern Nevada. METHODS: We defined a case as the isolation of GAS from a normally sterile site in a resident of nursing home A. To identify case patients, we reviewed resident records from nursing home A, the local hospital, and the hospital laboratory. We obtained oropharyngeal and skin lesion swabs from staff and residents to assess GAS colonization and performed emm typing on available isolates. To identify potential risk factors for transmission, we performed a cohort study and investigated concurrent illness among residents and surveyed staff regarding infection control practices. RESULTS: Six residents met the case patient definition; 3 (50%) of them died. Among invasive GAS isolates available for analysis, 2 distinct strains were identified: emm11 (3 isolates) and emm89 (2 isolates). The rate of GAS carriage was 6% among residents and 4% among staff; carriage isolates were emm89 (8 isolates), emm11 (2 isolates), and emm1 (1 isolate). Concurrently, 35 (24%) of the residents developed a respiratory illness of unknown etiology; 41% of these persons died. Twenty-one (30%) of the surveyed employees did not always wash their hands before patient contacts, and 27 (38%) did not always wash their hands between patient contacts. CONCLUSIONS: Concurrent respiratory illness likely contributed to an outbreak of invasive GAS infection from 2 strains in a highly susceptible population. This outbreak highlights the importance of appropriate infection control measures, including respiratory hygiene practices, in nursing home facilities.

Aged↗

Tightly clustered outbreak of group A streptococcal disease at a long-term care facility.

OBJECTIVE: To describe investigation of a tightly clustered outbreak of invasive group A streptococcal (GAS) disease associated with a high mortality rate in a long-term care facility (LTCF). DESIGN: Cross-sectional carriage survey and epidemiologic investigation of LTCF resident and employee cohorts. SETTING: A 104-bed community LTCF between March 1 and April 7, 2004. PATIENTS: A cohort of LTCF residents with assigned beds at the time of the outbreak. INTERVENTIONS: Reinforcement of standard infection control measures and receipt of chemoprophylaxis by GAS carriers. RESULTS: Four confirmed and 2 probable GAS cases occurred between March 16 and April 1, 2004. Four case patients died. The final case occurred during the investigation, before the patient was determined to be a GAS carrier. No case occurred during the 6 months after the intervention. Disease was caused by type emm3 GAS; 16.5% of residents and 2.4% of employees carried the outbreak strain. Disease was clustered in 1 quadrant of the LTCF and associated with nonintact skin. GAS disease or carriage was associated with having frequent personal visitors. CONCLUSIONS: Widespread carriage of a virulent GAS strain likely resulted from inadequate infection control measures. Enhanced infection control and targeted prophylaxis for GAS carriers appeared to end the outbreak. In addition to employees, regular visitors to LTCFs should be trained in hand hygiene and infection control because of the potential for extended relationships over time, leading to interaction with multiple residents, and disease transmission in such residential settings. Specific attention to prevention of skin breaks and proper wound care may prevent disease. The occurrence of a sixth case during the investigation suggests urgency in addressing severe, large, or tightly clustered outbreaks of GAS infection in LTCFs.

Aged↗

Effectiveness of seven-valent pneumococcal conjugate vaccine against invasive pneumococcal disease: a matched case-control study.

BACKGROUND: When seven-valent pneumococcal conjugate vaccine was introduced in the USA, many children were vaccinated on schedules that differed from those tested in clinical trials. Our aim was to assess the effectiveness of the vaccine against various pneumococcal serotypes, and to measure the effectiveness of the recommended dose schedule and of catch-up and incomplete schedules. METHODS: Invasive disease, defined as isolation of pneumococcus from a sterile site, was identified in children aged 3-59 months through the US Centers for Disease Control and Prevention's Active Bacterial Core surveillance. We tested isolates for serotype and antimicrobial susceptibility. Three controls, matched for age and zip code were selected for each case. We calculated the matched odds ratio for vaccination using conditional logistic regression, controlling for underlying conditions. Vaccine effectiveness was calculated as one minus the adjusted matched odds ratio times 100%. FINDINGS: We enrolled 782 cases and 2512 controls. Effectiveness of one or more doses against vaccine serotypes was 96% (95% CI 93-98) in healthy children and 81% (57-92) in those with coexisting disorders. It was 76% (63-85) against infections that were not susceptible to penicillin. Vaccination prevented disease caused by all seven vaccine serotypes, and by vaccine-related serotype 6A. Several schedules were more protective than no vaccination; three infant doses with a booster were more protective against vaccine-type disease than were three infant doses alone (p=0.0323). INTERPRETATION: The seven-valent pneumococcal conjugate vaccine prevents invasive disease in both healthy and chronically ill children. The vaccine is effective when used with various non-standard schedules.

Case-Control Studies↗

Serum opacity factor promotes group A streptococcal epithelial cell invasion and virulence.

Serum opacity factor (SOF) is a bifunctional cell surface protein expressed by 40-50% of group A streptococcal (GAS) strains comprised of a C-terminal domain that binds fibronectin and an N-terminal domain that mediates opacification of mammalian sera. The sof gene was recently discovered to be cotranscribed in a two-gene operon with a gene encoding another fibronectin-binding protein, sfbX. We compared the ability of a SOF(+) wild-type serotype M49 GAS strain and isogenic mutants lacking SOF or SfbX to invade cultured HEp-2 human pharyngeal epithelial cells. Elimination of SOF led to a significant decrease in HEp-2 intracellular invasion while loss of SfbX had minimal effect. The hypoinvasive phenotype of the SOF(-) mutant could be restored upon complementation with the sof gene on a plasmid vector, and heterologous expression of sof49 in M1 GAS or Lactococcus lactis conferred marked increases in HEp-2 cell invasion. Studies using a mutant sof49 gene lacking the fibronectin-binding domain indicated that the N-terminal opacification domain of SOF contributes to HEp-2 invasion independent of the C-terminal fibronectin binding domain, findings corroborated by observations that a purified SOF N-terminal peptide could promote latex bead adherence to HEp-2 cells and inhibit GAS invasion of HEp-2 cells in a dose-dependent manner. Finally, the first in vivo studies to employ a single gene allelic replacement mutant of SOF demonstrate that this protein contributes to GAS virulence in a murine model of necrotizing skin infection.

Animals↗

Extreme sequence divergence but conserved ligand-binding specificity in Streptococcus pyogenes M protein.

Many pathogenic microorganisms evade host immunity through extensive sequence variability in a protein region targeted by protective antibodies. In spite of the sequence variability, a variable region commonly retains an important ligand-binding function, reflected in the presence of a highly conserved sequence motif. Here, we analyze the limits of sequence divergence in a ligand-binding region by characterizing the hypervariable region (HVR) of Streptococcus pyogenes M protein. Our studies were focused on HVRs that bind the human complement regulator C4b-binding protein (C4BP), a ligand that confers phagocytosis resistance. A previous comparison of C4BP-binding HVRs identified residue identities that could be part of a binding motif, but the extended analysis reported here shows that no residue identities remain when additional C4BP-binding HVRs are included. Characterization of the HVR in the M22 protein indicated that two relatively conserved Leu residues are essential for C4BP binding, but these residues are probably core residues in a coiled-coil, implying that they do not directly contribute to binding. In contrast, substitution of either of two relatively conserved Glu residues, predicted to be solvent-exposed, had no effect on C4BP binding, although each of these changes had a major effect on the antigenic properties of the HVR. Together, these findings show that HVRs of M proteins have an extraordinary capacity for sequence divergence and antigenic variability while retaining a specific ligand-binding function.

Amino Acid Sequence↗

Multicentre surveillance of the prevalence and molecular epidemiology of macrolide resistance among pharyngeal isolates of group A streptococci in the USA.

OBJECTIVES: Rates of macrolide resistance in group A streptococci (GAS) were reported to be low in the US in the 1990s. However, we documented an unexpectedly high rate of macrolide resistance among GAS in Pittsburgh, PA, in 2001 and 2002. In an effort to define the current prevalence of macrolide-resistant GAS in the US, a multicentre surveillance project was initiated. METHODS: Between October 2002 and May 2003, 50 pharyngeal GAS isolates per month were requested from each of the nine participating sites representing a wide geographical distribution. Standard susceptibility testing was performed and the macrolide resistance phenotype was assessed using double-disc diffusion testing. Monthly and annual rates of macrolide resistance were calculated for each site. An adjusted overall rate of macrolide resistance was determined to account for differences in the numbers of GAS isolates sent from each centre. RESULTS: Overall, 171 of the 2797 collected isolates of GAS (6.1%) were resistant to erythromycin. The adjusted overall resistance rate was 5.2%. Rates of macrolide resistance varied by site (range 3.0-8.7%) and also by month (<2% to >10%). The M phenotype of macrolide resistance accounted for >60% of all macrolide-resistant isolates recovered in this study. CONCLUSIONS: These data suggest an increasing prevalence and broad geographical distribution of macrolide-resistant GAS in the US, indicating the need for ongoing local and national longitudinal surveillance to define the extent of this problem.

Anti-Bacterial Agents↗

Temporal changes in streptococcal M protein types and the near-disappearance of acute rheumatic fever in the United States.

BACKGROUND: The explanation for the very substantial decrease in the incidence of acute rheumatic fever in the United States, particularly over the past 50 years, is unclear. It has been proposed that certain M types of group A streptococci (GAS) include strains that are particularly rheumatogenic and that others are nonrheumatogenic. METHODS: We compared the M type distribution of GAS recovered from children from Chicago, Illinois, with acute pharyngitis during 1961-1968 to that of GAS recovered from Chicago children and children from across the United States in 2000-2004, with attention to changes in M types that previously were associated with rheumatogenic strains. RESULTS: The rheumatogenic types 3, 5, 6, 14, 18, 19, and 29 comprised 49.7% of 468 pharyngeal isolates during 1961-1968 but only 10.6% of 450 Chicago isolates during 2000-2004 (P < .001) and 17.9% of 3969 isolates nationwide during 2000-2004 (P < .001). Significant decreases in types 3, 5, and 6 and virtual disappearance of types 14, 18, 19, and 29 occurred between the 2 study periods. No change in the proportion of type 1 isolates, a highly heterogeneous group that includes some rheumatogenic strains, was observed. The nonrheumatogenic GAS types 2, 4, 22, and 28 increased from 4.9% to approximately 28% of pharyngeal isolates in Chicago and nationwide between the 2 study periods (P < .001). CONCLUSIONS: These data support the concept of rheumatogenic strains of GAS and indicate that the marked decrease in the incidence of acute rheumatic fever in the United States over the past 4 decades is correlated with the replacement of rheumatogenic types by nonrheumatogenic types in cases of acute streptococcal pharyngitis in children. The reasons underlying the observed change in distribution of M types remain to be elucidated.

Acute Disease↗

A community outbreak of conjunctivitis caused by nontypeable Streptococcus pneumoniae in Minnesota.

BACKGROUND: The Minnesota Department of Health (MDH) was notified of an outbreak of conjunctivitis in city A with cultures positive for Streptococcus pneumoniae. METHODS: MDH staff contacted clinics and schools in city A and city B regarding conjunctivitis cases, reviewed clinical findings of conjunctivitis cases in city A and collected isolates for subtyping. RESULTS: Between September 1 and December 12, 2003, cities A and B reported 735 conjunctivitis cases. Fifty-one percent of the cases were reported from schools, childcare centers and colleges. Adults were more likely to report itching, burning or swelling of the eye(s); children were more likely to report crusty eyes (P < 0.05). Forty-nine percent of conjunctival cultures (71 of 144) were positive for S. pneumoniae. All isolates were nontypeable by serotyping. Pulsed field gel electrophoresis identified 3 clonal groups with 84% of isolates belonging to one clonal group. Multilocus sequence typing revealed that isolates had the same multilocus sequence type as isolates from a 2002 outbreak at a New England college. CONCLUSIONS: This outbreak was widespread in the community and conjunctivitis clinical presentation varied by age. The predominant strains in this outbreak were related to a pneumococcal strain implicated in prior conjunctivitis outbreaks, suggesting these strains have a predilection for causing conjunctivitis.

Adolescent↗

Characterization of group A streptococci (Streptococcus pyogenes): correlation of M-protein and emm-gene type with T-protein agglutination pattern and serum opacity factor.

Strain characterization of group A streptococci (GAS) has traditionally been based on serological identification of M protein. Additional tests to determine T-protein serotype and production of streptococcal serum opacity factor (SOF) provide important information both to aid in and to supplement M-protein serotyping. Advances in DNA-sequencing technology in the late twentieth century resulted in the development of a method for determining the M type of GAS from the sequence of the gene encoding M protein, the emm gene. Although emm-sequence typing has largely replaced M typing in many laboratories, information provided by T typing and SOF determination continues to provide valuable supplementary information for strain characterization. A comprehensive summary of the correlation of T pattern and SOF production with M type was last published in 1993, several years before emm typing became widely available. Since then, the ease of M-type identification afforded by emm typing has resulted in an increase in the number of confirmed M/emm types of more than 50 %. However, comprehensive information about T-protein serotype and the correlation of SOF production with these new M/emm types is not widely available. This report presents a comprehensive summary of this information, not only for newly described types, but also updated information for previously described types. This information was extracted from combined records from streptococcal reference laboratories at the University of Minnesota and at the Centers for Disease Control and Prevention in Atlanta. Data from more than 40,000 strains (representing uncomplicated GAS infections, systemic invasive infections and strains associated with non-suppurative sequelae, collected from the US and diverse locations worldwide) were analysed.

Agglutination↗

Prevalence of first-step mutants among levofloxacin-susceptible invasive isolates of Streptococcus pneumoniae in the United States.

By use of a PCR-restriction fragment length polymorphism assay, we screened 496 levofloxacin-susceptible invasive pneumococcal strains (MIC<or=2 mg/liter) for quinolone resistance-determining region mutations known to confer fluoroquinolone resistance. Among those with a levofloxacin MIC of 2 mg/liter, 16.2% of isolates recovered from nursing home residents and 6.4% from non-nursing home residents had first-step mutations.

Adult↗

Genetically diverse group A streptococci from children in far-western Nepal share high genetic relatedness with isolates from other countries.

The genetic diversity of group A streptococci (GAS) throughout much of the world has not been adequately explored. To assess genetic variation among GAS in western Nepal, 120 noninvasive GAS, collected from eight different villages, were genetically characterized using emm typing, sof sequencing, and multilocus sequence typing (MLST). A high level of genetic diversity was observed among these isolates, with 51 genotypes based upon 51 multilocus sequence types (STs), 45 emm sequence types, and 28 sof sequence types. On the basis of shared ST-emm and sof-emm associations, 40 of the 51 genotypes were identical or highly related to genotypes characterized from locations outside of Nepal, even though most of the emm sequence and clonal types are rare among GAS within the United States. When analyzing all known STs highly related to Nepal STs, only one example of similar STs shared between a sof PCR-positive strain and a sof PCR-negative strain was observed. Since previous data indicate free exchange of MLST loci between sof-positive and sof-negative strains, there is possibly selection against the expansion of subclones resulting from horizontal transfers of sof or emm genes between sof-positive and sof-negative strains. All 45 emm types encountered in Nepal have also been documented from other countries. These data, together with data encompassing the past decade of emm type surveillance, support the possibility that most existing GAS emm types have been discovered. Similarly, since most (40/51) strain types were highly related to strains found elsewhere, it is likely that a major fraction of the existing GAS clonal complexes have been discovered.

Antigens, Bacterial↗

Sequential multiplex PCR approach for determining capsular serotypes of Streptococcus pneumoniae isolates.

Accurate serotyping is essential to monitor the changes in the seroepidemiology of Streptococcus pneumoniae. We devised a simple and schematic sequence-based system of seven multiplex PCRs, in a sequence order based upon Active Bacterial Core surveillance (ABCs) serotype distribution during 2002 to 2003, to reliably deduce specific pneumococcal serotypes. A total of 421 isolates from ABCs were randomly chosen to evaluate this system. Two hundred twenty-nine of the isolates (54.3%) were specifically assigned 1 of 17 serotypes by the multiplex PCR system, with the results in complete concordance with conventional serotyping. One hundred seventy-two additional isolates (40.9%) were assigned to 11 specific sets of 2 to 4 serotypes that with one exception (serotypes 6A and 6B) consisted of the single frequently occurring targeted serotype and 1 to 3 additional rare serotypes primarily within the same serogroup as the targeted serotype. Only 20 isolates (4.8%) could not be assigned specific serotypes or serotype sets, since they were either of rare serotypes not included in the assay design or were nonserotypeable. Overall, we found this system to be highly reliable, with the potential to greatly reduce our reliance upon conventional serotyping. Especially important is the capability of this system to give serotype-determining potential to any facility that lacks the expensive typing sera and expertise needed for conventional serotyping yet has the modest equipment necessary for DNA amplification and electrophoresis.

Bacterial Capsules↗

Pre- and postvaccination clonal compositions of invasive pneumococcal serotypes for isolates collected in the United States in 1999, 2001, and 2002.

Monitoring of serotypes and their clonal associations is critical as pneumococci adapt to the selective pressures exerted by the pneumococcal seven-valent conjugate vaccine (PCV7). We genotyped 1,476 invasive isolates from the Active Bacterial Core surveillance (705 [89.8%] of the isolates were obtained from children <5 years of age, and 771 [18.4%] of the isolates were obtained from individuals >5 years of age) in 2001 and 2002 (after the introduction of PCV7). The data were compared to the results for 1,168 invasive isolates (855 [83.9%] of the isolates were from children <5 years of age) collected in 1999. Among children <5 years of age, the incidence of invasive disease due to non-PCV7 serogroups together with serogroup 19A increased (P < 0.001). Eighty-three clonal sets, representing 177 multilocus sequence types (STs), were compiled from the 3-year isolate set. Among the non-PCV7 serogroups, newly emerging clones were uncommon; and a significant expansion of already established clones occurred for serotypes 3 (ST180), 7F (ST191), 15BCF (ST199), 19A (ST199), 22F (ST433), 33F (ST662), and 38 (ST393). However, additional minor clonal types within serotypes 1, 6A, 6B, 7C, 9N, 10A, 12F, 14, 15B/C, 17F, 19A, 19F, 20, 22F, and 33F that were absent in 1999 were found during 2001 and 2002. Although 23 clonal sets exhibited multiple serotypes, for most serotypes there were either no changes or modest changes in clonal compositions since the introduction of PCV7. The only example of an identical ST shared between non-PCV7 and PCV7 or PCV7-related serotypes was ST199; however, ST199 was prevalent within serotypes 15B/C and 19A before and after PCV7 introduction. Continued genotypic surveillance is warranted, since certain clones not targeted by PCV7 are expanding, and their emergence as significant pathogens could occur with maintained vaccine pressure.

Adult↗

Toxic shock due to Streptococcus pyogenes in a rhesus monkey (Macaca mulatta).

Recent years have seen a worldwide resurgence in serious infections caused by group A streptococci. This group includes Streptococcus pyogenes, one of the most common pathogens among children which causes diverse suppurative infections, such as pharyngitis, as well as nonsuppurative infections with sequelae, such as rheumatoid fever and rheumatic heart disease. S. pyogenes produces several superantigen-like erythrogenic toxins, which are believed to be associated with pyrogenicity, erythromatous skin reactions, and various immunologic and cytotoxic effects. These toxins also can cause myocardial necrosis. In addition, recently reported streptococcal infections in obstetric human patients appear to be clinically different from classic puerperal sepsis. Here, we report a case of spontaneous streptococcal infection in a pregnant female rhesus monkey (Macaca mulatta). In addition to lesions consistent with bacteremia and toxic shock, this animal had severe cardiac lesions resembling those described in humans with rheumatic heart disease. S. pyogenes was isolated from intracardiac blood, liver, placenta, and fetal tissues. This isolate also had a unique M protein gene.

Animals↗

Postvaccine genetic structure of Streptococcus pneumoniae serotype 19A from children in the United States.

BACKGROUND: The introduction of the 7-valent conjugate pneumococcal vaccine (PCV7) in children may result in serotype replacement. We estimated the rate of increase of invasive pneumococcal disease (IPD) caused by serotype 19A in children <5 years old and determined the genetic composition of these isolates. METHODS: Cases of IPD between July 1999 and June 2004 were identified through the Active Bacterial Core Surveillance. Serotype 19A isolates obtained from children <5 years old between January 2003 and June 2004 were characterized by serotyping, antibiotic susceptibility testing, and pulsed-field gel electrophoresis (PFGE). Select isolates representing homologous PFGE clusters were subjected to multilocus sequence typing, and eBURST was used to delineate clonal groups. RESULTS: Between July 1999 and June 2004, the overall rate of IPD decreased from 23.3 to 13.1 cases/100,000 population (P<.00001). In children <5 years old, the rate decreased from 88.7 to 22.4 cases/100,000 population (P<.00001), whereas the rate in persons > or =5 years old decreased from 18.4 to 12.4 cases/100,000 population (P<.0001). The rate of serotype 19A IPD in children <5 years old increased significantly from 2.6 cases/100,000 population in 1999-2000 to 6.5 cases/100,000 population in 2003-2004; this was accompanied by significant increases in penicillin nonsusceptibility (P=.008) and multidrug resistance (P=.002) among serotype 19A isolates. As was observed during the pre-PCV7 era, clonal complex (CC) 199 predominated within serotype 19A, representing approximately 70% of invasive serotype 19A isolates from children <5 years old during 2003-2004. New serotype 19A genotypes were observed during 2003-2004, including 6 CCs that were not found among pneumococcal serotype 19A isolates during surveillance in 1999. CONCLUSION: Serotype 19A is, at present, the most important cause of IPD by replacement serotypes, and it is increasingly drug resistant. CC199 is the predominant CC among type 19A serotypes in children <5 years old. Our data suggest that some of the increase in rates of infection with serotype 19A may be due to serotype switching within certain vaccine type strains.

Anti-Bacterial Agents↗

Cluster of deaths from group A streptococcus in a long-term care facility--Georgia, 2001.

BACKGROUND: Invasive group A streptococcus (GAS) affects approximately 10,500 persons annually; 1 in 5 patients >/=65 years die. In August 2001, CDC investigated a cluster of GAS deaths in a Georgia long-term care facility (LTCF). METHODS: We screened LTCF residents and staff for GAS carriage and conducted a retrospective cohort study among residents. We defined a case as GAS isolation associated with clinical infection. RESULTS: Eight cases were identified (median age: 79 years); 6 (75%) patients died. Carriage was similar in residents (10%) and staff (9%). All isolates among residents and 63% among staff were type emm 77. Risk factors for GAS disease or carriage among residents were receiving skin treatment (relative risk [RR] = 4.0, 95% confidence interval [CI] = 1.9-11.0) and having an infected or colonized roommate (RR = 2.0, 95% CI = 1.10-5.0). No wound care nurse carried GAS. Interventions included education about standardized infection control guidelines and appropriate hand hygiene; carriers were treated with antibiotics. No subsequent GAS cases were identified in the following year. CONCLUSIONS: Transmission of GAS in this outbreak likely occurred during wound care and ended with improved hand hygiene. This investigation highlights additional research and policy needs for control of severe GAS infections among the high-risk LTCF population.

Adult↗

Novel antibiotic-resistant pneumococcal strains recovered from the upper respiratory tracts of HIV-infected adults and their children in Kisumu, Kenya.

In a survey of genetic diversity within penicillin-nonsusceptible pneumococcal isolates in Kenya, we examined 162 upper respiratory isolates from 104 human immunodeficiency virus (HIV)-infected adults and 46 children in a cotrimoxazole prophylaxis study. Antibiotic resistance levels were high; 152 (94.4%) were cotrimoxazole nonsusceptible (134 fully resistant) and 124 (77%) were intermediately penicillin resistant. Isolates nonsusceptible to penicillin and cotrimoxazole (PNCNP) were found among 24 of the 29 serotypes encountered, 15 of which have rarely or never had documented nonsusceptibility to penicillin. These included serotypes 3, 4, 7C, 7F, 10A, 11A, 13, 15A, 15B, 16F, 17F, 19B, 21, 35A, and 35B. Segments of pbp2b genes from 9 PNCNP (serotypes 3, 13, 15A, 16F, 20, and 35A) were typical of resistance-conferring alleles in that they were highly divergent and contained two substitutions thought to be critical for resistance. Similarly, the dhfr genes from 3 PNCNP were divergent and contained a substitution required for cotrimoxazole resistance. Multilocus sequence typing (MLST) of 48 PNCNP revealed 33 sequence types (STs), none of which were previously recorded at http://www.mlst.net. Comparisons with all known STs revealed that 23 of these STs were unrelated to other known STs, whereas 10 STs were highly related to STs from internationally disseminated strains, including 2 of the 26 antibiotic-resistant clones recognized by the Pneumococcal Molecular Epidemiology Network. Based upon differing serotypes expressed by strains of identical or closely similar genotypes, there has been an extensive history of capsular switching within seven genetic clusters represented by these 10 STs and related STs described at http://www.mlst.net.

Adult↗