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Edward L Kaplan

Publications and source records attributed to Edward L Kaplan.

At least 19 recordsLinked to original sources
PubMed2006

Reduced ability of penicillin to eradicate ingested group A streptococci from epithelial cells: clinical and pathogenetic implications.

BACKGROUND: Group A streptococci (Streptococcus pyogenes; GAS) invades human epithelial cell lines. Failure of penicillin to eradicate GAS from the throats of patients, especially those who are GAS "carriers," has been increasingly reported. However, there has been no comprehensive evaluation of how effectively antibiotics that are used to treat GAS enter upper respiratory tract epithelial cells and kill internalized GAS. We examined the viability of ingested, intracellular GAS after epithelial cell exposure to antibiotics commonly recommended for therapy of GAS infections. METHODS: A human laryngeal epithelial cell line (HEp-2) was used. Three techniques were used to study antibiotic (penicillin V, erythromycin, azithromycin, cephalothin, and clindamycin) killing of ingested GAS: examination by electron microscopy of ultrathin sections of ingested GAS, qualitative determination of intra-epithelial cell antibiotic, and special stain evaluation of intracellular GAS viability after epithelial cell exposure to antibiotics. RESULTS: GAS survived intracellularly despite exposure of the GAS-containing epithelial cells to penicillin. In contrast, there was killing of ingested GAS after exposure of epithelial cells to either erythromycin or azithromycin. Electron microscopy confirmed a lack of intracellular GAS fragmentation (cell death) after exposure of epithelial cells to penicillin in contrast to obvious GAS fragmentation after epithelial cell exposure to erythromycin or azithromycin. Cephalothin, a cephalosporin, and clindamycin were more effective in killing ingested GAS than was penicillin, but they were less effective than erythromycin or azithromycin. CONCLUSIONS: These observations strongly suggest that if the GAS upper respiratory tract carrier state results from intra-epithelial cell GAS survival, the failure of penicillin to kill ingested GAS may be related to a lack of effective penicillin entry into epithelial cells. These unique observations may have clinical implications for understanding GAS respiratory tract carriers and managing GAS infections.

Anti-Bacterial Agents↗
PubMed2006

Treatment of streptococcal pharyngitis with once-daily compared with twice-daily amoxicillin: a noninferiority trial.

BACKGROUND: Two relatively small previous studies comparing once-daily amoxicillin with conventional therapy for group A streptococcal (GAS) pharyngitis reported similar rates of bacteriologic success for each treatment group. The purpose of this study was to further evaluate once-daily amoxicillin for GAS pharyngitis in a larger study. METHODS: In a single pediatric practice, from October through May for 2 consecutive years (2001-2003), we recruited children 3 to 18 years of age who had symptoms and signs suggestive of GAS pharyngitis. Patients with a positive rapid test for GAS were stratified by weight (<40 kg or >or=40 kg) and then randomly assigned to receive once-daily (750 mg or 1000 mg) or twice-daily (2 doses of 375 mg or 500 mg) amoxicillin for 10 days. We determined bacteriologic failure rates for GAS in the pharynx from subsequent swabs taken at 14 to 21 (visit 2) and 28 to 35 (visit 3) days after treatment initiation. We conducted a randomized, controlled, investigator-blinded, noninferiority trial to evaluate whether amoxicillin given once daily would have a bacteriologic failure rate no worse than that of amoxicillin given twice daily within a prespecified margin of 10%. GAS isolates were characterized to distinguish bacteriologic failures from new acquisitions. Adverse events were described and adherence was evaluated by review of returned daily logs and dosage bottles. RESULTS: Of 2139 potential study patients during the 2-year period, we enrolled 652 patients, 326 into each treatment group. Children in the 2 groups were comparable with respect to all demographic and clinical characteristics except that children <40 kg more often presented with rash in each treatment group. At visit 2, failure rates were 20.1% (59 of 294) for the once-daily group and 15.5% (46 of 296) for the twice-daily group (difference, 4.53%; 90% confidence interval [CI], -0.6 to 9.7). At visit 3, failure rates were 2.8% (6 of 216) for the once-daily group and 7.1% (16 of 225) for the twice-daily group (difference, -4.33; 90% CI, -7.7 to -1.0). Gastrointestinal and other adverse events occurred in the once-daily treatment group with a frequency comparable to that in the twice-daily treatment group. Presumed allergic reactions occurred in 0.9% (6 of 635). More than 95% (516 of 541) of patients complied with 10 days of therapy with no significant differences between groups. CONCLUSIONS: We conclude that amoxicillin given once daily is not inferior to amoxicillin given twice daily. Gastrointestinal and other events did not occur significantly more often in the once-daily treatment group. From the data in this large, investigator-blinded, controlled study, once-daily amoxicillin appears to be a suitable regimen for treatment of GAS pharyngitis.

Adolescent↗
PubMed2006

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↗
PubMed2005

Intrinsic reduced susceptibility of serotype 6 Streptococcus pyogenes to fluoroquinolone antibiotics.

BACKGROUND: Fluoroquinolone resistance is common in Staphylococcus aureus, is increasing in Streptococcus pneumoniae, and is reported in Streptococcus pyogenes. METHODS: We surveyed 384 clinical isolates of S. pyogenes, isolated during 2002-2003, for susceptibility to ciprofloxacin. We performed nucleotide sequencing of the parC and gyrA genes and determined the M/emm type for selected isolates. Additionally, we analyzed M/emm type 6 S. pyogenes isolated during 1918-2003 from diverse locations. RESULTS: Of the survey isolates, 10.9% had reduced zones of inhibition to ciprofloxacin in the disk-diffusion test and had elevated minimum inhibitory concentrations to other fluoroquinolones, compared with those of fully susceptible isolates. Of the resistant isolates, 90.5% were M/emm type 6, and all sequenced M/emm type 6 isolates contained a serine-to-alanine substitution at position 79 in parC. Strikingly, the same findings were also present in macrolide-resistant isolates from a recent outbreak of S. pyogenes infection in Pittsburgh and in the Lancefield reference strain of M type 6, which was isolated in 1918, decades before the development of fluoroquinolone antibiotics. CONCLUSION: M/emm type 6 S. pyogenes has intrinsic reduced susceptibility to fluoroquinolones, as a result of a polymorphism in parC. This finding was also demonstrated in erythromycin-resistant M/emm type 6 S. pyogenes, which raises concern for the emergence of multidrug-resistant S. pyogenes.

Adult↗
PubMed2005

Pneumonia outbreak associated with group a Streptococcus species at a military training facility.

BACKGROUND: Although group A streptococci (GAS) infections are a major cause of morbidity and mortality, outbreaks of associated pneumonia are rare. We report an outbreak of GAS pneumonia that occurred at a US military training camp. METHODS: Standard epidemiologic and laboratory procedures were used to characterize the outbreak and causative organism(s). A case-control study and determination of the prevalence of GAS infection among camp personnel were also performed. RESULTS: A total of 162 of 4500 Marine Corps personnel were hospitalized for respiratory symptoms during the period of 1 November and 20 December 2002, and 127 (78%) had radiographically confirmed pneumonia. The attack rate was 1.6 cases per 100 person-months. Thirty-four (27%) of 127 patients with pneumonitis had definite or probable GAS pneumonia; an additional 22 (17.3%) were coinfected with GAS and another pathogen. Pathogens, in addition to GAS, included Chlamydia pneumoniae (27 patients), Mycoplasma pneumoniae (19), adenovirus (5), and Streptococcus pneumoniae (2). A survey revealed that the pharyngeal carriage rate of GAS among camp personnel was 16%. Molecular characterization of the GAS isolates found emm type 3, multilocus sequence type 15. The epidemic ended after administration of additional prophylaxis with a single dose of intramuscular benzathine penicillin (1.2 million U) or azithromycin (1 g orally). Because the number of days from the last penicillin injection was correlated with a positive throat culture result and the occurrence of pneumonia, the dosing interval of benzathine penicillin was shortened from every 28-35 days to every 21 days. CONCLUSIONS: This is the largest outbreak of GAS pneumonia reported in >30 years. This outbreak emphasizes the potential for GAS to cause epidemics of severe infection and demonstrates the need for surveillance and consideration of appropriate antibiotic prophylaxis among particularly high-risk populations.

Adolescent↗
PubMed2005

Explaining the poor bacteriologic eradication rate of single-dose ceftriaxone in group a streptococcal tonsillopharyngitis: a reverse engineering solution using pharmacodynamic modeling.

OBJECTIVE: To explore pharmacokinetic factors underlying the poor bacteriologic eradication rate with a single 500-mg dose of ceftriaxone for streptococcal tonsillopharyngitis and to identify the minimum ceftriaxone dose required for effective treatment. METHODS: Population modeling techniques were applied to pharmacokinetic data derived from paired plasma and tonsil samples from 153 children to assess the contribution of pharmacokinetic variability to patients' responses to ceftriaxone. In addition, a Monte Carlo simulation was performed to determine (1) the amount of time that free ceftriaxone concentrations must exceed the minimum inhibitory concentration (MIC) of group A Streptococcus to achieve bacteriologic eradication and (2) the ceftriaxone dose required to maintain free drug concentrations above the target MIC for the requisite amount of time. Ceftriaxone MICs for group A Streptococcus were obtained from a previous trial, in which all MICs (n = 115) were < or = 0.064 mg/L; 33.9% were susceptible at < or = 0.016 mg/L, 66.4% were susceptible at 0.032 mg/L, and 1.7% were susceptible at 0.064 mg/L. RESULTS: Mean population pharmacokinetic parameters and their variances reflected substantial variability of clearance and half-life in the target population. Tonsillar ceftriaxone protein binding was 89.1%. The proportions of 1000 simulated patients with free ceftriaxone concentrations that exceeded MICs of 0.016 mg/L, 0.032 mg/L, and 0.064 mg/L at 24 hours were 71.7%, 65.4%, and 57.2%, respectively, and at 48 hours were 41.8%, 35.8%, and 28.6%, respectively. The amount of time that free ceftriaxone concentrations need to exceed MIC to achieve bacteriologic success was estimated to be 36 hours. Using this time criterion, two 500-mg doses of ceftriaxone separated by 18 hours should achieve a bacteriologic cure rate of approximately 95%. CONCLUSIONS: Pharmacokinetic variability and high ceftriaxone tonsillar protein binding explain the high microbiologic failure rate for a single 500-mg dose of ceftriaxone in group A streptococcal tonsillopharyngitis. Monte Carlo simulation suggests that a second dose administered 18 hours after the first will be required to achieve an acceptable bacteriologic cure rate.

Anti-Bacterial Agents↗
PubMed2005

Invasive group A streptococcal infection in high school football players, New York City, 2003.

After being notified that 2 high school football teammates from New York City were hospitalized with confirmed or suspected invasive group A streptococcal infections, we conducted an investigation of possible spread among other team members. This investigation highlights a need for guidelines on management of streptococcal and other infectious disease outbreaks in team sport settings.

Adolescent↗
PubMed2004

The relationship of carditis to the initial attack of Sydenham's chorea.

BACKGROUND: The natural history of valvular regurgitation detected by echocardiography in Sydenham's chorea has been lacking. METHODS: Clinical assessment and transthoracic color Doppler echocardiography were independently performed for each patient with an initial attack of Sydenham's chorea and also for each normal control (Khon Kaen University, Thailand; 1991-2001) at the time of their presentations. Serial clinical examinations and echocardiography were done for each patient at 1- and at 5-year follow-up. RESULTS: Of 44 patients, 17 (39%) had carditis (valvulitis) evident by auscultation at the time of the initial attack. Three (11%) of the 27 patients with no clinical evidence of carditis had echocardiographic evidence of acute mitral regurgitation (subclinical valvulitis). All 17 patients with carditis had echocardiographic evidence of acute mitral regurgitation. None of the 88 control children had evidence of pathologically significant valvular regurgitation. Of the 15 patients with carditis regularly followed, the persistence of a mitral regurgitation murmur and of pathologically significant valvular regurgitation by echocardiography were 33% (5/15) and 60% (9/15), respectively, at 1-year follow-up, but the persistence of both was 25% (1/4) at 5-year follow-up. CONCLUSIONS: Color Doppler echocardiography is a useful tool in the early diagnosis of rheumatic carditis (valvulitis) and at 1-year follow-up of rheumatic valvular heart disease in the patients with initial Sydenham's chorea but the incremental benefit beyond 5 years after the initial attack might be minimal.

Acute Disease↗
PubMed2004

Temporal association of the appearance of mucoid strains of Streptococcus pyogenes with a continuing high incidence of rheumatic fever in Utah.

OBJECTIVE: Our objective was to confirm an observed temporal association of increased numbers of rheumatic fever cases concomitant with the appearance of an increased prevalence of mucoid strains of Streptococcus pyogenes. During the resurgence of rheumatic fever (RF) that has occurred in the Intermountain area surrounding Salt Lake City, Utah, since 1985, the largest number of cases occurred in 1985 and 1986 and 12 years later in 1997 and 1998. During the initial outbreak and the later exacerbation of the resurgence, an increased number of mucoid strains of S pyogenes were present in the community. METHODS: The referred cases of RF that fulfilled Jones criteria have been systematically reviewed by the medical staff at Primary Children's Medical Center yearly since 1985. Before the resurgence of RF, a program was initiated by the microbiology laboratory at Primary Children's Medical Center to store frozen isolates of S pyogenes. All frozen specimens were randomly selected and entered into a log; the coded entry allowed for comments regarding the origin of the isolate and whether the isolate had a mucoid appearance on the blood agar culture plate. This log was reviewed in October 2002 to determine whether the percentage of frozen mucoid isolates stored during the resurgence of RF would support the clinical and epidemiologic suspicion that mucoid isolates seemed to be present with a higher frequency during the 2 periods of high incidence of RF. The percentage of mucoid isolates was compared with the yearly number of cases of RF. A Pearson r correlation analysis was completed to determine whether there was a significant association between the percentage of mucoid isolates and the number of cases of RF. RESULTS: The highest number of cases of RF was temporally associated with the highest percentage of mucoid isolates. There was statistically significant correlation between percentage of mucoid strains and the number of RF cases. CONCLUSIONS: The Utah experience with the resurgence of RF in a civilian population during the last decade and a half of the 20th century confirmed the temporal association of mucoid strains of S pyogenes, primarily M-type 18, with a high incidence of RF.

Adolescent↗
PubMed2004

The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) etiology for tics and obsessive-compulsive symptoms: hypothesis or entity? Practical considerations for the clinician.

Clinicians have been faced with much publicity and contradictory scientific evidence regarding a recently described condition termed pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS). It has been proposed that children with PANDAS experience tics, obsessive-compulsive behavior, and perhaps other neuropsychiatric symptoms as an autoimmune response to streptococcal infection. We review current scientific information and conclude that PANDAS remains a yet-unproven hypothesis. Until more definitive scientific proof is forthcoming, there seems to be insufficient evidence to support 1) routine microbiologic or serologic testing for group A streptococcus in children who present with neuropsychiatric symptoms or 2) the clinical use of antibiotic or immune-modifying therapies in such patients. The optimum diagnostic and therapeutic approach awaits the results of additional research studies.

Adjuvants, Immunologic↗
PubMed2003

Immune response to group A streptococcal C5a peptidase in children: implications for vaccine development.

The group A streptococcal C5a peptidase (SCPA) is a major surface virulence protein that facilitates the establishment of local infection by group A streptococci (GAS). We measured the human immune response to SCPA, using a standardized indirect enzyme-linked immunosorbent assay. Paired acute and convalescent serum samples from children with GAS-associated pharyngitis were assayed, and a strong immune response to SCPA was demonstrated that was independent of the infecting M type and the age of the patient. Western blot analysis of bacterial extracts revealed that all tested M types expressed SCPA. The immune response to SCPA correlated with the anti-streptolysin O and anti-DNase B responses. These data confirm the immunogenicity of SCPA in humans. Previous knowledge of SPCA's role in virulence, its highly conserved nature, and the results of mouse protection studies make SCPA an ideal vaccine candidate for the prevention of GAS disease.

Acute Disease↗