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S J Schrag

Publications and source records attributed to S J Schrag.

10 recordsLinked to original sources
PubMed2001

Effect of short-course, high-dose amoxicillin therapy on resistant pneumococcal carriage: a randomized trial.

CONTEXT: Emerging drug resistance threatens the effectiveness of existing therapies for pneumococcal infections. Modifying the dose and duration of antibiotic therapy may limit the spread of resistant pneumococci. OBJECTIVE: To determine whether short-course, high-dose amoxicillin therapy reduces risk of posttreatment resistant pneumococcal carriage among children with respiratory tract infections. DESIGN AND SETTING: Randomized trial conducted in an outpatient clinic in Santo Domingo, Dominican Republic, October 1999 through July 2000. PARTICIPANTS: Children aged 6 to 59 months who were receiving antibiotic prescriptions for respiratory tract illness (n = 795). INTERVENTIONS: Children were randomly assigned to receive 1 of 2 twice-daily regimens of amoxicillin: 90 mg/kg per day for 5 days (n = 398) or 40 mg/kg per day for 10 days (n = 397). MAIN OUTCOME MEASURES: Penicillin-nonsusceptible Streptococcus pneumoniae carriage, assessed in nasopharyngeal specimens collected at days 0, 5, 10, and 28; baseline risk factors for nonsusceptible pneumococcal carriage; and adherence to regimen, compared between the 2 groups. RESULTS: At the day 28 visit, risk of penicillin-nonsusceptible pneumococcal carriage was significantly lower in the short-course, high-dose group (24%) compared with the standard-course group (32%); relative risk (RR), 0.77; 95% confidence interval (CI), 0.60-0.97; P =.03; risk of trimethoprim-sulfamethoxazole nonsusceptibility was also lower in the short-course, high-dose group (RR, 0.77; 95% CI, 0.58-1.03; P =.08). The protective effect of short-course, high-dose therapy was stronger in households with 3 or more children (RR, 0.72; 95% CI, 0.52-0.98). Adherence to treatment was higher in the short-course, high-dose group (82% vs 74%; P =.02). CONCLUSION: Short-course, high-dose outpatient antibiotic therapy appears promising as an intervention to minimize the impact of antibiotic use on the spread of drug-resistant pneumococci.

Amoxicillin↗
PubMed2000

Group B streptococcal disease in the era of intrapartum antibiotic prophylaxis.

BACKGROUND: Group B streptococcal infections are a leading cause of neonatal mortality, and they also affect pregnant women and the elderly. Many cases of the disease in newborns can be prevented by the administration of prophylactic intrapartum antibiotics. In the 1990s, prevention efforts increased. In 1996, consensus guidelines recommended use of either a risk-based or a screening-based approach to identify candidates for intrapartum antibiotics. To assess the effects of the preventive efforts, we analyzed trends in the incidence of group B streptococcal disease from 1993 to 1998. METHODS: Active, population-based surveillance was conducted in selected counties of eight states. A case was defined by the isolation of group B streptococci from a normally sterile site. Census and live-birth data were used to calculate the race-specific incidence of disease; national projections were adjusted for race. RESULTS: Disease in infants less than seven days old accounted for 20 percent of all 7867 group B streptococcal infections. The incidence of early-onset neonatal infections decreased by 65 percent, from 1.7 per 1000 live births in 1993 to 0.6 per 1000 in 1998. The excess incidence of early-onset disease in black infants, as compared with white infants, decreased by 75 percent. Projecting our findings to the entire United States, we estimate that 3900 early-onset infections and 200 neonatal deaths were prevented in 1998 by the use of intrapartum antibiotics. Among pregnant girls and women, the incidence of invasive group B streptococcal disease declined by 21 percent. The incidence among nonpregnant adults did not decline. CONCLUSIONS: Over a six-year period, there has been a substantial decline in the incidence of group B streptococcal disease in newborns, including a major reduction in the excess incidence of these infections in black infants. These improvements coincide with the efforts to prevent perinatal disease by the wider use of prophylactic intrapartum antibiotics.

Adolescent↗
PubMed2000

Neonatal group B streptococcal disease: how infection control teams can contribute to prevention efforts.

Group B streptococcal (GBS) disease is a leading cause of morbidity and mortality among newborns. Many cases of newborn GBS disease can be prevented by the administration of intrapartum antibiotic prophylaxis. Current consensus guidelines for prevention of perinatal GBS disease have led to substantial declines in the incidence of GBS disease occurring in newborns <7 days of age (early-onset disease). Despite declines in the incidence of early-onset disease, approximately 20% of pregnant women are colonized with GBS at the time of labor and thus have the risk of transmitting the bacteria to their newborns. Consequently, continued and improved implementation of prevention efforts is essential. Infection control teams can contribute uniquely to prevention of perinatal GBS disease by serving as hospital champions of GBS disease prevention. In particular, teams can coordinate with administration and staff to encourage establishment and effective implementation of GBS prevention policies; facilitate improved laboratory processing of prenatal GBS screening specimens; monitor any adverse consequences of increased use of intrapartum antibiotics within the hospital; and investigate GBS cases that occur to determine whether they could have been prevented. By spearheading efforts to improve implementation of perinatal GBS disease prevention at the hospital level, hospital epidemiologists and infection control practitioners can play an important role in reducing the burden of early-onset GBS disease.

Adult↗
PubMed2000

Lack of association between Kawasaki syndrome and Chlamydia pneumoniae infection: an investigation of a Kawasaki syndrome cluster in San Diego County.

BACKGROUND: The etiology of Kawasaki syndrome (KS), the leading cause of acquired coronary artery disease in children, is unknown. Recent studies have suggested that Chlamydia pneumoniae, a common respiratory pathogen associated with an increased risk of heart disease, might lead to KS. OBJECTIVE: To assess whether KS was associated with an elevated risk of having a current or antecedent infection with C. pneumoniae. METHODS: Blood, urine and pharyngeal specimens from KS patients in San Diego County, CA, during a period of high KS incidence were analyzed for evidence of recent C. pneumoniae infection by culture, PCR and serology. Specimens collected from two control groups, family members of KS patients and age-matched children attending outpatient clinics for well child visits, were similarly analyzed. RESULTS: Thirteen cases were identified. Forty-five outpatient controls and an average of three family members per patient were enrolled in the study. All specimens tested negative for the presence of C. pneumoniae by PCR and culture except for one blood specimen from the mother of a case-patient. Serologic analysis of patients and a subset of outpatient and family controls revealed no evidence of current C. pneumoniae infection; 4 of 13 adult family controls had IgG titers consistent with past exposure to C. pneumoniae. Case patients were no more likely than outpatient controls to have had a respiratory illness in the preceding 2 months (11 of 13 patients vs. 35 of 45 controls; odds ratio, 1.57; 95% confidence interval, 0.3 to 11.9). CONCLUSIONS: We found no evidence that C. pneumoniae infection was associated with KS.

Adolescent↗
PubMed2000

Limiting the spread of resistant pneumococci: biological and epidemiologic evidence for the effectiveness of alternative interventions.

Streptococcus pneumoniae infections are a leading cause of respiratory illness in young children, the elderly, and persons with chronic medical conditions. The emergence of multidrug-resistant pneumococci has compromised the effectiveness of antibiotic therapy for pneumococcal infections. As antibiotic-resistant strains increase in prevalence, there is a need for interventions that minimize the spread of resistant pneumococci. In this review we provide a framework for understanding the spread of pneumococcal resistance and evaluate proposed interventions to reduce this spread. Pneumococci differ from many drug-resistant pathogens because asymptomatic carriers play a key role in transmission of resistant strains and the genes encoding resistance are spread primarily by transformation and conjugative transposons. Evidence suggests that modifications of treatment regimens that have proved effective at limiting resistance in other pathogens may not prevent the spread of pneumococcal resistance. In contrast, programs encouraging more judicious antibiotic use have been shown to be effective. Additionally, a newly developed conjugate pneumococcal vaccine holds great potential as an "antiresistance vaccine" that simultaneously reduces the burden of invasive disease and the prevalence of resistant strains. Several areas of future epidemiologic and laboratory research hold promise to contribute to the reduced spread of pneumococcal resistance.

Anti-Bacterial Agents↗
PubMed1999

Spontaneous mutation rate of measles virus: direct estimation based on mutations conferring monoclonal antibody resistance.

High mutation rates typical of RNA viruses often generate a unique viral population structure consisting of a large number of genetic microvariants. In the case of viral pathogens, this can result in rapid evolution of antiviral resistance or vaccine-escape mutants. We determined a direct estimate of the mutation rate of measles virus, the next likely target for global elimination following poliovirus. In a laboratory tissue culture system, we used the fluctuation test method of estimating mutation rate, which involves screening a large number of independent populations initiated by a small number of viruses each for the presence or absence of a particular single point mutation. The mutation we focused on, which can be screened for phenotypically, confers resistance to a monoclonal antibody (MAb 80-III-B2). The entire H gene of a subset of mutants was sequenced to verify that the resistance phenotype was associated with single point mutations. The epitope conferring MAb resistance was further characterized by Western blot analysis. Based on this approach, measles virus was estimated to have a mutation rate of 9 x 10(-5) per base per replication and a genomic mutation rate of 1.43 per replication. The mutation rates we estimated for measles virus are comparable to recent in vitro estimates for both poliovirus and vesicular stomatitis virus. In the field, however, measles virus shows marked genetic stability. We briefly discuss the evolutionary implications of these results.

Animals↗
PubMed1997

Adaptation to the fitness costs of antibiotic resistance in Escherichia coli.

Policies aimed at alleviating the growing problem of drug-resistant pathogens by restricting antimicrobial usage implicitly assume that resistance reduces the Darwinian fitness of pathogens in the absence of drugs. While fitness costs have been demonstrated for bacteria and viruses resistant to some chemotherapeutic agents, these costs are anticipated to decline during subsequent evolution. This has recently been observed in pathogens as diverse as HIV and Escherichia coli. Here we present evidence that these gentic adaptations to the costs of resistance can virtually preclude resistant lineages from reverting to sensitivity. We show that second site mutations which compensate for the substantial (14 and 18% per generation) fitness costs of streptomycin resistant (rpsL) mutations in E. coli create a genetic background in which streptomycin sensitive, rpsL+ alleles have a 4-30% per generation selective disadvantage relative to adapted, resistant strains. We also present evidence that similar compensatory mutations have been fixed in long-term streptomycin-resistant laboratory strains of E. coli and may account for the persistence of rpsL streptomycin resistance in populations maintained for more than 10,000 generations in the absence of the antibiotic. We discuss the public health implications of these and other experimental results that question whether the more prudent use of antimicrobial chemotherapy will lead to declines in the incidence of drug-resistant pathogenic microbes.

Adaptation, Physiological↗
PubMed1994

Effects of Schistosoma haematobium infection on reproductive success and male outcrossing ability in the simultaneous hermaphrodite, Bulinus truncatus (Gastropoda: Planorbidae).

The schistosome intermediate snail host, Bulinus truncatus (Mollusca: Planorbidae), has two reproductive (phally) morphs. Both aphallics and euphallics can self-fertilize, but aphallics cannot donate sperm because they do not develop a functional penis and prostate. This study investigated the interactions between phally and fitness consequences of Schistosoma haematobium infection in B. truncatus. Snails which developed patent infections produced 26% fewer eggs than controls and 35% fewer eggs than exposed snails which did not develop infections. This reduction was due to a lower lifetime production of egg masses and a smaller mean number of eggs/mass in infected snails relative to control or exposed snails. However, there was no evidence of increased mortality in infected snails. Contrary to reports of fecundity compensation in other intermediate host snails, egg production post-exposure during the pre-patent period did not increase relative to that of controls in either infected or exposed snails. Phally did not influence susceptibility to infection or length of the prepatent period. Furthermore, lifetime egg, egg mass and hatchling production, as well as mean eggs/mass and number of hatchlings reaching maturity, did not differ significantly between aphallics and euphallics within control of exposed experimental groups. However, within the infected group euphallics produced 38% fewer eggs, smaller egg masses, and fewer hatchlings reaching maturity than aphallics, supporting the prediction of a cost to the growth and maintenance of a full male tract. This cost was detectable only when snails were under the stress of infection. The proportion of euphallic offspring produced did not differ across experimental groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗