No abstract

clinicaltrials.gov Identifier: NCT00066118.

BackgroundUrinary mercury concentrations are widely used as a measure of mercury exposure from dental amalgam fillings. No studies have evaluated the relationship of these measures in a longitudinal context in children.ObjectiveWe evaluated urinary mercury in children 8–18 years of age in relation to number of amalgam surfaces and time since placement over a 7-year course of amalgam treatment.MethodsFive hundred seven children, 8–10 years of age at baseline, participated in a clinical trial to evaluate the neurobehavioral effects of dental amalgam in children. Subjects were randomized to either dental amalgam or resin composite treatments. Urinary mercury and creatinine concentrations were measured at baseline and annually on all participants.ResultsTreatment groups were comparable in baseline urinary mercury concentration (~ 1.5 μg/L). Mean urinary mercury concentrations in the amalgam group increased to a peak of ~ 3.2 μg/L at year 2 and then declined to baseline levels by year 7 of follow-up. There was a strong, positive association between urinary mercury and both number of amalgam surfaces and time since placement. Girls had significantly higher mean urinary mercury concentrations than boys throughout the course of amalgam treatment. There were no differences by race in urinary mercury concentration associated with amalgam exposure.ConclusionsUrinary mercury concentrations are highly correlated with both number of amalgam fillings and time since placement in children. Girls excrete significantly higher concentrations of mercury in the urine than boys with comparable treatment, suggesting possible sex-related differences in mercury handling and susceptibility to mercury toxicity.

We screened 615 gram-positive isolates from 150 healthy children for the presence of the erm(A), erm(B), erm(C), erm(F), and mef(A) genes. The mef(A) genes were found in 20 (9%) of the macrolide-resistant isolates, including Enterococcus spp., Staphylococcus spp., and Streptococcus spp. Sixteen of the 19 gram-positive isolates tested carried the other seven open reading frames (ORFs) described in Tn1207.1, a genetic element carrying mef(A) recently described in Streptococcus pneumoniae. The three Staphylococcus spp. did not carry orf1 to orf3. A gram-negative Acinetobacter junii isolate also carried the other seven ORFs described in Tn1207.1. A Staphylococcus aureus isolate, a Streptococcus intermedius isolate, a Streptococcus sp. isolate, and an Enterococcus sp. isolate had their mef(A) genes completely sequenced and showed 100% identity at the DNA and amino acid levels with the mef(A) gene from S. pneumoniae.The normal flora is thought to act as a reservoir for many bacterial antimicrobial resistance genes, including those that confer macrolide resistance (12). In 1999, there were 20 different rRNA methylases described in the literature, which coded for macrolide-lincosamide-streptogramin B resistance, and 24 efflux and inactivating genes, which coded for one or more of the macrolide-lincosamide-streptogramin B complex of antimicrobials (14). However, relatively few of these 44 genes are found in the majority of macrolide-resistant grampositive bacteria (1, 2, 13). Resistance to macrolides in the absence of resistance to lincosamides and streptogramin B has been associated with the presence of the mef(A) gene in Streptococcus pneumoniae (17,18). The mef(A) gene has become more common than erm(B) in macrolide-resistant S. pneumoniae isolates from North America (7,15). We have shown that the mef(A) gene is present in macrolide-resistant oral Streptococcus spp. and Enterococcus spp. isolated in Seattle, Wash., and Micrococcus luteus and Corynebacterium spp. isolated in the United Kingdom (5), as well as in gram-negative Acinetobacter junii and Neisseria gonorrhoeae (6). All of these species have been able to conjugally transfer the mef(A) genes to a variety of recipients. Recently, two genetic elements, Tn1207.1 (16) and mega (3), have been characterized from macrolide-resistant S. pneumoniae. A highly related gene has been sequenced from Streptococcus pyogenes, while related genes have been identified in Lancefield group C and G streptococci from Finland (4).In this study, we examined randomly selected gram-positive isolates collected from healthy Portuguese children for the presence of the common macrolide resistance genes, erm(A), erm(B), erm(C), erm(F), and mef(A). Representative mef(A)genes were sequenced, and the presence of the other seven open reading frames (ORFs) from Tn1207.1 was investigated.(The data in Table 2 were presented in part at the First Annual Symposium on Resistant Gram-Positive Infections in San Antonio, Tex., 3 to 5 Dec. 2000.) MATERIALS AND METHODSBacterial isolates. A total of 615 rand...

Of the 176 randomly selected, commensal, gram-negative bacteria isolated from healthy children with low exposure to antibiotics, 138 (78%) carried one or more of the seven macrolide resistance genes tested in this study. These isolates included 79 (91%) isolates from the oral cavity and 59 (66%) isolates from urine samples. The mef(A) gene, coding for an efflux protein, was found in 73 isolates (41%) and was the most frequently carried gene. The mef(A) gene could be transferred from the donors into a gram-positive E. faecalis recipient and a gram-negative Escherichia coli recipient. The erm(B) gene transferred and was maintained in the E. coli transconjugants but was found in 0 to 100% of the E. faecalis transconjugants tested, while the other five genes could be transferred only into the E. coli recipient. The individual macrolide resistance genes were identified in 3 to 12 new genera. Eight (10%) of the oral isolates and 30 (34%) of the urine isolates for which the MICs were 2 to >500 g of erythromycin per ml did not hybridize with any of the seven genes and may carry novel macrolide resistance genes.The use of macrolide and related antibiotics (ketolides, oxazolidinones, streptogramins, and lincosamide) has increased dramatically over the last 15 years. A number of different mechanisms of macrolide resistance have been reported for gram-negative bacteria. These mechanisms include two esterase genes [ere(A) and ere(B)] found in Escherichia coli and Enterobacter, Klebsiella, Citrobacter, and Proteus species (1) and more recently, in Providencia stuartii, Pseudomonas species, and Vibrio cholerae (5,17,22). These mechanisms also include three phosphorylase genes [mph(A), mph(B), and mph(D)] found in E. coli (14,15) and Pseudomonas (12) and one rRNA methylase gene [erm(B)] previously found in E. coli and Actinobacillus, Klebsiella, Neisseria, and Wolinella species (1, 4, 18-21). The strains described above were principally clinical isolates from hospital settings and/or from patients with clinical disease (17,18,20,21), with members of the family Enterobacteriaceae and Pseudomonas species primarily isolated from France and Japan