Foster Levy

A Decline in Mupirocin Resistance in Methicillin-Resistant Staphylococcus aureus Accompanied Administrative Control of Prescriptions

ABSTRACT Susceptibility to mupirocin was assessed in methicillin-resistant Staphylococcus aureus isolates selected from eras corresponding to differences in usage rate and prescription policies at a Veterans Affairs medical center. The eras studied encompassed from the time of introduction of the drug to its widespread use, through recommended judicious use, and finally to subsequent stringent administrative control. Prescriptions declined from 3.0 to 0.1 per 1,000 patient days. Precipitous declines first in the numbers of isolates with high-level resistance (from 31% to 4%) and then in those with low-level resistance (from 26% to 10%) accompanied prescription control.

Colonization of healthy children by Moraxella catarrhalis is characterized by genotype heterogeneity, virulence gene diversity and co-colonization with Haemophilus influenzae.

The colonization dynamics of Moraxella catarrhalis were studied in a population comprising 1079 healthy children living in Rotterdam, The Netherlands (the Generation R Focus cohort). A total of 2751 nasal swabs were obtained during four clinic visits timed to take place at 1.5, 6, 14 and 24 months of age, yielding a total of 709 M. catarrhalis and 621 Haemophilus influenzae isolates. Between January 2004 and December 2006, approximate but regular 6-monthly cycles of colonization were observed, with peak colonization incidences occurring in the autumn/winter for M. catarrhalis, and winter/spring for H. influenzae. Co-colonization was significantly more likely than single-species colonization with either M. catarrhalis or H. influenzae, with genotypic analysis revealing no clonality for co-colonizing or single colonizers of either bacterial species. This finding is especially relevant considering the recent discovery of the importance of H. influenzae-M. catarrhalis quorum sensing in biofilm formation and host clearance. Bacterial genotype heterogeneity was maintained over the 3-year period of the study, even within this relatively localized geographical region, and there was no association of genotypes with either season or year of isolation. Furthermore, chronological and genotypic diversity in three immunologically important M. catarrhalis virulence genes (uspA1, uspA2 and hag/mid) was also observed. This study indicates that genotypic variation is a key factor contributing to the success of M. catarrhalis colonization of healthy children in the first years of life. Furthermore, variation in immunologically relevant virulence genes within colonizing populations, and even within genotypically identical M. catarrhalis isolates, may be a result of immune evasion by this pathogen. Finally, the factors facilitating M. catarrhalis and H. influenzae co-colonization need to be further investigated.

bro β-lactamase and antibiotic resistances in a global cross-sectional study of Moraxella catarrhalis from children and adults

OBJECTIVES To compare and contrast the geographic and demographic distribution of bro beta-lactamase and antibiotic MIC(50/90) for 1440 global Moraxella catarrhalis isolates obtained from children and adults between 2001 and 2002. METHODS One thousand four hundred and forty M. catarrhalis isolates originating from seven world regions were investigated. The isolates were recovered from 411 children <5 years of age and 1029 adults >20 years of age. PCR-restriction fragment length polymorphism (RFLP) was performed to determine bro prevalence and to distinguish between bro types. MIC values of 12 different antibiotics were determined using the CLSI (formerly NCCLS) broth microdilution method. RESULTS Of the 1440 isolates, 1313 (91%) possessed the bro-1 gene and 64 (4%) possessed the bro-2 gene. Additionally, the prevalence of bro positivity between the child and adult age groups was significantly different (P < 0.0001), though bro-1 and bro-2 prevalences within age groups were not significantly different. Consistently higher beta-lactam MICs were observed for M. catarrhalis isolates originating in the Far East. Significant correlations in MICs were observed for several antibiotic combinations, including all five beta-lactams with each other, and among the two quinolones. CONCLUSIONS The worldwide prevalence of bro gene carriage in clinical isolates of M. catarrhalis is now approaching 95%, with children significantly more likely to harbour bro-positive isolates than adults. Further, statistically significant differences in the distribution of beta-lactam MICs were observed between different world regions, particularly with respect to the Far East.

A population genetic analysis of chloroplast DNA in Phacelia.

Hierarchical sampling from populations, incipient and recognized varieties within Phacelia dubia and P maculata has revealed high levels of intraspecific polymorphism in chloroplast DNA. Much of the variation is partitioned between populations as evidenced by population-specific variants at fixation in all three populations of P. dubia var. interior and in both populations of P. maculata. Nine of 16 populations were polymorphic for cpDNA haplotypes. A total of 16 haplotypes was found in a sample of 106 individuals; the most common occurred in eight of the 16 populations and in 31 per cent of the individuals in the entire sample. A phylogenetic analysis revealed four basic plastome types. The two major groups of plastomes were separated by four independent base-pair mutations which suggests an ancient split in the evolution of plastid genomes. Representatives from each major plastome division were found in each of five populations spanning two allopatric varieties of P. dubia. The geographical distribution of haplotypes and lack of evidence for recent admixture argue against migration as a source of the polymorphism. It is more likely that the current taxonomic varieties are descendants of a polymorphic common ancestor.

A genetic analysis of reproductive barriers in Phacelia dubia

Investigations into the genetic basis of reproductive barriers among recognized and putative varieties in Phacelia dubia have provided evidence that even among closely related taxa, multiple pathways can lead to reproductive isolation. A nuclear-based reproductive barrier, expressed as partial hybrid sterility of both pollen and ovules, isolated each pair of recognized varieties. There was no evidence of pre- or post-fertilization barriers; all reproductive barriers were manifested as hybrid gametic sterility. Reproductive relationships of two putative varieties were studied to examine the early stages of reproductive isolation in this group. Both putative varieties exhibited partial reproductive isolation from the recognized varieties in spite of their lack of morphological differentiation from recognized varieties. The barrier isolating one putative variety was similar to the barrier among recognized varieties. The second putative variety and a recognized variety were partially isolated by a unidirectional, nuclear-cytoplasmic barrier that reduced only pollen fertility. The nuclear-cytoplasmic barrier suggested a new application of Haldanes rule.

GENETIC TRENDS IN A POPULATION EVOLVING ANTIBIOTIC RESISTANCE

Abstract.— The evolution of antibiotic resistance provides a well‐documented, rapid, and recent example of a selection driven process that has occurred in many bacterial species. An exhaustive collection of Moraxella catarrhalis that spans a transition to chromosomally encoded penicillin resistance was used to analyze genetic changes accompanying the transition. The population was characterized by high haplotypic diversity with 148 distinct haplotypes among 372 isolates tested at three genomic regions. The power of a temporally stratified sample from a single population was highlighted by the finding of high genetic diversity throughout the transition to resistance, population numbers that remained high over time, and no evidence of departures from neutrality in the allele frequency spectra throughout the transition. The direct temporal analysis documented the persistence, antibiotic status, and haplotypic identity of strains undergoing apparent clonal expansions. Several haplotypes that were β‐lactamase nonproducers in early samples converted to producers in later years. Maintenance of genetic diversity and haplotype conversions from sensitive to resistant supported the hypothesis that penicillin resistance determinants spread to a diverse array of strains via horizontal exchange. Genetic differentiation between sample years, estimated by FST, was increasing at a rate that could cause complete haplotype turnover in less than 150 years. Widespread linkage disequilibrium among sites within one locus (copB) suggested recent mutation followed by clonal expansion. Nonrandom associations between haplotypes and resistance phenotypes provided further evidence of clonal expansion for some haplotypes. Nevertheless, the population structure was far from clonal as evidenced by a relatively low frequency of disequilibria both within sites at a second locus (M46) as well as between loci. The haplotype‐antibiotic resistance association that was accompanied by gradual haplotype turnover is consistent with a hypothesis of genetic drift at marker loci with directional selection at the resistance locus.

Nosocomial transmission clusters and risk factors in Moraxella catarrhalis.

We report an objective examination of nosocomial transmission events derived from long-term (10-year) data from a single medical centre. Cluster analysis, based on the temporal proximity of genetically identical isolates of the respiratory pathogen Moraxella catarrhalis, identified 40 transmission events involving 33 of the 52 genotypes represented by multiple isolates. There was no evidence of highly transmissible or outbreak-prone genotypes. Although most clusters were small (mean size 3.6 isolates) and of short duration (median duration 25 days), clustering accounted for 38.7% of all isolates. Significant risk factors for clustering were multi-bed wards, and winter and spring season, but bacterial antibiotic resistance, manifested as the ability to produce a beta-lactamase was not a risk factor. The use of cluster analysis to identify transmission events and its application to long-term data demonstrate an approach to pathogen transmission that should find wide application beyond hospital populations.

Blastomycosis in the Mountainous Region of Northeast Tennessee

BACKGROUND In the United States, cases of human blastomycosis are largely described in defined geographic areas, with Mississippi reporting the highest prevalence of disease in the southeast region. The infection is uncommonly recognized in mountainous areas, and our previous report of blastomycosis in the southern Appalachian mountains of northeast Tennessee appeared to be an exception to the usual disease distribution. METHODS Our current retrospective study was undertaken to determine whether blastomycosis has persisted as an endemic fungal infection in our northeast Tennessee geographic area and whether epidemiologic features have changed over a 25-year time period. RESULTS Results show that clinical aspects of the disease have remained fairly constant with few exceptions; mass-type pulmonary lesions have become more common, and itraconazole has emerged as the therapy of choice. Most notably, however, are the observations that blastomycosis persists as a major endemic fungal infection in our mountain region, more than half of all cases occurring during the period from 1996 to 2005 were found in a core area centered on two counties, Washington and Unicoi; three of five counties surrounding the core counties experienced rate increases compared to our previous study. CONCLUSIONS These findings suggest a further expansion of this endemic fungal disease beyond the core region.

Pattern and Rate of Decline of a Population of Carolina Hemlock (Tsuga caroliniana Engelm.) in North Carolina

Abstract We monitored a population of Carolina Hemlocks in northwestern North Carolina for four years to examine the rate and pattern of decline in response to infestation by Adelges tsugae (Hemlock Woolly Adelgid). Our yearly census of hemlock condition and severity of the adelgid infestation included trees of all sizes. We estimated declines in condition as the portions of the leaf canopy that were lost. Initially, infestation occurred throughout the population but was severe in only a small cluster of individuals. Within 1 year, the area of severe infestation increased in size to encompass 48% of the population. In another region of the population, there was a cluster of relatively healthy individuals comprised largely of seedlings. Of the 4 size-classes of trees, sapling-sized individuals experienced the highest rates of decline in condition. Most trees declined to poor health within 3 years of an observation of moderate to severe infestation.

Comparative activity of telavancin and other antimicrobial agents against methicillin-resistant Staphylococcus aureus isolates collected from 1991 to 2006.

Background: Increasingly frequent reports of vancomycin treatment failures for serious methicillin-resistant Staphylococcus aureus (MRSA) infections provide impetus for comparative in vitro studies to assess the activity of newer antimicrobial agents against a range of MRSA isolates. Methods: A sample of 168 MRSA derived from a long-term MRSA collection was subjected to susceptibility testing to telavancin, daptomycin, linezolid, tigecycline and vancomycin by broth micro-dilution. Data were reviewed for sporadic occurrence of isolates with reduced susceptibility. Analyses were performed to test for temporal trends toward decreasing susceptibility and to compare susceptibility of isolates from different infection sites. Results: No MRSA isolate from any time period was resistant to test antibiotics. For daptomycin, linezolid and tigecycline, there were no susceptibility differences between the pre- and postclinical availability periods. All newer agents were active against MRSA isolates with minimum inhibitory concentrations (MICs) of vancomycin >1 mg/l, but there were significant correlations in susceptibility among several pairs of antibiotics. Conclusions: Telavancin and other newer antistaphylococcal agents were fully active against MRSA from various infection sites including isolates with vancomycin MIC >1 mg/l.