Evidence of Multiple Virulence Subtypes in Nosocomial and Community-Associated MRSA Genotypes in Companion Animals from the Upper Midwestern and Northeastern United States

Objective: Not much is known about the zoonotic transmission of methicillin-resistant Staphylococcus aureus (MRSA) in companion animals in the United States. We report the rate of prevalence of S. aureus and MRSA recovered from clinical samples of animals requiring treatment at veterinary clinics throughout the upper midwestern and northeastern United States.Design: We compared phenotypes, genotypes, and virulence profiles of the MRSA isolates identified in companion animals, such as cats, dogs, horses, and pigs, with typical human nosocomial and community-associated MRSA (CA-MRSA) genotypes to assess implied zoonotic transmission or zooanthroponosis. Five hundred thirty-three coagulase-positive staphylococci (CPS) isolates recovered between 2006 and 2008 from a variety of animal-source samples were screened for S. aureus by S. aureus-specific 16S rDNA primers and were screened for methicillin-resistance. All MRSA isolates were genotyped by pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), and spa typing. They were also screened for common staphylococcal enterotoxin and adhesion genes by multiplex and singleplex PCR.Results: Among the 533 CPS isolates recovered, 66 (12.4%) were determined to be S. aureus and 24 (4.5%) were MRSA. The percent of animals that were positive for S. aureus were as follows: 6.6% (32 of 487) dogs, 39.6% (19 of 48) cats, 83.3% (10 of 12) horses, and 100% of pigs, rabbits, hamsters and rats. Notably, 36.4% of all S. aureus identified were MRSA. Methicillin-resistant S. aureus was present in clinical samples from 12 of 487 dogs (2.5%), 6 of 48 cats (12.5%), 5 of 12 horses (42%), and 1 of 2 pigs (50%). The 24 MRSA isolates resolved into 4 PFGE clones: USA100 (50%), USA300 (16.7%), USA500 (20.8%) and USA800 (12.5%) and 6 sequence types (ST5, ST8, ST105, ST830, and ST986) or 2 clonal complexes, CC5 and CC8. Five major virulence profiles (clusters A to E) were observed in these MRSA isolates. Genotypic and virulence profiles of cats and dogs were more similar to each other than to those of horses. A Panton-Valentine leukocidin positive isolate with ST8:USA300 background was identified in a pig causing skin and soft infection.Conclusion: The presence of human MRSA clones in these animals suggests possible reverse zoonotic transmission. This study reports the first case of a USA300 genotype in a pig. Presence of multiple virulence profiles within a MRSA genotype in these animals suggests the potential of emergence of new MRSA clones by gaining or losing additional virulence genes.     

Factors associated with medium-term response to psychostimulant medication

OBJECTIVE: To determine, in a sample of children first prescribed psychostimulants for attention deficit hyperactivity disorder (ADHD) between 1992 and 1994, which child and family factors, components of assessment, and aspects of management, were associated with a favourable treatment response, and with parental satisfaction with management. METHODOLOGY: Data were obtained by mail survey in March 1995. Factors considered potentially significant to treatment response and parental satisfaction were entered in a three-step hierarchical multiple regression equation. RESULTS: Responses were received from 788 (59.7%) of a possible 1319 parents. Items making a significant individual contribution to both improvement and parental satisfaction were: younger age of the child; amount of information provided by the clinician; shorter interval between review appointments; continued use of medication; and fewer treatment side effects. items contributing only to treatment response were: longer time taken over establishing the diagnosis; and the use of parent and teacher checklists in assessment. CONCLUSIONS: These data support early intervention for ADHD. A considered approach to assessment which includes the use of parent and teacher checklists is recommended. Providing adequate information to parents and children is essential. Review intervals of less than 6 months appear to foster better outcomes.     

Maternal meiosis I non-disjunction of chromosome 15: dependence of the maternal age effect on level of recombination

Non-disjoined chromosomes 15 from 115 cases of uniparental disomy (ascertained through Prader-Willi syndrome) and 13 cases of trisomy of maternal origin were densely typed for microsatellite loci spanning chromosome 15q. Of these 128 cases a total of 97 meiosis I (MI) errors, 19 meiosis II (MII) errors and 12 mitotic errors were identified. The genetic length of a map created from the MI errors was 101 cM, as compared with a maternal length of 137 cM based on CEPH controls. No significant differences were detected in the distribution of recombination events along the chromosome arm and a reduction was seen for most of the chromosome 15 intervals examined. It was estimated that 21% of tetrads leading to MI non-disjunction were achiasmate, which may account for most or all of the reduction in recombination noted. The mean age of mothers of cases involving MI errors which showed no transitions from heterodisomy to isodisomy was significantly lower (32.7) than cases showing one or more observable transitions (36.3) (P < 0.003, t -test). However, even among chiasmate pairs the highest mean maternal age was seen for multiple exchange tetrads. Chromosome- specific differences in maternal age effects may be related to the normal distribution of exchanges (and their individual susceptibilities) for each chromosome. However, they may also reflect the presence of multiple factors which act to ensure normal segregation, each affected by maternal age in a different way and varying in importance for each chromosome.      

Efficacy and safety of caspofungin for treatment of invasive aspergillosis in patients refractory to or intolerant of conventional antifungal therapy

BACKGROUND: Invasive aspergillosis (IA) is an important cause of morbidity and mortality among immunocompromised patients. Echinocandins are novel antifungal molecules with in vitro and in vivo activity against Aspergillus species. METHODS: We investigated the efficacy and safety of caspofungin in the treatment of IA. Ninety patients with IA who were refractory to or intolerant of amphotericin B, lipid formulations of amphotericin B, or triazoles were enrolled to receive caspofungin. RESULTS: Efficacy was assessed for 83 patients who had infection consistent with definitions of IA and who received >or=1 dose of study drug. Common underlying conditions included hematologic malignancy (48% of patients), allogeneic blood and marrow transplantation (25% of patients), and solid-organ transplantation (11% of patients). Seventy-one patients (86%) were refractory to and 12 patients (14%) were intolerant of previous therapy. A favorable response to caspofungin therapy was observed in 37 (45%) of 83 patients, including 32 (50%) of 64 with pulmonary aspergillosis and 3 (23%) of 13 with disseminated aspergillosis. Two patients discontinued caspofungin therapy because of drug-related adverse events. Drug-related nephrotoxicity and hepatotoxicity occurred infrequently. CONCLUSION: Caspofungin demonstrated usefulness in the salvage treatment of IA.     

Ketoprofen (25 mg) in the symptomatic treatment of episodic tension-type headache: double-blind placebo-controlled comparison with acetaminophen (1000 mg)

Therapies in current use for episodic tension-type headache (ETTH) are often unsatisfactory. Few trials have been conducted to demonstrate efficacy of any of them. This multicenter placebo-controlled randomized parallel-groups study compared the analgesic efficacy of single oral doses of ketoprofen 25 mg and acetaminophen 1000 mg as outpatient treatment of 1 attack of ETTH. Efficacy was assessed by patients as pain relief on a diary-entered 7-point categorical scale. A total of 457 patients treated 348 attacks, 330 of which were evaluable. There were no serious adverse events (AEs); gastrointestinal AEs were most common on all treatments. Total relief from pain after 2 h was recorded by l6% of patients on placebo, 28% on ketoprofen, and 22% on acetaminophen. Worthwhile effect or total relief (all other responses were regarded as treatment failures) were recorded by 36% on placebo, 70% on ketoprofen ( p <0.001), 61% on acetaminophen ( p <0.001). The difference between ketoprofen and acetaminophen was not significant ( p =0.24). Various secondary efficacy measures confirmed superiority of both active treatments over placebo, with some trends for slightly better outcome on ketoprofen than on acetaminophen This study demonstrates that ketoprofen is an effective alternative to standard therapy in ETTH.