Travel Destinations and Sexual Behavior as Indicators of Antibiotic Resistant Shigella Strains--Victoria, Australia.

BACKGROUND: Knowledge of relationships between antibiotic susceptibility of Shigella isolates and travel destination or other risk factors can assist clinicians in determining appropriate antibiotic therapy prior to susceptibility testing. We describe relationships between resistance patterns and risk factors for acquisition in Shigella isolates using routinely collected data for notified cases of shigellosis between 2008 and 2012 in Victoria, Australia. METHODS: We included all shigellosis patients notified during the study period, where Shigella isolates were tested for antimicrobial sensitivity using Clinical and Laboratory Standards Institute breakpoints. Cases were interviewed to collect data on risk factors, including recent travel. Data were analyzed using Stata 13.1 to examine associations between risk factors and resistant strains. RESULTS: Of the 500 cases of shigellosis, 249 were associated with overseas travel and 210 were locally acquired. Forty-six of 51 isolates of Indian origin displayed decreased susceptibility or resistance to ciprofloxacin. All isolates of Indonesian origin were susceptible to ciprofloxacin. Twenty-six travel-related isolates were resistant to all tested oral antimicrobials. Male-to-male sexual contact was the primary risk factor for 80% (120/150) of locally acquired infections among adult males, characterized by distinct periodic Shigella sonnei outbreaks. CONCLUSIONS: Clinicians should consider travel destination as a marker for resistance to common antimicrobials in returning travelers, where severe disease requires empirical treatment prior to receipt of individual sensitivity testing results. Repeated outbreaks of locally acquired shigellosis among men who have sex with men highlight the importance of prevention and control measures in this high-risk group.

The development of a rapid assay for prenatal testing of common aneuploidies and microdeletion syndromes.

OBJECTIVE: To develop a novel, rapid prenatal assay for pregnancies with high likelihood of normal karyotypes, using BACs-on-Beads(™) technology, a suspension array-based multiplex assay that employs Luminex(®) xMAP(®) technology, for the detection of gains and losses in chromosomal DNA. METHODS: Fifteen relatively common microdeletions were selected that are not detectable, or may be missed, by karyotyping and usually do not present with abnormal ultrasound findings. Chromosomes 13, 18, 21, X, and Y were included. We validated the assay with 430 samples. RESULTS: All microdeletions and aneuploidies were correctly identified, except for a 69,XXX incorrectly identified as a normal female and a male with ∼20% maternal cell contamination (MCC) that could not be distinguished from 69,XXY. MCC became apparent at 20 to 30%. Mosaicism was identified at 30 to 35% abnormal cells. CONCLUSION: We have developed an alternative to fluorescence in situ hybridization (FISH) aneuploidy screening and microarray analysis in otherwise normal pregnancies undergoing invasive testing. We demonstrated that the assay will detect all microdeletions and aneuploidies of regions covered on the assay. We developed analytical software that displays results for well-characterized syndromes but not abnormalities of unclear clinical significance. This assay is likely to be preferred by women seeking testing beyond routine karyotyping but who desire more information than provided by aneuploidy FISH.

Clinical utility of chromosomal microarray analysis.

OBJECTIVE: To test the hypothesis that chromosomal microarray analysis frequently diagnoses conditions that require specific medical follow-up and that referring physicians respond appropriately to abnormal test results. METHODS: A total of 46,298 postnatal patients were tested by chromosomal microarray analysis for a variety of indications, most commonly intellectual disability/developmental delay, congenital anomalies, dysmorphic features, and neurobehavioral problems. The frequency of detection of abnormalities associated with actionable clinical features was tallied, and the rate of physician response to a subset of abnormal tests results was monitored. RESULTS: A total of 2088 diagnoses were made of more than 100 different disorders that have specific clinical features that warrant follow-up. The detection rate for these conditions using high-resolution whole-genome microarrays was 5.4%, which translates to 35% of all clinically significant abnormal test results identified in our laboratory. In a subset of cases monitored for physician response, appropriate clinical action was taken more than 90% of the time as a direct result of the microarray finding. CONCLUSIONS: The disorders diagnosed by chromosomal microarray analysis frequently have clinical features that need medical attention, and physicians respond to the diagnoses with specific clinical actions, thus arguing that microarray testing provides clinical utility for a significant number of patients tested.