Methicillin-resistant Staphylococcus aureus in a teaching hospital: investigation of nosocomial transmission using a matched case-control study.

In early 1996 a hospital-wide methicillin-resistant Staphylococcus aureus (MRSA) epidemic was recognized in a 900-bed university hospital. In order to investigate hospital-specific transmission routes, a case-control study was carried out. Cases and controls were matched for age (+/- 10 years), sex, admission date (+/- 10 days) and clinical department on admission. Data on potential risk factors, were retrieved by chart review. Between June 1996 and February 1997, 67 patients with hospital-acquired MRSA were identified. Molecular typing showed that 85% of the cases carried an indistinguishable strain. The average time at risk for cases and controls was 17.3 and 23.7 days, respectively (P= 0.01). Seventeen patients (25.4%) developed infection. Conditional multivariate regression analysis showed that intensity of care (P= 0.002), number of transfers (P= 0.019), and fluoroquinolone therapy (P= 0.025) were independently associated with acquisition of MRSA. Intensity of care can be considered as a surrogate marker for a number of manipulations which represent the main risk factors for MRSA transmission. Frequent transfers within the hospital hinder, not only the epidemiological analyses, but also efforts to bring an outbreak under control. Our findings give epidemiological support to recent molecular studies which suggest that fluoroquinolone use may increase the transmissibility of MRSA in hospitals.

Relative frequency, heterogeneity and geographic clustering of PKU mutations in Norway.

We have analysed 236 Norwegian phenylketonuria (PKU) alleles by a combination of mutation scanning methods, restriction enzyme-based assays and DNA sequencing. Thirty-three different mutations constituted 99.6% of all mutant alleles (only 1 allele remains unidentified), 23 of these have been identified also in other European countries. Twenty were predicted missense mutations, 6 splice mutations, 4 nonsense mutations and 2 deletion mutations and 1 mutation disrupted the start codon. The 8 most common mutations represented 83.5% of the PKU alleles, with single allele frequencies ranging from 5.9 to 15.7%. Four of these mutations (R261Q, R408W, Y414C, and 1VS12nt1) are commonly occurring also in PKU patients in other European countries, while the other 4 (G46S, G272X, F299C, and R408Q) have higher frequencies in Norway than in any other country studied. Six mutations (I65T, L249F, P281L, Y356X, R158Q, and R252W) have frequencies between 0.8% and 2.1%, and 19 mutations were encountered only once. The majority of PKU mutations were found on the same RFLP/VNTR haplotype backgrounds in Norway as in other European populations, suggesting that only a few of the mutations may represent recurrent mutations (< 3.4%). Among 10 mutations only reported for our population, we detected 2 de novo mutations (0.8%) arisen in Norway. From the birthplaces of the probands' grandparents, each mutation seemed to have an individual geographic distribution within Norway, with patterns of local mutation clustering. Our observations are compatible with multiple founder effects and genetic drift for the distribution of PKU mutations within Norway.