Low prevalence of meticillin-resistant Staphylococcus aureus carriage at hospital admission: implications for risk-factor-based vs universal screening.

BACKGROUND: There is debate over the optimal policy for detecting meticillin-resistant Staphylococcus aureus (MRSA) colonization at hospital admission. The emergence of community-associated (CA)-MRSA may compromise targeted screening strategies based on risk factors for healthcare-associated (HA)-MRSA. AIM: To determine the prevalence of MRSA colonization at admission, and the genotype and molecular epidemiology of the strains involved. METHODS: A 12-month observational study was performed at a 1200-bed London tertiary referral hospital from 1 April 2008 to 1 March 2009. All available MRSA isolates were genotyped by spa and staphylococcal cassette chromosome mec (SCCmec) typing. FINDINGS: The overall MRSA colonization rate was 2.0% of 28,892 admissions (range 6.6% in critical care to 0.8% in obstetrics/gynaecology/neonatology). The overall frequency of previously unknown carriage of MRSA on admission was 1.4%. Most colonizing strains were epidemic HA-MRSA-15 and -16. However, heterogeneous CA strains accounted for 18% of recovered isolates, including 37.5% of MRSA from accident and emergency and 23.1% of MRSA from surgery. The CA-MRSA strain types had significantly different epidemiological associations from the HA-MRSA strains, so risk factors used for the identification of HA-MRSA may not detect CA-MRSA reliably. CONCLUSION: The low rate of HA-MRSA in the UK increases the relative proportion due to CA-MRSA, for which conventional risk-factor-based screening strategies may be less effective. Cost-benefit analyses of universal MRSA admission screening will need to take account of this new epidemiology.

Enhanced surveillance of meticillin-resistant Staphylococcus aureus bacteraemia in a London teaching hospital.

In 2001, the UK Department of Health introduced mandatory surveillance of meticillin-resistant Staphylococcus aureus (MRSA) bacteraemias (blood-culture-positive episodes) in English hospitals. We performed enhanced surveillance in their hospital between April 2001 and March 2003 to determine the epidemiology of MRSA bacteraemia across different specialities. There were 267 MRSA-blood-culture-positive episodes, giving a rate of 0.37 per 1000 occupied bed-days (OBD). Thirty-three (12.4%) episodes were false positives due to contaminants and 15 (5.6%) originated in the community or at another institution. Thirty-one (11.6%) episodes were in outpatients or occurred after recent discharge and were designated 'hospital associated'. The remaining 188 cases were clinically significant hospital-acquired episodes in inpatients, with a rate of 0.26 per 1000 OBDs. The highest rates were in the intensive therapy unit (ITU; 2.74 per 1000 OBDs) and the high-dependency unit (HDU; 1.68 per 1000 OBDs). Fifty-five non-ITU, non-HDU episodes occurred in patients who had been discharged from ITU or HDU prior to the development of bacteraemia but during the same admission. The number of MRSA bacteraemias related to ITU/HDU suggests that these wards may be hubs of MRSA infection. Haematology, oncology and renal (HOR) patients had the greatest number of hospital-associated episodes. The most common source of MRSA bacteraemia was a vascular access device (VAD) (108 episodes, 57%, 64% of which were central lines). The high bacteraemia rates in ITU, HDU and HOR patients were associated with high usage of VADs. The majority of episodes occurred in patients who were newly colonized with MRSA after admission. Thus, in this hospital, VADs and stays in ITU or HDU are important risk factors for bacteraemia, and VAD care and prevention of cross-infection are priorities for intervention. We recommend that the mandatory national surveillance scheme should collect additional data on MRSA bacteraemia to provide information for a national strategy for MRSA control and to allow appropriate comparison between institutions.

The pathogenesis of Shigella flexneri infection: lessons from in vitro and in vivo studies.

Shigella flexneri is a Gram-negative facultatively intracellular pathogen responsible for bacillary dysentery in humans. More than one million deaths occur yearly due to infections with Shigella spp. and the victims are mostly children of the developing world. The pathogenesis of Shigella centres on the ability of this organism to invade the colonic epithelium where it induces severe mucosal inflammation. Much information that we have gained concerning the pathogenesis of Shigella has been derived from the study of in vitro models of infection. Using these techniques, a number of the molecular mechanisms by which Shigella invades epithelial cells and macrophages have been identified. In vivo models of shigellosis have been hampered since humans are the only natural hosts of Shigella. However, experimental infection of macaques as well as the murine lung and rabbit ligated ileal loop models have been important in defining some of the immune and inflammatory components of the disease. In particular, the murine lung model has shed light on the development of systemic and local immune protection against Shigella infection. It would be naive to believe that any one model of Shigella infection could adequately represent the complexity of the disease in humans, and more sophisticated in vivo models are now necessary. These models require the use of human cells and tissue, but at present such models remain in the developmental stage. Ultimately, however, it is with such studies that novel treatments and vaccine candidates for the treatment and prevention of shigellosis will be designed.

An immunohistochemical analysis of onchocercal nodules: evidence for an interaction between macrophage MRP8/MRP14 and adult Onchocerca volvulus.

We have used a panel of MoAbs to investigate the phenotype of macrophages and other leucocytes infiltrating onchocercal nodules. Nodules were removed from individuals at the end of the second year of a community-based, placebo-controlled trial of annual ivermectin chemotherapy in northern Nigeria. No significant differences were seen in the distribution and phenotype of leucocytes in nodules from ivermectin- and placebo-treated individuals. Live adult worms were only seen in nine of the 21 nodules examined. Three regions were clearly discernible within nodules containing both live and dead worms; an outer fibrovascular capsule (zone A), an inner adult worm bundle with surrounding hyaline extracellular matrix interspersed with solitary cells (zone B), and a dense cellular infiltrate surrounding and in contact with a variable proportion of the worm (zone C). Macrophages were the predominant cell type in all zones of the nodule. Those in zone B were distinguished by their dendritic morphology and strong reactivity with MoAbs directed against class II molecules, FcRI (CD64) and CD68, whereas macrophages in zone C were larger, more heterogeneous in shape, and were distinguished by strong reactivity with MoAbs directed against CR4 (CD11c, CD18) and MRP8/MRP14, and with MoAb24. T cells were found primarily in zones A and C, whilst eosinophils were found in only six nodules. A unique staining pattern was seen using MoAbs reacting with the calcium-binding protein MRP8/MRP14. Most macrophages in zones A and B were negative; however, where the occasional positive macrophage was seen in zone B, MRP8/MRP14 was also found around the cell and on the neighbouring worm surface, giving the impression that MRP8/MRP14 was being secreted onto the adult worm. Macrophages in zone C were also MRP8/MRP14-positive, and often the whole infiltrate was surrounded with extracellular MRP8/MRP14, with greatest concentration seen adjacent to the worm. MRP8/MRP14 was not identified on the surface of microfilariae (MF) within the same nodules. Since MRP8/MRP14 was seen on the adult worm in the absence of a leucocytic infiltrate, it may have an early role to play in the immune response to Onchocerca volvulus.