Clinical features, epidemiology, antimicrobial resistance, and exotoxin genes (including that of Panton-Valentine leukocidin) of gentamicin-susceptible methicillin-resistant Staphylococcus aureus (GS-MRSA) isolated at a paediatric teaching hospital in New South Wales, Australia.

AIMS: To describe the epidemiological, clinical, and laboratory features of gentamicin-susceptible methicillin-resistant Staphylococcus aureus (GS-MRSA) seen at a paediatric teaching hospital. METHODS: Patients from whom GS-MRSA was isolated between 1 January 2001 and 31 December 2002 were enrolled. Retrospective chart review was performed. Susceptibility testing was performed with the Vitek2 system; PCR confirmed methicillin resistance. Phage typing and pulsed field gel electrophoresis (PFGE) was performed (utilising MLST/SCCmec-defined control strains). PCR detection of tst, luk-PV, and entA-entE was performed. RESULTS: Eighty-five per cent of all Staphylococcus aureus isolates during the study period were methicillin-sensitive, and 15% were MRSA (9% GS-MRSA, 6% gentamicin resistant-MRSA). 100 GS-MRSA infections in 98 children were identified: 59 cases of skin/soft tissue, four bone and joint, four surgical site infections, three pneumonia, eight other types, and 22 represented colonisation. Ninety-nine isolates were non-multidrug resistant, but 17 strains were resistant to erythromycin, 7 to tetracyclines, 12 to ciprofloxacin, 11 to fusidic acid, 1 each to rifampicin and mupirocin. 44 isolates were Oceania strain (ST30-MRSA-IV), 20 were Queensland strain (ST93-MRSA-IV), ten were UK EMRSA-15 (ST22-MRSA-IV), eight were WA MRSA-1 (ST1-MRSA-IV), two were WA MRSA-5 (ST8-MRSA-IV), one was WA MRSA-2 (ST78slv-MRSA-IV), one was WA MRSA-15 (ST59-MRSA-IV), and the remainder were sporadics. Twenty patients were Pacific Islanders, of whom 12 had the Oceania strain; ten were Aboriginal, of whom eight had the Queensland strain. Sixty-eight isolates possessed luk-PV, including all Queensland strains and 91% of Oceania strains. Enterotoxin genes were detected in 25% of the isolates, and tst was detected in four isolates. CONCLUSIONS: GS-MRSA is a significant paediatric problem in New South Wales: two minority groups are over-represented, multiple epidemic strains were detected, most community strains possess luk-PV, and many isolates are multidrug resistant.

Bacterial superantigen TSST-1 attenuates suppressive efficacy of glucocorticoids and calcineurin inhibitors against blastogenesis of peripheral blood mononuclear cells from patients with chronic renal failure on hemodialysis treatment.

BACKGROUND: Many cases of patients with chronic renal failure (CRF) on hemodialysis are known to be infected with Staphylococcus aureus (S. aureus) from the sites of blood vessel puncture for hemodialysis and the custody of the vascular access catheter. S. aureus produces superantigens, such as toxic shock syndrome toxin-1 (TSST-1), which may influence the sensitivity of peripheral-blood mononuclear cells (PBMCs) to immunosuppressive drugs after they are received postrenal transplantation. METHODS: We examined the drug-sensitivities of PBMCs stimulated with TSST-1 in 18 CRF patients on hemodialysis. PBMCs were isolated from venous blood before hemodialysis, and were cultured in the presence of concanavalin A (ConA) or TSST-1 and serial concentrations of the drugs. In vitro drug concentrations giving 50% inhibition (IC(50)) of PBMC blastogenesis were calculated. INF-gamma and IL-4 in supernatants of cultured PBMCs were measured with ELISA. RESULTS: The median (range) IC(50) values (ng/ml) for four drugs; tacrolimus, cyclosporine, methylprednisolone, and prednisolone, evaluated in ConA-stimulated PBMCs of CRF patients were 0.04 ng/ml (0.03-0.21), 3.0 (0.1-15.1), 3.0 (1-104), and 16.2 (5.9-35.4), respectively. The values for the four drugs evaluated in TSST-1-stimulated PBMCs were 0.22 (0.08-0.36), 18.9 (5.1-38.2), 328.3 (1.9-1000), and 150.9 (94.7-880), respectively, which were significantly higher than those evaluated in the ConA-stimulated PBMCs (p=0.003-0.023). Amounts of INF-gamma and IL-4 produced from cells were not significantly different between the ConA-or TSST-1-stimulated PBMCs in the presence or absence of immunosuppressive drugs. CONCLUSION: These observations raise the possibility that TSST-1 induced by S. aureus infection attenuates the clinical efficacy of glucocorticoids and calcineurin inhibitors in CRF patients after renal transplantation. Furthermore, INF-gamma and IL-4 related pathways appear not to play major roles in the TSST-1-induced attenuation of the drug sensitivities.

The staphylococcal superantigen-like protein 7 binds IgA and complement C5 and inhibits IgA-Fc alpha RI binding and serum killing of bacteria.

The staphylococcal superantigen-like proteins (SSLs) are close relatives of the superantigens but are coded for by a separate gene cluster within a 19-kb region of the pathogenicity island SaPIn2. rSSL7 (formally known as SET1) bound with high affinity (K(D), 1.1 nM) to the monomeric form of human IgA1 and IgA2 plus serum IgA from primate, pig, rat, and horse. SSL7 also bound the secretory form of IgA found in milk from human, cow, and sheep, and inhibited IgA binding to cell surface FcalphaRI (CD89) and to a soluble form of the FcalphaRI protein. In addition to IgA, SSL7 bound complement factor C5 from human (K(D), 18 nM), primate, sheep, pig, and rabbit serum, and inhibited complement-mediated hemolysis and serum killing of a Gram-negative organism Escherichia coli. SSL7 is a superantigen-like protein secreted from Staphylococcus aureus that blocks IgA-FcR interactions and inhibits complement, leading to increased survival of a sensitive bacterium in blood.