Eradication of a large outbreak of a single strain of vanB vancomycin-resistant Enterococcus faecium at a major Australian teaching hospital.

OBJECTIVE: To demonstrate that nosocomial transmission of vancomycin-resistant enterococci (VRE) can be terminated and endemicity prevented despite widespread dissemination of an epidemic strain in a large tertiary-care referral hospital. INTERVENTIONS: Two months after the index case was detected in the intensive care unit, 68 patients became either infected or colonized with an epidemic strain of vanB vancomycin-resistant Enterococcus faecium despite standard infection control procedures. The following additional interventions were then introduced to control the outbreak: (1) formation of a VRE executive group; (2) rapid laboratory identification (30 to 48 hours) using culture and polymerase chain reaction detection of vanA and vanB resistance genes; (3) mass screening of all hospitalized patients with isolation of carriers and cohorting of contacts; (4) environmental screening and increased cleaning; (5) electronic flagging of medical records of contacts; and (6) antibiotic restrictions (third-generation cephalosporins and vancomycin). RESULTS: A total of 19,658 patient and 24,396 environmental swabs were processed between July and December 2001. One hundred sixty-nine patients in 23 wards were colonized with a single strain of vanB vancomycin-resistant E. faecium. Introducing additional control measures rapidly brought the outbreak under control. Hospital-wide screening found 39 previously unidentified colonized patients, with only 7 more nonsegregated patients being detected in the next 2 months. The outbreak was terminated within 3 months at a cost of dollar 2.7 million (Australian dollars). CONCLUSION: Despite widespread dissemination of VRE in a large acute care facility, eradication was achievable by a well-resourced, coordinated, multifaceted approach and was in accordance with good clinical governance.     

In vivo activity of posaconazole against Mucor spp. in an immunosuppressed-mouse model

The in vivo activities of posaconazole, itraconazole, and amphotericin B in neutropenic mice with zygomycosis were compared. The in vitro MICs of posaconazole and itraconazole for the strains of Mucor spp. used in this study ranged from 0.125 to 8 microg/ml and 0.25 to 8 microg/ml, respectively. The in vitro MIC range for amphotericin B is 0.125 to 0.25 microg/ml. At twice-daily doses of >or=15 mg/kg of body weight, posaconazole prolonged the survival of the mice and reduced tissue burden.     

ADP and arachidonic acid induced platelet aggregation in schizophrenia and atypical psychoses

Platelet aggregatory responses to adenosine diphosphate (ADP) and arachidonic acid were examined in 6 drug-free schizophrenics, 5 other drug-free psychotics, 8 'acute-on-chronic' schizophrenics (on long-term neuroleptic therapy) and 38 healthy controls. Platelet aggregation and disaggregation following ADP was significantly lower in 'acute-on-chronic' schizophrenics (on drugs) compared with healthy controls, and disaggregation following 1 microM ADP was significantly less in drug-free schizophrenics. The difference between maximum aggregation induced by ADP and that induced by arachidonic acid was significantly greater in schizophrenics (both on drugs and drug-free) than in controls. These findings are related to possible abnormalities of central nervous system function in schizophrenia.     

Targeting of the receptor protein tyrosine phosphatase beta with a monoclonal antibody delays tumor growth in a glioblastoma model

The receptor protein tyrosine phosphatase beta (RPTPbeta) is a functional biomarker for several solid tumor types. RPTPbeta expression is largely restricted to the central nervous system and overexpressed primarily in astrocytic tumors. RPTPbeta is known to facilitate tumor cell adhesion and migration through interactions with extracellular matrix components and the growth factor pleiotrophin. Here, we show that RPTPbeta is expressed in a variety of solid tumor types with low expression in normal tissue. To assess RPTPbeta as a potential target for treatment of glioblastoma and other cancers, antibodies directed to RPTPbeta have been developed and profiled in vitro and in vivo. The recombinant extracellular domain of human short RPTPbeta was used to immunize mice and generate monoclonal antibodies that selectively recognize RPTPbeta and bind to the antigen with low nanomolar affinities. Moreover, these antibodies recognized the target on living tumor cells as measured by flow cytometry. These antibodies killed glioma cells in vitro when coupled to the cytotoxin saporin either directly or via a secondary antibody. Finally, in vivo studies showed that an anti-RPTPbeta immunotoxin (7E4B11-SAP) could significantly delay human U87 glioma tumors in a mouse xenograft model. Unconjugated 7E4B11 provides a modest but statistically significant tumor growth delay when delivered systemically in mice bearing U87 glioma tumors.