Famciclovir treatment of hepatitis B infection following liver transplantation: a long-term, multi-centre study.

Famciclovir is a novel guanosine nucleoside analogue with activity against herpes viruses and hepatitis B virus (HBV). Several preliminary reports have described efficacy of famciclovir in patients with recurrent hepatitis B after orthotopic liver transplantation (OLT). This report describes the largest study to date of long-term famciclovir treatment in patients with de novo or recurrent hepatitis B post-OLT. One hundred thirty patients with detectable serum HBV DNA after OLT received oral famciclovir 500 mg tid on a compassionate-use basis. Safety analyses included all treated patients; efficacy was assessed in all patients and a subgroup of 73 patients with complete baseline HBV DNA and alanine aminotransferase (ALT) data who had received > or =6 months of treatment. Efficacy parameters included serum levels of HBV DNA, ALT, and anti-HBe or anti-HBs seroconversion rates. Of the 70 patients treated for > or =6 months who could be evaluated for response/non-response to famciclovir, 52 (74%) were responders, defined as patients who experienced a 70% decrease or more in HBV DNA levels from baseline, or who became HBV DNA-negative, for at least two consecutive visits. In famciclovir responders, HBV DNA levels decreased by a median of 91% after 12 weeks of treatment, 95% after 6 months and >99% after 18 months of treatment. Marked differentiation between responders and non-responders could be made soon after the onset of treatment. Among anti-HBe positive patients with evidence of HBV replication, 12/13 were responders. Patients with high baseline ALT levels experienced more rapid suppression of HBV DNA during therapy with famciclovir. Famciclovir therapy was safe and well tolerated; serious adverse events were reported infrequently. Famciclovir treatment may be beneficial in patients with hepatitis B infection post-OLT.

Staphylococcus aureus endocarditis presenting as meningitis and mimicking meningococcal sepsis.

A case of Staphylococcus aureus meningitis (SAM) secondary to endocarditis is presented. The presence of a petechial rash affecting the lower limbs led to an initial presumptive diagnosis of meningococcal meningitis. There were no stigmata of endocarditis at presentation, though these subsequently developed. Underlying endocarditis should be diligently sought in any patient presenting with spontaneous SAM, even if typical stigmata are initially absent. In view of the association with skin lesions and neurological complications, S. aureus endocarditis may mimic the classical presentation of meningococcal sepsis.

Vancomycin-resistant Corynebacterium species causing prosthetic valve endocarditis successfully treated with imipenem and ciprofloxacin.

Endocarditis caused by a Corynebacterium sp. resistant to vancomycin, penicillin G, erythromycin, gentamicin and rifampicin arose in a 44-year-old woman 4 months after replacement of the mitral valve with a prosthesis. She was successfully treated with a 79-day course of intravenous imipenem and ciprofloxacin and replacement of the prosthesis 48 days after treatment began.

The tangible cost implications of a hospital outbreak of multiply-resistant Salmonella.

A hospital outbreak of multiply-resistant Salmonella heidelberg infection, which affected 17 patients and 2 staff, is described. The tangible cost of the outbreak was estimated at 21 pounds 151, 17 pounds 989 (85.1%) of which was borne by the hospital. The cost to the Microbiology Department was 3596 pounds (17.0% of the total). A detailed analysis of the costs and implications for staffing disruption is given and a comparison is made with the costs of preventive activities. Ways of containing expenses in the event of an outbreak and the economic implications for clinical budgeting and privatization of the laboratory service are considered.

T-cell-mediated protection of mice against virulent Mycobacterium tuberculosis.

We sought to protect CBA mice against tuberculosis using in vivo transfer of a T-cell line previously shown to be capable of I-A-restricted recognition of peritoneal macrophages infected in vitro with Mycobacterium tuberculosis. This line induces total bacteriostasis in vitro. In mice that received 500 rads of irradiation 48 h before infection, the T-cell line caused significant prolongation of life when given intravenously with a challenge dose of 5 x 10(6) organisms. Similar experiments with two other T-cell lines showed that these lines offered no protection. Bacterial load at the time of death was inversely related to the time of survival. Thus, death occurred at a lower bacterial load in adoptively protected mice, implying the contribution of an immunopathological component in these animals. The protective T-cell line, which was CD4+ CD8-, had no effect on the rate of growth of strain BCG in CBA nu/nu mice or M. tuberculosis in fully T-cell-deprived mice. This could indicate that CD8+ cells play a role in this system or that there is a need for the recruitment of interleukin 2-producing cells in the recipient. Experiments with monoclonal antibodies to selectively deplete T-cell subsets in normal CBA mice showed that depletion of CD4+ cells strikingly shortened survival, whereas depletion of CD8+ cells did not. However, CD8-depleted mice died with a lower bacterial load than those found in nondepleted controls, and the lesions in CD8-depleted mice were histopathologically distinct. These results suggest that the CD8+ cells either down-regulate bacteriostasis or cause immunopathology in this model and that it is the CD4+ cells that are the major protective subset in long-term protection experiments.

Prevalence and specificity of the enhancing effect of three types of interleukin 2 on T cell responsiveness in 97 lepromatous leprosy patients of mixed ethnic origin.

Peripheral blood mononuclear cells from 97 predominantly lepromatous leprosy patients and 11 control subjects were tested in a lymphoproliferative assay for response to Mycobacterium leprae (whole and sonicated), and sonicated M. vaccae, M. tuberculosis, and M. scrofulaceum, in the presence and absence of three types of interleukin 2 (IL-2) (crude, purified, and recombinant). IL-2 enhanced the response to sonicated M. tuberculosis and M. leprae organisms more often in patients than in control subjects, but not significantly so and only in a minority of patients. This effect was significantly more common (though still only found in a minority of 46%) using M. leprae organisms as antigen, than when using sonicates of M. leprae (19%) or M. vaccae (19%). However it was nearly as frequent using sonicated M. tuberculosis, or M. scrofulaceum. Thus in only nine patients was the effect specific to M. leprae. Enhancement by IL-2 could not be related to the type of IL-2 used, the dose of antigen, or the amount of endogenous IL-2 released by the cells tested. Similarly it was not related to the extent to which IL-2 caused increased background proliferation in control wells, which occurred to an equal extent using cells from control subjects, nor was it related to the extent of antigen-driven proliferation. The data have also been analysed in relation to duration of disease (50 years to a few weeks) and ethnic origin. No correlations have been revealed. Thus enhancement by IL-2 of the lymphoproliferative response to mycobacterial antigens does occur using cells from lepromatous leprosy patients, but it is found in a minority of patients, it is not specific to M. leprae, and can occur with cells from normal donors.

Responsiveness to live M. tuberculosis, and common antigens, of sonicate-stimulated T cell lines from normal donors.

Live mycobacteria are more efficient vaccines against mycobacterial disease than killed ones. A possible explanation is the existence of important protective antigens released by live bacilli, which are not present in any significant quantity in dead ones. Conversely, internal mycobacterial antigens may be irrelevant to protection if not released by live bacilli. We show here, using T cell lines derived by limiting dilution from the peripheral blood of normal donors stimulated with sonicated BCG, that a variable percentage of sonicate responsive T cells is unable to respond to live M. tuberculosis. The possibility that such lines have an immunopathological, rather than protective role, is discussed.