Outpatient parenteral antimicrobial therapy is safe and effective for the treatment of infective endocarditis: a retrospective cohort study.

BACKGROUND: Outpatient parenteral antibiotic therapy has been shown to be efficacious, safe and cost-effective for a variety of infections. The data from managing infective endocarditis (IE) with hospital in the home (HITH) are limited. We evaluated the safety and outcomes of patients with IE treated with HITH at our centre. AIMS: To evaluate the safety, efficacy and 1-year outcomes of patients with IE treated under HITH at our centre over 9 years. METHOD: A retrospective analysis of the clinical outcomes of all cases of IE treated with HITH at a tertiary referral centre was undertaken for patients treated between June 2002 and July 2011 (9 years). Outcome measures included clinical cure, readmission rate, relapses and 1-year mortality. RESULTS: Sixty-eight cases of IE were treated with HITH over the study period, including 29 native valve infections, 24 prosthetic valve infections, 12 pacemaker lead infections, 1 defibrillator lead infection, 1 myocardial wall infection and 1 aortic graft infection. Thirteen cases had valve replacement surgery and 12 cases had removal of infected pacemaker leads. Staphylococcus aureus (18 cases), Coagulase-negative staphylococcus (10 cases) and viridians-group streptococcus (18 cases) were the most common pathogens. Median duration of antimicrobial therapy with HITH was 24 days (range 4 to 42 days). There were three readmissions during antimicrobial therapy with HITH. Two patients relapsed. There were two deaths and one patient was lost to follow up. One-year survival was 96% (65/68). CONCLUSION: Outpatient antimicrobial therapy with HITH is safe and effective in carefully selected cases of IE.

Crusted scabies: clinical and immunological findings in seventy-eight patients and a review of the literature.

OBJECTIVES: To describe the clinical and immunological features of crusted scabies in a prospectively ascertained cohort of 78 patients. METHODS: All patients requiring inpatient treatment for crusted scabies in the 'top end' of the northern territory of Australia over a 10 year period were prospectively identified. Demographics, risk factors, and immunological parameters were retrospectively compiled from their medical records and pathology databases. RESULTS: More than half the patients with crusted scabies had identifiable immunosuppressive risk factors. Eosinophilia and elevated IgE levels occurred in 58% and 96% of patients, respectively, with median IgE levels 17 times the upper limit of normal. Seventeen percent had a history of leprosy but 42% had no identifiable risk factors. There was a decrease in mortality after the introduction of a treatment protocol consisting of multiple doses of ivermectin combined with topical scabicides and keratolytic therapy. CONCLUSIONS: Crusted scabies often occurs in patients with identifiable immunosuppressive risk factors. In patients without such risk factors, it is possible that the crusted response to infection results from a tendency to preferentially mount a Th2 response. The treatment regime described was associated with a reduction in mortality. This is the largest reported case series of crusted scabies.

Characterisation of a myofibroblast-like cell line from an angiosarcoma.

We have isolated a cell line (ASMM) by serial passage of cells from explant cultures of an angiosarcoma resected from the calf of a 62 year old female. ASMM has been in continuous culture for over eighteen months (>150 population doublings) and has a Fibroblast-like morphology with a doubling time of approximately 72 h. ASMM has a normal diploid karyology and is unable to generate tumors in nude mice or produce colonies in soft agar. Examination of the cytoskeletal proteins shows both desmin and vimentin and a low level of alpha-smooth muscle actin, which can be upregulated by treatment with TGF beta. Low levels of basal VCAM-1 are significantly upregulated with TNF alpha and reduced by the presence of TCF beta. Basal ICAM-1 is also upregulated with TNF alpha and we show an additional upregulation through TGF beta. ASMM expresses high levels of the hyaluronate receptor CD44, including the variant exons 6, 8 and 10. In addition, ASMM synthesises high levels of hyaluronate (HA), as did the original tumor. Unlike human umbilical vein endothelial cells (HUVECs) these cells were unable to generate capillary-like tubes when seeded onto basement membrane gels, and generated cords of cells containing many synthetic organelles and intermediate filaments. We were unable to detect the expression of factor VIII-related antigen, von Willebrand factor (vWF), CD31 or CD34, and were not able to induce expression of E-selectin after TNF alpha stimulation. In conclusion, this cell line represents a partially transformed population of cells which show characteristics consistent with myofibroblast-like cells. The production of high levels of HA and expression of CD44 may help to explain the high degree of agressiveness of the tumor from which ASMM was derived, as these molecules have been shown to play a role in cell motility and adhesion.

Ivermectin for Sarcoptes scabiei hyperinfestation.

OBJECTIVES: Crusted (Norwegian) scabies is an unusual variant of scabies caused by hyperinfestation with Sarcoptes scabiei. It has high morbidity, and secondary bacterial skin sepsis may result in life-threatening bacteremia. An open label study of oral ivermectin was carried out in patients with crusted scabies refractory to topical therapy. METHODS: Patients with refractory crusted scabies were prescribed oral ivermectin, one to three doses of 200 mg/kg at 14-day intervals, combined with topical scabicide and keratolytic therapy. RESULTS: Of the 20 patients who received ivermectin, 8 had a complete initial clinical response, a partial response was achieved in 9, and minimal improvement occurred in 3. Three doses of ivermectin were curative for 8 of 10 cases, but recurrence of scabies from presumed reinfestation occurred in at least half of these. CONCLUSION: The authors conclude that ivermectin is effective for crusted scabies; however, multiple doses may be required to achieve a cure, and recurrence 6 or more weeks after completing treatment is common.

Neurologic disorders are prevalent in HIV-positive outpatients in the Asia-Pacific region.

BACKGROUND: A total of 8.3 million HIV-positive people live in the Asia-Pacific region. The burden of HIV-associated neurocognitive impairment and symptomatic sensory neuropathy in this region is unknown. METHODS: Between July 2005 and March 2006, we undertook a cross-sectional study at 10 sentinel sites within eight Asia-Pacific countries to determine the prevalence of moderate to severe HIV-related neurocognitive impairment and symptomatic sensory neuropathy. We clinically assessed and administered sensitive neuropsychological and peripheral neuropathy screening tools to 658 patients infected with HIV. Univariate and logistic regression analyses were applied to the data. RESULTS: The results showed that 76 patients (11.7%) (95% CI 9.3-14.2) were significantly neurocognitively impaired, 235 patients (36.4%) (95% CI 32.7-40.2) were depressed, and 126 patients (19.7%) (95% CI 16.6-22.8) had either definite or probable symptomatic sensory neuropathy; 63% of this last group had exposure to stavudine, didanosine, or zalcitabine. Several potential confounders including depression (OR 1.49, 95% CI 0.88-2.51, p = 0.11) and prior CNS AIDS illness (OR 1.28, 95% CI 0.50-2.89, p = 0.54) were not significantly associated with neurocognitive impairment. CONCLUSIONS: A total of 12% of patients had moderate to severe HIV-related neurocognitive impairment, 20% of patients had symptomatic sensory neuropathy, and 36% of patients had evidence of depression. This study provides a broad regional estimate of the burden of HIV-related neurologic disease and depression in the Asia-Pacific region.

Prior antiretroviral therapy experience protects against zidovudine-related anaemia.

OBJECTIVE: We investigated the use of antiretroviral therapy regimens containing zidovudine or stavudine, using data from the TREAT Asia HIV Observational Database (TAHOD), a multicentre, prospective, observational study of an HIV-infected cohort in the Asia-Pacific Region. METHODS: A proportional hazards regression analysis of factors associated with the time to discontinuation of initial regimens containing zidovudine or stavudine and a logistic regression analysis to identify factors associated with a diagnosis of anaemia within 6 months of commencement of zidovudine in initial or subsequent regimens were performed. RESULTS: Patients who started zidovudine were more likely to stop within the first 9 months of treatment than those who started on stavudine; the reverse was true after 9 months. Anaemia (haemoglobin

Chromobacterium violaceum in tropical northern Australia.

Chromobacterium violaceum is an unusual cause of infection which may have fatality rates of over 60% when systemic illness occurs. We describe four patients infected with this organism who were successfully treated at Royal Darwin Hospital between 1991 and 1996. In tropical Australia, C. violaceum infection should be considered along with melioidosis in patients who present with a septic illness with skin lesions and/or organ abscesses after exposure to soil in the wet season.

Evaluation of PCR for diagnosis of melioidosis.

Previously published PCR-based diagnostic tests for melioidosis were evaluated for clinical usefulness. A Burkholderia pseudomallei 16S rRNA-derived primer set had a sensitivity approaching 100% for clinical samples from 22 culture-confirmed cases of melioidosis and enabled diagnosis of 3 culture-negative cases. However, samples from 10 of 30 inpatients from Royal Darwin Hospital with other diagnoses were positive by PCR, giving a specificity of 67% and a positive predictive value of only 70%. Although there are a number of intriguing possible explanations for our results, concerns of inappropriate therapy resulting from a positive result by PCR have led us to forgo the advantage of rapid PCR diagnosis for melioidosis until a better system is validated.

Endemic melioidosis in tropical northern Australia: a 10-year prospective study and review of the literature.

In a prospective study of melioidosis in northern Australia, 252 cases were found over 10 years. Of these, 46% were bacteremic, and 49 (19%) patients died. Despite administration of ceftazidime or carbapenems, mortality was 86% (43 of 50 patients) among those with septic shock. Pneumonia accounted for 127 presentations (50%) and genitourinary infections for 37 (15%), with 35 men (18%) having prostatic abscesses. Other presentations included skin abscesses (32 patients; 13%), osteomyelitis and/or septic arthritis (9; 4%), soft tissue abscesses (10; 4%), and encephalomyelitis (10; 4%). Risk factors included diabetes (37%), excessive alcohol intake (39%), chronic lung disease (27%), chronic renal disease (10%), and consumption of kava (8%). Only 1 death occurred among the 51 patients (20%) with no risk factors (relative risk, 0.08; 95% confidence interval, 0.01-0.58). Intensive therapy with ceftazidime or carbapenems, followed by at least 3 months of eradication therapy with trimethoprim-sulfamethoxazole, was associated with decreased mortality. Strategies are needed to decrease the high mortality with melioidosis septic shock. Preliminary data on granulocyte colony-stimulating factor therapy are very encouraging.