Incidence of catheter-related infections within 30 days from insertion of Hickman-Broviac catheters.

AIM: To evaluate the incidence of surgical site infections and bacteremias occurring within 30 days from insertion of partially implanted central venous catheters. PATIENTS AND METHODS: Four hundred eighteen devices positioned in children with cancer or undergoing bone marrow transplant were followed prospectively. RESULTS: During a follow-up of 12,394 catheter-days, a total of 13 infectious episodes were documented, with an overall incidence of 3.1% and 1.05 episodes/1,000 catheter-days. Coagulase-negative staphylococci represented the causative pathogens of all episodes. Overall, surgical wound infections occurred in 1.4% of all catheters, with a rate of 0.48/1,000 catheter-days, while isolated bacteremias were observed in 1.7% of all inserted devices, with a rate of 0.57/1,000 catheter-days. CONCLUSIONS: Infections are rare events within 30 days from insertion of partially implanted central venous catheters and coagulase-negative staphylococci represent the most frequently isolated cause of these complications.

Aspergillus galactomannan enzyme-linked immunosorbent assay cross-reactivity caused by invasive Geotrichum capitatum.

We report three cases of invasive Geotrichum capitatum infection in patients with acute leukemia for which an enzyme-linked immunosorbent assay (ELISA) for Aspergillus galactomannan was positive, with no evidence of aspergillosis. Supernatants obtained from suspensions of 17 G. capitatum strains gave positive reactions with the Aspergillus galactomannan ELISA. These clinical and laboratory data seem to suggest that G. capitatum produces a soluble antigen that is cross-reactive with Aspergillus galactomannan.

Intracranial aspergillosis in children successfully treated with antifungal therapy and surgical intervention.

Invasive aspergillosis is an uncommon but often lethal complication in immunocompromised patients. Despite the progress obtained with new antifungal drugs, intracranial aspergillosis often requires a combined medical and surgical approach. Most cases previously reported in immunocompromised children were fatal. We describe 4 immunosuppressed children with intracranial aspergillosis successfully treated with surgery and antifungal long-term therapy.

Zidovudine administration during pregnancy and mitochondrial disease in the offspring.

Prophylactic administration of zidovudine (ZDV) to mother-child pairs reduces HIV transmission. ZDV can impair mitochondrial (mt) DNA polymerase gamma, leading to mtDNA depletion. Signs of mitochondrial dysfunction have been observed in a few children with prenatal exposure to nucleoside analogues, although no mtDNA depletion was demonstrated. Other studies failed to confirm mitochondrial disorders in children who were exposed to antiretroviral agents in utero. A child, whose HIV-infected mother received ZDV from the fourth month of pregnancy, developed neonatal encephalomyopathy, anaemia and hyperlactataemia. At 2 weeks of age, a muscle biopsy exhibited red-ragged-like fibres, proliferation of abnormal mitochondria and a 90% depletion of mtDNA without qualitative abnormalities. At 6 months, the depletion was less profound (about 50% of normal values). Severe psychomotor delay and visual disturbances persisted at 30 months, but they were greatly reduced at 5-year follow-up. These laboratory and clinical findings clearly demonstrated that mtDNA alteration was acquired and not consequent to an inherited disorder. Fetal exposure to ZDV may have caused the mtDNA depletion, which, although temporary, led to irreversible but not progressive brain damage.

The human 26S proteasome is a target of antiretroviral agents.

BACKGROUND: Proteasomes constitute the degradative machinery of the ubiquitin/adenosine triphosphate-dependent proteolytic pathway, which is involved in many cell functions, including immune response and apoptosis, and in HIV maturation and infectivity. OBJECTIVE: To examine whether proteasomes are targeted by antiretroviral agents. METHODS: Chymotrypsin-like, trypsin-like and peptidyl-glutamyl-peptide hydrolysing activities of purified human 26S and 20S proteasomes, the latter depleted or enriched in 11S regulator, were assayed after incubation with indinavir, lamivudine and zidovudine at 1-80 microM alone and in combination. To assess the drug effects on cellular functions regulated by proteasomes, the accumulation of ubiquitin-tagged proteins, the processing of the nuclear factor kappa B precursor p105, and the degradation of the inhibitor of nuclear factor kappa B, isoform alpha (IkappaBalpha) were evaluated by Western immunoblotting in Jurkat cells after incubation for 6 h with the drugs above. RESULTS: Trypsin-like and mostly chymotrypsin-like activities of purified 26S proteasome were inhibited by each drug from 10 to 80 microM, more by double combinations and mostly by the triple combination. The peptidyl-glutamyl-peptide hydrolysing activity of the 26S proteasome and the three peptidase activities of the 20S proteasome, depleted or enriched in 11S regulator, were unaffected. The accumulation of ubiquitin-tagged proteins, reduced IkappaBalpha degradation and p105 processing were appreciable in intact cells with the triple drug combination. CONCLUSION: The human 26S proteasome is a target of antiretroviral agents. This suggests that the antiviral action and some clinical and immunological benefits of combined antiretroviral therapy rely not only on its known effects on viral enzymes, but also on host cell components.