Updates
By Carol A. Kemper, MD, FACP
KS Fails to Respond to Cidofovir
Source: J Infect Dis. 2003;187:149-153.
Anecdotal reports have suggested that KS, which is believed to be, in part, due to the presence of human herpes virus 8, may respond to antiherpes drugs. Cidofovir, which is one of the most active agents in vitro against HHV-8, was administered to 7 patients with severe KS. Five of the patients had HIV-related KS and 2 had classical KS (6 of the patients had 50 or more lesions). Sadly, all 7 patients had progression of their disease at a median of 2 months of therapy (range, 5-27 weeks). No decrease in HHV-8 viral load was detected in peripheral blood mononuclear cells. Progression of disease occurred in the 5 patients with HIV/AIDS despite that fact that the several had fairly high CD4 cell counts (mean CD4 count, 214 cells/mm3 with a range of 66-1041), and 4 were receiving highly active antiretroviral therapy.
Acyclovir & Renal Dysfunction
Source: Vomiero G, et al. Pediatr Nephrol. 2002;17:633-637.
Historically, acyclovir has been reported to precipitate renal impairment in up to 16% of patients, although more recent clinical experience suggests that, with adequate hydration, this problem occurs far less frequently. Investigators at the Children’s Hospital of Eastern Ontario had an unusually negative experience in 17 pediatric patients (aged 1-14) who received a combination of high-dose ceftriaxone and acyclovir for meningo-encephalitis. In retrospective analysis, 12 patients (70%) developed renal insufficiency, 3 of whom (17.6%) developed acute renal failure. The degree of renal impairment was associated with the higher acyclovir dosages. Urinalyses were consistent with a tubular proteinuria pattern, and renal biopsy in a single patient showed a tubular toxic picture. Vomiero and associates speculate that the combination of the 2 agents may somehow potentiate the renal toxicity of acyclovir.
Broad-Range Bacterial PCR in Meningitis
Source: Saravolatz LD, et al. Clin Infect Dis. 2003;36:40-45.
DNA amplification techniques may significantly enhance our ability to quickly diagnosis bacterial meningitis. Using a broad-range primer sequence for bacterial 16s RNA, which is highly conserved, Saravolatz and colleagues examined the specificity and sensitivity of a polymerase chain reaction (PCR) assay for the diagnosis of meningitis in 74 cerebrospinal fluid specimens obtained from 70 patients. Fifteen patients had positive culture results, and 2 patients had positive Gram staining but negative cultures. Positive CSF cultures included a broad range of organisms, including S epidermidis (5), S pneumoniae, Group B strep (2), Neisseria meningitidis (1), and Gram-negative bacilli (5). PCR was positive in all 17 cases with direct microbial findings, as well as 1 of 57 of the remaining cases.
Based on these results, both the sensitivity (100%) and specificity (98.2%) of the assay are very high; the positive predictive value was 94.4% and the negative predictive value was 100%. Given this negative predictive value, Saravolatz et al suggest that the administration of antibiotic therapy could be safely avoided or discontinued more quickly in patients with negative PCRs, although more clinical experience is needed. Also, while the results of this assay could theoretically be available in hours and could improve clinical decision-making, few hospitals have the capability to perform PCRs in-house. Unfortunately, send-out tests always take longer and, in my experience, often delay clinical decisions.
Why is BCG Less Virulent than MTb?
Source: Lewis KN, et al. J Infect Dis. 2003;187:117-123.
The genetic mutational basis of TB vaccine bacille Calmette-Guerin (BCG) has remained a mystery for years. Ever since Calmette described the organism, which is naturally attenuated, researchers have attempted to determine the genetic difference between it and MTb. Attention has focused on RD1, a single 9.5-kb region of DNA, which is present in all MTb strains but absent in all BCG strains. After deletion of this region from a strain of MTb (MTb:RD1), bacterial growth and cytotoxicity was assessed in human peripheral blood monocyte-derived macrophages. The growth of MTb:?RD1 in cell monolayers over a 7-day period was similar to BCG controls, in contrast with intact MTb strains, which destroyed > 80% of the cell monolayer. In addition, MTb:RD1 and BCG grew similarly slow in mice receiving aerosol challenge. Interestingly, although the bacterial burden in mice was ultimately similar for both attenuated and virulent strains, the degree of inflammation and granuloma formation in lung tissue was significantly less with the attenuated strains. Despite similar bacterial burdens, only 2 of 15 mice challenged with virulent MTb were still alive at week 39, compared with all 18 mice challenged with MTb:RD1. These data suggest that RD1 either directly or indirectly—by controlling other genes—is essential to MTb virulence. What RD1 actually does is now the mystery.
KS Fails to Respond to Cidofovir; Acyclovir & Renal Dysfunction; Broad-Range Bacterial PCR in Meningitis; Why is BCG Less Virulent than MTb?.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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