Treatment of Human Brucellosis with Netilmicin and Doxycycline

Abstract

We conducted a prospective, noncomparative, multicenter study to assess the safety and efficacy of doxycycline and netilmicin in the treatment of human brucellosis. The study included 64 patients who had acute brucellosis without endocarditis or neurobrucellosis. The treatment schedule consisted of the administration of 100 mg of doxycycline (or 5 mg/[kg.d] if body weight < or = 40 kg) twice a day orally for 45 days, plus 300 mg of netilmicin (6 mg/[kg.d] if body weight < or = 50 kg) intramuscularly once daily for 7 days. Therapeutic failure was noted in 5 patients (7.7%; 95% confidence interval [CI], 2.5%-17.1%), of whom 2 had spondylitis, 1 had sacroiliitis, and 1 had a splenic abscess that required splenectomy. Relapse was noted in eight patients (12.5%; 95% CI, 5.6%-23.2%). When relapse was considered in combination with initial lack of efficacy, 13 patients (21.9%; 95% CI, 12.3%-33.9%) failed to respond to therapy. Fifteen patients (23%; 95% CI, 13.5%-35.2%) had adverse effects, and one patient (1.5%) had a treatment-limiting adverse effect. Combination therapy with netilmicin/doxycycline may be effective in treating acute brucellosis. However, prospective controlled trials must confirm these results.

A Foodborne Outbreak of Brucellosis at a Police Station Cafeteria, Lima, Peru

“…6,[24][25][26][27][28] It is known that patients with Brucella infection may well be asymptomatic despite being proven by culture to be bacteremic. 29,30 Nonetheless, our present report reinforces the need for active surveillance and contact tracing after apparent point source outbreaks given the subclinical or early cases that are not identified in a timely manner because of non-specific symptoms. This outbreak also reinforces the need to consider different cultural issues regarding potential food point exposures in brucellosis transmission.…”

Use of Aminoglycosides in Treatment of Infections Due to Intracellular Bacteria

“…Thus, combination therapy has been advocated, including the two gold standard regimens currently recommended by the WHO, i.e., the combination of doxycycline with either streptomycin or rifampin for at least 6 weeks (160). More recently, gentamicin and netilmicin have been used as alternatives to streptomycin, with promising results (158,159). The combination of doxycycline plus streptomycin has been found to be superior to that of doxycycline plus rifampin (10,32,160,161), with 0 to 8% relapses with the former regimen versus 5 to 17% with the latter (79,160).…”

New complex Ad vectors incorporating both rtTA and tTS deliver tightly regulated transgene expression both in vitro and in vivo

“…In addition, well-characterized and safe inducers of the system (tetracycline and doxycycline) are available. 4,5,16 Two types of Tetregulatable systems, Tet-Off and Tet-On, have been developed, and both have been successfully used to regulate transgene expression in established cell lines and transgenic animals. 4 Previously, we described a strategy to combine both the transactivator and the transgene expression cassettes on a single vector backbone, as this arrangement has advantages in both uniform delivery of regulatable expression and in the reduced production costs.…”

“…13 Our vector delivered high levels of FasL-GFP activity that could be regulated by doxycycline, which is a widely accepted analog of tetracycline with a good safety profile in humans and an ability to regulate both tTA and rtTA with high specificity. [14][15][16] However, the extent of regulation achievable with our vector was limited to a range of between 20-and 70-fold (depending on the cell line), due to the low but significant background activity of the TRE promoter. 17 This activity, normally selected against in established cell lines and transgenic animals, has been reported in numerous transient expression studies.…”