Doxycycline therapy for leptospirosis. Weekly epirubicin versus doxorubicin as second line therapy in advanced breast cancer. A randomized clinical trial. Use of doxycycline for leptospirosis after high-risk exposure in São Paulo, Brazil.
To study antibiotic efficacy, 29 patients with leptospirosis were treated in a randomized, double-blinded fashion with doxycycline, 100 mg orally twice a day, or placebo. Therapy was given for 7 days in a hospital, and patients were followed for 3 weeks afterwards. Duration of illness before therapy and severity of illness were the same in both groups. Doxycycline reduced the duration of illness by 2 days and favorably affected fever, malaise, headache, and myalgias. Treatment prevented leptospiruria and had no adverse effects. Doxycycline is effective in therapy for patients with leptospirosis. Forty-nine patients with advanced breast cancer who had failed from first-line cyclophosphamide, methotrexate, and 5-fluorouracil (CMF regimen) chemotherapy, were randomized to treatment with either epirubicin (Epi) or doxorubicin (Dox) at a dose of 20 mg/m2 given intravenously (i.v.) weekly to compare the efficacy and toxicity of these two anthracyclines given in such a schedule. Of 43 evaluable patients 36% (eight of 22) treated with Epi and 38% (eight of 21) treated with Dox achieved a complete plus partial response rate (95% confidence limits 16-56% +/- 20% and 18-58% +/- 20%, respectively). Patients who obtained a major therapeutic response to previous CMF exhibited a significantly higher response rate with both the drugs: seven of eight (87.5%) compared with one of 13 (8%); p less than 0.05 for Epi and six of seven (86%) compared with two of 15 (13%); p less than 0.05 for Dox. The median duration of response was 4.5 months with Epi compared with 7 months with Dox, and the median survival of the two groups of patients were superimposable (12 months with Epi versus 11 months with Dox). The median cumulative dose was 220 mg/m2 (range 160-620) and 240 mg/m2 (range 160-860) for Epi and Dox, respectively. Gastrointestinal and hematological toxicities were moderate for both the drugs, with fewer episodes of nausea and vomiting, stomatitis, and leukopenia following Epi administration. A very low incidence of alopecia was recorded for both the drugs. Regarding cardiac evaluation, no significant differences were evident; however, the only case that developed symptomatic congestive heart failure was in the Dox arm, after a cumulative dose of 820 mg/m2 at 11.5 months. Epi given weekly at low doses preserves efficacy in the treatment of patients with advanced breast cancer, and given at equimolar doses, has a slightly better therapeutic index than the parent compound. A clinical trial pilot study, double-blinded, randomized, and controlled with a placebo to assess the effectiveness of oral doxycycline (200 mg, single dose) in preventing leptospirosis after high exposure to potentially contaminated water was performed in São Paulo, SP, Brazil. Confirmed cases were defined as those with leptospira IgM antibody and symptoms; asymptomatic cases were those presenting with IgM antibodies but no symptoms; and suspected cases were individuals with symptoms but no IgM antibody. Forty subjects were given doxycycline and 42 were given placebo. In the drug-treated group there were 2 confirmed cases, 11 asymptomatic cases, and 6 suspected cases. In the placebo group there were 5 confirmed, 6 symptomatic, and 5 suspected cases. Even though we found a protective association of doxycycline for confirmed leptospirosis cases (RR = 2.3) and seroconversion only (RR = 2.0), the association was not statistically significant because of the small number of individuals enrolled in this pilot study. We observed that the 22% of the volunteers already had IgM antibodies to leptospirosis at the first sampling. Finally, the attack rate to confirmed, asymptomatic, and suspected cases of Leptospirosis was 8.5%, 22%, and 13%, respectively, in this population.
Regular use of weekly oral doxycycline 200 mg increases the odds for nausea and vomiting with unclear benefit in reducing Leptospira seroconversion or clinical consequences of infection.