Biomedical subjects
Publications and source records attributed to E Martínez-Alfaro.
We describe the case of a prosthetic valve endocarditis in a 72-year-old woman. Corynebacterium striatum was isolated in the blood samples. This organism has been described in a few cases of native valve endocarditis, but this is the first case reported of prosthetic valve endocarditis.
Epididymoorchitis is a focal form of human brucellosis described in 2%-20% of patients with brucellosis. We assessed 59 cases of Brucella epididymoorchitis (BEO) between 1991 and 1999. The median age of patients was 34 years (range, 15-75 years). The onset of symptoms was acute in 46 patients (78%). Scrotal pain and swelling (100% of patients), fever (88%), and sweating (73%) were the most common symptoms. Brucella species was isolated from blood cultures in 41 patients (69%) and from epididymal aspiration in 4 patients. Treatment consisted of a combination of a doxycycline and an aminoglycoside (n=39) or rifampin (n=10); trimethoprim-sulfamethoxazole with rifampin (n=3); or trimethoprim-sulfamethoxazole as monotherapy (n=7). The median duration of therapy was 45 days (range, 21-90 days). The infections of 9 patients (15%) failed to respond to therapy, and 15 patients relapsed (25%). Three patients with necrotizing orchitis whose infections were unresponsive to antibiotics required an orchiectomy. In general, classical brucellosis therapy is adequate for BEO.
Ten patients with brucellosis were treated with azithromycin and gentamicin to assess the treatment's safety and efficacy. Seven patients had an excellent therapeutic response at the end of therapy; however, relapse was noted in 3. When relapse was considered in combination with an initial lack of efficacy, 5 patients (50%; 95% confidence interval, 18.7%-81.3%) did not respond to therapy; these results do not favor the use of azithromycin to treat brucellosis in humans.
Thirty-five patients aged 14-74 years (average, 54 years) who had brucellar spondylitis were treated between January 1991 and December 1997. The time from onset of symptoms to diagnosis of spondylitis ranged from 1 week to 8 months (median, 9 weeks). Back or neck pain (100% of patients), fever (66%), and constitutional symptoms (57%) were the most common symptoms. Cultures of blood specimens from 26 patients (74%) were positive for Brucella melitensis. The duration of antimicrobial therapy (median, 120 days; range, 45-535 days) varied according to clinical response and the presence of epidural and paravertebral masses. One of the 35 patients underwent surgical treatment of a spinal epidural abscess. Therapy failed for 9 patients (26%; 95% confidence interval [CI], 12%-43%), and 5 (14%; 95% CI, 5%-30%) had a relapse. There were no deaths or severe sequelae in this study. Brucellar spondylitis causes considerable suffering and absenteeism from work, but long-term clinical responses are favorable.
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Demographic, clinical, and laboratory data from 200 consecutive patients with acute brucellosis were analysed with univariate and multivariate methods to identify correlates of relapse. A risk score for predicting relapse was then calculated by using Cox proportional hazard model. The independent predictors of relapse were temperature of 38.3 degrees C or higher, positive blood cultures at baseline, and the duration of symptoms before treatment <10 days. Stratification according to the risk score demonstrated that rates of relapse were significantly different between risk groups (P<0.0001). The low-risk group had a 4.5% probability (6 of 135) of relapse at 12 months. In contrast, relapse was present in 15 of 47 patients in the medium-risk group (P<0.0017); and in 12 of 18 patients in the high-risk group (P<0.0001). This study provides a rational basis for estimating the risk of relapse in patients with acute brucellosis, and may be helpful in deciding what subjects might benefit from extra attention.
We report the case of a patient with Brucella melitensis osteomyelitis involving non-joint prosthetic implant of the femur. This is the first case published of osteomyelitis by Brucella sp. in a patient with prosthetic implant in bone and the second one with both intra- or extra-articular prosthetic bone implant. Brucella melitensis is a rare organism which causes osteomyelitis in patients with prosthetic hardware, and should be added to the list of suspected organisms responsible for this disease, especially in endemic areas of brucellosis.
The objective of the present prospective, noncomparative, multicenter study was assess the safety and efficacy of gentamicin and doxycycline therapy for human brucellosis. In the first part of the study, a cohort of 17 patients received 100 mg of doxycycline (or 50 mg/kg of body weight per day if the body weight was < 40 kg) orally every 12 h for 45 days (cohort 1). In the second part of the study a subsequent cohort of 35 patients was treated with doxycycline at the same dosage for 30 days (cohort 2). All patients were treated intramuscularly with gentamicin at 240 mg (or 5 mg/kg per day if the body weight was < 50 kg) once daily for the first 7 days. Both cohorts showed a favorable response during therapy, and there were no therapeutic failures. Relapse was noted in 1 (5.9%; 95% confidence interval [95% CI], 0.15 to 28.7%) of the 17 patients in cohort 1 and in 8 (22.9%; 95% CI, 10.4 to 40.1%) of the 35 patients in cohort 2. Nineteen patients (36.5%; 95% CI, 23.6 to 51.0%) had adverse effects, with no differences between cohorts, and no patients had a treatment-limiting adverse effect. The study indicates that the combination of doxycycline for 45 days and gentamicin for 7 days is an effective and well-tolerated therapy for human brucellosis. The relapse rates obtained with doxycycline treatment for 30 days appear to be higher than those obtained with doxycycline treatment for 45 days.
Brucellosis (infection with Brucella spp.) is a common zoonosis in many parts of the world. Human brucellosis is a multisystem disease that may present with a broad spectrum of clinical manifestations. Treatment of brucellosis must effectively control acute illness and prevent complications and relapse. The choice of regimen and duration of antimicrobial therapy should be based on the presence of focal disease and underlying conditions which contraindicate certain specific antibiotics. The regimen of first choice is combination therapy with doxycycline for 45 days and streptomycin for 14 days. Gentamicin or netilmicin for the first 7 days may be substituted for streptomycin. Second-choice regimens consist of combinations of doxycycline and rifampicin (rifampin) for 45 days, or monotherapy with doxycycline for 45 days. Surgery should be considered for patients with endocarditis, cerebral or epidural abscess, spleen abscess or other abscesses which are antibiotic-resistant. Tetracyclines are generally contraindicated for pregnant patients and children < 8 years old. Rifampicin 900 mg once daily for 6 weeks is considered the drug of choice for treating brucellosis in pregnant women. In children < 8 years old the preferred regimen is rifampicin with cotrimoxazole (trimethoprim-sulfamethoxazole) for 45 days. An alternative regimen consists of a combination of rifampicin for 45 days with gentamicin 5 to 6 mg/kg/day for the first 5 days.
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.
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Brucellosis is a common zoonosis in many parts of the world; the best regimen for the treatment of brucellosis has not been clearly determined. We have carried out a multicenter, open, controlled trial in five general hospitals in Spain to compare the efficacy and safety of doxycycline and rifampin (DR) versus doxycycline and streptomycin (DS) for the treatment of human brucellosis. The study included 194 ambulatory or hospitalized patients with acute brucellosis, without endocarditis or neurobrucellosis. The diagnostic criterion was isolation of Brucella species from blood or other tissues (n = 120) or a standard tube agglutination titer of 1/160 or more for anti-Brucella antibodies with compatible clinical findings (n = 74). Patients were randomly assigned to receive either 100 mg of doxycycline twice daily plus rifampin, 900 mg/day, in a single morning dose for 45 days (DR group) or the same dose of doxycycline for 45 days plus streptomycin, 1 g/day, intramuscularly for 14 days (DS group). A lack of therapeutic efficacy developed in 8 of the 100 patients in the DR group (8%) and in 2 of the 94 patients in the DS group (2%)(P = 0.10). Relapses occurred in 16 of the 100 patients in the DR group (16%) but in only 5 of the 94 patients in the DS group (5.3%) (P = 0.02). When relapse was considered in combination with initial lack of efficacy, 26 patients in the DR group (24%) and 7 patients in the DS group (7.45%) failed to respond to therapy (P = 0.0016). In general, therapy was well tolerated and only four patients (4%) in the DR group and two (2%) in the DS group had episodes of adverse effects necessitating discontinuation of treatment (P> 0.2). We conclude that a doxycycline-and-rifampin regimen is less effective than the doxycycline-and-streptomycin regimen in patients with acute brucellosis.
BACKGROUND: The aim of this study was to determine whether a conclusion could be obtained through meta-analysis of the published trials on the relative efficacy of rifampicin and doxycycline versus streptomycin and doxycycline or another tetracycline (SD). METHODS: The comparative and randomized trials identified by a search in the reference data base MEDLINE from 1967 to 1992 and through manual review of the articles cited in these studies or other reviews were included. The evaluation of quality was performed by a standardized scale. The differences in efficacy were expressed as odds ratio and the results were contrasted by the Mantel-Haenszel method. Heterogenicity was graphically analyzed by the Woolf method with an adjustment being made for small subgroups. The confidence intervals were calculated for each trial and for the combined data by the Cornfield method. RESULTS: Six trials including 581 patients of whom 544 were considered evaluable were analyzed. In the RD treatment group 261 (242 valid) patients were included with 268 (253 valid) being included in the SD group. Five cases of initial therapeutic failure were observed in each group without significant differences. The secondary effects described were very variable. Nonetheless no secondary effects obliging discontinuation of treatment were presented in the RD group with only one in the SD group with no differences between the two groups. Recurrences were presented in 5% and 39% in the RD group and in 0 and 17% in the SD group. In total 37 (16%) in the former group and 13 (5%) in the latter group. The Mantel-Haenszel odds ratio with respect to recurrence was 3.81 (CI 95%, 1.82-8.17; p = 0.00009). The total number of cures was 196 (81%) in the RD group and 232 (92%) in the SD group (Mantel-Haenszel odds ratio 0.36; CI 95%, 1.19-0.64; p = 0.0004). The inclusion of the quality index of the trials did not modify the statistical significance achieved. CONCLUSIONS: In human brucellosis the treatment of rifampicin and doxycycline presents a greater number of recurrence and lower number of cure than the classical treatment with streptomycin and tetracycline drugs.
BACKGROUND: The aim of this study was to determine the risk of active tuberculosis in intravenous drug addict (IVDA) patients seropositive and seronegative for the HIV. METHODS: A retrospective study of a cohort of IVDA males in 2 drug addict detoxication communities was carried out. Patients with tuberculosis, under treatment or chemoprophylaxis for tuberculosis and those with a stay of less than 3 months were excluded. Patients included underwent a serologic study to detect antibodies versus HIV and a Mantoux test with 2 U. PPDRT23. Subjects who were HIV+ with a Mantoux test < 5 mm were given a delayed cutaneous sensitivity test with 7 antigens. The incidence index of tuberculosis was studied. Logistic regression analysis was performed to evaluate the relative risk of tuberculosis in HIV+ controlled by other variables (having been in prison, previous liver disease, country of origin, age, length of IVDA and length of follow up). RESULTS: Of the 198 patients admitted 132 were included. Forty-seven were HIV+ and 85 HIV-. Fourteen of the former (30%) and 44 of the latter (51%) had a positive reaction to the Mantoux test (OR 0.4; confidence interval 95% 0.18-0.92; p < 0.05). Eight seropositive (17%) patients with a negative Mantoux test presented anergia to the delayed cutaneous sensitivity tests. After a mean follow up of 12.0 +/- 9.0 months, 4 patients out of the 47 HIV+ (8.5% or 6.93 cases/100 individuals/year; CI 95% 0.13-13.72) presented tuberculosis versus none of the 85 HIV- (p < 0.05) patients. Of the 4 patients diagnosed of tuberculosis, the initial reaction to the Mantoux test was negative in 2 (one pulmonary and the other milliar tuberculosis). Two of the 4 patients diagnosed of tuberculosis died. CONCLUSIONS: The risk of active tuberculosis is specially high in HIV seropositive intravenous drug addicts. The response to the Mantoux test has little sensitivity for demonstration of tuberculous infection in HIV seropositive patients.
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