Late initiation of HAART among HIV-infected patients in Spain is frequent and related to a higher rate of virological failure but not to immigrant status.

PURPOSE: To determine whether immigrant status is associated with late initiation of highly active antiretroviral treatment (HAART) and/or poor response to antiretrovirals. METHODS: GESIDA 5808 is a multicenter, retrospective cohort study (inclusion period January 2005 through December 2006) of treatment-naïve patients initiating HAART that compares HIV-infected patients who are immigrants with Spanish-born patients. A late starter (LS) was defined as any patient starting HAART with a CD4+ lymphocyte count <200 cells/µL and/or diagnosis of an AIDS-defining illness before or at the start of therapy. The primary endpoint was time to treatment failure (TTF), defined as virological failure (VF), death, opportunistic infection, treatment discontinuation/switch (D/S), or missing patient. Secondary endpoints were time to treatment failure as observed data (TTO; censoring missing patients) and time to virological failure (TVF; censoring missing patients and D/S not due to VF). RESULTS: LS accounted for 56% of the patients. Lower educational and socioeconomic level and intravenous drug use (IVDU) were associated with categorization as LS, but immigrant status was not. Cox regression analysis (hazard ratio [HR]; 95% CI) between LS and non-LS patients showed no differences in TTF (0.97; 0.78-1.20) or TTO (1.18; 0.88-1.58), although it did reveal a difference in TVF (1.97; 1.18-3.29). CD4+ lymphocyte recovery was equivalent for both LS and non-LS patients (159 vs 173). CONCLUSIONS: In our cohort, immigrant status was not shown to be related to late initiation of HAART. Although LS patients did not have a longer TTF for any reason, TVF was significantly shorter. Despite universal free access to HAART in Spain, measures to ensure early diagnosis and treatment of HIV infection are necessary.

Epididymoorchitis due to Brucella mellitensis: a retrospective study of 59 patients.

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.

Recognition and optimum treatment of brucellosis.

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.

Vertebral osteomyelitis caused by Streptococcus agalactiae.

Streptococcus agalactiae is a rare cause of vertebral osteomyelitis. We present four cases of spondylitis caused by this micro-organism and a review of 20 cases previously described in the literature. Only seven patients (29%) were under 50 years of age. Diabetes mellitus and neoplasms were the most frequent underlying conditions, although 37.5% of the patients did not have any predisposition. Neck or back pain was the most common symptom. Diagnosis depended mainly on magnetic resonance imaging. Blood cultures were positive in 50% of the patients. The duration of antibiotic therapy was 6 weeks for most patients. The outcome was favourable, with none of the patients suffering serious sequelae.

Brucellar osteomyelitis involving prosthetic extra-articular hardware.

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.

Multivariate model for predicting relapse in human brucellosis.

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.

Corynebacterium striatum first reported case of prosthetic valve endocarditis.

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.

[Meta-analysis of the efficacy of the combination of +rifampicin and doxycycline in the treatment of human brucellosis]. / Metaanálisis sobre la eficacia de la combinación de rifampicina y doxiciclina en el tratamiento de la brucelosis humana.

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.

[Risk of tuberculosis in parenteral drug addicts with human immunodeficiency virus seropositivity. A cohort study in detoxication communities]. / Riesgo de tuberculosis en adictos a drogas por vía parenteral seropositivos frente al virus de la inmunodeficiencia humana. Un estudio de cohortes en comunidades para deshabituación de toxicómanos.

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.

[Compliance, tolerance and effectiveness of a short chemoprophylaxis regimen for the treatment of tuberculosis]. / Cumplimentación, tolerancia y eficacia de una pauta corta de quimioprofilaxis para el tratamiento de la tuberculosis.

OBJECTIVE: To evaluate compliance, side effects and the efficacy of a short course of chemoprophylaxis for tuberculosis with isoniazid plus rifampin during 3 months, compared with the classic course of isoniazid for 9 months. PATIENTS AND METHODS: Prospective, comparative, randomized and open study of patients with the suitable criteria for chemoprophylaxis, in accordance with the guidelines of the Centers for Disease Control of 1990. Patients were divided into 2 groups: the group of isoniazid plus rifampin, received isoniazid (300 mg per day) plus rifampin (600 mg per day) for 3 months, and the group of isoniazid, that received isoniazid at a dose of 300 mg per day for 9 months. RESULTS: 238 patients were included, of which 42 refused chemoprophylaxis. Of the remaining 196 patients, 98 were included in each group. Both groups were comparable at base level. The side effects, neither light nor severe showed significant differences. The appearance of adverse effects obliged the suspension of treatment in 7 patients in group isoniazid and of 9 patients in group isoniazid plus rifampin. Three patients in group isoniazid plus rifampin and 11 in group isoniazid stopped treatment (OR 4.14, 95% CI 1.02-19.45; p = 0.04). Efficacy was comparable in the two groups; only one case of tuberculosis was detected in a patient who gave up chemoprophylaxis at day 30. CONCLUSIONS: Tolerance in group isoniazid plus rifampin compared with group I was similar. Compliance was better in the short-term group with a lower percentage of abandonment. On comparing, both groups have shown similar efficacy in preventing the appearance of tuberculosis.

[Estimation of surgical wound infection rates using a post-hospital surveillance program]. / Estimación de las tasas de infección de herida quirúrgica mediante un programa de vigilancia tras el alta hospitalaria.

BACKGROUND: The decrease in the time spent in hospital of patients who have undergone surgery lessens wound observation time, and thus could underestimate the true rates of surgical wound infection (SWI). The aim of this study was to assess the use of a programme to detect SWI, by carrying out a control 30 days after patients have been discharged from hospital. PATIENTS AND METHODS: A study of a prospective cohort of 2,015 patients who were operated in 6 surgical services at a general hospital, was carried out to detect the incidence of SWI. The control at one month after discharge from hospital was done through a telephone survey using a specific questionnaire. RESULTS: SWI incidence was observed in 134 patients (6.7%), 38% of which were detected on the month after discharge from hospital. In the postoperatory control the major SWI rates were detected in the clean procedures and in the clean-contaminated procedures with 46% and 37%, respectively. The telephone interview enabled contact with 72.3% of the patients intervened. CONCLUSIONS: The post-discharge control of patients who have undergone surgery enabled the detection of more than a third of SWI cases. The telephone interview system has been effective in our study as a postdischarge method of the localization of patients.

[Evaluation of 2 tuberculosis chemoprophylaxis regimens in patients infected with human immunodeficiency virus. The GECMEI Group]. / Evaluación de dos pautas de quimioprofilaxis tuberculosa en pacientes infectados por el virus de la inmunodeficiencia humana. Grupo GECMEI.

OBJECTIVE: To assess the compliance, tolerance and efficacy of a short chemoprophylaxis regimen (IR) for tuberculosis using isoniazid (INH) plus rifampin (RIF) during 3 months versus a standard regimen (I) of isoniazid during 12 months in HIV positive patients. MATERIAL AND METHODS: Prospective, comparative, randomized and open clinical trial in four general hospitals and one prison hospital of Castilla-La Mancha. Prophylaxis was administered to PPD-positive patients and to anergic patients according to the CDC recommendations (1991). Patients were randomized in two treatment groups: regimen IR, isoniazid 300 mg daily and rifampin 600 mg daily; regimen I, isoniazid 300 mg during 12 months. RESULTS: 133 patients were included, 64 to regimen I and 69 to regimen IR. Regimen IR had a better tolerance with a 28% of adverse effects versus 55% in regimen I. Hepatotoxicity was more frequent in regimen I with a RR = 2.2 (CI 95% 1.23-4.01). Severe hepatotoxicity leading to treatment withdrawal was related to drug administration time and was more frequent in the 12 months regimen group. Short regimen showed a better compliance, without significant differences. Tuberculosis incidence rate was a 4.23 cases/100 persons--year for regimen I and 2.08 in regimen IR, with a relative risk for developing tuberculosis with regimen IR group of 0.51 (CI 95% 0.09-2.8) versus regimen I group, without statistical significance. Prison stay was associated to a significant risk for tuberculosis, regardless of both regimens (RR = 9.2 CI 95%, 1.06-80.2). CONCLUSIONS: In HIV-infected patients with PPD(+) or anergic, regimen with IR is at least as effective as regimen I for preventing the development of tuberculous disease, and has less adverse effects.

[Vertebral osteomyelitis: description of a series of 103 cases and identification of predictive variables of the etiological group]. / Osteomielitis vertebral: descripción de una serie de 103 casos e identificación de variables predictivas del grupo etiológico.

BACKGROUND: Vertebral osteomyelitis (VO) is an infrequent disease that requires early antibiotic treatment to prevent serious disabling sequels. The aim of our study was to identify clinical variables capable to guide the initial treatment. PATIENTS AND METHODS: Our retrospective study involved 103 patients seen during a 13 years period, mostly (94%) diagnosed by magnetic resonance imaging. Patients were classified as having brucellar (50 patients), pyogenic (29 patients), tuberculous (20 patients), and other (4 patients) spondylitis. Clinical and laboratory variables entered into a multivariate analysis to identify those independently associated with each etiologic subgroup. RESULTS: Brucellar spondylitis was associated with epidemiological exposure (LR+: 14,9; LR-: 0,02), and with a blood neutrofil percentage < or = 65% (LR+: 6,6; LR-: 0,12). The presence of an underlying chronic disease (LR+: 29,5; LR-: 0,01), an erythrocyte sedimentation rate > or = 60 mm/h (LR+: 11,3; LR-: 0,07), and the absence of constitutional symptoms (LR+: 5,2; LR-: 0,18), were independent predictors of a pyogenic spondylitis. Finally, previous exposure or tuberculous disease (LR+: 11,2; LR-: 0,06), and a delay of > or = 8 weeks in first consulting (LR+: 10,6; LR-: 0,07) were associated with tuberculous spondylitis. CONCLUSION: The combination of a few clinical and laboratory variables facilitates the differential diagnosis between pyogenic, brucellar and tuberculous vertebral osteomyelitis, allowing the choice of the initial antibiotic treatment.

[Clinical trial comparing efficacy and safety of four highly active antiretroviral therapy (HAART) in antiretroviral-naive treatment with advanced HIV infection]. / Ensayo clínico comparativo de eficacia y seguridad de cuatro pautas de tratamiento antirretroviral de alta eficacia (TARGA) en pacientes naive con infección por VIH avanzada.

BACKGROUND: Comparison of efficacy and safety of four highly active antiretroviral therapy regimens (HAART) including two nucleoside analogues (NA) and a protease inhibitor (PI) in HIV positive patients with advanced infection and antiretroviral naive. PATIENTS AND METHODS: Multicenter, randomized and open labeled clinical trial in ten community hospitals of Castilla-La Mancha and Madrid. Regimen 1 contains zidovudine (AZT), lamivudine (3TC) and indinavir (IDV) regimen 2 includes AZT, 3TC and ritonavir (RTV), regimen 3 was didanosine (DDI), estavudine (D4T) and IDV, and regimen 4 included DDI, D4T and RTV. Decrease in viral load of HIV (VC) has been assessed as primary endpoint and as secondary one, the increase of the numbers of CD4 lymphocytes, percentage of disease progression, adverse reactions and adherence. Measurements were made at baseline visit and at 6, 12, 24, 36 and 48 weeks. RESULTS: A total of 98 patients with a mean baseline CD4 count of 122 x 10(6)/l (range of 5-340) and a baseline viral load of 5.1 log copies/ml were included. At 48 weeks, a mean increase of the CD4 and decrease of the viral load without significant difference between the 4 regimens (103 cells/2.62 log in regimen 1; 169 cells/2.86 log in regimen 2; 171 cells/2.56 log in regimen 3 and 141 cells/1.71 log in regimen 4) were observed in the analysis of the patients in treatment. Treatment was discontinued due to adverse reactions: 24% in regimen 1, 48% in regimen 2, 26% in regimen 3 and 32% in regimen 4, without significant difference. Analyzing by PI groups, 41% of the patients with RTV and 25% of those with IDV discontinued treatment due to adverse effects. There was withdrawal from treatment due to disease progression in 7% of the RTV patients and in 9% of IDV patients. CONCLUSIONS: In the HIV positive patients with advanced infection, efficacy between the four regimens of HAART is similar, but there is a tendency to require more withdrawal due to adverse effects in the RTV group than in those of IDV, the two used as single PI.

Brucellar spondylitis: review of 35 cases and literature survey.

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.

Azithromycin and gentamicin therapy for the treatment of humans with brucellosis.

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.

Treatment of human brucellosis with netilmicin and doxycycline.

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.