Factors predictive of relapse in adult bacterial osteomyelitis of long bones.

BACKGROUND: Osteomyelitis is a difficult-to-cure infection with a high relapse rate despite combined medical and surgical therapies. Some severity factors, duration of antimicrobial therapy and type of surgical procedure might influence osteomyelitis relapse. METHODS: 116 patients with osteomyelitis were followed for ≥1 year after hospital discharge. Demographic, microbiological and clinical data, eight severity factors and treatment (surgical and antibiotic) were analyzed. RESULTS: Mean age was 53 years and 74.1% were men. Tibia (62.1%) and S. aureus (58.5%) were the most commonly involved bone and bacteria, respectively. Mean follow-up was 67.1 months. Forty-six patients underwent bone debridement, 61 debridement plus flap coverage and 9 antimicrobial therapy only. Twenty-six patients (22.4%) relapsed, at a mean of 11.2 months since hospital discharge. Duration > 3 months (p = 0.025), number of severity factors (P = 0.02) and absence of surgery (P = 0.004) were associated with osteomyelitis relapse in the univariate analysis. In the Cox regression analysis, osteomyelitis duration > 3 months (P = 0.012), bone exposure (P = 0.0003) and type of surgery (P < 0.0001) were associated with relapse. Regarding the surgical modalities, bone debridement with muscle flap was associated with better osteomyelitis outcomes, as compared with no surgery (P < 0.0001) and debridement only (P = 0.004). CONCLUSIONS: Osteomyelitis extending for > 3 months, bone exposure and treatment other than surgical debridement with muscular flap are risk factors for osteomyelitis relapse.

Factors associated with long-term CD4 cell recovery in HIV-infected patients on successful antiretroviral therapy.

OBJECTIVES: The aim of the study was to study the factors associated with immunological recovery in HIV-infected patients with suppressed viral load. METHODS: Nadir and current CD4 cell counts were recorded in 821 patients, as well as many demographic, epidemiological, lifestyle, clinical, therapeutic, genetic, laboratory, liver fibrosis and viral hepatitis parameters. RESULTS: The median age of the patients was 44.4 years [interquartile range (IQR) 40.3-48.0 years], the median time since HIV diagnosis was 15.3 years (IQR 10.5-18.9 years), the median time of suppressed viral load was 7.0 years (IQR 4.0-10.0 years) and the median time on the current antiretroviral regimen was 2.8 years (IQR 1.4-4.7 years). The median nadir and current CD4 counts were 193.0 (IQR 84.0-301.0) and 522.0 (IQR 361.0-760) cells/µL, respectively, separated by a median period of 10.2 years (IQR 5.9-12.9 years). The median CD4 count gain during follow-up was 317.0 (IQR 173.0-508.0) cells/µL. Many variables were associated with CD4 cell gains in univariate analyses, including age, gender, epidemiology, prior clinical conditions, fibrosis stage, transient elastometry, aspartate aminotransferase (AST), nadir CD4 count and hepatitis B and C virus infections and genotypes, as well as the durations of follow-up since nadir CD4 count, overall antiretroviral treatment, current antiretroviral regimen, protease inhibitor therapy and suppression of viral load. Multivariate analysis revealed that longer duration of HIV suppression (P < 0.0001), more advanced clinical Centers for Disease Control and Prevention (CDC) stages (P < 0.0001), younger age (P = 0.0003), hepatitis C virus genotypes 1 and 4 (P = 0.003), sexual acquisition of HIV (P = 0.004), and lower transient elastometry values (P = 0.03) were independent predictors of CD4 cell gains. Overall, the model accounted for 14.2% of the variability in CD4 count. CONCLUSIONS: In addition to the duration of HIV suppression, HIV-related diseases, HIV epidemiology, age, hepatitis C virus genotypes, and liver fibrosis were independently associated with long-term immunological recovery.

Early lipid changes with atazanavir/ritonavir or darunavir/ritonavir.

OBJECTIVES: Ritonavir-boosted atazanavir and darunavir are protease inhibitors that are recommended for initial treatment of HIV infection because each has shown better lipid effects and overall tolerability than ritonavir-boosted lopinavir. The extent to which lipid effects and overall tolerability differ between treatments with atazanavir and darunavir and whether atazanavir-induced hyperbilirubinaemia may result in more favourable metabolic effects are issues that remain to be resolved. METHODS: A 96-week randomized clinical trial was carried out. The primary endpoint was change in total cholesterol at 24 weeks. Secondary endpoints were changes in lipids other than total cholesterol, insulin sensitivity, total bilirubin, estimated glomerular filtration rate, and CD4 and CD8 cell counts, and the proportion of patients with plasma HIV RNA < 50 HIV-1 RNA copies/mL and study drug discontinuation because of adverse effects at 24 weeks. Analyses were intent-to-treat. RESULTS: One hundred and seventy-eight patients received once-daily treatment with either atazanavir/ritonavir (n = 90) or darunavir/ritonavir (n = 88) plus tenofovir/emtricitabine. At 24 weeks, mean total cholesterol had increased by 7.26 and 11.47 mg/dL in the atazanavir/ritonavir and darunavir/ritonavir arms, respectively [estimated difference -4.21 mg/dL; 95% confidence interval (CI) -12.11 to +3.69 mg/dL; P = 0.75]. However, the ratio of total to high-density lipoprotein (HDL) cholesterol tended to show a greater decrease with atazanavir/ritonavir compared with darunavir/ritonavir (estimated difference -1.02; 95% CI -2.35 to +0.13; P = 0.07). Total bilirubin significantly increased with atazanavir/ritonavir (estimated difference +1.87 mg/dL; 95% CI +1.58 to +2.16 mg/dL; P < 0.01), but bilirubin changes were not associated with lipid changes. Secondary endpoints other than total bilirubin were not significantly different between arms. CONCLUSIONS: Atazanavir/ritonavir and darunavir/ritonavir plus tenofovir/emtricitabine did not show significant differences in total cholesterol change or overall tolerability at 24 weeks. However, there was a trend towards a lower total to HDL cholesterol ratio with atazanavir/ritonavir and this effect was unrelated to bilirubin.

Didanosine (ddI) associates with increased liver fibrosis in adult HIV-HCV coinfected patients.

The role of exposure to antiretrovirals (ARV) and serum matrix metalloproteases (MMPs) on liver fibrosis (LF) progression in human immunodeficiency virus (HIV) mono or HIV- hepatitis C virus (HCV) coinfection is unclear. Thus, 213 Caucasian adult HIV-infected patients were studied, 111 of whom had HCV-coinfection and 68 were HCV-monoinfected. Patients with ethanol consumption >50 g/day, hepatitis B coinfection, non-infective liver diseases or HAART adherence <75% were excluded. LF was assessed by transient elastometry (TE, Fibroscan). Serum levels of MMPs (MMP -1,-2,-3,-8,-9,-10 and -13) and their tissue inhibitors (TIMP-1,-2 and -4) were measured by ELISA microarrays. Associations with LF were statistically analysed. Protease inhibitors, usually administered to patients with advanced LF were excluded from the analysis. Increased LF was significantly associated with d4T (P = 0.006) and didanosine (ddI) use (P = 0.007), months on d4T (P = 0.001) and on ARV (P = 0.025), duration of HIV (P < 0.0001) and HCV infections (P < 0.0001), higher HIV (P = 0.03) and HCV loads (P < 0.0001), presence of lipodystrophy (P = 0.02), male gender (P = 0.02), older age (P = 0.04), low nadir (P = 0.02) and current CD4(+) T-cells (P < 0.0001), low gain of CD4(+) T-cells after HAART (P = 0.01) and higher MMP-2 (P = 0.02) and TIMP-2 serum levels (P = 0.02). By logistic regression the only variables significantly associated with increased LF were: use of ddI (OR 8.77, 95% CI: 2.36-32.26; P = 0.005), male gender (OR 7.75, 95% CI: 2.33-25.64, P = 0.0008), HCV viral load (in log) (OR 3.53, 95% CI: 2.16-5.77; P < 0.0001) and age (in years) (OR 1.21, 95% CI: 1.09-1.34, P = 0.0003). We conclude that only higher HCV viral load, older age, male gender, and use of ddI associated independently with increased LF in our study.

Evaluation of the possible influence of hepatitis C virus and liver fibrosis on HIV type 1 immunological and virological outcomes.

OBJECTIVES: The aim of the study was to evaluate the possible effect of hepatitis C virus (HCV) coinfection on the viroimmunological outcomes of HIV-1 infection. METHODS: A cross-sectional study of 805 patients with active HCV infection receiving or not receiving antiretroviral therapy (ART) was carried out. RESULTS: A number of parameters were significantly associated with undetectable HIV-1 viral load in univariate analyses, such as age, toxic habits, CD4 cell count, liver test results, HCV viral load and ART. However, only current ART (P<0.0001), CD4 cell count (P<0.0001), age (P=0.004) and current injecting drug use (P=0.02) were independently associated with undetectable viral load in multivariate analysis. None of the many HCV- and liver fibrosis-related parameters analysed showed a significant association with HIV-1 viral load or CD4 cell count in multivariate analyses, with the exception of the annual fibrosis progression index which almost reached statistical significance in the subgroup of ART-untreated patients (P=0.06) and was inversely predictive of CD4 cell count in the whole group (P=0.007). However, its relative weight was modest, as it only explained 0.8% of the total variability in CD4 cell count. CONCLUSIONS: HCV-related parameters did not significantly affect virological and immunological outcomes of HIV-1 infection in ART-treated and untreated patients. In contrast, liver fibrosis, as measured using the annual fibrosis progression index, was inversely associated with CD4 cell count, although its weight was relatively small. Therefore, HCV- and liver fibrosis-related factors do not seem appreciably to influence these outcomes from a practical viewpoint in ART-naïve patients, nor impair CD4 and HIV-1 viral load responses to ART.

Effect of simplification from protease inhibitors to boosted atazanavir-based regimens in real-life conditions.

BACKGROUND: Atazanavir (ATV) boosted with ritonavir (ATV/r) is a potent, well-tolerated, once-daily protease inhibitor (PI). Few data are available on this agent as a treatment simplification option for patients taking other PIs. OBJECTIVE: The aim of the study was to determine the effectiveness and safety of ATV-containing regimens in patients who have simplified their antiretroviral treatment. METHODS: SIMPATAZ was a multicentre, prospective, noninterventional study in patients who had undetectable HIV RNA on their current PI-containing therapy and who were switched to an ATV/r-based regimen. Patients underwent a routine physical examination, and data were collected on HIV RNA levels, CD4 cell counts, liver function, lipid parameters, adverse reactions, adherence to treatment and patient satisfaction. RESULTS: A total of 183 patients were enrolled in the study and included in the analysis (80% were male, 29% had AIDS, and 52% were coinfected with HIV and hepatitis B virus or hepatitis C virus). The median baseline CD4 count was 514 cells/µL. Median exposure to previous HIV therapy was 8 years, and 32% of patients had a history of PI failures. Lopinavir boosted with ritonavir was the most frequent PI replaced (62%) and tenofovir+lamivudine /emtricitabine the backbone most used during the study (29%). The study drug was discontinued early by 25 patients (14%), two of whom discontinued as a result of adverse events (Hodgkin lymphoma and vomiting). Two patients died (lung cancer and myocardial infarction). At month 12, 93% of the study population had an undetectable HIV RNA viral load. Hyperbilirubinaemia >3 mg/dL and increased alanine aminotransferase levels>200 IU/L were observed in 38.5% and 4.4% of patients, respectively. Median changes from baseline to month 12 in total cholesterol, triglycerides and low-density lipoprotein cholesterol were -13 mg/dL (-7%; P<0.0001), -19 mg/dL (-13%; P<0.0001) and -7 mg/dL (-6%; P=0.021), respectively. CONCLUSIONS: In a real-world setting, switching from other PIs to ATV/r is a well-tolerated and safe option for improving the lipid profile and for retaining virological response in controlled pretreated patients.

Association of HIV transmission categories with sociodemographic, viroimmunological and clinical parameters of HIV-infected patients.

To analyse sociodemographic, viroimmunological and clinical parameters in different HIV-transmission categories at baseline and during treatment, 3039 patients were followed up for 12 months after the initiation of a nelfinavir-based regimen. Multiple baseline parameters were significantly different in the diverse categories, including CD4 counts (P<0.0001) and viral load (P=0.02). There were differences in the groups regarding the CD4 response (P=0.01), but not the virological response (P=0.4), to therapy over time. Multivariate analyses revealed that transmission categories were significantly related to baseline CD4 counts (P=0.01), viral load at 12 months (P=0.0006), poorer adherence to therapy of injecting drug users (IDUs) vs. each of the other groups (P<0.001) and failure to complete the 12-month evaluation of IDU vs. heterosexual (P=0.003) and men who have sex with men (MSM) groups (P=0.02). We conclude that transmission categories had a significant influence on several baseline parameters and viroimmunological outcomes following highly active antiretroviral therapy (HAART), as well as on adherence to therapy and to medical appointments.

Multidrug-resistant Acinetobacter meningitis in neurosurgical patients with intraventricular catheters: assessment of different treatments.

BACKGROUND: The treatment of multidrug-resistant Acinetobacter baumannii meningitis is a serious therapeutic problem due to the limited penetration of antibiotics into the CSF. We describe the clinical features and the outcome of a group of patients with nosocomial neurosurgical meningitis treated with different therapeutic options. METHODS: All patients with nosocomial post-surgical meningitis due to A. baumannii diagnosed between 1990 and 2004 were retrospectively reviewed. RESULTS: During the period of study, 51 cases of this nosocomial infection were identified. Twenty-seven patients were treated with intravenous (iv) monotherapy: carbapenems (21 cases), ampicillin/sulbactam (4 cases) and other antibiotics (2 cases). Four patients were treated with iv combination therapy. Nineteen patients were treated with iv and intrathecal regimens: colistin by both routes (8 cases), carbapenems plus iv and intrathecal (4 cases) or only intrathecal (5 cases) aminoglycosides, and others (2 cases). Seventeen patients died due to the infection. One patient died without treatment. The mean (SD) duration of therapy was 17.4 (8.3) days (range 3-44). Although no patients treated with colistin died, we did not observe statistically significant differences in the mortality among the groups with different treatments. CONCLUSIONS: Nosocomial Acinetobacter meningitis has a high mortality. Combined therapy with iv and intrathecal colistin is a useful and safe option in the treatment of nosocomial Acinetobacter meningitis.

Bacterial osteomyelitis: microbiological, clinical, therapeutic, and evolutive characteristics of 344 episodes.

OBJECTIVE: Osteomyelitis is a difficult-to-cure infection, with high relapse rate despite adequate therapy. Large published osteomyelitis series in adults are rare. METHODS: A total of 344 adult osteomyelitis patients were studied and followed > 12 months after hospital discharge. Demographic, microbiological, clinical, therapeutic and outcome data were analyzed. RESULTS: Mean age was 52.5 ± 18.3 years and 233 (67.7%) were male. Main osteomyelitis types were post-surgical (31.1%), post-traumatic (26.2%) and hematogenous (23%). Tibia (24.1%) and femur (21.8%), and methicillin-susceptible S. aureus (29.6%) were the most commonly involved bone and bacteria, respectively. Median follow-up was 12.0 (IQR 0-48) months. Inflammatory markers were increased in 73.6%. Overall, patients were treated by IV and oral routes with one (IV: 44.5%, oral: 26.7%), two (IV: 30.1%, oral: 21.8%) or ≥ 2 (IV: 15.2%, oral: 6.1%) antibiotics. Median duration on IV/oral antimicrobials was 28.0 (IQR 24-28) and 19.5 (IQR 4-56) days, respectively. Anti-staphylococcal ß-lactams cloxacillin/cefazolin (19.2%) and ciprofloxacin (5.5%) were the most frequently used IV and orally, respectively. Overall 234 (68.0%) underwent surgery, 113 (32.8%) debridement, 97 (27.4%) debridement + muscle flap and 24 (7%) amputation. At the end of follow-up 208 patients (60.6%) did not have relapsed. Operated patients had significantly less relapses (p<0.0001). A total of 23 (6.7%) died, 11 (3.2%) by infectious complications and 48 (14%) were lost in the follow-up. CONCLUSIONS: Osteomyelitis is due to different causes complicating its therapy. Risk factors or causal microorganism could influence its treatment and outcome. Aggressive surgery along with adequate antimicrobial therapy are mandatory for cure.

Acute-subacute lead poisoning. Clinical findings and comparative study of diagnostic tests.

A prospective study of an epidemic outbreak of acute lead poisoning characterized by unusual clinical and analytic manifestations was carried out. Its source was traced to lead-contaminated flour. Thirty-two adult patients presented with classic clinical symptoms of saturnism; however, 13 severely poisoned patients simultaneously manifested unusual clinical features such as hemolytic anemia and multiorgan dysfunction. We compared the diagnostic value of the different toxicity markers in 68 of 136 adults exposed to lead. Porphyrin precursors, urine levels of lead, and results from an edetic acid-provocative test gave poor diagnostic information and low correlation values with lead levels in blood. However, erythrocyte delta-aminolevulinic acid dehydratase activity showed a closer correlation with lead levels in blood, although we observed a frequent overlap of results in severe cases. The test for levels of lead in blood was the most reliable, suitable, and simplest test performed, and gave the best correlation with the external dose of lead, the clinical situation, and the toxicologic effects described by 12 different analytic data.

Cytomegalovirus antigenemia surveillance in the treatment of cytomegalovirus disease in AIDS patients.

OBJECTIVE: Surveillance of quantitative cytomegalovirus (CMV) antigenemia among AIDS patients with CMV treated complications in order to determine its value in assessing the response to treatment and survival. METHODS: A longitudinal follow-up of antigenemia measurement at diagnosis, after induction therapy with ganciclovir or foscarnet, and every 3 months during maintenance therapy was carried out in 25 patients with CMV retinitis and in 8 with extraocular CMV disease. Positive antigenemia was defined as the presence of any amount of immunofluorescent pp65-positive leukocytes/10(5) cells. RESULTS: Mean antigenemia values were: 77+/-148/10(5) leukocytes at retinitis diagnosis; 45+/-114 after induction therapy; and 7+/-18 and 1.5+/-4 after 6 months and one year of therapy, respectively. Patients achieving undetectable antigenemia increased from 44% at baseline to 68% at postinduction and 80% during follow-up. Seven patients (28%) who remained free of relapses presented significant minor baseline antigenemias and became negative after induction therapy. Patients with extraocular disease showed erratic antigenemia values and absent therapeutic response. CMV blood cultures before and after induction therapy were positive in 39% and 21% of patients, respectively. Kaplan-Meier analysis revealed a significantly longer survival for patients with retinitis when compared to those with extraocular complications, and for patients with negative antigenemia after induction in comparison with those who failed to achieve it. CONCLUSIONS: Low basal antigenemia and antigenemia clearance after induction therapy are variables directly related to good response to treatment and survival. Continuous surveillance of antigenemia during treatment could permit designing of individual strategies to obtain a better response.

[Use of aminopenicillins: first cause of error in the prescription of antimicrobial agents at a hospital]. / El uso de aminopenicilinas: primera causa de error en la prescripción de antimicrobianos dentro de un hospital.

The patterns of use and quality of prescription of ampicillin and amoxycillin (A/A) as compared with the rest of antimicrobials (AM) was evaluated by means of the review of the therapeutic sheets of 4572 admitted patients, in coincidence with 5 calculations of prevalence in a university hospital. 25.7% of patients received AM. These were used in 865 instances, and 6% were disqualified. A/A participated in 57% of these errors (p = 0.002 as related with the rest of AM). 309 patients received AM as prophylactic drugs, and 70% of them did not comply with the standard rules. The election of A/A for prophylaxis was associated with 71% of these errors (p less than 0.0001). Nine out of every 10 prophylactic administrations of A/A were abnormal owing to incorrect indication (77%), dosage (10%), oral route (62%) or excessive duration (82%). The high prevalence of prescription of aminopenicillins (30%) was associated with 68% of the errors in the use of AM, owing, among other reasons, to the high resistance rates of the major recovered organisms excluding enterococci. The nonjustified overuse of aminopenicillins was the leading detected problem; it can be managed by a restrictive antibiotic policy and educational measures oriented to an adequate medical prescription.

[Trends observed in the use of antimicrobial agents at a Spanish hospital from 1986 and 1991]. / Tendencias registradas en el empleo de antimicrobianos en un hospital español entre 1986 y 1991.

BACKGROUND: The recent introduction of new antimicrobials allows important changes in the controversial field of their prescription. Longitudinal analysis of the quality and tendencies of the use of antibiotics constitutes one of the basic tools for adapting antibiotic policy. METHODS: This study was undertaken in a university hospital with antibiotic policy plans and institutional protocols of antibiotic prophylaxis. The use of antimicrobials with prophylactic and therapeutic aims has been analyzed by 12 prevalence studies over 6 years in a sample equivalent to 10.2% of the population admitted. A comparison between the first three counts (1986-1987) and the last three (1990-1991) was performed. RESULTS: A mean of 26.6% of the patients admitted used antibiotics. Nonetheless, while its use as treatment grew with progressive deterioration in the quality of use, its use for prophylaxis decreased and improved. Parallel, the use of restricted antibiotics grew from 12 to 19%. The comparison of the habits of prescription between the onset and the end of the study showed the following important changes: decrease in the use of aminopenicillins and cotrimoxazole and increase in the use of first and third generation cephalosporins, antifungal drugs, tobramycin, vancomycin, the group of urinary antiseptics and quinolones and the miscellaneous group of antimicrobials of minor use. CONCLUSIONS: Antibiotics for therapy have been used more and worse, despite the restrictive barriers. The control methods have been effective in prophylaxis with the exception of its excessive prolongation which remains the principal problem. Changes have been registered in the pattern of use of antibiotics in favor of new more effective drugs against multiresistant flora.

[Replication indexes of the human immunodeficiency virus: predictive value of viral culture and blood antigens]. / Indices de replicación del virus de la inmunodeficiencia humana: valor predictivo de los cultivos virales y de la antigenemia.

BACKGROUND: To investigate the relation between markers of load and replication of the HIV [viral culture in plasma and in mononuclear cells of peripheral blood (MCPB) and antigen p24 (p24Ag) with the number of CD4+ cells and the prognosis of the patients. METHODS: A retrospective study was performed in 188 patients who were analyzed and followed over a mean period of 431 days. The criteria of clinical progression (AIDS related complex, and new opportunistic infections), immunologic progression (CD4+ < 0.1 and < 0.05 + 10(9)/l) and death. Cocultures of HIV in free plasma and in MCPB were performed with the detection of complete AgHIV in the supernatant of the culture being used for analysis. Circulating p24Ag was determined by an ELISA technique without previous dissociation of the immunocomplexes. RESULTS: HIV cultures in plasma, in MCPB and p24Ag were positive in 27, 48 and 33% of the patients, respectively. The sensitivity of the indexes increased in agreement with the clinical progression of the patients and was inversely proportional to the depletion of the CD4+ lymphocytes (79% of the patients with CD4+ lymphocytes < 0.05 x 10(9)/l presented positive HIV culture in plasma). Viremia in plasma and to a lesser measure p24Ag correlated with variables recognized as bad prognosis and were found to be predictive of unfavorable evolution. Multivariate analysis demonstrated that pertenence to a symptomatic group and the presentation of a number of CD4+ lymphocytes of less than 0.2 x 10(9)/l were independent factors associated to the positivity of the viral culture in plasma and p24Ag. The culture positive in MCPB was principally related with the volume of blood analyzed. The risk of death was 6.38 fold greater in the presence of a positive plasma culture and 2.02 fold greater in the presence of positive p24Ag. In contrast, the unquantified positive HIV culture in MCPB showed no statistical significance in relation with patient survival. CONCLUSIONS: Positive HIV culture in plasma was the greatest prognostic index in patients with a number of CD4+ lymphocytes less than 0.2 x 10(9)/l. Unquantified cell culture had no predictive significance. To establish the prognosis of patients, the indexes of viral replication should not be used in isolation.

[Hospital infection caused by enterococci. The previous use of antibiotics as risk factors in a case-control study]. / Infección hospitalaria por enterococos. El uso previo de antibióticos como factor de riesgo a través de un estudio de casos y controles.

BACKGROUND: Nosocomial infection by enterococci is of growing importance and recognition. The risk factors, morbidity and prognosis of the same were investigated by a case and control study in a third level university hospital. METHODS: One hundred patients with nosocomial infection by enterococci were compared with 100 randomly selected control patients with non enterococcic nosocomial infection. Cases and controls were taken from a series of 10,926 patients examined in search of nosocomial infection by successive cut offs of prevalence. RESULTS: The prevalence of nosocomial infection by enterococci was found to be 9.9 per 1,000 admissions. Analysis among cases and controls by the odds ratio indicated a positive association for nosocomial infection by enterococci for the following risk factors: male sex (1.8), receipt of intensive care (3.6), predisposing diseases (3.1), urinary catheter (3), abdominal-genital surgery (2.4) or nephro-urologic surgery (4.6), other previous infections (1.9) and previous exposure to antibiotics (3.7), mainly aminoglucosides (4.2). Urinary infections and those of the surgical wound predominated, 15 patients had bacteremia, with mortality related with infection being 2%, preinfection hospital stay was 34.7 days and the mean stay was of 8.3 days but these data were not statistically different in the control group. The enterococcic infections were most frequently polymicrobian (odds ratio 5.5) received worse antibiotic coverage (5.1) and presented greater number of therapeutic failures or recurrences (2.5). CONCLUSIONS: Nosocomial infection by enterococci is relatively frequent and virulent. The risk factors identified in this study are in agreement with those found in most series. The previous use of aminoglucosides was specially capable of selecting enterococci but only 13% demonstrated high level resistance to gentamicin.

[Antiphospholipid antibodies in human immunodeficiency virus infection]. / Anticuerpos antifosfolípido en la infección por el virus de la inmunodeficiencia humana.

BACKGROUND: The frequency, clinical significance and prognosis of the lupic anticoagulant and the anticardiolipin antibodies were analyzed in patients with the human immunodeficiency virus infection. METHODS: A group of 34 consecutive patients seropositive to HIV with lupic anticoagulant was studied in relation with 75 seropositive subjects without circulating anticoagulant and a control group of plasma of 23 seronegative individuals. The lengthening of thromboplastin time (relation > 1.3) was used as a screening test. The anticardiolipin antibodies IgG were studied by commercial enzymoimmunoassay. RESULTS: Lupic anticoagulant was detected in 21% of the patients with AIDS and in 3% of the seropositive patients without AIDS. The anticoagulant was found in 13 of 53 cases with tuberculosis, in 8 of 57 with pneumonia by Pneumocystis carinii, in 4 of 32 with bacteremia and in 3 out of 8 with lymphoma. In another six patients other minor processes and/or HIV seropositivity were coexistent. Thrombosis was not seen in any case, and the rate of thrombocytopenia (18%) was that to be expected in this population. The patients with anticoagulant had a greater prevalence to developing AIDS, opportunistic infections and tuberculosis with respect to the seropositive group without anticoagulant, however, no differences were observed in the prevalence and levels of anticardiolipin antibodies and other nonspecific autoimmune phenomena. Periodic follow up of the patients with anticoagulant demonstrated persistence of the anticoagulant in 31% and reappearance of the same in 23% with new infections. CONCLUSIONS: No correlation was found between the different antiphospholipid antibodies in the patient infected by the human immunodeficiency virus. Low titers of anticardiolipin antibodies are indicative of disease progression.

[Infectious endocarditis of the native valve: its epidemiological profile and an analysis of its mortality between the years 1984 and 1993]. / Endocarditis infecciosa sobre válvula natural: perfil epidemiológico y análisis de la mortalidad entre los años 1984 y 1993.

BACKGROUND: The description of the epidemiologic profile and analysis of the mortality of infectious endocarditis (IE) observed from 1984-1993. METHODS: One hundred thirty episodes of IE in a native valve (30 in drug addicts [IVDA] and 20 cases of nosocomial acquisition) were analyzed with right/left/bilateral localization (42/84/4, respectively), infection of the mitral/aortic/tricuspid valve (52/47/34, respectively) and the etiology was determined as Staphylococcus aureus in 52 cases, 41 Streptococcus, 13 negative coagulase Staphylococcus, and 11 Enterococcus. High risk IE were identified by uni and multivariate analysis (MVA). RESULTS: The incidence of IE ranged from 0.36 and 0.70 cases x 1.000 admitted adults/year (mean: 0.50). Transthoracic echocardiography detected bacterial vegetations in 67% of the cases with the validity to predict the development of embolisms being 55%. MVA showed the embolic episodes (present in 45% of the IE) to be associated with the IVDA patients and prolonged fever. The latter complication, being defined as > or = 10 days of fever under appropriate treatment, was observed in 32% of the cases and was due to mild (n = 15) and severe causes (n = 27). Postembolic septic complications were associated to fever with MVA. Twenty three patients died (18%), 2 IVDA and 5 nosocomial IE, mainly due to heart failure (n = 13). The independent risk factor predictors for death (p < 0.05) were: age > or = 60 years (mortality 34%), cerebral embolisms (55%), severe heart failure (37%), and the exclusion of the patient as a candidate for surgery (73%). To the contrary, right IE (mortality 0%) and cardiac surgery (5%) favoured survival. CONCLUSIONS: To improve the prognosis of infectious endocarditis in high risk patients more opportune cardiac surgery accepting greater risks should be performed.

[Progressive multifocal leukoencephalopathy associated with human immunodeficiency virus infection: the clinical, neuroimaging, virological and evolutive characteristics in 35 patients]. / Leucoencefalopatía multifocal progresiva asociada a la infección por el virus de la inmunodeficiencia humana: características clínicas, de neuroimagen, virológicas y evolutivas de 35 pacientes.

BACKGROUND: The clinical, neuroimaging, virologic and evolutive characteristics of progressive multifocal leukoencephalopathy (PML) in 35 AIDS patients are studied. PATIENTS AND METHODS: PML was diagnosed by clinical and neuroimaging criteria in 32 patients and by autopsy in other three. The detection of JC virus (JCV) was done by PCR and further hybridization of the amplified DNA in peripheral blood lymphocytes, urine and CSF. RESULTS: 127 of 930 HIV positive patients were admitted by neuropsychiatric symptoms and of them 35 (SD 27.6%) by PML. The PML patients had a mean CD4 lymphocytes count of 75.3 (82.0)/x 10(6)/l and a HIV viral load of 330,698 (538,971) copies of RNA/ml. Thirty patients did not receive any anti-retroviral therapy or only transcriptase inhibitors monotherapy and five triple anti-retroviral therapy, including a proteases inhibitor. Multiple hypodense lesions on CT (53.1%) and T2 hyperintense lesions on MRI (58.3%) were the most frequent neuroimaging findings. JCV was detected in 20/21 (95.2%) LMP patients: 18/19 detections in lymphocytes, 6/8 in CSF and 4/6 in urine. The mean survival without and with antiretroviral therapy were 3.0 (0.47) and 21.4 (4.4) months (p < 0.001) in 34 patients followed. PML progressed to death in 31/34 patients (91.2%), and remained stable in 3/34 (8.8%). A patient was lost for follow-up. CONCLUSIONS: The application of clinical and neuroimaging criteria and the detection of JCV in CSF are useful for high presumption diagnosis of PML without brain biopsies. JCV detection in lymphocytes and in urine have a much lower predictive value. The evolution and survival of this disease can improve with triple anti-retroviral therapy including a protease inhibitor.

[The clinical significance of culturing Toxoplasma gondii on blood and other organic media]. / Significado clínico del cultivo de Toxoplasma gondii en sangre y en otros medios orgánicos.

BACKGROUND: The aim of this study was to determine the value of the Toxoplasma gondii culture in blood and in other organic fluids in HIV positive and negative patients. METHODS: Retrospective analysis (October 1990-May 1992) was carried out including all patients with positive cultures for T. gondii admitted to the Hospital Central of Asturias. The parasite was identified by monoclonal antibodies against the tachyzoite membrane. All patients with positive cultures were treated with pyrimethamine and sulphadiazine. RESULTS: Three hundred two samples from 256 patients, seropositive and seronegative for HIV, were analyzed. Of the seropositive group 8/45 (18%) had positive cultures for T. gondii versus 9/211 (4.3%) of the seronegative group (p = 0.002). Of the 19 positive samples, 15 were from blood, 3 from bronchoalveolar lavage and one from the vitreous fluid. Four out of 9 patients (44%) with AIDS and encephalic toxoplasmosis (ET) had blood cultures positive for T. gondii. Another 4 patients with AIDS presented toxoplasmenia without visceral involvement. Of the 9 HIV seronegative patients (3 immunodepressed patients), 4 had pulmonary toxoplasmosis, one ocular toxoplasmosis, and other clinical forms of toxoplasmosis were seen in the remaining 4. All the patients evolved to cure except 2 cases coinfected by cytomegalovirus who died. CONCLUSIONS: The identification of Toxoplasma gondii may be performed by blood cultures in half of the patients with AIDS and encephalic toxoplasmosis and in an undetermined percentage of the other clinical forms both in immunocompetent and immunodepressed subjects. In addition, toxoplasmemia has been registered in AIDS patients preceding any other organic seating of the parasite. Early antitoxoplasma therapy may, therefore, be effective.

[The prognostic value of cytomegalovirus antigenemia and viremia for the development of cytomegalovirus disease and the survival of AIDS patients]. / Valor predictivo de la antigenemia y la viremia por citomegalovirus para el desarrollo de enfermedad por citomegalovirus y la supervivencia en pacientes con SIDA.

OBJECTIVES: To analyse risk factors for morbidity and survival associated with blood cytomegalovirus (CMV) detection with the antigenemia method among AIDS patients. PATIENTS AND METHODS: CMV antigenemia and CMV blood cultures in 277 AIDS patients IgG-CMV sero-positive with a CD4 level lower than 200 x 10(6)/l under antiretroviral monotherapy were analysed. We consider cases the 116 patients with one or more positive blood samples tested for pp65 antigenemia or CMV culture. They were matched with 161 control patients with negative antigenemia or viremia. RESULTS: Multivariate analysis pointed out a significant positive association for blood CMV reactivation with the following variables: CMV disease development and CMV urine detection, sex-acquired HIV infection, CD4+ < 50 x 10(6)/l and matched time from AIDS diagnosis to CMV blood culture correlated with positive antigenemias. Quantitative antigenemia title showed predictive value for risk of CMV disease although 23% of retinitis patients had persistent undetectable antigenemia. CMV invasive disease developed in 48% of cases and 11% of controls (relative risk [RR]: 7.9; 95% confidence interval [CI]: 4.2-14.7). Mortality after 12 months of follow-up was 73% vs 52% respectively (p < 0.001). Time survival curves after CD4+ count adjusting remained significantly lower for case patients (median, 127 days vs 355 days; p < 0.01 by log-rank test). Increased death rate was found in patients with CMV disease (74%), followed by patients with CMV antigenemia but no disease (70%) and patients without antigenemia or CMV disease (mortality 49%). CONCLUSIONS: CMV blood detection in AIDS patients may be considered as a bad prognosis marker for CMV morbidity and survival. This risk increases with higher CMV antigenemias. Therefore, pre-emptive anti-CMV therapy should be considered in this restricted population.