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.

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.

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.

Meropenem monotherapy is as effective as and safer than imipenem to treat brain abscesses.

The efficacy of carbapenems versus cefotaxime (8g/day)+metronidazole (1.5-2g/day) [combined standard chemotherapy (CSC)] for the treatment of brain abscess was compared. Fifty-nine adult patients with brain abscesses received either imipenem or meropenem (3-4g/day) or CSC for a mean of 5 weeks, in addition to neurosurgery in most cases. Cure was obtained in 84.7% of cases; 42/47 (89.4%) on carbapenems [18/22 (81.8%) on imipenem versus 24/25 (96.0%) on meropenem] and 8/12 (66.7%) on CSC (P=0.06). Seven patients with multiple abscesses were treated with imipenem (1 died; cure rate 85.7%), five with meropenem (all survived; cure rate 100%) and five with CSC (2 died; cure rate 60%) (P<0.4). Neurosurgery was performed in 43/59 cases (72.9%); 17 (77.3%) in the imipenem group, 21 (84.0%) in the meropenem group and 5 (41.7%) in the CSC group (P=0.02). There was no significant difference in the rate of relapse requiring re-intervention. Treatment with meropenem was associated with a lower mortality than CSC (P=0.026). Seizures were observed only with carbapenems [8/22 (36.4%) for imipenem versus 2/25 (8.0%) for meropenem; P=0.03]. Carbapenems were more effective than CSC for treatment of brain abscesses. Because meropenem induced significantly fewer seizures than imipenem with at least the same clinical efficacy, the former appears to be a better choice to treat this infection.

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.

Post-surgical enterococcal meningitis: clinical and epidemiological study of 20 cases.

Enterococcal post-surgical meningitis is an uncommon disease. 20 episodes of nosocomial post-surgical enterococcal meningitis diagnosed between 1994 and 2003 were retrospectively studied. During the period of study 20 cases of post-surgical enterococcal meningitis (60% female, mean age 55+/-18 y, range 16-78 y) were reviewed. The mean time between admission at the hospital and surgery was 26 (SD = 15) d (range 7-61 d). The most frequent underlying diseases were: intracerebral haemorrhage (55%), brain neoplasms (25%), head trauma (15%) and hydrocephalus (5%). 11 patients had previously received antibiotic treatment. The isolates identified were Enterococcus faecalis (n = 18) (90%), E. faecium (1) and E. durans (1). 11 patients had polymicrobial infections. The treatment most frequently used was vancomycin alone or with other antibiotics (11). In 5 patients intrathecal vancomycin (20 mg/d) was also added. The mortality rate was not different in intrathecally treated patients. Cerebrospinal fluid (CSF) devices were removed in 8 patients. Four patients died due to the infection. Mortality was significantly associated with lack of removal of the CSF devices (p = 0.04). Enterococcal spp. are a cause of nosocomial meningitis associated with neurosurgical procedures and the presence of neurological devices.

The Toll-like receptor 4 (Asp299Gly) polymorphism is a risk factor for Gram-negative and haematogenous osteomyelitis.

Osteomyelitis is a bone infection caused mostly by Staphylococcus aureus but also by Gram-negative bacteria. Toll-like receptors (TLRs), after recognizing microbial products, induce a signal in neutrophils, leading to NF-kappaB activation and transcription of pro-inflammatory genes. Polymorphisms in TLR2 (Arg753Gln) and TLR4 (Asp299Gly, Thr399Ile) genes are associated with bacterial infections, we therefore studied these polymorphisms in osteomyelitis patients. Homozygotes for the TLR4 (Asp299Gly) polymorphism were significantly more frequent among the 80 osteomyelitis patients than in the 155 healthy controls (3/80, 3.8%versus 0/155, 0%; P = 0.038). Carriers of one or two G alleles of this tlr4 polymorphism were more likely to have Gram-negative, haematogenous and/or chronic osteomyelitis than those without this mutation (P < 0.031). Patients with the TLR4 (Thr399Ile) mutant, which cosegregates with the TLR4 (Asp299Gly), were also carriers of this second polymorphism. No differences for the TLR2 (Arg753Gln) genotypes were found between patients and controls. Neutrophils of patients homozygous for the TLR4 (Asp299Gly) polymorphism showed lower LPS-induced apoptosis reduction, phosphorylation of the inhibitor of NF-kappaB, and lower IL-6 and TNF-alpha levels (P < 0.05). We report here for the first time an association between this TLR4 polymorphism and susceptibility to Gram-negative bacteria and haematogenous osteomyelitis.

Eikenella corrodens brain abscess after repeated periodontal manipulations cured with imipenem and neurosurgery.

Eikenella corrodens is a facultatively anaerobic gram-negative rod that colonizes the oral cavity and very rarely produces central nervous system (CNS) infections. Frontal lobe abscesses are occasionally associated with a dental source of infection. We report a case of an adult man with overzealous dental cleaning habits who developed a right frontal brain abscess caused by E. corrodens. He underwent neurosurgical drainage of the pus and was successfully treated with imipenem 4 g/i.v./day for 4 weeks with no complications. Repeated periodontal trauma could explain the Eikenella brain abscess in this case.

[Postsurgical meningitis caused by Acinetobacter baumannii: study of 22 cases and review of the literature]. / Meningitis postquirúrgica por Acinetobacter baumannii: estudio de 22 casos y revisión de la literatura.

BACKGROUND: Postsurgical Acinetobacter baumannii meningitis is associated with relevant morbidity and mortality. It has been related to neurosurgery, intraventricular catheters (IC) or CSF fistula. Thus, features, epidemiology and clinical course of this infection were studied. METHODS: Retrospective analysis of 22 episodes of nosocomial postsurgical Acinetobacter baumannii meningitis. Twenty episodes occurred in males. The mean age of patients was 46 years (range: 16-83 years). RESULTS: All patients were admitted to the ICU. In 50% of patients a history of intraventricular hemorrhage was recorded, 36% had had a skull fracture and the remaining patients had a brain tumor. In 18 cases the portal of entry was considered to be IC, in two an epidural catheter, and in two a CSF fistula. Patients showed a clinical picture indistinguishable from other types of meningitis, fever being the most common symptom (100%). CSF findings were consistent with bacterial meningitis. In one case the microorganism was recovered from blood. Fifteen patients recovered, three died as a direct result of the infection, and the remaining patients relapsed. Non recovery of patients was significantly associated with non removal of catheter (p < 0.05). CONCLUSIONS: Postsurgical Acinetobacter baumannii meningitis occurs frequently in patients previously colonized with this microorganism in other sites and is enhanced by the presence of an IC. Catheter removal is essential for recovery of patients.

Meningitis postquirúrgica por Acinetobacter baumannii: estudio de 22 casos y revisión de la literatura / Postsurgical meningitis due to Acinetobacter baumannii: study of 22 cases and review of the literature

Introducción. La meningitis postquirúrgica por Acinetobacter baumannii se asocia a una importante morbimortalidad. Se ha relacionado con intervenciones neuroquirúrgicas, catéteres intraventriculares (CI) o fístula de líquido cefalorraquídeo (LCR). Por este motivo se determinaron sus características, epidemiología y evolución. Métodos. Se analizaron de forma retrospectiva, entre 1992-2000, 22 episodios de meningitis nosocomial postquirúrgica por Acinetobacter baumannii, 20 de los cuales eran hombres con una edad media de 46 años (rango: 16-83). Resultados. Todos los enfermos estaban ingresados en la Unidad de Cuidados Intensivos. En un 50 por ciento de los pacientes se recogió el antecedente de una hemorragia intraventricular, un 36 por ciento presentaba un traumatismo craneoencefálico y el resto tenía una neoplasia. En 18 casos se consideró que la puerta de entrada era el CI, en 2 un catéter epidural y en 2 una fístula de LCR. Los enfermos presentaban un cuadro indistinguible de otras meningitis, siendo la fiebre el síntoma más frecuente (100 por ciento), Los hallazgos del LCR fueron compatibles con una meningitis bacteriana. En un caso se aisló el microorganismo en sangre. En 15 casos se produjo la curación, 3 enfermos fallecieron a consecuencia directa de la infección y el resto recidivaron. La ausencia de curación se asoció de forma significativa (p < 0,05) a la no retirada del catéter. Conclusiones. La meningitis postquirúgica por Acinetobacter baumannii aparece con frecuencia en enfermos colonizados previamente en otras localizaciones y se favorece por la presencia de CI. La retirada del catéter es fundamental en su curación (AU)

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Visceral leishmaniasis and other severe infections in an adult patient with p47-phox-deficient chronic granulomatous disease.

We report a rare case of a male patient without known immunodeficiency consecutively diagnosed with visceral leishmaniasis, brain abscess and cavitating pneumonia in the 3rd decade of life. Chronic granulomatous disease (CGD) was diagnosed by a nitroblue tetrazolium test. A p47-phox mutation of the NADPH oxidase of the leukocytes was suspected by immunoblotting and confirmed by DNA analysis. The patient was homozygous for this mutation while his mother and sister were heterozygous asymptomatic carriers. After the CGD diagnosis the patient started a chronic prophylactic regimen with subcutaneous interferon-gamma (0.05 mg/m2 of body surface/three times a week), and oral trimethoprim-sulfamethoxazole and itraconazole (both at 5 mg/kg/day) with no subsequent infections after 12 months of follow-up.

[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.

[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.

Successful intrathecal ethanol block for intractable spasticity of AIDS-related progressive multifocal leukoencephalopathy.

OBJECTIVE: To study the efficacy of intrathecal ethanol block to relieve intractable spasticity in AIDS-related progressive multifocal leukoencephalopathy (PML) when long-term intrathecal baclofen infusion cannot be used. METHODS: A 33-year-old man with AIDS-related PML developed very severe spastic paraparesis (Ashworth rigidity score, 4) and painful muscle spasms. The patient was unable to sit in his wheelchair and remained bed bound. Combined oral baclofen and tizanidine at therapeutical doses were used without any effect on the spasticity. The patient refused the placement of an intrathecal catheter for long-term baclofen infusion. A single intrathecal ethanol (6 ml) injection in the L2-L3 intervertebral space with the patient placed in a lateral Trendelenburg (40 C) position was performed. RESULTS: The procedure was very effective in improving the stiffness (Ashworth rigidity score. 2, after the technique) and the muscle spasms disappeared. No side effects during or after the injection were observed. CONCLUSION: Intrathecal ethanol block is a last but very useful choice for treatment of intractable spasticity in PML and other neurologic disorders in AIDS patients when other oral treatments have failed and intrathecal baclofen infusion is not suitable.