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.

Alopecia areata incognita in Cronkhite-Canada syndrome.

Cronkhite-Canada syndrome is an acquired inflammatory polyposis syndrome in which alopecia, onychomadesis and hyperpigmentation occur concurrently with gastrointestinal symptoms. The pathophysiology of alopecia in Cronkhite-Canada syndrome has not been definitively elucidated. We present evidence for alopecia areata incognita as a possible mechanism of hair loss.

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.

Autosomal recessive chronic granulomatous disease presenting with cutaneous dermatoses and ocular infection.

Dermatoses such as eczematous dermatitis and cutaneous infection are recognized presentations of primary immunodeficiency (PID). However, atopic dermatitis affects approximately 10% of infants, and cutaneous infections are not uncommon in children, therefore the challenge for the dermatologist is to distinguish the few patients that have PID from the many that do not. We report on a 6-year-old girl who was ultimately diagnosed with autosomal recessive chronic granulomatous disease (AR-CGD) after presenting to various hospitals with dermatitis, scalp plaques recalcitrant to treatment, and recurrent infections over a 3-year period, and describe some aspects of her diagnosis and management. This report highlights the importance of considering rare disorders such as AR-CGD in the differential diagnosis of recurrent or recalcitrant dermatological infections in children.

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.

Resistin is elevated following traumatic joint injury and causes matrix degradation and release of inflammatory cytokines from articular cartilage in vitro.

OBJECTIVE: Resistin is a secreted factor that is elevated in rheumatoid arthritis (RA) and believed to drive joint inflammation in vivo. This study was undertaken to determine if resistin is present in the joint following joint injury and to elucidate the role of resistin in cartilage degradation. METHODS: The level of resistin was measured in paired synovial fluid (SF) and serum samples from patients following joint injury (anterior cruciate ligament, ACL or meniscus tear). Localization of resistin was visualized by immunohistochemistry of synovial tissue and cartilage from healthy and OA donors. Mouse and human cartilage cultures were used to assess the effect of resistin on cartilage metabolism. RESULTS: In trauma patients, resistin levels declined with increasing time post injury. The resistin levels were highest in samples collected up to 1 week following traumatic injury (SF: 2980 pg/ml, serum: 7901 pg/ml) and lowest in samples collected 6-26 years post injury (SF: 686 pg/ml, serum: 5682 pg/ml). Resistin was shown to be expressed in macrophage-like cells in both healthy and OA synovial tissue. Treatment of mouse cartilage cultures with recombinant resistin led to a dose dependent loss of proteoglycan and induction of inflammatory cytokine and PGE(2) production. Recombinant resistin inhibited proteoglycan synthesis in human cartilage explants. CONCLUSION: Resistin is elevated both systemically and locally in the weeks immediately following joint injury and has a direct effect on cartilage matrix turnover and cytokine production. Resistin may play a role in the early stages of trauma-induced OA and may represent a new therapeutic target to slow joint destruction in OA.

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.