Cost-effectiveness of linezolid versus vancomycin for hospitalized patients with complicated skin and soft-tissue infections in France.

UNLABELLED: Studies have shown similar clinical cure rates and shorter length of hospitalization when using linezolid compared to vancomycin in patients with complicated skin and soft-tissue infections due to suspected or proven methicillin-resistant Staphylococcus aureus (MRSA). OBJECTIVE: This study had for aim to compare the cost-effectiveness of linezolid versus vancomycin in French healthcare settings. METHOD: A decision-analytic model followed an average patient from the initiation of an empiric treatment until cure, death or second-line treatment failure. A clinical data probability was obtained from clinical trials, resource utilization data (including treatment duration and length of hospitalization) and prevalence of MRSA was obtained from a Delphi panel, and costs from published sources. RESULTS: First-line cure rate for linezolid-treated patients was 90.7% versus 85.5% for vancomycin; the total cure rates after two lines of treatment were 98.5% and 98.0%, respectively. The average total cost was 7,778euro for linezolid versus 8,777euro for vancomycin. The mean estimated length of hospitalization after two lines of treatment was 10.7 days for linezolid versus 13.3 days for vancomycin. The increased effectiveness and reduced cost lead to more frequent prescription. This did not change after one-way sensitivity analyses. CONCLUSION: Linezolid may be considered as a cost-effective treatment for patients with complicated skin and soft-tissue infections suspected to be MRSA related in France.

Human-to-human transmission of tuberculosis caused by Mycobacterium bovis in immunocompetent patients.

Human-to-human transmission of Mycobacterium bovis in two immunocompetent patients from the same family was confirmed by spoligotyping (pattern F35, which was only observed in cattle from the same area in France). A single allelic difference between animal and human isolates was observed with mycobacterial interspersed repetitive units containing variable-number tandem repeats, suggesting a jump across the species barrier.

[Epidemiological aspects of human Q fever in Indre-et-Loire between 2003 and 2005 and comparison with caprine Q fever]. / Aspects épidémiologiques de la fièvre Q humaine en Indre-et-Loire entre 2003 et 2005 et confrontation à la fièvre Q caprine.

OBJECTIVE: Chronic infection is the major risk of Q fever. C. burnetii infections result from the inhalation of contaminated aerosols. Indre-et-Loire is a rural French area with numerous goat farms. We evaluated human Q fever epidemiology and compared it with Q fever in goats. DESIGN: This retrospective study was made between 2003 and 2005. The diagnosis of C. burnetii infection was based on serologic findings from all the subdivision laboratories. Antibodies were detected by using indirect immunofluorescence. Farm animal data was processed by ELISA on blood samples from goats and cattle after Q fever related abortion in 2006 and results of PCR-processed milk samples from 156 goat farms. RESULTS: Forty human cases were studied: 38 acute Q fever (11 pneumonia, 10 hepatitis, 10 pneumonia with hepatitis, two isolated fever) and six chronic Q fever (four endocarditis). Sixteen patients (40%) had been professionally exposed, 10 (25%) of whom were goat farmers. Eight (20%) had been in contact with placenta. All the human cases were located in the south of Indre-et-Loire. Twenty percent of the volunteer goat farms had at least one milk sample positive for Q fever by PCR. Forty-nine of the 75 goat abortion samples were positive in ELISA. Ninety-two of the goat farms with positive samples were located in the south of Indre-et-Loire. CONCLUSION: This study revealed similar location of human and caprine Q fever. Identifying such geographical correlation may lead to improving prevention and detection.

Epidemiology of vertebral osteomyelitis (VO) in France: analysis of hospital-discharge data 2002-2003.

Vertebral osteomyelitis (VO) is a rare event. To estimate the incidence of VO in France for 2002-2003, national hospital-discharge data were used. Hospital stays were categorized as definite, probable or possible VO. Unique patient identification numbers allowed the investigators to link patients with multiple hospital stays and to analyse data for individual patients. A sample of medical records was reviewed to assess the specificity of the VO case definition. In 2002-2003, 1977 and 2036 hospital stays corresponding to 1422 and 1425 patients (median age 59 years, male:female ratio 1.5) were classified as definite (64%), probable (24%) and possible (12%) VO. The overall incidence of VO was 2.4/100,000. Incidence increased with age: 0.3/100,000 (70 years). The main infectious agents reported were Staphylococcus spp. (38%) and Mycobacterium tuberculosis (31%). The most frequent comorbidities were septicaemia (27%) and endocarditis (9%). Three percent of patients died. A review of 90 medical records confirmed the diagnosis of VO in 94% of cases. Using a hospital database and a specific case definition, nationwide surveillance of VO is possible.

Optimal duration of antibiotic therapy in vertebral osteomyelitis.

OBJECTIVES: To compare the risk of relapse of vertebral osteomyelitis (VO), according to the duration of antibiotic therapy (< or =6 weeks versus >6 weeks). METHODS: We performed a 10-year retrospective study to assess the risk of VO relapse and to verify that this risk was not enhanced in patients who received 6 weeks of antibiotic therapy (Group 1) as compared with those who received a longer treatment (Group 2). VO was diagnosed based on clinical manifestations, magnetic resonance imaging and/or computed tomography findings, and isolation of a pyogenic organism in blood cultures and/or a discovertebral biopsy. Relapse was diagnosed based on isolation of the same organism in blood cultures and/or a discovertebral biopsy. Outcome was evaluated 6 months post-treatment and in December 2004. RESULTS: Group 1 included 36 patients (mean age, 58 +/- 15 years) and Group 2 included 84 patients (mean age, 67 +/- 15 years) (P = 0.003). Clinical data and microorganisms were comparable in the 2 groups. In the first 6 months, 6 (5%) patients died (Group 1, n = 2; Group 2, n = 4), and 5 (4%) in Group 2 relapsed, 2 with recurrent VO and 3 with recurrent bacteremia. In 2004, 91 patients were evaluated (mean follow-up, 40.6 +/- 31 months): 77 (85%) were cured, 13 (14%) died (Group 1, n = 3; Group 2, n = 10), 1 had VO due to a different microorganism (Group 2), and no long-term relapses occurred. CONCLUSION: Our results suggest that antibiotic therapy of VO could be safely shortened to 6 weeks without enhancing the risk of relapse.

Long-term assessment of nevirapine-containing highly active antiretroviral therapy in antiretroviral-naive HIV-infected patients: 3-year follow-up of the VIRGO study.

OBJECTIVES: Data on the durability of antiretroviral regimens over a 3-year period have only rarely been reported. The aim of this study was to evaluate the long-term efficacy and safety of one or two daily doses of nevirapine (NVP), in combination with stavudine (d4T) and didanosine (ddI), in HIV-infected patients. METHODS: This study was a follow-up of the VIR (amune) Grand Ouest (VIRGO) study, a 12-month open-label trial to assess the safety and immunovirological activity of NVP-d4T-ddI combination therapy in antiretroviral-naive HIV-1-infected adults with baseline CD4 counts > or =200 cells/microL and plasma viral loads > or =5000 HIV-1 RNA copies/mL. Of the 100 patients included in the study, the 67 patients remaining on the initial triple therapy at the end of the study (1 year) were offered an extra 24 months of follow-up. RESULTS: Of the 60 patients who extended follow-up, 46 were still being treated with d4T-ddI-NVP at month 36; 91% (39/43) had a plasma viral load <500 copies/mL (data were missing for three patients). CD4 cell counts increased over 36 months. Safety and tolerance were good with no unexpected long-term toxicity. CONCLUSION: After 3 years of treatment with NVP-d4T-ddI, nearly half of the patients were still receiving the initial antiretroviral therapy with a sustained and durable immunovirological benefit. Long-term toxicity was mainly related to the nucleoside reverse transcriptase inhibitor components of the regimen.

[Generalized granuloma annulare: remission during treatment of HIV infection]. / Granulome annulaire généralisé: guérison au cours du traitement d'une infection par le VIH.

INTRODUCTION: Granuloma annulare is a benign dermatosis characterized by pale or erythematous papules grouped in rings or in arch form figures. We report the observation combining a granuloma annulare and a Human Immunodeficiency Virus (HIV) infection, with regression of the granuloma annulare on initiation of treatment of the HIV infection. OBSERVATION: A 33 year-old man presented with an eruption of multiple, erythematous papules predominating on the trunk and limbs but sparing the face. Histology confirmed the diagnosis of generalized granuloma annulare. We diagnosed an HIV infection. Remission of the granuloma annulare was obtained concomitantly when immune restoration was obtained following the prescription of an antiretroviral tritherapy. DISCUSSION: Since 1985, several cases of atypical forms of granuloma annulare have been reported in HIV-infected patients. Nevertheless, the precise relationship between the two diseases is unknown. The case we report on raises the question of the relationship between granuloma annulare and immunodepression.

Non-touch fittings in hospitals: a procedure to eradicate Pseudomonas aeruginosa contamination.

Non-touch taps, now common in hospitals, can easily be contaminated with Pseudomonas aeruginosa. We report our experience with 87 non-touch taps in a newly built wing of our teaching hospital contaminated with P. aeruginosa from the central pipe water system. Serotyping and genotyping of strains revealed genetic diversity of isolates, but also showed that major clones were able to persist for long periods of time in non-touch taps despite chlorination. It is notoriously difficult to decontaminate such taps with biocides and disinfectants. We describe an easy and economical procedure for the eradication of P. aeruginosa contamination from non-touch taps that does not require their removal.

Spread of Stenotrophomonas maltophilia colonization in a pediatric intensive care unit detected by monitoring tracheal bacterial carriage and molecular typing.

In our pediatric intensive care unit in Tours (France), intubated and ventilated inpatients are systematically monitored for tracheal bacterial colonization twice a week. This led us to detect five patients colonized with Stenotrophomonas maltophilia over a 4-month period. Molecular typing of the isolates using random amplified polymorphism DNA (RAPD) and pulsed-field gel electrophoresis (PFGE) confirmed that four of the five isolates were genetically related. The strict isolation of carriers and improvements in hygiene measures stopped the spread. This systematic strategy prevented pulmonary nosocomial infections or allowed their early detection. Moreover, it has made it possible to assess the efficiency of care practices continuously.

Pneumocystis carinii pneumonia in patients with hematologic malignancies: a descriptive study.

Objectives. A retrospective multicentric study was conducted over a five-year period to evaluate the clinical and laboratory characteristics and outcome of patients with proven Pneumocystis carinii pneumonia (PCP) complicating hematologic malignancies.Results. The study included 60 HIV-negative patients with 18 non-Hodgkin's malignant lymphoma (30%), 13 chronic lymphocytic leukaemia (21.7%), 10 acute leukemia (16.6%), 5 multiple myeloma (8.3%), 4 Waldenström's diseases (6.6%), 4 chronic myeloid leukemia (6.6%), 3 myelodysplasia (5%), 2 Hodgkin's diseases (3.3%) and 1 thrombopenia. Bronchoalveolar lavage was diagnostic in all patients. Forty-nine patients received cytotoxic drugs (81.7%), 25 (41.7%) a long-term corticotherapy and 15 (25%) underwent bone marrow transplantation. Twenty-seven patients (45%) required admission in the intensive care unit, 35 (58.3%) received an adjunctive corticotherapy and 18 mechanical ventilation (30%). Twenty patients (33.3%) died of PCP. A previous long-term corticotherapy (p=0.04), high respiratory (p=0.05) and pulse rates (p=0.02), elevated C reactive protein (p=0.01) and mechanical ventilation (OR=13.37; IC: 1.9-50) were associated with a poor prognosis. Adjunctive corticotherapy did not modify the prognosis.Conclusions. These results suggest that PCP can occur during the course of various hematologic malignancies, not only lymphoproliferative disorders. Prognosis remains poor. The diagnosis should be advocated more frequently and earlier to improve the prognosis.

Clinical, biologic, and behavioral predictors of early immunologic and virologic response in HIV-infected patients initiating protease inhibitors.

Predictors of virologic (plasma HIV RNA viral load [VL] < 500 copies/ml) and immunologic (rise in CD4+ cell count > 50 cells/mm3) response after 4 months of therapy (M4) were studied in 750 HIV-1-infected patients prospectively enrolled at the initiation of a protease inhibitor (PI)-containing regimen. A virologic response was observed in 80% of patients, and an immunologic response was observed in 64%. Sixty-two percent of patients self-reported full adherence to therapy at 1 month of therapy (M1) and M4. In multivariate analysis, a virologic response was more frequent in fully adherent patients (odds ratio [OR] = 2.0; p =.001). An immunologic response was associated with age < 36 years (OR =1.4; p =.03), baseline VL (OR = 1.5 per 1 log10 copies/ml higher; p <.01), decrease in VL at M1 (OR = 1.5 per 1 log10 copies/ml decrease; p <.01), baseline total lymphocyte count (OR = 1.7 per 50% lower; p <.001), and baseline CD4+ cell percentage > or = 20% (OR =1.9; p <.001) but not with adherence to therapy. Full adherence seems to be a major predictor of a virologic response to PI-containing triple therapy. An immunologic response may be possible despite incomplete adherence, at least early in therapy.

Therapeutic drug monitoring of HIV protease inhibitors using high-performance liquid chromatography with ultraviolet or photodiode array detection.

Published data suggest that therapeutic drug monitoring of human immunodeficiency virus protease inhibitors would improve the management of antiretroviral therapy. The authors have developed a high-pressure liquid chromatographic assay allowing simultaneous determination of six protease inhibitors (ritonavir, saquinavir, indinavir, nelfinavir, amprenavir, and lopinavir), using carbamazepine as internal standard. Detection was based on a dual wavelength ultraviolet spectrophotometer and can be improved by the use of a photodiode array detector. Monitoring was performed 1 month after initiation of therapy or in instances of therapeutic failure, side effects, suspicion of noncompliance, drug interactions, or malabsorption. Trough concentrations were 0.15 to 13.6 mg/L for ritonavir, 0.06 to 9.7 mg/L for indinavir, 0.03 to 5.5 mg/L for saquinavir, and 0.15 to 4.15 mg/L for nelfinavir. Concentrations below the limit of quantification were observed in 63/438 (14%) of the patients. Target concentrations are not well established, and reported in vitro inhibitory concentrations may be of limited value. The authors therefore chose to compare observed concentrations with mean plasma concentrations reported in clinical trials. Observed saquinavir and indinavir concentrations were often below or close to these target concentrations, particularly when used as a single protease inhibitor. Concentration-controlled studies should now be used to select proper target concentrations for each protease inhibitor, either prescribed alone or in combination.

Hepatitis C virus co-infection is a negative prognostic factor for clinical evolution in human immunodeficiency virus-positive patients.

A longitudinal study of human immunodeficiency virus (HIV)-infected individuals followed-up in 13 centres was performed to assess the influence of hepatitis C virus (HCV) on the clinical and immunological evolution of HIV-infected patients. Eight-hundred and twelve HIV-infected patients with known HIV acquisition date, 89 co-infected with HCV, were included in the cohort. Clinical progression was defined as: 30% decrease of Karnofsky's index; and/or 20% body weight loss; and/or acquired immune deficiency syndrome (AIDS)-defining illness; and/or death (except by accident, suicide, or overdose). Immunological progression was defined as a decrease of initial CD4 count to below 200 mm(-3). If immunological progression was not statistically different between groups (P=0.25), clinical progression was significantly faster in HCV-HIV co-infected patients in univariate (P=0.02) and multivariable survival analysis (hazard ratio=1.63, P=0.03). This argues for active management of hepatitis C chronic infection among HCV-HIV co-infected patients.

The VIRGO study: nevirapine, didanosine and stavudine combination therapy in antiretroviral-naive HIV-1-infected adults.

The virological and immunological efficacy of the triple regimen containing nevirapine (once or twice daily), didanosine (once daily) and stavudine, in antiretroviral-naive patients infected with HIV-1, was evaluated in an open-label, prospective, non-randomized, multi-centre, 52-week study. The first 60 patients (VIRGO I) received nevirapine as the standard dose, 200 mg twice daily; the subsequent 40 patients (VIRGO II) received nevirapine at a dose of 400 mg once daily. All patients received 400 mg of didanosine once daily and 40 mg of stavudine twice daily, adjusted for body weight. At baseline, the median CD4 cell count and plasma viral load (pVL) were 414 cells/mm3 and 4.59 log10 copies/ml in VIRGO I, and 412 cells/mm3 and 4.87 log10 copies/ml in VIRGO II. Using an intent-to-treat, 'non-completer equals failure', analysis, 78% (95% CI, 68-88%) of patients in VIRGO I and 68% (95% CI, 53-83%) of those in VIRGO II had a pVL <500 copies/ml at 24 weeks; the proportions achieving a pVL of <50 copies/ml were 62% (95% CI, 50-74%) and 50% (95% CI, 35-65%), respectively. The week 24 median CD4 cell count increase was 168 cells/mm3 (VIRGO I) and 139 cells/mm3 (VIRGO II). At week 52, 39/45 (87%) of VIRGO I patients had pVL <500 copies/ml and 30/45 (67%) <50 copies/ml. Of the 100 patients, 44 experienced grade 2 to 4 adverse events; 20 permanently discontinued study medication because of an adverse event. Combination therapy with the three reverse transcriptase (RT) inhibitors stavudine, once-daily didanosine and either once- or twice-daily nevirapine could be considered as an alternative option for first-line antiretroviral therapy.

Stavudine, didanosine and nevirapine in antiretroviral-naive HIV-1-infected patients.

In an ongoing, open-label, non-comparative study, the safety and efficacy of nevirapine/stavudine/didanosine were evaluated in 100 antiretroviral-naive adults with CD4 cell counts > or = 200 cells/mm3 and plasma HIV-1 RNA (pVL) > or = 5000 copies/ml. Sixty patients received nevirapine twice daily (VIRGO I) and 40 received nevirapine once daily (VIRGO II); all patients received didanosine once a day. After median follow-ups of 44 weeks in VIRGO I and 30 weeks in VIRGO II, the following virological results were observed (ongoing study): an intent-to-treat, non-completer equals failure analysis at week 24 showed the proportions of patients with pVL <500 copies/ml were 78% in VIRGO I (60% <50 copies/ml) and 75% in VIRGO II. An on-treatment analysis at week 52 showed 80% of patients with a pVL <500 copies/ml and 59% with <50 copies/ml in VIRGO I. The mean CD4 cell count increase was +171 cells/mm3 at week 24 and +218 cells/mm3 at week 52 in VIRGO I and +158 cells/mm3 at week 24 in VIRGO II. Cutaneous rash (grades 1 to 3) occurred in 24% of patients leading to nevirapine discontinuation in eight of 24 patients. Five other patients discontinued therapy during the first 24 weeks because of hepatic cytolysis, peripheral neuropathy or biological pancreatitis. The nevirapine/stavudine/didanosine combination is a convenient and safe regimen, with rapid and potent immunological and antiviral effects sustained over 12 months.

Efficacy and safety of stavudine and didanosine combination therapy in antiretroviral-experienced patients.

OBJECTIVES: To assess the efficacy, tolerance, and safety of combination antiretroviral therapy with didanosine and stavudine in HIV-infected patients with CD4+ cell counts > 100 x 10(6)/l and HIV plasma RNA > 10(4) copies/ml previously treated with other antiretroviral agents for at least 3 months. DESIGN: In this open, multicentre, non-randomized, Phase II pilot study, adult patients were administered didanosine (200 mg twice daily) plus stavudine (40 mg twice daily) for 6 months. Patients for whom the first regimen had led to undetectable HIV RNA levels were offered a second 6-month course of treatment; those who had achieved insufficient immunological and virological gains in the first 6 months were given a new combination. METHODS: Primary evaluation of efficacy was based on viral load measured by branched DNA second-generation testing (lower limit of detection, 500 copies/ml) and CD4+ cell counts; secondary evaluations included AIDS-defining events and clinical side-effects. RESULTS: Sixty-five patients with median prior antiretroviral therapy of 24 months (65 with zidovudine, 29 with zalcitabine) were included in the study. At baseline, median CD4+ cell count was 198 x 10(6)/l and median plasma HIV RNA was 80000 copies/ml (4.9 log10 copies/ml). In this heavily pretreated population, an increase in the mean CD4+ cell count was observed (+70 x 10(6)/l at 24 weeks). In addition, rapid and prolonged antiviral activity was seen, with a mean maximal decrease of 1.1 log10 copies/ml at week 4, a mean decrease of 0.89 log10 copies/ml at week 24, and a plasma RNA viraemia < 500 copies/ml achieved in 14% of patients at week 24. CONCLUSIONS: Combination therapy with stavudine and didanosine is safe and leads to a sustained antiviral effect, even in patients with prolonged prior antiretroviral exposure and low CD4+ cell counts.

[Extrapulmonary tuberculosis in the central western region. Retrospective study of 217 cases (Gericco 1991-1993)]. / Tuberculose extrapulmonaire dans la région centre-ouest. Etude rétrospective de 217 cas (Gericco 1991-1993).

OBJECTIVES: To analyze the epidemiological, clinical and diagnostic characteristics of extrapulmonary tuberculosis in western France observed from 1991 to 1993 in different patients populations (HIV+ infected patients, immunosuppressed non-HIV infected patients, non-immunosuppressed patients) and according to various localizations (lymph nodes, bone and joints, genital organs, nervous system and meninges, miliary disease). METHODS: This retrospective study included 217 cases of extrapulmonary tuberculosis diagnosed from 1991 to 1993 in western France by GERICCO (Groupe d'Epidémiologie et de Recherche en Infectiologie Clinique du Centre-Ouest). Demographic, clinical, biological, microbiological and radiographic characteristics as well as clinical course on specific therapy were assessed. RESULTS: Extrapulmonary tuberculosis generally occurred most often in immunosuppressed patients but 34% of cases were observed in people without any underlying disease or risk factors. Delay to diagnosis was especially long in the non-immunosuppressed patients (mean = 96 days) but shorter in the HIV-infected patients (mean = 59 days). It was shorter in case of nervous system involvement (mean = 52 days) or military disease (mean = 80 days) than in bone and joints (mean = 120 days) and lymph nodes (mean = 102 days). Microbiologically proven tuberculosis represented only 75% of cases despite numerous investigations. Overall prognosis was good except in nervous system and meninges localizations. Failures were mainly due to death in immunosuppressed patients. CONCLUSION: Extrapulmonary tuberculosis remains frequent even in patients lacking risk factors. In 50% of cases, confirmation of diagnosis takes more than one month. In case of doubt, clinicians should not wait for laboratory results before implementing empirical specific therapy.

[Multifocal tuberculosis. Apropos of 49 cases in the midwest region. GERICCO (Group for Epidemiology and Research in Clinical Infections of the Central West of France), 1991-1993]. / Tuberculose multifocale. A propos de 49 cas dans la région Centre-Ouest (Géricco, 1991-1993).

Diffuse or multifocal tuberculosis (TB) accounts for 9% to 10% of cases of extrapulmonary TB and carries a poor prognosis with a mortality rate of 16% to 25%. Forty-nine cases of multifocal TB defined as involvement of two extrapulmonary sites with or without pulmonary TB were reviewed. Mean patient age (+/- SD) was 50 +/- 18 years. Twenty-three per cent of patients were immigrants. A history of TB and contact with a TB patient were found in 23% and 18% of cases, respectively. Of the 52% of immunocompromised patients, 38% were HIV-positive. The skin tuberculin test was positive in 67% of cases. Mean time from symptom onset to admission was 80 +/- 77 days (median, 58 days). The 49 patients had a total of 128 TB foci. Six patients had positive blood cultures. The tubercle bacillus was recovered from the extrapulmonary sites in 88% of cases. Mean treatment duration was nine months. Recovery from the TB was achieved in 64% of cases. The overall mortality rate was 47%, and 33% of patients died as the direct result of TB. Most deaths occurred in immunocompromised patients. A high index of suspicion for multifocal TB should be maintained in immunocompromised patients, even those who test negative for the HIV.

[Methods and monitoring of antibiotic therapy of infectious endocarditis]. / Modalités et surveillance de l'antibiothérapie des endocardites infectieuses.

Antibiotic treatment of infective endocarditis has to be discussed when the microorganism has been identified. Antibiotics must be started as soon as possible, just after blood samplings in case of clinical bacteraemia, or as soon as blood cultures are positive. In case of negative blood cultures, diagnosis of endocarditis has to be reconsidered, according to Duke's criteria, and antibiotics must not be started until there is strong evidence in favour of infective endocarditis. Antibiotic treatment must be bactericidal, intravenously administered, for a long time to sterilize vegetations. Duration of antibiotics depends on the microorganism, and whether there is a valvular prosthesis or not. Hospitalization is often mandatory, but there is a trend towards the use of outpatient treatments, only possible in some indications.