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.

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.

[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.

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.

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.

[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.

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.

Opportunistic infections occurring during highly active antiretroviral treatment.

OBJECTIVE: To analyse the characteristics of opportunistic infections in patients receiving highly active antiretroviral treatment (HAART). DESIGN AND METHODS: A retrospective study performed in seven hospitals, included all patients starting treatment by ritonavir or indinavir between 26 March and 31 December 1996. Patients were evaluated for the development of AIDS-defining events. Clinical evaluation, plasma HIV-1 RNA quantification, CD4 cell count were recorded at baseline and at the onset of the event. RESULTS: Four hundred and eighty-six patients were included: 44.2% had a CD4 cell count below 50 x 10(6) cells/l. Fifty clinical events were recorded in 46 patients with a mean follow-up of 6.1 months, of which 34 events (68%) were observed during the first 2 months of HAART. Eighteen of these occurred despite a reduction of viral load by at least 1.5 log10) and a 100% increase of the CD4 cell count compared with that at the onset of the event, corresponding to 11 cytomegalovirus infections, five mycobacterial infections, one case of cryptococcosis, and one case of Varicella-Zoster virus-related acute retinal necrosis. Among the 16 events observed after the second month, six occurred despite a marked biological improvement, corresponding to a recurrence in five of six patients who had stopped their maintenance therapy. Events were one cytomegalovirus infection, two mycobacterial infections, one episode of oesophageal candidiasis and one cryptococcal meningitis. CONCLUSION: In patients at high risk of developing an opportunistic infection prior to the institution of a HAART regimen, prophylaxis should not be discontinued during the first 2 months of treatment, and maintenance therapy should be carried on despite a significant increase in the CD4 cell count.

Prevalence and persistence of antibody titers to recombinant HIV-1 core and matrix proteins in HIV-1 infection.

Numerous studies have established the correlation between antibodies to the core protein p24 of HIV-1 and the progression of the acquired immunodeficiency syndrome. In this study, we analyzed the immune response to two recombinant gag proteins, p24 and p17, in order to evaluate their diagnostic or prognostic significance. Immune response to the immunodominant domain of the transmembrane glycoprotein gp41 was used as a reference. Sera collected from individuals from France and Burundi (Central Africa) at various CDC stages of HIV-1 infection were tested using three sandwich enzyme-linked immunoassays developed with a synthetic peptide corresponding to the immunodominant domain of gp41, SP gp41, or recombinant p24 and p17 cloned and expressed in Escherichia coli. These assays allowed detection of titer antibodies to the three cited antigens. Antibodies to SP gp41 were detected in every HIV-1-positive patient from France and Burundi, generally at a high and stable level. Results obtained with p24 confirmed the value of antibodies to p24 as a prognostic marker only in European and North American populations, since the African population had very high levels of these antibodies even at an advanced stage of the disease. They also confirmed that initial antibody response to p24 is more predictive of outcome than antibody titer change over time. Although antibodies to p17 decline during progression to AIDS, they are frequently absent in French patients at early, asymptomatic stages and therefore could not be used as a prognostic marker. In contrast, antibodies to p17 are significantly less common in African patients with AIDS when compared with symptomless HIV-1-infected African individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Isolated motor control dysfunction related to progressive multifocal leukoencephalopathy during AIDS with normal MRI.

We describe the case of a human immunodeficiency virus-infected 34-year-old man with progressive multifocal leukoencephalopathy (PML). His case displayed unusual features, including a bizarre movement disorder, predominant involvement of the subcortical U fibers on neuropathologic examination, and the absence of MRI abnormalities suggestive of PML. Anatomic-clinical correlations are discussed.

Tamponade due to Rhodococcus equi in acquired immunodeficiency syndrome.

Infection with Rhodococcus equi has been described as a cause of cavitary pneumonia in AIDS patients. We report such a case, complicated by bacteremia, tamponade, and possible brain and liver abscesses. Medical treatment was successful with pericardiocentesis and antibiotherapy with teicoplanin, gentamicin, clarithromycin, rifampicin, supplemented by empirical treatment of cerebral toxoplasmosis. Antibiotherapy was terminated after 6 months, without relapse 2 months later.

Characterisation and functional aspects of monoclonal antibodies specific for surface proteins of coagulase-negative staphylococci.

Mouse monoclonal antibodies (MAbs) raised against whole cells of Staphylococcus epidermidis strain 354 were characterised morphologically and functionally. Nine MAbs showed strong reactivity with coagulase-negative staphylococci (CNS). Only two MAbs were specific for CNS; both belonged to the IgG1 subclass, and one, MAb 36.4, reacted only with the strain used for immunisation. In immunoblotting, both CNS-specific MAbs 36.3 and 36.4 reacted strongly with cell-wall protein bands of 220 Kda of S.epidermidis strain 354 and weak reactivity was observed with a 110-Kda band. MAb 36.3 reacted also with 220-230 Kda bands of two other S.epidermidis strains (291 and ATCC 35984) and a 160-180 Kda band of S.epidermidis strain 354. Only MAb 36.4 promoted phagocytosis of strain 354 by polymorphonuclear leucocytes (PMNL) and monocytes, whereas MAb 36.3 and the other MAbs lacked this activity. Opsonisation of S. epidermidis with MAb 36.4 in the presence of complement enhanced uptake by PMNL, but not by monocytes. Furthermore, S.epidermidis strain 354 opsonised with MAb 36.4 induced chemiluminescence of PMNL. Immuno-gold electronmicroscopy with both MAbs 36.3 and 36.4 demonstrated a homogeneous distribution of gold particles on the surface as well as close to the surface of S.epidermidis.

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.

Surface proteins of coagulase-negative staphylococci: their role in adherence to biomaterials and in opsonization.

During the last decade coagulase-negative staphylococci (CN-Staph) have clearly emerged as pathogens in patients equipped with foreign devices. This has fueled the interest in these bacteria considerably and as a result, knowledge of the biology of CN-Staph as well as insight into the pathogenesis of biomaterial-associated infections due to these bacteria are rapidly expanding. Adherence of bacteria to biomaterials is a necessary step in the process of these infections. Evidence is accumulating that surface proteins of CN-Staph are essential in the early phases of adherence to biomaterials. By using monoclonal antibodies in immunoblotting and immune electron micrography we have identified a cell wall protein complex apparently located on the surface of CN-Staph and involved in adherence to biomaterials. Further studies will be oriented at characterization of the protein adhesin(s) and at identification of the surface structures with which the adhesion is associated.

[Situations and procedures with risk of bacterial endocarditis (intracardiac surgery excluded)]. / Situations et gestes à risque d'endocardite infectieuse (en dehors des interventions intracardiaques).

Situations which can be considered at risk for infective endocarditis are those causing a bacteremia, which is necessary for the development of an endocarditis. Such situations can be identified by clinical studies evaluating the rate at which a bacteremia occurs after some procedures or because of lesions, then the risk of endocarditis after such a bacteremia. Without considering preexisting cardiac lesion and age, some situations seem to be at risk of subsequent endocarditis: acute bacterial infection for which antibiotherapy is necessary; procedures involving the mouth with the exception of superficial caries and bloodless supragingival prosthetic preparations; oesophageal dilatation, laser endo-oesophageal procedures, sclerosis of oesophageal varices; colonoscopy and sigmoidoscopy for cancer lesions, gastrointestinal procedures on a potentially infected gastrointestinal tract (cholecystectomy, colectomy...); tonsillectomy and adenoidectomy; naso-tracheal intubation; instrumental procedures involving the ureter or kidney, and prostatic or urinary tract biopsies and surgery; procedures performed on infected skin. In cardiac patients at high risk, in addition to the above retrograde cholangiography, colonoscopy and rectosigmoidoscopy, lithotripsy. In these situations the risk of endocarditis is probably linked to the rate of bacteremia, the size of inoculum, and the bacteria, compared with spontaneous bacteremia without any procedure, where the inoculum is low and bacteria is considered as non pathogenic. A prophylaxis has to be discussed in such situations, which are probably involved in less than 10% of endocarditis.

[Pulmonary malacoplakia and Rhodococcus equi pneumonia in a patient infected with the human immunodeficiency virus. A case report with review of the literature]. / Malacoplasie pulmonaire et pneumonie à Rhodococcus equi chez un patient infecté par le virus de l'immunodépression humaine. A propos d'un cas avec revue de la littérature.

We report a case of pulmonary malakoplakia in a patient suffering from AIDS secondary to a Rhodococcus equi pneumonia. The association between these two pathologies only occurring in the immunodepressed does not seen fortuitous. Deficiency in cellular immunity and macrophage cellular activity as well as failure of intracellular bactericidal and phagolysosomal function are very probably the links. The treatment of this opportunistic germ rests on prolonged poly-antibiotic therapy or indeed surgical excision.

[Neuromeningeal listeriosis in adults, excluding pregnancy. Prognosis and development of neurologic manifestations. Retrospective study of 63 cases]. / Listériose neuro-méningée de l'adulte, en dehors de la grossesse. Pronostic et évolution des manifestations neurologiques. Etude rétrospective de 63 observations.

Patients' constitutional background, treatment and neurological manifestations were analyzed in a retrospective study of 63 cases of neuromeningeal listeriosis in adults. Age over 60 and coma at the onset were of poor prognosis, but immunodepression (present in only 38% of the cases) did not seem to affect the outcome. The ampicillin-aminoglycoside combination did not appear to improve the vital and functional prognoses more than ampicillin alone. The neurological manifestations observed at the end of hospitalization in 16 of the 42 patients who were cured were not necessarily permanent: among the 13 patients who could be followed up for a mean period of 6.5 years, 5 recovered completely, 5 recovered partially and 3 remained unchanged at neurological examination.