Cédric Arvieux

Value of Preoperative Investigations in Diagnosing Prosthetic Joint Infection: Retrospective Cohort Study and Literature Review

The diagnosis of a prosthetic joint infection is difficult, but crucial for appropriate treatment. Scintigraphy with specific markers for infection (labelled white cells or immunoglobulin-G) has been reported as a more reliable diagnostic tool than clinical assessment (fever, fistula), laboratory studies (polynuclear neutrophil count, erythrocyte rate sedimentation, and C-reactive protein), and preoperative aspiration. In the first part of this study, we retrospectively reviewed 230 patients admitted with a suspected prosthetic joint infection, and examined the validity of the different diagnostic tools for the group as a whole and for subgroups according to the Coventry classification. In the second part, we reviewed 35 articles about preoperative evaluation of infection in prosthetic joints and compared them to our findings. Our study indicates that C-reactive protein and joint aspiration are the most useful tools to diagnose prosthetic joint infection even in situations of chronic infection (Coventry type II).

Yellow fever vaccine is safe and effective in HIV-infected patients.

We retrospectively studied 12 HIV-infected patients vaccinated with the 17D yellow fever (YF) strain. At vaccination, the mean CD4 cell count was 561 ± 363 cells/mm 3 . A neutralizing YF antibody response in serum was obtained in all patients. There were no significant changes in CD4 cell count or viral load compared with baseline. One patient reported transient fever and pharyngitis. YF vaccine appears safe and effective in HIV-infected patients with CD4 cell counts > 200 cells/mm 3 .

Increasing Incidence of Severe Epstein-Barr Virus-Related Infectious Mononucleosis: Surveillance Study

ABSTRACT Older patients are more susceptible to severe Epstein-Barr virus (EBV)-related infectious mononucleosis (IM). This condition may increase in industrialized countries where primary EBV infection occurs later in life. Between 1990 and 2004, 38 patients were admitted to our department with EBV-related IM. Two patients died. The annual incidence increased significantly (r = 0.623; P = 0.013).

Amprenavir or fosamprenavir plus ritonavir in HIV infection: pharmacology, efficacy and tolerability profile.

Amprenavir is an HIV-1 protease inhibitor, the first in vitro activity studies of which were published in 1995. During in vivo development, it became clear that the pharmacokinetics of the drug would result in patients taking a large number of pills daily. The first comparative studies of amprenavir versus other protease inhibitors showed it had comparatively weak activity. Thus, studies using low doses of ritonavir to enhance the pharmacokinetic profile of amprenavir were first communicated in 2000. Only a small number of clinical trials in HIV-1-infected patients have been published.The pharmacokinetics of amprenavir have been documented in both healthy individuals and in HIV-1-infected patients. Amprenavir trough plasma concentrations increase 3- to 10-fold and the area under the concentration-time curve (AUC) increases 2- to 3-fold when using amprenavir 450 or 600mg combined with ritonavir 100mg twice daily. Peak concentrations of amprenavir are less influenced by ritonavir coadministration, with a 1- to 2-fold increase. As there is no pharmacokinetic advantage to increasing ritonavir doses, the combination has only been used with low doses of ritonavir (100mg twice daily or 200mg once or twice daily). Concomitant use of currently available non-nucleoside reverse transcriptase inhibitors (NNRTIs) — efavirenz or nevirapine — is possible when amprenavir is coadministered with ritonavir, despite the pharmacokinetic interactions described when they are used with amprenavir alone.Fosamprenavir (GW 433908) is a prodrug of amprenavir primarily metabolised to amprenavir in the epithelial cells of the intestine. At steady state, plasma trough concentrations and AUC are slightly greater with fosamprenavir (two pills of 700mg twice daily) than amprenavir (eight soft gel capsules of 150mg twice daily).The clinical adverse effects of amprenavir are similar whether administered unboosted or in combination with ritonavir. Skin rashes do not appear to be more frequent. With regard to lipid profiles, the addition of ritonavir to amprenavir induces an increase in cholesterol and triglyceride levels; however, prospective comparative studies are lacking.In short-term prospective trials in antiretroviral-naive individuals, virological suppression with highly active antiretroviral therapy containing amprenavir plus ritonavir is similar to or higher than with unboosted amprenavir, with a smaller pill intake. Few comparative data are available in treatment-experienced patients. In several small studies, different salvage regimens which included amprenavir plus ritonavir achieved undetectable viral levels in half of the patients.Although the I50V amino acid substitution is the key mutation conferring resistance to amprenavir, the accumulation of several mutations is needed to ncrease the IC50 (concentration that produces 50% inhibition) of amprenavir. When used with ritonavir, the accumulation of six or more mutations among L10F/I/V, K20M/R, E35D, R41K, I54V, L63P, V82A/F/T/S and I84V leads to clear decrease in viral response to treatment.In salvage regimens, coadministration of amprenavir with lopinavir/ritonavir induces variations in lopinavir and amprenavir concentrations (decrease or increase in both drug concentrations) compared with the combination with ritonavir alone. Currently, close pharmacokinetic follow-up is mandatory when such combinations are used.There are sufficient data available today to support coadministration of reduced doses of amprenavir with low doses of ritonavir. Compared with amprenavir alone, this results in the administration of fewer pills with equivalent or higher efficacy, but without new clinical adverse effects. The concentrations of amprenavir achieved are high enough for use in treatment-experienced patients who have an accumulation of amino acid substitutions in the HIV-1 protease gene. It also allows combinations with NNRTIs.The pharmacokinetic properties of fosamprenavir and the first clinical trials in treatment-naive and treatment-experienced patients should allow it to be considered as a better alternative to amprenavir in countries where fosamprenavir is already available.

Detection of herpesvirus genomes by polymerase chain reaction in cerebrospinal fluid and clinical findings

BACKGROUND The viruses of the Herpesviridae family, in particular herpes simplex virus types 1 (HSV-1) and 2 (HSV-2), cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella zoster virus (VZV), and human herpesvirus 6 (HHV-6), are responsible for numerous infections of the central nervous system (CNS). These infections manifest as diverse clinical signs, many of which are not specific. The diagnosis of these infections is necessary to make it possible to adapt treatment appropriately, as treatment is specific for the particular virus concerned. OBJECTIVES To apply a polymerase chain reaction (PCR) technique for the diagnosis in a single reaction of the six herpesviruses most frequently detected in the cerebrospinal fluid (CSF) and to analyse clinical events in patients presenting positive results in PCR for herpesviruses. STUDY DESIGN We studied 141 patients, from whom 180 CSF samples were collected. The clinical files of the patients were consulted retrospectively, and a list of clinical signs was recorded. After testing by targeted PCR, at the clinicians demand, we tested these samples by herpes consensus PCR, which detects six herpesviruses (HSV-1, HSV-2, CMV, EBV, VZV, HHV-6), in a single PCR. RESULTS Targeted PCR tests identified 25 CSF samples (13.9%), corresponding to 18 patients (12%), as positive. The herpes consensus PCR test detected 49 samples (27.2%) as positive, resulting in the identification of 54 individual viruses (four samples displayed co-infection) from 39 patients (27%). 130 CSF samples, from 101 patients, tested negative by both techniques. 23 HIV-positive patients (30.6%), three HIV-negative immunocompromised patients (27%), and 14 immunocompetent patients (25%) were CSF PCR-positive. In HIV-positive patients, CMV was the virus most frequently identified (13%), followed by EBV (10.6%), VZV (5.3%) and finally HSV-1 and HSV-2 (both 1.3%). We did not detect HHV-6 in any of these samples. We detected only HSV-2, EBV and VZV in the 11 HIV-negative immunocompromised patients. CSF samples of immunocompetent patients contained mostly VZV (9%) and HSV-1 (7.3%). CONCLUSIONS The herpes consensus PCR for a given virus was more sensitive than the standard, targeted PCR used in our laboratory. The clinical signs presented by patients infected with HSV-1, HSV-2 and CMV were similar to those reported in previous studies. For VZV, we report the possibility of mild, transient cerebral viral reactivation. Our data on the detection of EBV by PCR suggest that the PCR test is of predictive value for cerebral lymphoma in immunocompromised patients. The possible role of HHV-6 in a subacute neurological disorder merits further investigation.

Simultaneous quantitative assay of atazanavir and 6 other HIV protease inhibitors by isocratic reversed-phase liquid chromatography in human plasma

Several liquid chromatography methods for assay of antiretroviral drugs in human plasma have been described, but none included atazanavir. The authors describe a user-friendly, validated, and rapid technique, derived from a procedure the authors have already published, allowing simultaneous quantification of amprenavir, indinavir, lopinavir, nelfinavir (and its M8 metabolite), ritonavir, saquinavir, efavirenz, and nevirapine. Assays were performed after diethyl ether liquid-liquid extraction from 250 μL plasma samples. Chromatographic separation was achieved on an X-TERRA column using a 58% water (with 3 mM pyrrolidine) and 42% acetonitrile mobile phase; 240 nm ultraviolet wavelength was used for atazanavir detection. This method has been in routine use in our laboratory for antiretroviral drug monitoring and now allows quantitative assay of a novel HIV protease inhibitor, atazanavir, with satisfactory intra- and interassay precision (CV < 12%).

Optimizing combination rifampin therapy for staphylococcal osteoarticular infections

Staphylococcus spp. causes more than half of all osteoarticular infections of native structures or implanted material. The ability of Staphylococcus spp. to persist within infected bone tissue and to produce a bacterial biofilm, most notably in infections of implanted material, can lead to treatment failures and microbiological relapses. Rifampin is a cornerstone of the treatment of staphylococcal osteoarticular infections, particularly those of implanted material. Rifampin is a bactericidal antibiotic that diffuses very well within bone tissue and bacterial biofilms. The mechanism of action is inhibition of bacterial DNA transcription to mRNA independently from bacterial division, which results in activity against even dormant Staphylococcus spp. organisms. However, the high risk of emergence of rifampin-resistant mutants requires the concomitant administration of another antibiotic. Several antibiotics are recommended in the French guidelines issued by the French-Speaking Society for Infectious Diseases (Société de Pathologie Infectieuse de Langue Française [SPILF]). Here, we discuss the results from in vitro, animal, and clinical studies that explain the advantages and drawbacks of each antibiotic used with rifampin to treat osteoarticular infections due to Staphylococcus spp.

Effect of twice-daily nevirapine on adherence in Hiv-1-infected patients: a randomized controlled study

Objective:For optimal adherence, once-daily dosing is best. Whether this applies to antiretroviral therapy is unknown. We thus aimed to determine the effect of once-daily dosing on adherence to nevirapine. Design:A three-phase (3-month observational, 4-month randomized, 5-month interventional) open-label, clinical trial at four French academic medical centres during 2005–2006 among 62 chronically HIV-1-infected subjects with long-lasting viral suppression under a twice-a-day nevirapine-based antiretroviral combination. Methods:Adherence was measured using electronic monitoring devices and validated by sequential plasma drug levels. Participants were randomly assigned to switch to nevirapine 400 mg once-daily (n = 31) or continue nevirapine 200 mg twice-a-day (n = 31). After the randomized phase, participants had an opportunity to choose their antiretroviral dosage. Primary outcome was the mean percentage of adherence. Results:Fifty-two patients qualified for electronic data analysis. During the randomized phase, the mean adherence rate was non-significantly superior by 0.5% in once-daily versus twice-a-day dosing (P = 0.68), adjusting for previous twice-a-day adherence rate (P < 0.0001). Once-daily group increased days without dose [odds ratio (OR) 1.7; 95% confidence interval (CI) 1.0, 2.8; P = 0.04], adjusting for previous drug interruptions (P < 0.0001). In the longitudinal analysis, once-daily dosing was significantly associated with at least two consecutive days without dose (OR 4.4; 95% CI 1.9, 10.3; P < 0.001). Conclusion:Changing from twice to once-daily nevirapine does not improve adherence. Supporting continuous adherence to antiretroviral therapy in the ‘once-a-day era’ remains a challenge, even if more potent regimens can achieve viral suppression at lower adherence levels.

Benefits of Management Strategy Adjustments During an Outbreak of Enterovirus Meningitis in Adults

Enteroviruses (EVs) are the most common identifiable cause of the aseptic meningitis syndrome. Widespread seasonal outbreaks of EV meningitis result in a high financial cost to the community, in part because of the difficulty of discriminating between viral and bacterial meningitis. During a nationwide outbreak of EV meningitis due to echovirus 30 in France we tested the hypothesis that a management strategy including early testing of cerebrospinal fluid (CSF) by means of EV PCR in all adult patients with acute aseptic meningitis on admission might reduce the duration of hospitalization and thus the expenditure on health resources. We compared the characteristics of adult patients with acute aseptic meningitis seen in our institution before (n = 21) and after (n = 27) implementation of this strategy. The strategy was cost-effective in that it significantly reduced (i) the mean duration of hospital stay (from 103 to 80 h; p = 0.04); and (ii) the mean duration of antibacterial treatment (from 115 to 69 h; p = 0.02). Systematic testing of CSF in adult patients with aseptic meningitis by means of EV PCR may be cost-effective during an outbreak of EV meningitis.

Multiple Organ Failure during Primary HIV Infection

The appearance of primary HIV infection ranges from an asymptomatic presentation to a symptomatic illness resembling infectious mononucleosis. Severe unusual presentations include acute myopericarditis, renal failure, and opportunistic infections such as esophageal candidiasis, cytomegalovirus infection, and Pneumocystis jirovecii pneumonia. We report a case of multiple organ failure during primary HIV infection.