Effect of achieving bone sterilisation on bone architecture and bone marrow, in an experimental rabbit model of osteomyelitis caused by carbapenemase-producing Enterobacterales.

OBJECTIVES: Natural history and treatment of bone infections caused by carbapenemase-producing Enterobacterales (CPE) are poorly defined. We evaluated the effect of treatment on the progression of subacute osteomyelitis in a rabbit model. METHODS: Two isolates were used: a KPC-producing Klebsiella pneumoniae and an Escherichia coli harbouring blaOXA-48 and blaCTX-M15 inserts, both susceptible to gentamicin, colistin, fosfomycin, and ceftazidime-avibactam. Osteomyelitis was induced in rabbits by tibial injection of 2 × 108 colony-forming units/mL. Antibiotics were started 14 d later, for 7 d, in 6 groups of 12 rabbits. Three days after treatment completion (D24), rabbits were euthanised and bones were cultured. Bone marrow and bone architecture macroscopic changes were evaluated through analysis of pictures by investigators unaware of the rabbit treatment group and microbiological outcome, using scales ranging from 0 (normal) to 3 (severe lesions) depending on modifications. RESULTS: Bone marrow modifications induced by local infection were similar between prematurely deceased animals and non-sterilised animals (P = 0.14) but differed significantly from animals that achieved bone sterilisation after treatment (P = 0.04). Conversely, when comparing bone deformity, rabbits who died early (n = 13) had similar bone architecture as those achieving bone sterilisation (P = 0.12), as opposed to those not sterilised after treatment (P = 0.04). After a multivariate logistic regression, bone marrow scale ≤2 was associated with bone sterilisation (P < 0.001), and bone architecture scale ≤2 was associated with bone sterilisation (adjusted odds ratio = 2.7; 95% confidence interval 1.14-6.37) and KPC infection (adjusted odds ratio = 5.1; 95% confidence interval 2.17-12.13). CONCLUSION: Effective antibacterial treatment reduces bone architecture distortion and bone marrow changes. These variables may be used as proxy for bone sterilisation.

Hip Joint Infections Caused by Multidrug-Resistant Enterobacterales Among Patients With Spinal Cord Injury: Experience of a Reference Center in the Greater Paris Area.

Background: We aimed to describe the management and treatment of hip joint infections caused by multidrug-resistant Enterobacterales among patients with spinal cord injury (SCI). Methods: We included all hip joint infections associated with grade IV decubitus ulcers caused by extended-spectrum beta-lactamase producing Enterobacterales (ESBL-PE) and carbapenemase-producing Enterobacterales treated in a reference center for bone and joint infections over 9 years in a retrospective study. Results: Seventeen SCI patients with ischial pressure ulcers breaching the hip capsule (mean age 52 ± 15 years) were analyzed. In 16 patients, paraplegia was secondary to trauma and 1 was secondary to multiple sclerosis. Infections were mostly polymicrobial (n = 15; 88.2%), notably caused by Klebsiella pneumoniae (n = 10) and Staphylococcus aureus (n = 10). The carbapenemases identified were exclusively OXA-48-type (n = 3) including 2 isolates coexpressed with ESBL-PE within the same bacterial host. Multidrug-resistant Enterobacterales were commonly resistant to fluoroquinolones (n = 12; 70.6%). Most therapies were based on carbapenems (n = 10) and combination therapies (n = 13). Median duration of treatment was 45 (6-60) days. Of 17 cases of hip joint infections, 94.1% (n = 16) benefited from a femoral head and neck resection. Infection control was initially achieved in 58.8% (n = 10) of cases and up to 88.2% after revision surgeries, after a median follow-up of 3 (1-36) months. Conclusions: Hip infections among SCI patients caused by multidrug-resistant Enterobacterales are often polymicrobial and fluoroquinolones-resistant infections caused by Klebsiella pneumoniae and S aureus, highlighting the need for expert centers with pluridisciplinary meetings associating experienced surgeons, clinical microbiologists, and infectious disease specialists.

Native bone and joint infections caused by extended-spectrum ß-lactamase-producing Enterobacterales: experience of a reference centre in the Greater Paris area.

Antibiotic treatment of native osteomyelitis caused by extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-PE) is a challenge. Limited epidemiological and outcome data are available. This retrospective cohort study included osteomyelitis patients with ESBL-PE infections treated in a reference centre for bone and joint infections (BJIs) between 2011-2019. Twenty-nine patients with native BJI (mean age, 44.4 ± 15.7 years) were analysed. Fifteen cases were paraplegic patients with ischial pressure sores breaching the hip capsule. Other cases included eight other hip infections, four tibial infections and two foot infections. Infections were mostly polymicrobial (n = 23; 79.3%), including Staphylococcus aureus (n = 13; 8 methicillin-resistant). Klebsiella pneumoniae (n = 13) was the most frequent ESBL-producing species identified, followed by Escherichia coli (n = 10), including 3 E. coli/K. pneumoniae co-infections, and Enterobacter spp. (n = 9). ESBL-PE were rarely susceptible to fluoroquinolones (n = 4; 13.8%). Most therapies were based on carbapenems (n = 22) and combination therapies (n = 19). The median duration of treatment was 41 (5-60) days. Primary control of the infection was achieved in 62.1% (18/29) of cases and up to 86.2% after second look surgeries, after a median follow-up of 6 (1-36) months. Infection with ESBL-producing K. pneumoniae was associated with failure (P = 0.001), whereas age, infection location, prior colonisation and antimicrobial therapy were not found to be predictors of outcome. ESBL-PE native BJIs are often polymicrobial and fluoroquinolone-resistant infections caused by K. pneumoniae, highlighting the need for expert centres with pluridisciplinary meetings with experienced surgeons.

Efficacy of generic meropenem products in combination with colistin in carbapenemase-producing Klebsiella pneumoniae experimental osteomyelitis.

Guidelines for the management of carbapenemase-producing Enterobacterales (CPE) infections recommend a combination of two active agents, including meropenem if the minimum inhibitory concentration (MIC) is ≤8 mg/L. The therapeutic equivalence of meropenem generics has been challenged. We compared the bactericidal activity of meropenem innovator (AstraZeneca) and four generic products (Actavis, Kabi, Mylan and Panpharma), both in vitro and in vivo, in association with colistin. In vitro time-kill studies were performed at 4 × MIC. An experimental model of KPC-producing Klebsiella pneumoniae osteomyelitis was induced in rabbits by tibial injection of a sclerosing agent followed by 2 × 108 CFU of K. pneumoniae KPC-99YC (meropenem MIC = 4 mg/L; colistin MIC = 1 mg/L). At 14 days after inoculation, treatment for 7 days started in seven groups of ≥10 rabbits, including a control group, a colistin group, and one group for each meropenem product (i.e. the innovator and four generics), in combination with colistin. In vitro, meropenem + colistin was bactericidal with no viable bacteria after 6 h, and this effect was similar with all meropenem products. In the osteomyelitis model, there was no significant difference between meropenem generics and the innovator when combined with colistin. Colistin-resistant strains were detected after treatment with colistin + meropenem innovator (n = 3) and generics (n = 3). The efficacy of four meropenem generics did not differ from the innovator in vitro and in an experimental rabbit model of KPC-producing K. pneumoniae osteomyelitis in terms of bactericidal activity and the emergence of resistance.

Population pharmacokinetics and dosing simulations of amoxicillin in obese adults receiving co-amoxiclav.

BACKGROUND: Pneumonia, skin and soft tissue infections are more frequent in obese patients and are most often treated by co-amoxiclav, using similar dosing regimens to those used for non-obese subjects. No data are available on amoxicillin pharmacokinetics among obese subjects receiving co-amoxiclav. MATERIALS AND METHODS: Prospective, single-centre, open-label, non-randomized, crossover pharmacokinetic trial having enrolled obese otherwise healthy adult subjects. A first dose of co-amoxiclav (amoxicillin/clavulanate 1000/200 mg) was infused IV over 30 min, followed by a second dose (1000/125 mg) administered orally, separated by a washout period of ≥24 h. We assayed concentrations of amoxicillin by a validated ultra HPLC-tandem MS technique. We estimated population pharmacokinetic parameters of amoxicillin by non-linear mixed-effect modelling using the SAEM algorithm developed by Monolix. RESULTS: Twenty-seven subjects were included in the IV study, with 24 included in the oral part of the study. Median body weight and BMI were 109.3 kg and 40.6 kg/m2, respectively. Amoxicillin pharmacokinetics were best described by a two-compartment model with first-order elimination. Mean values for clearance, central volume, intercompartmental clearance and peripheral volume were, respectively, 14.6 L/h, 9.0 L, 4.2 L/h and 6.4 L for amoxicillin. Oral bioavailability of amoxicillin was 79.7%. Amoxicillin Cmax after oral administration significantly reduced with weight (P = 0.013). Dosing simulations for amoxicillin predicted that most of the population will achieve the pharmacodynamic target of fT>MIC ≥40% with the regimen of co-amoxiclav 1000/200 mg (IV) or 1000/125 mg (oral) q8h for MICs titrated up to 0.5 mg/L (IV) and 1 mg/L (oral). CONCLUSIONS: Pharmacokinetic/pharmacodynamic goals for amoxicillin can be obtained in obese subjects.

Colistin-containing cement spacer for treatment of experimental carbapenemase-producing Klebsiella pneumoniae prosthetic joint infection.

Carbapenemase-producing Enterobacteriaceae (CPE) are emerging multidrug-resistant bacteria responsible for invasive infections, including prosthetic joint infections (PJIs). Local administration of colistin may provide bactericidal concentrations in situ. This study evaluated the efficacy of a colistin-impregnated cement spacer, alone and in combination with systemic antibiotics, in a rabbit model of CPE-PJI. Elution of 3 MIU of colistimethate sodium (CMS) in 40 g of poly(methyl methacrylate) cement was studied in vitro. In vivo, 5 × 108 CFU of KPC-producing Klebsiella pneumoniae (colistin and meropenem MICs of 1 mg/L and 4 mg/L, respectively) were injected close to a prosthetic knee. Surgical debridement and prosthesis removal were performed 7 days later, and rabbits were assigned to six treatment groups (11-13 rabbits each): drug-free spacer; colistin-loaded spacer; colistin intramuscular (i.m.); colistin i.m. + colistin spacer; colistin i.m. + meropenem subcutaneous (s.c.); and colistin i.m. + meropenem s.c. + colistin spacer. Systemic treatment was administered at doses targeting pharmacokinetics in humans, and rabbits were euthanised 7 days later to evaluate bacterial counts in infected bones. In vitro, CMS elution was low (<0.1% at 24 h) but reached a local concentration of ≥20 mg/L (>20 × MIC). In vivo, combinations of local and systemic colistin, with or without meropenem, were the only regimens superior to the control group (P ≤ 0.05) in terms of viable bacterial counts and the proportion of rabbits with sterile bone, with no emergence of colistin-resistant strains. Colistin-loaded cement spacer in combination with systemic antibiotics were the most effective regimens in this CPE-PJI model.

Implementation of a simple innovative system for postprescription antibiotic review based on computerized tools with shared access.

BACKGROUND: Controlling antibiotic use in healthcare establishments limits their consumption and the emergence of bacterial resistance. AIM: To evaluate the efficiency of an innovative antibiotic stewardship strategy implemented over three years in a university hospital. METHODS: An antimicrobial multi-disciplinary team (AMT) [pharmacist, microbiologist and infectious disease specialist (IDS)] conducted a postprescription review. Specific coding of targeted antibiotics (including broad-spectrum ß-lactams, glycopeptides, lipopeptides, fluoroquinolones and carbapenems) in the computerized physician order entry allowed recording of all new prescriptions. The data [patient, antibiotic(s), prescription start date, etc.] were registered on an AMT spreadsheet with shared access, where the microbiologist's opinion on the drug choice, based on available microbiology results, was entered. When the microbiologist and pharmacist did not approve the antibiotic prescribed, a same-day alert was generated and sent to the IDS. That alert led the IDS to re-evaluate the treatment. FINDINGS: From 2012 to 2014, 2106 targeted antibiotic prescriptions were reviewed. Among them, 389 (18.5%) generated an alert and 293 (13.9%) were re-evaluated by the IDS. Recommendations (mostly de-escalation or discontinuation) were necessary for 136 (46.4%) and the prescribers' acceptance rate was 97%. The estimated intervention time was <30 min/day for each AMT member. This system allowed correct use of targeted antibiotics for 91.8% of prescriptions, but had no significant impact on targeted antibiotic consumption. CONCLUSION: This computerized, shared access, antibiotic stewardship strategy seems to be time saving, and effectively limited misuse of broad-spectrum antibiotics.

Real-time mobile teledermoscopy for skin cancer screening targeting an agricultural population: an experiment on 289 patients in France.

BACKGROUND: The incidence of skin cancer has reached epidemic proportions in the white population and is significantly elevated in agricultural populations, who are exposed to ultraviolet radiation during their professional activities. In 2014, the Agricultural Social Insurance Mutual Benefit Fund (MSA) offered its customers who work in agriculture and live in rural areas with reduced access to dermatologists the ability to participate in a 1-day teledermoscopic (TDS) screening event. OBJECTIVE: This study's aim was to assess the feasibility of real-time mobile TDS triage of a large number of agricultural workers by trained medical officers and occupational physicians. METHODS: Fifteen TDS screening centres were located in different areas of France. Individuals older than 18 years who worked in agriculture and lived in rural area near a TDS screening centre were invited to participate in a 1-day screening event and were examined by an MSA physician. In cases of suspicious skin lesions, clinical and dermoscopic images were obtained and transferred immediately to four dermatologists who were simultaneously present at the tele-platform for diagnosis and decision-making. Low-quality images were retaken. RESULTS: Two-hundred eighty-nine patients underwent skin cancer screening. Among 199 patients (69%), 390 suspicious lesions were identified and generated 412 pictures. All lesions were analysed by dermatologists. For 105 patients (53%), no follow-up was required. Seventeen patients were referred to local dermatologists for rapid examination, including 12 cases of suspected malignant melanocytic lesions. Among the 12 patients with suspected melanoma, face-to-face visits were conducted within 10 days for 11 of them, and 1 case of melanoma was confirmed by histopathology. CONCLUSIONS: Our study suggests that teledermoscopy performed in the context of occupational medicine and targeted to agricultural populations is feasible and could be useful for improving skin cancer screening in at-risk populations while avoiding face-to-face examinations by a dermatologist in 53% of cases.

Critical analysis of experimental models of periprosthetic joint infection.

INTRODUCTION: Because the extreme diversity of clinical situations makes formal clinical trials difficult to carry out, animal models of periprosthetic infection in orthopaedics are needed to understand the aetiology and pathology of these infections, and to test new treatment methods. These experimental models must reproduce the features of the infections encountered in clinical practice. One of the model variables is the method of inoculation: local (intra-articular), intravenous or intra-arterial. Another is the timing of the inoculation: intra-operative or postoperative. Together, these options simulate the different contamination methods: direct, by proximity or blood-borne. However, the chosen inoculation route can also affect the infection rate and severity in the various models, and in some cases do not accurately reproduce the postoperative infections encountered clinically. HYPOTHESIS: The direct inoculation method is the most effective for inducing a local infection on a foreign body in a joint, and the least iatrogenic. METHODS: A critical analysis of published studies was carried out to evaluate each model against three endpoints, according to the type of inoculation. The primary endpoint was the infection rate, which should be as close as possible to 100%. The secondary endpoints were the mortality rate and rate of spontaneous healing, both of which should be as low as possible. Twenty-one articles were reviewed. RESULTS: Intra-articular and intra-medullary inoculations had induction rates between 70 and 100%; intra-arterial inoculations had an induction rate of 100%, while intravenous inoculation had a rate of 47 to 77%. The mortality rates were lower with the intra-articular and intramedullary inoculations (5 to 23%) than for the intra-arterial inoculations (37%) and intravenous inoculations (28 to 56%). The spontaneous healing rate was 0 to 30% for intra-articular and intramedullary inoculations, 30 to 53% for intravenous inoculations and 0% for intra-arterial inoculations. CONCLUSION: Direct inoculation methods are most effective at reproducing chronic periprosthetic joints infections, without putting the animal's life at risk or allowing for spontaneous healing. The simulation of blood-borne infections is more random.

Chronic gonococcal arthritis with C5 deficiency presenting with brief flare-ups: case study and literature review.

Gonococcal arthritis is typically acute and appears within 3 weeks after initial infection. Chronic gonococcal arthritis is now exceptionally rare, since the advent of the antibiotic era. Numerous host factors are involved in gonococcal dissemination, such as complement deficiency, HIV and gonococcus strain characteristics. Gonococcal arthritis shares the same risk factors. In this instance, our patient was a 16-year-old girl suffering from persistent polyarthralgia with joint swelling presenting with brief flare-ups for a period of 1 year. She disclosed a single episode of unprotected sexual intercourse 1 year ago, i.e. just before developing her first rheumatological symptoms. Therefore, we performed a joint aspiration (arthrocentesis), and synovial fluid was inoculated directly into aerobic and anaerobic blood culture bottles, which tested positive for Neisseria gonorrhoeae within 24 h. Clinical presentation was consistent with previous reports of chronic gonococcal arthritis. Further investigation revealed a C5 complement deficiency, which might explain the chronic Neisseria process. A favourable outcome was reached after a ten-day course of IV ceftriaxone, with no apparent sequelae found during follow-up 6 weeks later. This case demonstrates an unusual gonococcal arthritis with brief flare-ups for the course of a year, followed by a subacute form. N. meningitidis infections, similar to N. gonorrhoeae, are typically acute and may sometimes be involved in chronic processes. However, this characteristic appears to be rare in the case of N. gonorrhoeae. Risk factors for this chronic process will be discussed with a review of the literature.

Comparison of six generic vancomycin products for treatment of methicillin-resistant Staphylococcus aureus experimental endocarditis in rabbits.

Concerns have recently emerged about the potency and the quality of generic vancomycin (VAN) products approved for use in humans, based on experiments in a neutropenic mouse thigh infection model. However, other animal models may be more appropriate to decipher the bactericidal activities of VAN generics in vivo and to predict their efficacy in humans. We aimed to compare the bactericidal activities of six generic VAN products currently used in France (Mylan and Sandoz), Spain (Hospira), Switzerland (Teva), and the United States (Akorn-Strides and American Pharmaceutical Products [APP]) in a rabbit model of aortic valve endocarditis induced by 8 × 10(7) CFU of methicillin-resistant Staphylococcus aureus (MRSA) strain COL (VAN MIC, 1.5 µg/ml). In vitro, there were no significant differences in the time-kill curve studies performed with the six generic VAN products. Ten rabbits in each group were treated with intravenous (i.v.) VAN, 60 mg/kg of body weight twice a day (b.i.d.) for 4 days. Mean peak serum VAN levels, measured 45 min after the last injection, ranged from 35.5 (APP) to 45.9 µg/ml (Teva). Mean trough serum VAN levels, measured 12 h after the last injection, ranged from 2.3 (Hospira) to 9.2 (APP) µg/ml. All generic VAN products were superior to controls (no treatment) in terms of residual organisms in vegetations (P < 0.02 for each comparison) and in the spleen (P < 0.005 for each comparison). Pairwise comparisons of generic VAN products found no significant differences. In conclusion, a stringent MRSA endocarditis model found no significant differences in the bactericidal activities of six generic VAN products currently used in Europe and America.

[Physicians referent for antimicrobial therapy. Results of a survey conducted during a French Infectious Diseases Society meeting]. / Les référents en antibiothérapie et leurs fonctions. Résultats d'une enquête menée lors de la 5e Journée des référents en antibiothérapie.

We conducted a survey among participants to a French ID Society sponsored meeting for antimicrobial management teams (AMT). We analysed 115 responses. Respondents were mostly physicians (79%) followed by microbiologists (11%), infection control practitioners (9%) and hospital pharmacists (7%). Only 43% were ID board certified while 47% had a university degree on antibiotic use. AMT activities concerning diagnostic and therapeutic advice, residents training and antibiotic use audit were mostly managed by physicians. Antimicrobial resistance and antibiotic consumption were managed, respectively, by the microbiologist and the hospital pharmacist. This survey shows the interest of a multidisciplinary antimicrobial management team. However, the cornerstone of the AMR is clearly the physician. Small hospital could contract part time physician and work through regional teams.

Evaluation of pharmacokinetic interaction between cetirizine and ritonavir, an HIV-1 protease inhibitor, in healthy male volunteers.

BACKGROUND: Serious adverse effects have been observed with some non-sedative H1-antihistamines (terfenadine and astemizole) when they were associated with drugs known to inhibit their metabolism. However, this is not a class effect, and this interaction should be considered on a case-by-case basis. The aim of this study was to evaluate the potential of pharmacokinetic interaction between cetirizine and ritonavir, the most potent cytochrome P450 (CYP) inhibitor. METHODS: An open-label, single-center, one-sequence crossover pharmacokinetic study was conducted in three running periods: cetirizine (CTZ) alone, ritonavir (RTV) alone and then CTZ plus RTV. For each period, steady-state pharmacokinetics were obtained. RTV and CTZ plasma concentrations were determined using validated liquid chromatography methods. The statistical method was based on a 90% confidence interval (CI) for the ratio of population geometric means (combination/drug alone) for each drug and for each parameter [area under the plasma concentration versus time curve (AUC(0-tau,ss)), value of maximum plasma concentration (C(max,ss))] and compared to bioequivalence ranges 80-125% and 70-143% for AUC(0-tau,ss) and C(max,ss), respectively. RESULTS: Among the 17 male subjects enrolled (26.4 +/- 8.6 years), 16 completed the study (1 withdrawal after the first period). The RTV pharmacokinetic parameter values were not affected by CTZ co-treatment. With RTV, a 42% increase in the CTZ AUC(0-tau,ss) (3406 versus 4840 microgh/l, 90% CI of 128-158%), a 53% increase in the CTZ elimination half-life (7.8 h versus 11.9 h, P = 0.001), a slight increase (15%) in the CTZ apparent volume of distribution (V(d,ss)/f) (34.7 l versus 39.8 l, P = 0.035), a 29% decrease in the CTZ apparent total body clearance (49.9 ml/min versus 35.3 ml/min, P < 0.001) and bioequivalent C(max,ss) (374 microg/l versus 408 microg/l) were observed. No serious drug related adverse effects were notified. CONCLUSIONS: CTZ does not significantly affect the pharmacokinetic parameters of RTV, and the association does not, thus, require a modification of the dosage of the protease inhibitor. The increased extent of exposure to CTZ in healthy subjects, in the presence of RTV administered at high doses, remained in the same range as previously observed in the elderly or in mildly renally impaired subjects.

Bioactive polymers grafted on silicone to prevent Staphylococcus aureus prosthesis adherence: in vitro and in vivo studies.

As joint prostheses become infected preventive strategies are needed. Silicone prostheses were coated with a COO - and SO3 - bearing bioactive copolymer, Q5, synthesized by radical polymerization and the adherence of Staphylococcus aureus (S. aureus)to them was evaluated in vitro and in vivo. Copolymer Q5 contains tris(trimethylsiloxy) methacryloxy propyl silane favoring the compatibility with the silicone matrix, cinnamoyl ethyl methacrylate allowing a network formation at the surface of the silicone prostheses, two ionic monomers: methacrylic acid and sodium styrene sulfonate. In vitro experiments were conducted on Q5-coated silicone lenses and on Q5-coated silicone prostheses. In both cases, materials were incubated with fi-bronectin (Fn) because of its important role in S. aureus adherence to implant surfaces. The percentage of adhesion inhibition was observed at approximately 40% for the coated materials compared to the untreated silicone. Rabbits underwent double-blind partial knee replacements with Q5-coated or control implants fitted into the intramedullary canal of the tibia, and 10 7 bacteria were injected into the knees. The number of bacteria adherent on the prostheses was determined 24 hr later. Signifi-cantly fewer bacteria adhered to Q5-coated than control prostheses (2.26 +/- 0.76 vs 3.86 +/- 0.54 log10 CFU/ml; p < 0.0035). Bioactive polymer coating could provide a new method of preventing joint-prosthesis infections. (Journal of Applied Biomaterials & Biomechanics 2003; 1: 178-85).

[Prosthetic valve endocarditis due to Coxiella burnetii: six cases]. / Endocardites à Coxiella burnetii sur prothèse: six observations.

PURPOSE: Prosthetic valve endocarditis is a dangerous complication of valvular surgery (3-6%). Among involved pathogens, Coxiella burnetii is an occasional agent, though isolated with increasing frequency. We report our experience with this peculiar endocarditis and lay stress on specific diagnostic and therapeutic difficulties. METHODS: Between 1990 and 1995, six patients retrospectively met the diagnosis criteria for definite endocarditis due to Coxiella burnetii. RESULTS: Five Algerian men and one French woman presented with prosthetic valve endocarditis with negative blood cultures (on bioprosthesis: four cases, on mechanical valve: two cases). The main clinical and biological feature was febrile congestive heart failure with hepatomegaly, splenomegaly, hepatic and renal abnormalities, inflammatory syndrome, hypergammaglobulinemia, anemia and lymphopenia. Serological testing for Coxiella burnetii provided diagnosis in all cases. Echocardiography displayed vegetations in all cases. Valvular replacement was performed in four patients. With antibiotic therapy including doxycycline or/and hydroxychloroquine, quinolones or rifampicine, all patients experienced complete clinical, biological and echographic remission. CONCLUSION: Q fever prosthetic valve endocarditis presents as a systemic disorder occurring in patients with valvular heart disease. From now on, early diagnosis and efficient medical treatment may provide permanent prosthetic sterilization.

[Evaluation of three testing strategies for detection of hepatitis C in a hospital medical consultation and in an HIV testing center]. / Evaluation de trois stratégies de dépistage de l'hépatite C en consultation hospitalière de Médecine générale et dans un Centre de dépistage anonyme et gratuit du virus de l'immunodéficience humaine.

AIMS: Testing for hepatitis C virus (HCV) is recommended. The purpose of this study was to evaluate the efficacy of HCV testing in a medical consultation without an appointment and in an HIV testing center based on three testing strategies: 1997 French Consensus Conference, "Lettre de la Direction Générale de la Santé" (January 1996), and extension to other risk factors. PATIENTS AND METHODS: For 6 months a free blood test was offered to any patient with a risk factor according to the literature. RESULTS: There were 1 736 new patients at the medical consultation and 1 616 at the testing center. The patients were younger at the testing center than at the medical consultation (31.1 vs 43.3 years; P<0.001). Acceptance of screening was better at the testing center (97.8% vs 75.2%; P<0.001). There were more patients exposed to one of the risk factors at the testing center (31.2% vs 13.9%; P<0.001). Tests were more efficient at the testing center: 30 HCV positive patients/1 616 (1.86%) vs 11/1 736 (0.63%, P<0.01). Tests based on the 1997 French Consensus Conference provided detection in 27/30 (90%) of HCV positive patients at the testing center but only 4/11 (36.3%) at the medical consultation (P<0.01). CONCLUSION: Testing was effective in both places but was more efficient at the testing center. Efficacy of the testing strategies differs significantly according to the place of screening. At the testing center, screening can be restricted to patients with a history of intravenous drug use and blood transfusion. At the medical consultation, screening should be extended to other risk factors.

A comparison of the steady-state pharmacokinetics and safety of abacavir, lamivudine, and zidovudine taken as a triple combination tablet and as abacavir plus a lamivudine-zidovudine double combination tablet by HIV-1-infected adults.

STUDY OBJECTIVE: To investigate the steady-state pharmacokinetics of a triple combination tablet containing abacavir (ABC) 300 mg, lamivudine (3TC) 150 mg, and zidovudine (ZDV) 300 mg taken twice/day, and those of ABC 300 mg twice/day plus a double combination tablet containing 3TC 150 mg and ZDV 300 mg twice/day (ABC-COM). DESIGN: Open-label, crossover study. SETTING: Two hospital-based clinical research units. PATIENTS: Twelve men infected with human immunodeficiency virus-1. INTERVENTION: Steady-state pharmacokinetics of ABC, 3TC, and ZDV were assessed after dosing with ABC-COM and the triple combination tablet. MEASUREMENTS AND MAIN RESULTS: Steady-state pharmacokinetics of ABC, 3TC, and ZDV were similar for the triple combination tablet versus ABC-COM for the following: geometric mean (GM) area under the serum concentration-time curve, ABC 6.08 versus 5.87, 3TC 5.51 versus 5.53, and ZDV 1.38 versus 1.46 microg x hr/ml; GM maximum serum concentration (Cmax-ss), ABC 3.09 versus 3.19, 3TC 1.26 versus 1.40, and ZDV 1.19 versus 1.15 microg/ml; median time to Cmax-ss, ABC 0.75 versus 0.75, 3TC 1.50 versus 1.24, and ZDV 0.75 versus 0.75 hours; and GM oral clearance, ABC 51 versus 49, 3TC 27 versus 27, and ZDV 217 versus 206 L/hour. The GM half-lives of ABC and ZDV were similar for both treatments, 1.69 versus 1.58 and 2.30 versus 2.08 hours, respectively. CONCLUSION: Steady-state pharmacokinetics of ABC, 3TC, and ZDV were similar in patients who took them as ABC-COM or as a triple combination tablet.

Prevalence of high-grade dysplasia and cancer in the anal canal in human papillomavirus-infected individuals.

BACKGROUND & AIMS: The incidence of anal cancer is higher in patients with anal canal condyloma, a sexually transmitted disease, than in the general population. We determined the prevalence of anal dysplasia and cancer in patients with anal canal condyloma with respect to human immunodeficiency virus (HIV) status, immunity status, and human papillomavirus types. METHODS: In 174 consecutive patients (114 HIV positive, 60 HIV negative) with anal canal condyloma, lesions were cured, and the patients were then followed up prospectively. Langerhans cells (LCs) in normal anal mucosa were quantified, and viruses (Epstein-Barr virus, cytomegalovirus, human simplex virus 1, and various human papillomavirus [HPV] types) were characterized on inclusion. During follow-up (median 26 months), relapsed condylomas were resected and examined histologically. HIV load and CD4 T-lymphocyte counts in serum were determined at each visit. RESULTS: Several factors differed significantly between HIV-positive and HIV-negative patients: LCs/mm anal tissue (15 vs. 30), oncogenic HPV (27% vs. 13%), other current anal infections (44% vs. 0%), and sex ratio (93% vs. 73% male). During follow-up, condylomas relapsed in 75% of the HIV-positive patients, with 19 high-grade dysplasias (HGDs) and 1 invasive carcinoma, but in only 6% of HIV-negative patients, with 1 HGD. Male sex, HIV positivity, and <15 LCs/mm tissue were independent risk factors for condyloma relapse. HIV positivity, HGD before inclusion, and condyloma relapse were independent risk factors for HGD and cancer. Serum HIV load was associated with relapse, whereas CD4 T-lymphocyte counts were not. CONCLUSIONS: The prevalence of HGD and carcinoma is higher in HIV-positive than in HIV-negative patients, probably because of HPV activity. HIV-positive patients with high serum HIV load and/or a history of anal dysplasia should be examined by anoscopy, and condylomas should be analyzed histologically.