Search

Resume Justification–objectif La moxifloxacine (IZILOX ® ) est indiquee dans les infections bacteriennes respiratoires. Au cours de son developpement clinique, un allongement de QTc, d'environ 6 ms en moyenne, a ete observe. Cet effet est susceptible d'etre a l'origine de torsades de pointes. Cependant la tolerance de la moxifloxacine a ete bonne au cours du developpement. Afin de confirmer, sur un large echantillon de patients, le bon profil de tolerance de la moxifloxacine au terme des etudes de developpement, l'etude IMMEDIAT* a ete mise en place en France en medecine de ville. Methode Cette etude observationnelle, prospective, non controlee mais monitoree a ete conduite chez 13 578 patients ayant une infection des voies respiratoires traitee par moxifloxacine a la dose de 400 mg/j pendant cinq a dix jours conformement a l'AMM. Les evenements indesirables (EI) pouvant correspondre a une manifestation clinique d'un trouble du rythme ventriculaire (evenements dits « critiques ») ont ete recueillis puis evalues par un Comite scientifique charge de determiner l'origine potentiellement cardiaque de l'evenement detecte et d'estimer l'imputabilite au traitement. Resultats Sur les 13 578 patients recrutes, 1046 evenements indesirables (678 patients [5 %]) ont ete rapportes, dont 854 (564 patients [4,15 %]) ont ete consideres comme lies au traitement. Parmi ces 1046 evenements indesirables (EI), 95 (62 patients [0,46 %]) etaient des EI graves. Un total de 189 EI critiques (159 patients [1,2 %]) ont ete valide par le Comite scientifique. Apres analyse, 34 EI (28 patients [0,21 %]) ont ete consideres comme potentiellement d'origine cardiaque. Parmi ces 34 EI, seul 25 (19 patients [0,14 %]) etaient consideres comme possiblement relies a la moxifloxacine : palpitations (13 patients), tachycardie (quatre patients), malaise (quatre patients), vertige (trois patients) et pâleur (un patient). Tous ces evenements ont ete transitoires et ont eu une evolution favorable. Conclusion Cette etude post-AMM confirme, dans les conditions d'usage en pratique de ville, le bon profil de tolerance de la moxifloxacine suggere par les etudes pre-AMM sans mise en evidence d'evenements indesirables inattendus.

Studies of acute exacerbations of chronic bronchitis (EXCB) included in the approval documents of levofloxacin (LVF) were reviewed in light of the good conditions of use defined by the French marketing approval and the AFSSAPS recommendations. The approval documents included two American studies comparing LVF 500 mg/d for 5-7 days with cefaclor 750 mg/d for 7-10 days or cefuroxime axetil (CXM) 500 mg/d for 7-10 days. A new descriptive analysis of efficacy was performed on a population meeting the recommendation criteria for antibiotic treatment in patients with clinical signs of obstruction. This analysis was stratified by number of risk factors (RF) for the following aggravating conditions: age above 65 years, diabetes or corticosteroid therapy. In the American studies, clinical efficacy, measured by rate of success in the total population, in the EXCB population requiring antibiotic therapy with or without risk factors, and in the EXCB population with at least one and at least two of the above-cited risk factors was 93.4% (351/376), 93.0% (268/288), 90.4% (122/135) and 94.4% (34/36) respectively with LVF and 92.2% (354/384), 92.5% (273/295), 87.7% (128/146) and 79.3% (23/29) respectively with the compared drugs. In the European study, the clinical efficacy in the total population, in the EXCB population requiring antibiotic therapy with or without risk factors, and in the EXCB population with at least one and at least two of the above-cited risk factors was 81.9% (195/238), 82.4% (182/221), 78.9% (112/142) and 75.0% (27/36) respectively with LVF and 72.5% (166/229), 74.0% (154/208), 73.1% (95/130) and 58.3% (21/36) respectively with the compared drugs. The efficacy of levofloxacin is thus confirmed for EXCB with signs of obstruction. When stratifying for RF, the efficacy of LVG persists with increasing numbers of RF, a result not observed with the compared drugs.

This chapter talks about dihydrofolate reductase inhibitors (DHFR), nitroheterocycles (furans), and 8-hydroxyquinolines. Trimethoprim and brodimoprim contain two nitrogen atoms on the pyrimidine ring which are easily protonable according to the pH of environment. Co-trimoxazole is one of the main antibacterial agents for the treatment of uncomplicated cystitis. Pharmacology studies show that the combination of compounds does not modify their behavior and that if co-trimoxazole is compared with the other combinations an advantage may be found for trimethoprim-sulfadiazine in urinary tract infections and renal insufficiency. Many 6-6 fused rings have been prepared with the aim of increasing the selectivity for T. gondii and P. carinii DHFR. A series of hybrids was synthesized. Within this series one analog was 500-fold more potent than trimethoprim against P. carinii and T. gondii and displayed an excellent selectivity. The combination of epiroprim and dapsone is highly effective against P. carinii pneumonia in rats and T. gondii infection in mice. In vitro, the sulfones are active against T. gondii, particularly dapsone. In murine P. carinii pneumocystosis, dapsone is effective in treatment and prevention. In humans, the combination trimethoprim-dapsone in curative treatment and dapsone alone in preventive treatment are effective. Like the sulfonamides, the sulfones interfere with folate synthesis. They also have a potent antioxidant action. Lastly, dapsone inhibits the transport of adenosine through the erythrocyte wall and prevents its incorporation in the nucleic acid of plasmodia and probably toxoplasmas and P. carinii.

The glycopeptide and lipoglycopeptide antibiotics are natural antibiotics obtained from cultures of certain microorganisms. These antibiotics inhibit bacterial cell wall peptidoglycan synthesis but cannot cross the cell wall of gram-negative bacteria. Their antibacterial spectrum includes aerobic and anaerobic gram-positive bacteria. The glycopeptides may be divided into at least five groups on the basis of their chemical structures. Due to their large mass, glycopeptides cannot cross the lipoprotein cell wall of gram-negative bacteria and are therefore totally inactive against them. The molecules belonging to group II (Avoparcin Type) are mainly actinodin, avoparcin, chloropolysporin, galacardin, helvecardin, and synmonicin. Resistance to vancomycin and teicoplanin is due to synthesis of modified precursors that display decreased affinity for both compounds. Six types of resistance have been reported to date: VanA, VanB, VanC, VanD, VanE, and VanG. The combination of a glycopeptide with an aminoglycoside is synergistic against the majority of strains of staphylococci and enterococci. The in vitro activity of dalbavancin was investigated by following NCCLS-recommended methods and comparatively with vancomycin, linezolid, and quinuprisitin-dalfoprisitin (Q-D).

Resume L'utilisation des quinolones comporte un risque individuel qui depend de la pharmacologie des produits concernes, des interactions medicamenteuses eventuelles, des effets secondaires des medicaments. Tous ces elements sont en relation etroite avec l'etat fonctionnel du patient, los comorbidites et les comedications frequentes, notamment chez les sujets âges. Il est necessaire de tenir compte de la pharmacologie de certaines fluoroquinolones pour adapter eventuellement la posologie a la fonction renale. Il faut connaitre les interactions medicamenteuses susceptibles d'occasionner des effets indesirables, en particulier neurologiques. Certains effets indesirables sont lies a la structure du medicament, notamment les troubles digestifs, la cristallurie, certains troubles du systeme nerveux central et la phototoxicite. Certains effets indesirables graves des fluoroquinolones ne semblaient pas previsibles lors de la phase des essais cliniques. Ils ont ete decouverts chez certains patients grâce a la surveillance ayant suivi le lancement de ces molecules : hemolyse, hypoglycemie, manifestations hepatiques graves, manifestations cardiaques liees a un allongement de l'intervalle QT. Les contreindications, telles que l'insuffisance renale, les antecedents de tendinopathie et l'existence d'anomalies cardiaques prealables ou d'une prise concomitante de medicaments allongeant l'espace QT, doivent etre respectees.

Resume Propos. L'infection par le virus de l'hepatite C (VHC) a une forte prevalence (10–30 %) chez les patients infectes par le virus de l'immunodeficience humaine (VIH), mais on dispose de peu de donnees sur l'influence reelle de l'hepatite C sur la mortalite de ces patients. L'objet de notre travail etait de determiner l'incidence de la mortalite par cirrhose ou carcinome hepatocellulaire dus au VHC chez les patients infectes par le VIH. Methodes. Il s'agit d'une etude retrospective menee par 63 services francais de medecine interne et/ou de maladies infectieuses representant une file active de 26 497 patients infectes par le VIH, dont 4465 (16,8 %) co-infectes par le VHC. Les parametres suivants etaient etudies : nombre total de deces, nombre de deces dus au sida, a une cirrhose et/ou a un carcinome hepatocellulaire, a une autre cause. Resultats. Parmi l'ensemble des 26 497 patients, 543 deces furent observes en 1997 (incidence de 2 %), dont 459 deces dus au sida (incidence de 1,7 %), 36 par cirrhose et/ou carcinome hepatocellulaire (incidence de 0,13 %), 48 dus a d'autres causes (incidence de 0,18 %). Dans le sous-ensemble des 4 465 patients co-infectes par le VIH-VHC, 29 deces (incidence de 0,64 %) etaient dus a une cirrhose ou un carcinome hepatocellulaire impliquant le VHC. La comparaison de ces resultats avec ceux d'une enquete similaire menee en 1995 montre pour seule difference significative la diminution du nombre de deces dus au sida depuis l'utilisation de traitements antiretroviraux hautements actifs. Conclusions. L'impact de l'hepatite C sur la mortalite des patients infectes par le VIH suivis dans les services francais de medecine interne et/ou de maladies infectieuses restait tres faible en 1997. L'augmentation de la duree de vie des patients liee aux progres therapeutiques recents pourrait dans l'avenir modifier ces donnees.

Resume Les personnes âgees sont particulierement exposees a l'infection, tant en milieu communautaire, qu'a l'hopital et en institution. Sont particulierement importantes, l'infection respiratoire, et sa prevention, les relations entre nutrition et infection, l'infection urinaire. Il apparait egalement necessaire, en 1996, de mettre l'accent sur l'importance de realiser chez le sujet âge des essais cliniques pour depister des effets secondaires inattendus, et preciser les modalites therapeutiques dans des indications specifiques a l'adulte âge.

Resume L'efficacite et la tolerance d'une nouvelle cephalosporine orale de troisieme generation, le cefotiam hexetil ** (CTM) a la dose de 200 mg matin et soir ont ete comparees avec celles du cefuroxime axetil *** (CFX) a la dose de 250 mg matin et soir sur une periode de dix jours de traitement. Cent vingt-cinq patients adultes ambulatoires souffrant d'otite moyenne chronique ont ete randomises par des ORL dans cette etude multicentrique prospective en double aveugle, double placebo. Le diagnostic d'otite est retenu sur l'observation d'une otorrhee, d'une hypoacousie et d'une perforation tympanique laissant sourdre un ecoulement plus ou moins purulent. L'usage d'antibiotique ou de corticoides de facon concomitante pendant les 15 jours precedant l'inclusion etait l'un des criteres majeurs de non inclusion. Cent vingt-cinq patients ont ete evalues pour l'analyse de l'efficacite (61 dans le groupe CTM et 64 dans le groupe CFX). Les deux populations etaient comparables a l'inclusion en ce qui concerne les signes demographiques et cliniques. Le taux de succes clinique en fin de traitement (guerison + amelioration) n'a pas ete significativement different entre les deux groupes (CTM : 67,2 % versus CFX : 69,8 %). A J30 le nombre de recidives n'est pas statistiquement different (CTM 4,2 % versus CFX 3,7 %). Le nombre d'effets secondaires a ete moins frequent dans le groupe CTM (11,5 % versus 15,9 %), difference non significative. En conclusion, CTM 200 mg matin et soir est aussi efficace et aussi bien tolere que CFX 250 mg matin et soir dans le traitement des otites moyennes chroniques de l'adulte.

Resume L'efficacite et la tolerance d'une nouvelle cephalosporine orale de troisieme generation, le cefotiam hexetil ** (CTM) a la dose de 200 mg matin et soir ont ete comparees avec celles du cefuroxime axetil *** (CFX) a la dose de 250 mg matin et soir sur une periode de dix jours de traitement. Quatre vingt-trois patients adultes ambulatoires souffrant d'otite moyenne aigue ont ete randomises par des ORL dans cette etude multicentrique prospective en double aveugle, double placebo. Le diagnostic d'otite est retenu sur l'observation d'une otalgie, d'une hypoacousie et d'une perforation tympanique laissant sourdre un ecoulement plus ou moins purulent. L'usage d'antibiotique ou de corticoides de facon concomitante pendant les 15 jours precedant l'inclusion etait l'un des criteres majeurs de non inclusion. Quatre vingt-deux patients ont ete evalues pour l'analyse de l'efficacite (38 dans le groupe CTM et 44 dans le groupe CFX). Les deux populations etaient comparables a l'inclusion en ce qui concerne les signes demographiques et cliniques, a l'exception des maladies associees (p = 0,03). Le taux de succes clinique en fin de traitement n'a pas ete significativement different entre les deux groupes (CTM : 95% versus CFX : 90 %). Le nombre d'effets secondaires a ete moins frequent dans le groupe CTM (8 % versus 23 %). En conclusion, CTM 200 mg matin et soir est aussi efficace et aussi bien tolere que CFX 250 mg matin et soir dans le traitement des otites moyennes aigues de l'adulte.

Resume En 1995, l'evolution des maladies infectieuses communautaires inspire des reflexions personnelles sur quelques sujets d'interet. En pathologie communautaire respiratoire, il semble necessaire d'observer avec prudence l'evolution de la sensibilite des pneumocoques aux penicillines et d'examiner avec reserve les molecules nouvelles pour ce qui est de la pathologie pulmonaire. En ORL, il faut tenir compte de la resistance du pneumocoque et envisager une reduction des durees de traitement. L'infection urinaire donne lieu a de nouvelles classifications et le choix des antibiotiques, les durees de traitement, semblent maintenant bien codifies. En 1995, on peut souligner l'evolution des risques infectieux en milieu communautaire; en effet certaines pathologies anciennes reapparaissent parfois sous des aspects cliniques inhabituels, de nouvelles pathologies, de nouveaux agents bacteriens ou viraux, deviennent plus frequents et meritent d'etre connus. Tant au niveau des tutelles que dans l'exercice courant, la surveillance de l'infection est a l'ordre du jour, la prevention devient un but des plus importants avec d'une part une nouvelle politique des vaccinations et d'autre part une politique globale de prevention de la diffusion des maladies infectieuses et de la resistance des germes aux anti-infectieux. De nouvelles techniques sont introduites; l'essentiel reste la prise de conscience de l'existence de nouveaux risques infectieux.

Multi-resistant strains of Gram-negative bacteria are rapidly emerging as a frequent cause of serious bacterial infection in the hospital environment. Effective treatment must include an antibiotic with activity against these organisms. In an open multicentre study, cefepime was evaluated as empirical therapy in 156 hospitalized patients (mean age 57 years) with serious infection of the urinary tract (n = 43), lower respiratory tract (n = 101) and skin and soft tissue (n = 12). In 18 patients, septicaemia/bacteraemia was also diagnosed. Cefepime, 2 g bd, was administered for a maximum of 16 days (mean 8). Of 98 pathogens isolated, 75 were Gram-negative and 23 were Gram-positive species. Ninety-four of the pathogens were susceptible to cefepime, including multi-resistant isolates such as Pseudomonas aeruginosa and Enterobacter cloacae. The overall clinical cure rate, excluding septicaemia/bacteraemia, was 92% (94/102); the corresponding bacterial eradication rate was 95% (52/55). In patients with septicaemia/bacteraemia, the clinical cure rate was 87% (13/15) despite eradication of 100% (11/11) of the assessable pathogens. Cefepime was well-tolerated, although 14 (9%) patients experienced local intolerance at the infusion site. Other drug-related adverse events were reported in six (4%) patients and included diarrhoea, pruritus, rash and urticaria. Cefepime is safe and effective as empirical treatment for serious infections commonly found in the hospital setting. Clinical cure and bacterial eradication can be achieved with a convenient bd dosing schedule.

Resume Les endocardites a bacille du rouget du porc sont rares. Nous rapportons ici l'observation d'un patient professionnellement expose, ayant presente l'association d'une atteinte bivalvulaire, aortique et tricuspidienne, alors qu'il etait traite par macrolide pour une bronchite. Cette observation nous permet de rappeler l'interet du diagnostic et du traitement precoce de l'erysipeloide afin d'eviter la survenue de localisations valvulaires.

Resume Le cefuroxime axetil est la premiere cephalosporine orale disposant d'un spectre large et d'une bonne stabilite face aux beta-lactamases. Il s'agit d'un ester de la cefuroxime. Par rapport aux aminopenicillines, aux cephalosporines de premiere generation, a l'erythromycine, cette molecule a une grande activite contre les germes actuellement les plus souvent rencontres dans les infections respiratoires basses — surinfections de bronchopneumopathies chroniques et pneumopathies — chez les sujets âges, et une stabilite aux beta-lactamases produites notamment par Haemophilus influenzae et Branhamella catarrhalis. Le spectre antibacterien, la pharmacocinetique chez le sujet âge, la bonne tolerance, l'efficacite clinique, font de cet antibiotique un produit interessant dans le traitement des infections respiratoires basses chez les patients âges n'ayant pas d'immunodepression severe.

We report 3 patients who developed signs of systemic infection and renal insufficiency after intravesical bacillus Calmette-Guérin (BCG) instillations for a bladder cancer. Renal biopsy showed tubulo-interstitial nephritis with or without epithelioid granulomas in 2 cases, and mesangial glomerulonephritis in the last case. All patients had granulomatous hepatitis in association. It seems that hematogenous dissemination via a traumatic instillation of BCG and/or an immune-complex mechanism may have contributed to the renal damage, which was only partially reversible in 2 patients.

The purpose of this paper is to describe the impact of exposure to influenza on hospitalizations and deaths in the elderly residents of long-term care facilities (LTCFs). An observational, longitudinal, prospective, multicenter, cohort study collected influenza and influenza-like cases, diseases, hospitalizations, and deaths of dependent elderly residents of French LTCFs during the 2004-2005 seasonal influenza epidemic. A total of 8,041 residents of 98 participating LTCFs were included. The mean age was 85 +/- 9 years; 93% were vaccinated against influenza and 64% of the residents were exposed to influenza during the epidemic. Exposure to influenza increased both the all-cause risk of hospitalization (9.2% of the residents exposed vs. 7.4% of the residents not exposed) (relative risk, RR [95% confidence interval, CI] = 1.24 [1.05; 1.47]) and the all-cause risk of death (5.8% vs. 4.3%) (RR [95% CI] = 1.36 [1.10; 1.70]). Exposure to influenza increased the risks of death and hospitalization. Additional measures should be taken to avoid influenza exposure and apply recommendations more thoroughly in the particularly susceptible population of elderly LTCF residents.

Resume La ceftazidime est aujourd'hui largement utilisee dans les infections hospitalieres nosocomiales. Sa place dans le traitement des infections communautaires chez les patients a fort potentiel de complications est a mieux definir. Chez ce type de patients, la presence de criteres predictifs de la severite de l'infection, a l'arrivee en service hospitalier, influe sur le choix de l'antibiotherapie probabiliste. L'âge et la pathologie associee sont des elements essentiels. Les caracteristiques microbiologiques, pharmacocinetiques et cliniques de la ceftazidime permettent de preciser ses indications dans ces infections communautaires severes, la place de la monotherapie et les posologies a preconiser.

In young adults, the elimination half-life of cefodizime is 3.5-4 h. A pharmacokinetic study was performed in eight patients, aged 63 to 85 years, divided into two groups with the following creatinine clearances (group I: greater than or equal to 50 ml/min and group II: less than 30 ml/min). Cefodizime was administered as a 1.0-g iv bolus. In group I, pharmacokinetic parameters did not differ from those observed in young healthy volunteers in a previous study. In group II, the half-life was increased (3.42-7.41 h). There is a linear correlation between the creatinine clearance and total clearance. The daily dose given needs to be based not on the age of the patient but on the degree of renal impairment. In elderly patients with severe renal impairment, the daily dose should be reduced if the creatinine clearance falls below 30 ml/min.

Moxifloxacin (Izilox) is prescribed for bacterial respiratory tract infections. ECG analysis done in clinical trials showed a mean QT prolongation at 6 ms that could lead to Torsades de Pointe. However, Izilox was well tolerated during clinical trials. To confirm the correct safety profile of Izilox in a large sample of patients, a French PMS study - MMEDIAT - was carried out in usual medical practice.This prospective observational uncontrolled and monitored study was conducted in 13,578 patients with respiratory tract infection and treated with moxifloxacin 400 mg daily (duration: 5 to 10 days in accordance to the Market Authorization). Any clinical event being potentially a surrogate of a ventricular rhythm disorder ("critical event") were collected and analyzed by a Scientific Committee in charge to determine the potential cardiac origin of the reported event and to establish a causal relationship with the treatment.Among 13,578 patients, 1046 adverse events (678 patients [5%]) were reported, including 854 drug related events (564 patients [4.15%]). Of these 1046 adverse events, 95 (62 patients [0.46%]) were serious. A total of 189 critical adverse events (159 patients [1.2%]) were reviewed by the Scientific Committee. After analysis, 34 adverse events (28 patients [0.21%]) were assessed from potential cardiac origin. Of these 34 adverse events, 25 (19 patients [0.14%]) were assessed as drug-related: palpitations [13 patients], tachycardia [4 patients], malaise [4 patients], vertigo [3 patients] and pallor [1 patient]. All adverse events were transient and had favourable outcome.This PMS study confirmed that Izilox is well-tolerated in usual medical practice, in adequation with the safety data obtained in clinical trials.

Studies of acute exacerbations of chronic bronchitis (EXCB) included in the approval documents of levofloxacin (LVF) were reviewed in light of the good conditions of use defined by the French marketing approval and the AFSSAPS recommendations. The approval documents included two American studies comparing LVF 500 mg/d for 5-7 days with cefaclor 750 mg/d for 7-10 days or cefuroxime axetil (CXM) 500 mg/d for 7-10 days. A new descriptive analysis of efficacy was performed on a population meeting the recommendation criteria for antibiotic treatment in patients with clinical signs of obstruction. This analysis was stratified by number of risk factors (RF) for the following aggravating conditions: age above 65 years, diabetes or corticosteroid therapy. In the American studies, clinical efficacy, measured by rate of success in the total population, in the EXCB population requiring antibiotic therapy with or without risk factors, and in the EXCB population with at least one and at least two of the above-cited risk factors was 93.4% (351/376), 93.0% (268/288), 90.4% (122/135) and 94.4% (34/36) respectively with LVF and 92.2% (354/384), 92.5% (273/295), 87.7% (128/146) and 79.3% (23/29) respectively with the compared drugs. In the European study, the clinical efficacy in the total population, in the EXCB population requiring antibiotic therapy with or without risk factors, and in the EXCB population with at least one and at least two of the above-cited risk factors was 81.9% (195/238), 82.4% (182/221), 78.9% (112/142) and 75.0% (27/36) respectively with LVF and 72.5% (166/229), 74.0% (154/208), 73.1% (95/130) and 58.3% (21/36) respectively with the compared drugs. The efficacy of levofloxacin is thus confirmed for EXCB with signs of obstruction. When stratifying for RF, the efficacy of LVG persists with increasing numbers of RF, a result not observed with the compared drugs.

This retrospective study concerned 18 female and 23 male patients with cardiac sarcoidosis (CS). The average age at CS diagnosis was 38 years. CS was observed in white (73% of cases) and in black or Caribbean patients (27% of cases). All patients had extracardiac histologic proof of sarcoid tissue. In 63% of cases, the CS arose during the follow-up of systemic sarcoidosis. Systemic sarcoidosis was not specific except for a high frequency of neurosarcoidosis. Revealing cardiac signs were clinical in 63% of cases and electrical in 22%. In most patients these signs were associated with an abnormal echocardiography (77%) and/or a defect on thallium-201 or sestamibi imaging (75%). Thirty-nine patients received steroid therapy (initial dose mostly equal to 1 mg/kg per day), associated in 13 cases with another immunosuppressive treatment. In 26% of cases the immunosuppressive treatment was associated with a specific cardiac treatment. In the long-term follow-up (average follow-up, 58 mo), 87% of the cases showed an improvement, and 54% were cured from a clinical and laboratory point of view (electrocardiogram, 24-hour monitoring, echocardiography, radionuclide imaging). There was no sudden death. Two patients worsened, which can be explained in 1 case by very late treatment and in the other case by lack of treatment, except for a pacemaker. Our experience leads us to treat CS with corticosteroids as soon as possible and to use another immunosuppressive treatment where there is an insufficient therapeutic response or where there are contraindications to corticosteroids.

Levofloxacine is a fluoroquinolone presenting good anti-pneumococcal activity, including against strains with reduced sensitivity to penicillin. Four randomized controlled studies have compared the efficacy of levofloxacine versus other antibiotics (amoxacillin-clavulanic acid, amoxicillin, ceftriaxone, ceftriaxone plus cefuroxime +/- erythromycin) for the treatment of acute community-acquired pneumonia in adults. Grouping the 1,738 analyzable patients in these four studies, a meta-analysis was performed on the sub-group of 275 patients with documented pneumococcal infection (86 with bacteriemia) in order to compare the efficacy of levofloxacine with that of the comparer antibiotics. The trials were homogeneous, allowing the meta-analysis. The overall rate of clinical success was 88.6% in the levofloxacine group and 86.7% in the comparer group. The interval of confidence for the difference in the rate of estimated clinical success was between -5.65% and +9.39%. Bacteriologically, the rate of eradication was 90.2% and 90.4% respectively with an interval of confidence for the difference between -7.83% and +7.36%. The results of this meta-analysis confirmed that the efficacy of levofloxacine for the treatment of acute community-acquired pneumococcal pneumonia is not inferior to that of the comparers; the interval of confidence for the difference in the estimated rate of success did not include the breaking point of non-inferiority (-10% set for the clinical studies) and included zero.

Summary Background Randomized clinical trials of valaciclovir in recurrent herpes labialis are lacking. Objectives To determine whether a single course of valaciclovir, i.e. 500, 1000 or 2000 mg, administered during the prodrome of herpes facialis, could be beneficial. Methods Three hundred and forty-five out-patients with herpes labialis were screened and randomized for a multicentre, double-blind clinical trial. Ninety-six patients had no recurrence after 6 months of follow-up; 249 patients were finally included in the intent-to-treat (ITT) population. The main outcome measure was the rate of aborted episodes at day 3. The three treatment groups were similar at baseline. Results There was no statistically significant difference between the groups in rates of aborted lesions at day 3 in the ITT population, in particular between the 500 mg and 2000 mg treatment groups. Conclusions Although a placebo group was not included in this pilot study, a single dose of valaciclovir was not considered beneficial in patients with recurrent herpes facialis.

We conducted a descriptive epidemiology study to examine the conditions of management of infectious lung disease in institutionalized elderly populations (population profile, diagnostic and therapeutic modalities) and to analyze the general and mental consequences in terms of independence (impact of the infectious event on the subject's life style).A pragmatic survey was conducted by a multicentric observatory composed of 573 general practitioners, practicing in nursing homes. The series included 1790 patients aged over 70 years and residing in nursing homes who developed infectious lung disease over a 10-month period. The MMSE score was used to assess mental status and the Barthel index to assess functional handicap. Each patient was evaluated at the time of the final diagnosis (prescription of an antibiotic or decision for hospitalization) and at most 3 days after the end of this treatment or at discharge from hospital.The elderly population (84 +/- 7 years) was predominantly composed of women. The patients were treated for an acute respiratory infection considered in 30% of the cases to be acute lobar pneumonia. Subgroups of patients were identified for analysis: death (3.7%), x-ray confirmation of the diagnosis (11.5%), hospitalized patients (10.2%). In addition to major deterioration of the general health status, a consequence of the infection more than of the severity of the respiratory symptoms, the development of an acute episode coincided with reduced intellectual functions and onset of a state of confusion. In 70% of the cases, this resulted in a loss of independence of variable importance--simple difficulty for moving around to major functional handicap. The infectious episode was cured or improved (persistence of minor signs not requiring specific treatment) in 94.3% of the cases with appropriate antibiotics: single-drug regimen in 93.7% give per os (75%) or intravenously (25%) using aminopenicillin (with or without a beta lactamase inhibitor) in 80% of the cases. Antibiotic treatment was associated with physical therapy in more than half the cases, and with general conticosteroids in 40%. The treatment scheme was modified in 9.4% of the cases (change of antibiotic in 6%).This survey confirms the high risk related to general conditions in elderly institutionalized patients who develop respiratory infection. More than the infection itself, the rapid degradation of the general health status, or decompensation of comorbid states can create life-threatening situations or favor the development of irreversible handicaps.

Among 8 patients with giant cell arteritis (GCA) (6 women, 2 men) whose clinical presentations were compatible with temporal arteritis (TA), 6 were followed for 37-105 (mean 74.9) months, one died shortly after treatment onset, and the last was asymptomatic (10 mg steroids/day) when lost to followup at 29 months. All 8 patients had bilateral leg claudication of recent onset; for 6 patients, this was the first symptom. All leg angiograms showed multiple, bilateral, long and smooth stenoses, thromboses, or both. Biopsies of diseased leg arteries from 4 patients provided histological proof of GCA; another case was histologically proven post mortem. Among the 5 patients who met at least 3 American College of Rheumatology criteria of GCA or TA, 3 without histologically documented leg GCA also had biopsy proven temporal GCA (n = 1), or headaches and claudication and angiographic inflammatory arteritis of the arms (n = 2). All patients received steroids; 3 had bypasses, one with endarterectomy. Five are asymptomatic after 24-100 months of steroids (mean 50.6). Revascularization was not successful; one amputation was necessary. Large artery involvement in GCA can affect the legs. Bilateral and rapidly progressive intermittent claudication of recent onset is the most common symptom, even in the absence of headaches or the presence of a silent inflammatory syndrome. Early diagnosis allows rapid initiation of steroid therapy, which is usually able to generate a sufficiently good response to avoid vascular surgery.

Several studies have suggested that the progression of hepatitis C virus (HCV) infection is more severe in patients infected by the human immunodeficiency virus (HIV). Two national retrospective multicenter cohort surveys were performed in France that included 17,487 HIV-infected patients during 1995 and 26,497 during 1997. The following data was evaluated: total number of deaths; number of deaths linked to AIDS, cirrhosis, or hepatocellular carcinoma (HCC); and number of deaths related to other (non-HCV--linked) causes. In 1995, the causes of death were as follows: AIDS, 1307 (7.47%); cirrhosis or HCC, 21 (0.12%); and other (non-HCV--linked) causes, 99 (0.56%). In 1997, the causes of deaths were as follows: AIDS, 459 (1.73%); cirrhosis or HCC 36 (0.13%); and other (non-HCV--linked) causes, 48 (0.18%). Comparative results between the 1995 and 1997 surveys showed a dramatic decrease in AIDS-related mortality rates (7.47% vs. 1.73%; P

From January 1996 to January 1997, 321 patients with an average age of 46 +/- 16 years and chronically infected with hepatitis C virus (HCV) were prospectively enrolled in a study designed to determine the prevalence of extrahepatic manifestations associated with HCV infection in a large cohort of HCV patients, to identify associations between clinical and biologic manifestations, and to compare the results obtained in human immunodeficiency virus (HIV)-positive versus HIV-negative subsets. In a cross-sectional study, clinical extrahepatic manifestations, viral coinfections with HIV and/or hepatitis B virus, connective tissue diseases, and a wide panel of autoantibodies were assessed. Thirty-eight percent (122/321) of patients presented at least 1 clinical extrahepatic manifestation including arthralgia (60/321, 19%), skin manifestations (55/321, 17%), xerostomia (40/321, 12%), xerophthalmia (32/321, 10%), and sensory neuropathy (28/321, 9%). Main biologic abnormalities were mixed cryoglobulins (110/196, 56%), thrombocytopenia (50/291, 17%), and the presence of the following autoantibodies: antinuclear (123/302, 41%), rheumatoid factor (107/280, 38%), anticardiolipin (79/298, 27%), antithyroglobulin (36/287, 13%) and antismooth muscle cell (27/288, 9%). At least 1 autoantibody was present in 210/302 (70%) of sera. By multivariate logistic regression analysis, 4 parameters were significantly associated with cryoglobulin positivity: systemic vasculitis (p = 0.01, odds ratio OR[ = 17.3), HIV positivity (p = 0.0006, OR = 10.2), rheumatoid factor positivity (p = 0.01, OR = 2.8), and sicca syndrome (p = 0.03, OR = 0.27). A definite connective tissue disease was noted in 44 patients (14%), mainly symptomatic mixed cryoglobulinemia and systemic vasculitis, HIV coinfection (23%) was associated with 3 parameters: anticardiolipin (p = 0.003, OR = 4.18), thrombocytopenia (p = 0.01, OR = 3.56), and arthralgia or myalgia (p = 0.017, OR = 0.23). HIV-positive patients presented more severe histologic lesions (p = 0.0004). Extrahepatic clinical manifestations in HCV patients involve primarily the skin and joints. The most frequent immunologic abnormalities include mixed cryoglobulins, rheumatoid factor, antinuclear, anticardiolipin, and antithyroglobulin antibodies. Cryoglobulin positivity is associated with systemic vasculitis and rheumatoid factor and HIV positivity. HIV coinfection is associated with arthralgia or myalgia, anticardiolipin antibodies, and thrombocytopenia.

Hepatitis C (HCV) has a high prevalence (10-30%) among human immunodeficiency virus (HIV)-infected patients. However, little information is available regarding the impact of hepatitis C on survival. The objective of our study was to determine the incidence of hepatitis C-related deaths in HIV-HCV co-infected patients.The study was a retrospective (1-year), multicenter cohort survey conducted in 63 departments of either internal medicine or infectious diseases in France. It included 26,497 HIV-infected patients, of whom 4,465 (16.8%) presented coinfection due to the hepatitis C virus. The following parameters were studied for the year 1997: total number of deaths, number of deaths related to either AIDS, cirrhosis, hepatocellular carcinoma, or other causes.Among the 26,497 patients, 543 deaths (incidence: 2%) were observed in 1997; 543 deaths were due to AIDS (incidence: 1.7%), 36 to cirrhosis and/or hepatocellular carcinoma (incidence: 0.13%), and 48 (incidence: 0.18%) to another cause. In the subgroup including 4,465 HIV-HCV-coinfected patients, 29 deaths (incidence: 0.64%) were due to either HCV-related cirrhosis or hepatocellular carcinoma. These results were compared with those of a previous similar survey conducted in 1995, before the era of highly active antiretroviral therapy. The only significant difference is the dramatic regression of deaths due to AIDS.The impact of hepatitis C virus on the mortality among HIV-infected patients whose follow-up took place in departments of either internal medicine or infectious diseases in France was very low in 1997. The expected increase in the life span in these patients could modify these results in the future, due to recent improvements in the HIV infection treatment.

Resume Les auteurs rapportent un cas de septicemie a Saccharomyces cerevisiae chez un patient cancereux, traite et gueri par amphotericine B et 5 fluorocytosine par voie parenterale. L'emploi du fluconazole a dose preventive per os chez ce patient n'avait pas prevenu le developpement de cette septicemie, probablement en raison de posologies insuffisantes.

Levofloxacin is a new fluoroquinolone active against S. pneumoniae. Oral and intravenous administration is available. The aim of this study was to determine its efficacy in community-acquired pneumonia.Five clinical trials included 1989 patients eligible for analysis. The dosage was 500 mg once or twice a day depending on the studies. Levofloxacin was compared with amoxicillin (3 g/d), amoxicillin/clavulanic acid (1500 mg/d), ceftriaxone (1-4 g/d combined or not with a macrolide and/or relay cefuroxime axetil).In these studies and among the patients eligible for analysis, microbiologically proven S. pneumoniae pneumonia occurred in 170 of the patients treated with levofloxacine and in 140 treated with the comparator. Bacteriemia was evidenced in 51/170 of the levofloxacin-treated patients (30%) and in 45/140 (32%) of the comparator-treated patients. At treatment end, clinical success rate was 93.5% (159/170) for levofloxacin and 90.7% (127/140) for comparators. S. pneumoniae eradication rate was comparable for levofloxacin (94.9%) and comparators (95.3%). In patients with bacteriemia, the clinical success rate was 86.2% (44/51) for levofloxacin and 84.4% (38/45) for comparators.These findings establish the efficacy of levofloxcin for the treatment of pneumococcal pneumonia, a major treatment challenge in community-acquired pneumonia. This compound has its place in the context of good use of antibiotics. Levofloxacin should be used in priority for patients with risk factors for complications with rapidly unfavorable course or as second intention treatment when re-evaluating insufficient therapeutic response.

Infection with Hepatitis C virus is a significant public health problem that has important clinical and financial consequences. Understanding of the epidemiology of HCV is needed to help define future therapeutic and preventive strategies. So far, the importance and characteristics of the epidemics have been best appreciated in specialist units dealing with liver disease. The purpose of our study was to survey the number and characteristics of hepatitis C antibody positive patients in Departments of Internal Medicine and Infectious Diseases. We conducted a multicentre national prospective analysis of all positive HCV-antibody patients, either inpatient or outpatient, reported over a period of one month across France. Two thousand and two cases were identified. Epidemiological, clinical and therapeutic characteristics are described. Risk factors were identified in 86%. For 10% of the patients, hepatitis C seropositivity was discovered during the period of survey. At the time of first diagnosis, 47% of patients presented with no clinical or biological abnormality. Coinfection with HIV was frequent (59%). Only 20.3% of the patients had received or were receiving a treatment with interferon. Within the limits of the methodology used, this study shows that Hepatitis C infection is a substantial clinical problem in French Departments of Internal Medicine and Infectious Diseases. Our findings may help the public health authorities in better appreciating the impact of hepatitis C and making policy decisions.

Adult onset Still's disease (AOSD) is a systemic disorder with an uncertain outcome at the time of diagnosis. The clinical response to nonsteroidal antiinflammatory drugs (NSAIDs) is often unsatisfactory in adult patients. Chronic use of steroids is frequently required, but may result in severe side effects. We report the results of an uncontrolled, unblinded trial of intravenous immunoglobulin (IVIG) in 7 patients with AOSD.Seven consecutive patients unresponsive or poorly responsive to NSAIDs were enrolled. None of them had received steroids previously. AOSD was defined by the Yamaguchi criteria (J Rheumatol 1992; 19: 424). IVIG were administered every 4 weeks. NSAIDs were initially maintained. A positive response was defined by the disappearance of fever and arthritis within 2 weeks after the first IVIG infusion.Two patients failed to respond. Five patients initially considered to be good responders were given a total of 4 to 6 IVIG infusions. One of them relapsed at the time of the fourth IVIG infusion. The four others had a favourable clinical and biological course. At the time of evaluation 3 patients were symptom-free and off therapy, while one was still receiving low dose NSAIDs.This short, uncontrolled, unblinded study suggests that IVIG might represent a potential alternative to classical steroid therapy in patients with AOSD refractory to NSAIDs. These preliminary results need to be confirmed, however, in a double-blind randomized study.

We established a RT-PCR technique by using MUC-1, P19 cytokeratine primers on MCF 7 cell line, in order to detect up to ten cells on only 10 ml of blood.