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Context: Subcutaneous administration of antibiotic therapy is routinely practiced by 95% of infectious disease specialists, despite this practice is usually off label. Teicoplanin may constitute an acceptable alternative in the treatment of staphylococcal bone and joint infection. It could be theoretically used by subcutaneous route, and then allow to reduce the length of hospitalization and avoid long-term venous central catheter. Nevertheless, this administration route has not been well evaluated yet. Our objective was to assess the trough concentration of teicoplanin obtained during subcutaneous administration in staphylococcal bone and joint infection (target trough concentration ≥ 15 mg/L), and to describe its efficacy and tolerance. Methods: All patients receiving teicoplanin by subcutaneous route for a staphylococcal bone and joint infection (excepting diabetic foot infection) between 2002 and 2015 were included in a retrospective multicentric cohort study in three French hospital centers (Chambery, Lyon, and Strasbourg). Results: Forty episodes of bone and joint infections were assessed, including 34 orthopedic device-related infections (85%) and 21 chronic infections (53%). The median age was 75 years (IQR, 62-84). The median glomerular filtration rate (GFR) was 68 ml/min/m2 (IQR, 56-91). Twenty-four isolates were methicillin-resistant (58%), including 13 Staphylococcus aureus and 11 coagulase negative Staphylococci, with a MIC for teicoplanin of 0.5 mg/L (IQR, 0.38-0.81) and 0.75 mg/L (IQR, 0.5-1), respectively. The median duration of treatment by teicoplanin was 46 days (IQR, 29-79), primarily in combination with rifampin (n = 23) or a fluoroquinolone (n = 16). Sixteen patients (40%) received a loading dose by intravenous route before switching to subcutaneous route. A median loading dose of 9.4 mg/kg/12 h (IQR, 6.1-13.1) was used in 35 patients (88%) (16 by IV route, 18 by SC route, 1 by IM route). The maintenance dose was 7.3 mg/kg/injection (IQR, 5.3-12.1). A 3 injections per week scheme of 15 mg/kg/injection (IQR, 10.3-15.9) was conducted in 13 (33%) patients. A trough concentration ≥ 15 mg/L was reached in 34 patients (85%) in a median delay of 4 days (IQR, 3-6). The trough concentrations during the first 20 days were not significantly different between the IV and SC (p = 0.462) routes. Trough concentrations reached by subcutaneous route were significantly higher if the loading dose was ≥ 9 mg/kg/injection (p < 10-3). Fifteen treatment failures were observed (37.5%), including 8 superinfections. Nine adverse effects were reported in 6 patients (15%), mainly haematological (n = 3) and cutaneous (n = 2). Conclusion: In our series, the use of teicoplanin by subcutaneous route allowed to achieve a target trough concentration ≥ 15 mg/L. This target was reached faster if the loading dose was ≥ 9mg/kg/injection. Subcutaneous route consequently allowed facilitating the long-term parenteral antibiotherapy of staphylococcal bone and joint infections. Its clinical efficacy and its tolerance appeared to be acceptable, but have to be validated by future larger prospective trials.; Introduction : L’antibiothérapie sous-cutanée (SC) est pratiquée par 95% des infectiologues en France, le plus souvent en dehors de toute indication règlementaire. La téicoplanine est une alternative potentielle dans le traitement des infections ostéo-articulaires (IOA) staphylococciques. La possibilité théorique de l’utiliser en SC permet de limiter hospitalisation et abord veineux centraux prolongés. Toutefois, cette voie d’administration n’a que peu été évaluée. Notre objectif était d’analyser les taux résiduels (TR) de téicoplanine obtenus lors de son utilisation par voie SC dans les IOA à staphylocoque (objectif thérapeutique > 15 mg/L) et d’en décrire l’efficacité et la tolérance. Matériels et Méthodes : Étude rétrospective multicentrique (2002-2015) incluant tout patient traité par téicoplanine en SC pour une IOA à staphylocoque (infections de pied diabétique exclues) dans 3 centres : Strasbourg, Lyon et Chambéry. Résultats : Quarante épisodes d’IOA ont été inclus, dont 34 sur matériel (85%) et 21 chroniques (53%). L’âge médian était 75 ans (IQR, 62-84). Le débit de filtration glomérulaire (DFG) médian était de 68 mL/min/m2 (IQR, 56-91). Vingt-quatre souches étaient méti-R (58%), dont 13 Staphylococcus aureus (S.A) et 11 Staphylocoques à Coagulase Négative (SCN), avec des Concentrations Minimales Inhibitrices (CMI) respectives pour la téicoplanine de 0.5 mg/L (IQR, 0.38-0.81) et 0.75 mg/L (IQR, 0.5-1). La durée médiane du traitement par téicoplanine était de 46 jours (IQR, 29-79), principalement en association avec la rifampicine (n=23) ou une fluoroquinolone (n=16). Seize patients (40%) ont été traités par téicoplanine par voie intraveineuse (IV) avant le relais par voie SC. Une dose de charge (DDC) de 9.4 mg/kg/12h (IQR, 6.1-13.1) a été utilisée chez 35 patients (88%) (16 par voie IV, 18 en SC, 1 en IM). La dose d’entretien était de 7.3 mg/kg/injection (IQR, 5.3-12.1). Un relais en 3 injections par semaine de 15 mg/kg (IQR, 10.3-15.9) a été effectué chez 13 (33%) patients. Un TR ≥ 15 mg/L a été atteint chez 34 patients (85%) dans un délai médian de 4 jours (IQR, 3-6). Les TR mesurés durant les 20 premiers jours n’étaient pas significativement différents entre les voies IV et SC (p=0.462). Les TR atteints par voie SC étaient significativement plus élevés si la DDC était ≥ 9mg/kg/injection (p

Infectious endocarditis in children requires prolonged antibiotic therapy. In adults, antibiotics administrated subcutaneously such as teicoplanin are an alternative to intravenous treatment.We report the use of subcutaneous teicoplanin, after an initial antibiotic treatment administrated intravenously, for 2 children treated for infectious endocarditis following an initial cardiac surgery. Serum concentrations of teicoplanin were within the target range after the adaptation in the teicoplanin subcutaneous dosages. The treatment was effective for both cases. No specific side effects related to the treatment were reported.Subcutaneous administration could be used for prolonged antibiotic therapy for the treatment of infectious endocarditis in children, after an initial intravenous treatment. Variability of the bioavailability of antibiotics administrated subcutaneously requires regular testing. Prospective, randomized trials comparing intravenous and subcutaneous administration of teicoplanin should be conducted to assess the efficacy and safety of this treatment.

The authors had for aim to assess the inter- and intra-individual variability of teicoplanin pharmacokinetic parameters in geriatric patients.A cohort of 90 geriatric patients, treated with teicoplanin, was used to build two models describing the pharmacokinetics of teicoplanin, at the beginning and at the end of treatment respectively.The inter- and intra-individual variability of parameters were important as shown respectively by the coefficients of variation of pharmacokinetic parameters ranging from 125 to 694% and the half-life change during the treatment (by a factor of three to more than 30) for 60% of patients.The results revealed that elderly patients presented significant variability, which was only partly explained by the renal function. Therapeutic monitoring of teicoplanin in geriatric patients should be undertaken at the end of the loading dose and repeatedly during the maintenance phase to prevent over- or underexposure.

Teicoplanin is a glycopeptid antibiotic used for treatment of serious infections caused by Gram+ bacteriae. The treatment scheme corresponds to an initial loading dose followed by maintenance dose. High interindividual pharmacokinetic variability and strong relation between high through concentrations, dose and clinical success, support the need of therapeutic drug monitoring using through concentrations. Achieving through concentrations ≥ 10-15 mg/L or ≥ 20-40 mg/L, regarding the measurement method and the infection severity, is recommended to increase clinical success rate. The level of proof of therapeutic drug monitoring is evaluated: "necessary".

Vancomycin (V) and teicoplanin (T) are glycopeptides used in severe infections and can induce different kinds of cutaneous adverse reactions (CAR).To determine the value of immunoallergic investigations in CAR in which glycopeptides are suspected.Retrospective study (2000-2007) in eight patients with CAR suspected of being caused by glycopeptides. Six weeks after abatement of the reaction, in accordance with ESCD's guideline for drug testing, immunoallergic skin tests investigations were carried out (drug patch-tests, prick-tests and intradermal tests) in succession for all the drugs taken during the CAR. If negative, a glycopeptide challenge was proposed.The study included eight patients (five women, three men; mean age=53); three patients presented a reaction to vancomycin, four reacted to teicoplanin and one reacted to both drugs. CARs consisted of six maculopapular rashes, one case of DRESS and one of urticaria. Skin tests confirmed involvement of glycopeptides in four of eight cases with cross-reactivity between V and T in two patients. Four patients exhibited good tolerance to rechallenge tests with glycopeptides.This study shows that skin tests may be useful in glycopeptide-induced CAR in determining the responsible drug and also in the event of rechallenge. Allergic cross-reactivity (V and T), observed in two of our patients, although already been reported in the literature, but does not occur systematically.

The main characteristics of clindamycin are adequate for treatment of osteoarticular infections (OAI): good bone diffusion, broad spectrum of antibacterial activity and oral use.A number of 61 patients was included in an observational retrospective study of efficacy and tolerance.Prosthetic infections accounted for 50.8% of the cases and chronic osteitis for 36.1%. The causative micro-organisms were Staphylococci (72.2%) and Streptococci (15.3%); 86.5% of these strains were susceptible to erythromycin, 9.6% were erythromycin resistant and susceptible to lincomycin. Clindamycin was associated with either ofloxacine, rifampicin, or teicoplanin in 88.5% and the average course duration was 101 days. A surgical procedure was performed in 84% of cases. Complete cure was obtained in 91.1% at 18 months of follow up. Only one cutaneous rash and one Clostridium difficile-associated diarrhea occurred. The other adverse effects were gastrointestinal in 36%, cutaneous in 6.6%, and hematological in 1.6%, but did not lead to discontinuation of therapy.Clindamycin can be used in OAI in association with or as an alternative to rifampicin, fluoroquinolones, or glycopeptides according to microbiological data.

The aim of this study was to evaluate the rate of glycopeptides-resistant enterococci (GRE) fecal carriage (species and resistance determinants). Strains isolated between 1999 and 2005 during systematic screening for multiresistant bacteria in patients hospitalized in 3 intensive care units (ICU) of the University Hospital of Montpellier were studied.The systematic screening was weekly performed. Rectal swabs were cultured on D-Coccosel agar medium containing 4 mg/l vancomycin and MICs for vancomycin and teicoplanin were determined by E-test. Strains were subjected to both phenotypic and genotypic identification and vanA, vanB and vanC genes were detected by PCR.We analyzed 13003 samples for 5113 patients. Among them, 401 (7.84%) patients were GRE carriers with 280 Enterococcus gallinarum (vanC(1)), 102 Enterococcus casseliflavus-flavescens (vanC(2)-C(3)), 5 Enterococcus faecalis (3 vanA, 2 vanB), and 14 Enterococcus faecium (10 vanA, 4 vanB). A unique case of cross contamination between two patients was observed. During the same time, only one strain of GRE was isolated during an infectious process in another unit. Carriage rate of E. faecium and E. faecalis vanA or vanB was 0.37%: 68.4, 21 and 10.6% in the gastrointestinal, in the polyvalent and the respiratory ICU, respectively.Our results were in agreement with national data showing a relatively low GRE fecal carriage rate in ICUs, E. faecium vanA being the mainly encountered GRE. Since 2004, GRE detection is increasingly reported in France and an emerging E. faecium vanA clone has been identified during outbreaks. In contrast, only one E. faecium vanB strain has been isolated in our institution since this date and a unique strain of E. faecalis vanA was isolated during an infectious process since 1999. These data underlined the efficacy of transmission prevention measures established when GRE are identified.

Spondylodiscitis, a septic infection of the intervertebral disc Spondylodiscitis, a septic infection of the intervertebral disc and adjacent vertebrae, is an unusual infection, mainly affecting children and elderly people. It is classically associated with tuberculosis, but other germs such as Staphylococcus aureus, Streptococcus pyogenes or mitis, and some even more unususal ones (e.g. Kingella kingae), are often encountered in our countries. Non tuberculous spondylodiscitis is found in approximately 2% of pediatric bone infections. Medullar compression and bone destruction can occur, especially when diagnosis is delayed, hence the value of early diagnosis and treatment. We report the case of a non tuberculous spondylodiscitis occurring in a 22 month-old baby

The authors had for aim to analyze the indications, quality, and volumes of glycopeptide (GP) prescriptions in all in-patient units of a general hospital. CLINICAL MATERIAL AND METHODOLOGY: A 4 month prospective study assessed the compliance of curative and prophylactic treatment prescriptions administered according to guidelines. The assessment criteria were as follows: prescription indicated or not, prescription modalities (administration of loading dose, performing of serum tests, dosage appropriateness, appropriateness with antibiogram data when available).Over the 46 assessed prescriptions, 84.7% were curative treatments (N = 39), whereas 15.2% (N = 7) were written out for surgical antibioprophylaxis. The prescription incidence and density were, respectively, 0.60 prescription/100 admissions and 20.8 DDJ/1000 hospitalization days, i.e. 24% of the total antibiotics budget. Prescriptions were always indicated for surgical antibioprophylaxis, but met standards in only 14% of cases. As for curative prescriptions, treatments were appropriate in 56.5% of cases, but only 18% met standards. GP use modalities proved incorrect at various levels: non existing load dose and lack of serum tests, subinhibiting daily doses, no dose lowering when possible, exaggerated duration of surgical antibioprophylaxis. Average GP serum levels were 16 mg/L and were higher than the target level in no more than 40% of properly prescribed treatments.Prescription modalities and treatment monitoring must be improved, given the development of bacterial resistance.

The influence of BHI media commercially available on the results of glycopeptides MIC measured by E-test method was studied on 36 S. aureus isolates (21 MRSA and 15 MSSA). The MIC obtained with the vancomycin and the teicoplanin determined by the E-test method, on the ready prepared BHI plates (AES) and the plate prepared at the laboratory among the four dehydrated bases (AES, Biorad, Oxoid, and Becton Dickinson), were compared. The mean of the MIC showed variations from 3.14 (Biorad) to 5.25 mg/L (Oxoid) and from 3.33 (Biorad) to 9.75 mg/L (ready prepared AES) respectively for the vancomycin and for the teicoplanin. A variance analysis (Test de Friedman) showed a significant difference between the five media (p0.001) with the two antibiotics. The comparison of media 2 by 2 allowed that all combinations excepted one (Biorad vs Becton with the vancomycin) were statistically different (p0.001). The variation of the MIC observed in relation to the origin of the product of BHI media requires the inclusion of glycopeptide-intermediate S. aureus reference strains to control the prepared culture media.

The aim of the present study was to investigate the prevalence of vancomycin resistance in clinical methicillin resistant Staphylococcus aureus (MRSA) isolates in our hospital by screening on Mueller–Hinton agar with 5 mg/l teicoplanin (MH-Teico), as recommended by the Comite de l’Antibiogramme of the Societe Francaise de Microbiologie (CA-SFM). Seventeen of 1002 clinical MRSA isolated from 404 patients showed in 2003 growth of at least four colonies on this medium, but only one was confirmed as homogeneous vancomycin-resistant S. aureus (VISA) and five as heterogeneous VISA (hVISA) by population analysis. None of the patients presented with severe infection but awareness is needed and screening on MH-Teico as recommended by CA-SFM is a convenient method. Surveillance should be focused on patients with risk factors for selection of such strains: patients with a prolonged course of glycopeptide therapy and persistence of MRSA infection or colonization.

All the patients hospitalised at Besançon Hospital between October 2000 and December 2000 were included in a prospective study in order to determine the incidence of bloodstream infections caused by coagulase-negative staphylococci (CNS), the prevalence of decreased susceptibility to glycopeptides and the molecular epidemiology of these pathogens. CNS isolates from bloodstream infections were collected and characterised by analysis of antibiotic susceptibility and restriction fragment length polymorphism using pulsed field gel electrophoresis. Forty-five episodes of CNS bacteremia occurred in 43 patients. The crude incidence of infected patients was 0,51 per 1,000 days of hospitalisation. These 45 bacteremia represented 23.3% of the total number of bacteraemia. Forty three of 45 bacteremia were studied, 36 were positive with a single PFGE pattern, 5 bacteraemias with 2 PFGE patterns, and 2 bacteraemias with 3 PFGE patterns. We identified 52 distinct PFGE patterns and 42 major PFGE patterns (35 were isolated in a single patient, 5 in 2 patients and 2 in 3 patients). The dendrogram generated showed deep but limited branching, each large branch corresponding to a species. Of these CNS isolates, 28.8% and 25.0% showed decreased susceptibility to teicoplanin, with the reference method and E-test respectively. The 16 strains belonging to multiple PFGE patterns were not more resistant to teicoplanin. Clonal dissemination did not seem to play a major role in the spread of glycopeptides resistance among CNS.

The detection of methicillin-resistant S. aureus (SA) (MRSA) refractory to glycopeptides is a serious clinical issue. The prevalence of hetero-resistant GISA (hGISA) strains at H. Maréchal Joffre, France is reported.858 non-repeat SA were isolated during 1999. 367 (43%) of these, from 257 patients, were MRSA (mean incidence 11.9/1000 admissions). All MSRA detected during 1999 were screened for vancomycin (VAN) resistance (BHI+4 mg/l VAN). Isolates recovered were retested using Etest strips (2 McFarland inoculum on BHI) and population analysis profile/area under the curve (PAP-AUC) analysis with hGISA SA Mu3 as a comparator. 58 selected strains were screened for teicoplanin resistance(TEI) using SFM recommended screen (2 McFarland inoculum on MH+5 mg/L TEI) and MIC (0.5 MF inoculum swabbed on MH agar) methods. 188 (51.3%) grew on VAN screen agar (6.1/1000 admissions). 58 strains (7.6%) possessed Etest VAN MIC8 mg/l all others being VAN8 mg/l. Of these 58 isolates, 10 were stably heterogeneously resistant to both VAN and teicoplanin (MIC8 mg/l). PAP-AUC showed 12 strains to have PAP-AUC ratios0.95 but1.5 (ie. hGISA, not GISA). All 7 isolates defined as hGISA by both Etest and PAP-AUC comprised 1 PFGE clone (3 bands difference). Additionally 2 distinct PFGE types were detected among the other 5 hGISA identified PAP-AUC. The 12 hGISAs, were derived from 12 patients with severe underlying disease. None were on glycopeptide therapy prior to hGISA isolation. This is the first report of endemic hGISA, comprising 3 clonal types. The isolation of hVISA seems not to be associated with patient-specific glycopeptide therapies.

The therapeutic drug monitoring aims at optimising the prescribed dosages to improve efficacy and prevent toxicity. The aim of this study were to review the main pharmacodynamic and pharmacokinetic properties of aminoglycosides, glycopeptides and ceftazidime. Then, the therapeutic drug monitoring of these antibiotics and their methods of analysis is reviewed.

With the objective of clarifying the modes of using glycopeptides in intensive care, a survey with a declared intention was performed in June 2001, in the form of a postal questionnaire; it was possible to exploit 742 answers. Analysis of the results showed that 15% of the doctors completing the questionnaire had not employed glycopeptides within the past six months. Preference was given to vancomycin, and 65% of practitioners prescribed this drug only, while 1% of them only prescribed teicoplanin. For vancomycin, a central route is used in 9 out of 10 cases, with a preference for continuous infusion (69% versus 48%). A loading dose is prescribed in 70% of continuous infusions (or = 15 mg.kg-1 in 69% of cases), and in 19% of intermittent infusions (or = 15 mg.kg-1 in 90% of cases). The mean vancomycin dosage is 30 mg.kg-1.d-1; in the case of intermittent administration this involves two (51%), three (17%) or four (27%) injections per day. The target concentrations are residual serum vancomycin levels of between 13.5 and 23.6 mg.L-1 with intermittent administration or plateau levels of 18.3 to 29.4 mg.L-1 with continuous infusion. Teicoplanin is administered intravenously (92%) and/or via the i.m. route (34%). The mean dosage is10 mg.kg-1.d-1 in seven out of ten cases. A loading dose is administered every 12 hours at the same dosage in 77% of cases (or = 3 injections for 65% of prescribers). The residual teicoplanin concentrations sought are between 14.3 and 25 mg.L-1. Monitoring of serum levels is ensured at least once a week in 97% of cases with vancomycin and 66% of cases with teicoplanin. In conclusion, is seems that the methods of using glycopeptides vary considerably. The great heterogeneity of practices suggests a lack of compliance by prescribing practitioners with current recommendations. It also seems that a precise definition of the target plasma levels to be achieved in different indications is necessary.

Fifty-seven methicillin resistant S. epidermidis with decreased susceptibility to teicoplanin were obtained from 14 neutropenic patients on a period of 11 months (19 February-31 December 1998) from essentially blood culture (30 strains) and ORL specimens (21 strains). The MIC90 of methicillin, gentamicin, ofloxacin and telcoplanin were respectively 1024, 1024, 512 and 32 mg/l. We applied pulsed field gel electrophoresis (PFGE) after Smal digestion to 21 isolates choosed between eight patients with multiple isolates (two strains). For epidemiological control, a MetiR and TeicoR S. epidermidis isolated from blood culture taken from Caen CHU was include in study. Twenty-one isolates were separated by PFGE into eight group, from I to VIII. The control strain was classed in group IX. Group I include 14 strains which can be subdivised on three sub-types (differed by a single to three bands): seven strains have the pulsotype Ia and obtained respectively from five strains in transplantation unit and two strains in hematology unit. Two strains have the pulsotype Ib and isolated in the two units. Five strains have the pulsotype Ic and obtained also from transplantation unit (four strains) and hematology unit (one strain). All the other pulsotypes were identified in only one strain, frequently in association with the pulsotype I. Until recently, infections due to coagulase negative staphylococci have been regarded as endogenous in origin, these results with some pulsotype of S. epidermidis MetiR and TeicoR in the two separate units suggered a nosocomial origin, probably by medical staff transmission because no S. epidermidis TeicoR was isolated from environmental control during all the period.

This clinical and economical study compared two glycopeptides regimen i.e., vancomycin and teicoplanin in the treatment of osteoarticular infection involving methicillin-resistant staphylococcus. After randomization, 15 patients (group 1) received vancomycin (23 F per gram) in continuous infusion through a central venous catheter and 15 others (group 2) intramuscular teicoplanin (311-357 F a 400 mg vial). The clinical study focused on treatment tolerance in an in-patient setting as well as in a non in-patient one. The cost analysis focused on total expenses including those of antibiotics, those of medical devices for antibiotic administration and those of the complications caused by the antibiotics use. Total expenses per patient averaged 8744 F with vancomycin and 8555 F with teicoplanin (NS). The apparent money saving by using a cheap antibiotic (i.e. vancomycin) was illusionary as one took in account the expenses for medical devices e.g., central venous catheters required to administer vancomycin and the complications due to the use of these devices.

To review pharmacology, pharmacokinetic and therapeutic use of glycopeptides in intensive care units.Extraction from Medline database of French and English articles on glycopeptides and search along with major review articles.The collected articles were reviewed and selected according to their quality and originality. The more recent data were selected.Glycopeptides are bactericidal antibiotics which are only active against Gram positive species acting by inhibiting peptidoglycan synthesis. They had been in clinical use for almost 30 years without high-level resistance underlining. For ten years, there have been disturbing reports of first, resistance to vancomycin in enterococcal species and more recently in strains of Staphylococcus aureus by complex and large mechanisms of action. This new resistances may lead to a therapeutic impasse and a fatal issue for infected patients. The only response to this situation is the respect of prescription rules and the careful use of antibiotics.Considering their spectrum, glycopeptides are an antibiotic family which importance is fundamental to treat infected patients of intensive care units. Staff members of intensive care units are responsible for their good use.

Glycopeptides which have excellent in vitro activity against the Gram-positive causal agents of meningitis unfortunately have a poor CSF penetration. Vancomycin distribution into CSF is improved when administered by a continuous intravenous route and staphylococcal shunt related infection have been reported to be cured. Teicoplanin has good in vitro activity against a lot of staphylococci, and activity superior to vancomycin, against streptococci and is less toxic. In three children with shunt ventriculitis (S epidermidis 2, S. faecalis 1) despite a continuous infusion, vancomycin 15 mg/kg over 60 minutes onset, then 50 mg/kg/day was clinically and bacteriologically ineffective with very poor CSF levels even if high blood levels. After failure of vancomycin we used teicoplanin as a continuous i.v. infusion 6 mg/kg over 60 mn onset, then 12 mg/kg/day. This treatment was quickly effective and well tolerated.

To assess the pharmacokinetics of a single dose of teicoplanin in critically ill patients treated with continuous arteriovenous haemofiltration (CAVH).Prospective open clinical study.Eleven patients with acute renal insufficiency and suspected of a Gram negative infection.After injection of teicoplanin, 6 mg.kg-1 over 30 minutes the plasma and haemofiltrate concentrations were measured over 24 hours with high power liquid chromatography (HPLC).In plasma, the mean half-life of the first phase was 0.6 +/- 0.2 hour and terminal half-life was 16.4 +/- 5 8 hours, total clearance 30.4 +/- 7.1 mL.h-1.kg-1, volume of distribution was 0.7 +/- 0.3 L.kg-1 and the mean resident time 19.2 +/- 7.4 hours. In the haemofiltrate, the amount of teicoplanin eliminated after 24 hours was less than 1% in seven patients, between 1.8 and 3.7% in three and reached 7% in one patient.During CAVH, the elimination of a single dose of teicoplanin in the haemofiltrate is low.

E-test was evaluated by comparison with the reference agar dilution method on 15 enterococci and 15 staphylococci with variable resistance to glycopeptides and isolated from clinical samples: 15 enterococci with 3 glycopeptide-resistant (2 E. facalis and 1 E. faecium), 1 glycopeptide intermediate E. gallinarum and 11 glycopeptide-sensible E. faecalis; 15 staphylococci with 4 teicoplanine-resistant (1 S. aureus, 1 S. epidermidis and 2 S. hominis), 3 teicoplanin-intermediate (1 S. epidermidis, 2 S. haemolyticus) and 8 teicoplanin sensible strains (6 S. aureus, 1 S. epidermidis and 1 S. hominis). Repeatability (10 determinations by strain) and exactitude were tested for all strains. Our data shows very good results for repeatability and exactitude with the reference method except in the case of coagulase negative staphylococci and teicoplanin. Some technical problems appear in our experience: for staphylococci, a 48 h incubation is necessary to detect teicoplanin-intermediate strains but 24 h is sufficient for enterococci. E-test is expensive, require a strict methodology, but is a good method to detect glycopeptide resistance for staphylococci and enterococci except for coagulase negative staphylococci and teicoplanine.

By repeated and successive treatments of five strains of methicillin-resistant Staphylococcus aureus with sub-inhibitory concentrations of vancomycin and of teicoplanin, the authors have confirmed that selection of resistant strains could be obtained more easily with teicoplanin than with vancomycin. Moreover, we have shown that treatments with subinhibitory concentrations of teicoplanin could also influence the activity of vancomycin, although the strains have never been in contact with the latter antibiotic. This could account, at least in part, for the downhill evolution of the activity of glycopeptides against staphylococci, observed this last years. Indeed, the efficacy of these antibiotics upon which treatment of severe infections due to multiresistant staphylococci relies, is lowering. Considering the challenge, this risk is worth being not only evaluated by a reinforced epidemiologic surveillance, but also limited by more severe criteria for the prescription and the follow-up of treatments with glycopeptides.

The activity of vancomycin (Va) and teicoplanin (Tc) against 114 coagulase-negative staphylococci (CNS) strains was evaluated by disk-diffusion and agar dilution minimal inhibitory concentration (MIC) determination. Results were analysed by species and methicillin-resistance (MR) status. MICs for Va were in the susceptible range (4 mg/l) for all strains, with inhibition zone diameters of 17 mm or more in every case. MICs for teicoplanin were 8 or 16 mg/l for 19 CNS strains (including 18 with MR) of which 14 yielded an inhibition zone diameter of 17 mm or more (false susceptibility). Parameters which should lead to MIC determination for Tc regardless of disk diffusion findings include the species (S. haemolyticus), methicillin resistance, Tc zone diameter, and an at least 3 mm difference between the Va and Tc zone diameters.

Vancomycin and teicoplanin are two commercially available glycopeptide antibiotics. They have identical spectra of activity and similar mechanisms of action, and both are complex molecules. In vitro, vancomycin is more active against coagulase-negative staphylococci, while teicoplanin is more active against enterococci and pneumococci. The activity of the two antibiotics against Staphylococcus aureus is similar. The serum pharmacokinetics of vancomycin and teicoplanin are highly different, teicoplanin having a longer elimination half-life (40 hours versus 6-8 hours for vancomycin), but a higher degree of protein binding (90% versus 55%). We compared the two antibiotics on the basis of their inhibitory quotient kinetics, using the MIC90 values for the above bacterial species as the microbiological parameters, and the total and free (non-protein bound) serum concentrations as the pharmacokinetic parameters. The inhibitory quotient kinetics of vancomycin were always more favorable in terms of the free concentrations, even against those bacteria for which the teicoplanin MIC was lower.

The activities of vancomycin and teicoplanin against 148 strains of Gram-positive cocci were tested using agar diffusion and liquid microdilution MIC determination. Tested strains included 84 staphylococci, 32 S. aureus, 52 coagulase-negative staphylococci (CNS), 52 enterococci, and 12 streptococci. Most strains (136) were susceptible to both agents, with inhibition diameters of 17 mm or more. MRSA strains exhibited lower geometric MIC means with teicoplanin (0.90 micrograms/ml) than with vancomycin (1.79 micrograms/ml); this difference was found for methicillin-susceptible S. aureus strains (1.07 and 1.38 micrograms/ml for teicoplanin and vancomycin, respectively). In contrast, methicillin-susceptible and methicillin-resistant strains of CNS exhibited similar MICs (1.60 micrograms/ml approximately). Enterococci were more susceptible to teicoplanin (MIC 0.25 micrograms/ml) than to vancomycin (MIC 1.35 micrograms/ml). Both vancomycin and teicoplanin were thus found to be consistently effective against Gram-positive cocci; however, teicoplanin proved more effective than vancomycin against enterococci and methicillin-resistant S. aureus strains and may therefore be a valuable therapeutic alternative for these multiresistant organisms.

The minimum inhibitory concentrations (MICs) of vancomycin and teicoplanin were determined for 32 coagulase-negative staphylococci strains recovered from blood specimens from pediatric intensive care patients. All the strains were susceptible to vancomycin (MIC less than 4 mg/l). Sixteen strains were susceptible to teicoplanin (MIC less than 4 mg/l) and the sixteen remaining strains exhibited intermediate susceptibility, with MICs of 8 mg/l (10 strains) or 16 mg/l (6 strains). Inhibition zone diameters seen with vancomycin during agar diffusion susceptibility testing were consistently greater than 17 mm. Inhibition zones obtained with teicoplanin were 17 mm or more in diameter for 30 strains and under 17 mm in diameter for 2 strains. For 14 strains (44%), agar diffusion testing failed to detect the decreased susceptibility to teicoplanin revealed by MIC determinations. The agar diffusion method does not seem reliable for the determination of in vitro susceptibility to teicoplanin.

We report the case of a 38-year old man who developed erythroderma during treatment with teicoplanin for staphylococcal septicaemia. The clinical symptoms, which included high fever, shock and erythroderma, were suggestive of staphylococcal toxic shock. After teicoplanin was withdrawn and replaced by vancomycin the disease followed a favourable course. The reintroduction test was positive. This case illustrates the problems associated with the diagnosis of erythroderma in intensive care patients and confirms that it is possible to prescribe vancomycin in cases with allergic reaction to teicoplanin.

The efficacy and the safety of teicoplanin were evaluated for the treatment of febrile episodes in neutropenic patients. A total of 18 patients received teicoplanin once daily as an intravenous injection of 200 mg in 6 patients (after a loading dose of 400 mg) or 400 mg in 12 patients (loading dose: 800 mg). The mean duration of therapy was 15.9 days (range 9 to 39 days). In all patients teicoplanin was combined with another antibiotic usually a beta-lactam. Thirteen of 18 patients were successfully treated. Three febrile episodes proved to be microbiologically documented infections and were cured by teicoplanin: one Streptococcus mitis and two methicillin-resistant (methi-R) Staphylococcus epidermidis bacteremias. Neither toxicity nor side effects were observed in the reported group. Six patients experiencing reactions to vancomycin (2 cases of cutaneous allergy) or to vancomycin and amphotericin B combination (4 cases of nephrotoxicity) were subsequently treated with teicoplanin without any evidence of cross-sensitivity. We observed emergence of teicoplanin-resistant coagulase-negative Staphylococcus in 3 patients receiving teicoplanin: 20, 18 and 8 days after a first febrile episode cured by teicoplanin and a beta-lactam, they developed fever while receiving the same antibiotic regimen. Methi-R Staphylococcus epidermidis was isolated from blood cultures in the first patient and methi-R Staphylococcus haemolyticus in the two other patients. In one patient, successfully treated by teicoplanin for a first febrile episode related to a methi-R Staphylococcus epidermidis, emergence of Staphylococcus haemolyticus occurred 8 days later while the patient was on teicoplanin therapy (6 mg/kg). MICs of teicoplanin were 16 mg/l for the two Staphylococcus strains isolated in this patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Corynebacteria groups JK and D2 are opportunistic pathogens. They are sometimes responsible for severe infections, especially in immunocompromised patients. They are resistant to many antibiotics. Under these conditions it seemed important to discover which antibiotics among those regularly active, have a killing effect, what their bactericidal speed is, and how they react to combination with other antibiotics. Glycopeptids have a killing effect within 24 hours. Pristinamycin, rifampin, fusidic acid, when active, are bacteriostatic. Their combination with vancomycin is indifferent but in one case the combination vancomycin + rifampin is synergistic.

Teicoplanin was evaluated in 25 severe infections caused by Gram-positive bacteria alone [13], in combination [9], alone then in combination [3], in an open study. Of 22 infections that could be evaluated, there were 18 cures and improvements (81.8%), 2 recurrence and 2 failures. Serum concentrations are unpredictable and steady after 5 days i.v. teicoplanin. Trough and peak concentrations are respectively less than 5 mg/l and less than 20 mg/l in 13 infections and higher in 9, unrelated with success or failure. A trough concentration greater than CMI and kind of infection seem deciding. The choice of the antibiotic combined with teicoplanin warrant more data.

Daptomycin (LY 146032) is a semi-synthetic antibiotic whose structure consists of a cyclic peptide with a lipophilic chain. It inhibits synthesis of the bacterial wall differently than vancomycin and teicoplanin. The bactericidal activity of daptomycin was compared with that of vancomycin and of teicoplanin with regard to 54 Gram positive strains of bacteria: (S. aureus meti S and meti R; S. epidermidis meti S and meti R; E. faecalis, E. faecium, and Corynebacterium group JK). Vancomycin and teicoplanin have the same slow and time-dependent bactericidal activity. The activity of daptomycin is different: rapid and concentration-dependent, similar to that of the aminoglycosides. In the case of the Corynebacteria, however, the activity of daptomycin is comparable to that of vancomycin and of teicoplanin slow and time-dependent.

Sixty-six cases of Gram positive infections were treated with teicoplanin in an open multicenter study, comprising 7 centers in Eastern France. There were 38 male patients and 28 females. Teicoplanin was given at a dose of 400 mg daily for a mean duration of 18.4 days. The most common infections were due to Staphylococcus aureus, found in 43 out of 56 documented cases. 69 (89.9%) of the 78 Gram + strains isolated had an MIC for teicoplanin of less than or equal to 2 mg/l. There were 44 serious infections (30 septicemia, 10 endocarditis, 1 joint and bone infection, 2 mediastinitis, 1 toxic shock syndrome) and 22 less serious infections (4 urinary infections, 14 skin and soft tissue infections, 3 lower respiratory infections, 1 hepatic abscess). In 42 cases concurrent medication was given: beta-lactamase in 11 cases, rifampicin in 10 cases, aminoglycosides in 22, phosphomycin in 3, pefloxacin in 5. The clinical cure and improvement rate was 90.10%. Adverse events were reported in 11 patients, and in only 3 cases was the therapy stopped. All were reversible on stopping therapy. Teicoplanin was found to be well tolerated and effective in the treatment of Gram positive infections in this study.

In this study, teicoplanin was administered to burnt patients by IV and IM route in monotherapy or in association with other antibiotics. 12 cases of septicaemia and 8 severe cutaneous cocci Gram + infections were treated. Dosage varied from 5 mg/kg to 14 mg/kg. Clinical cure was observed in 89% of cases, and eradication of cocci Gram + in 83%. The MICs of Staphylococcus were between 0.25 micrograms/ml and 4 micrograms/ml, with a majority of methicillin-resistant Staphylococcus at 1. Average through serum concentrations were 7.4 micrograms/ml, and peak serum concentrations were 26 micrograms/ml (1 hour after injection). Tolerance was good in 19 of the 20 cases (95%). Skin levels of teicoplanin were found to be 1.6 times the through serum level. It was noted that in burnt patients whose UBS is superior to 100, the dose should be increased by about 50%.