RESUMEN
BACKGROUND: The optimal dose of ribavirin to be used in combination with Peg-IFN in patients with HCV genotypes 2 and 3 undergoing short treatment has not been established. AIM: To explore the relationship between starting ribavirin doses, expressed as mg/kg body weight and both rapid viral response at treatment week 4 (RVR) and sustained virological response (SVR) in patients treated for 12-14 weeks with peg-interferon alpha-2b and ribavirin. METHODS: A post hoc analysis of data collected from two multicenter clinical trials was performed. Multiple regression analyses were employed to identify independent baseline and on-treatment predictors of RVR and SVR. For each dose of ribavirin, the empirical estimated probability of response was computed and the continuous exposure index was dichotomized by using a recursive partitioning and amalgamation method. RESULTS: A nonlinear relationship was ascertained between ribavirin dose and RVR, but not SVR. A dose of 15.2 mg/kg was selected as the best splitting value for discriminating RVR vs. non-RVR. Regression analysis identified low baseline viraemia, genotype 2 and high ribavirin dose as independent prognostic factors for RVR. The likelihood of an SVR was not correlated with baseline ribavirin dose, but was independently predicted by adherence to the full dose throughout treatment and normal platelet counts. CONCLUSIONS: Starting high ribavirin doses appears capable of increasing the rate of RVR in patients with HCV genotypes 2 and 3 undergoing short treatment. Maintenance of the full planned dose throughout treatment is essential for achieving optimal SVR rates.
Asunto(s)
Antivirales/administración & dosificación , Hepatitis C Crónica/tratamiento farmacológico , Virus de Hepatitis/genética , Interferón-alfa/administración & dosificación , Polietilenglicoles/administración & dosificación , Ribavirina/administración & dosificación , Adulto , Ensayos Clínicos como Asunto , Quimioterapia Combinada , Femenino , Genotipo , Hepatitis C Crónica/genética , Humanos , Interferón alfa-2 , Masculino , Persona de Mediana Edad , ARN Viral , Proteínas Recombinantes , Estadística como Asunto , Factores de Tiempo , Resultado del Tratamiento , Carga Viral , Adulto JovenRESUMEN
Guidelines for the treatment of patients infected with hepatitis C virus of genotypes 2 and 3 (HCV-2 and HCV-3, respectively) recommend a 24-week course of Peg-interferon (Peg-IFN) alpha-2a combined with ribavirin, despite 50% of patients in registration trials attaining a sustained virologic response (SVR) following Peg-IFN alpha-2a monotherapy. The aim of this study was to delineate patient characteristics that might help to identify individuals likely to benefit from ribavirin discontinuation. One hundred and forty-four HCV-2- and HCV-3-infected patients initiated Peg-IFN alpha-2a (180 microg/week) and ribavirin (1000 or 1200 mg/day); those with viral clearance at week 4 were randomized to either Peg-IFN alpha-2a monotherapy (n = 59) or continuing combination therapy (n = 61) until week 12. Overall, all but one patient with a rapid virologic response (RVR) responded by the end of therapy and the overall SVR rates were lower after discontinuation of ribavirin (54%vs 82%; P < 0.001). In RVR patients who discontinued ribavirin, low baseline viraemia helped predict SVR (odds ratio 11.2, 95% CI 2.7-47.1). SVR rates were similar in patients receiving mono- or combination therapy with low (< or =300,000 IU/mL) and intermediate viraemia (86%vs 81% and 70%vs 71%, 86% refers to low viraemic patients receiving monotherapy and 81% to those receiving combination therapy. Similarly, 70% refers to patients with intermediate viraemic levels receiving monotherapy and 71% to those receiving combination therapy), but different in those with high (>700,000 IU/mL) viraemia (37%vs 88%; P = 0.004). Thus in HCV-2- and HCV-3-infected patients, withdrawal of ribavirin and continuation of Peg-IFN alpha-2a monotherapy may be appropriate to attain an SVR, providing viraemia is cleared early during therapy and associated with low baseline viral load. These results warrant future investigations, as discontinuing ribavirin could lead to considerable savings in cost and quality of life related to over-treatment.
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Antivirales/uso terapéutico , Hepacivirus/clasificación , Hepatitis C/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Ribavirina/uso terapéutico , Privación de Tratamiento , Adulto , Femenino , Genotipo , Hepacivirus/genética , Hepacivirus/aislamiento & purificación , Humanos , Interferón alfa-2 , Masculino , Persona de Mediana Edad , Proteínas Recombinantes , Resultado del Tratamiento , Carga ViralRESUMEN
We determined whether triple therapy comprising amantadine (AMA), ribavirin (RBV) and either peginterferon (PEG-IFN) alpha-2a or conventional IFN alpha-2a would improve sustained virological response (SVR) rates over dual therapy with IFN alpha-2a and RBV in patients with chronic HCV infection. A total of 362 treatment-naïve patients were randomized to 48 weeks of treatment with: PEG-IFN alpha-2a 180 microg/week (group A) or IFN alpha-2a 3 MU tiw (groups B and C). All patients received RBV 1000 or 1200 mg/day and those in groups A and B received AMA 200 mg/day. SVR was defined as an undetectable HCV RNA after 24 weeks of untreated follow-up. At the end of therapy, 74.4% (95% CI 0.66-0.82) of patients in group A were HCV RNA-negative compared with 42.5% (95% CI 0.33-0.50) of those in group B (P = 0.0001) and 48.8% (95% CI 0.40-0.56) of those in group C. SVR was achieved in a significantly greater proportion of patients in group A compared with groups B and C: 65.3% (95% CI 0.53-0.56), 33.3% (95% CI 0.25-0.41) and 44.6% (95% CI 0.36-0.53; P = 0.0001) respectively. In patients with genotype 1, SVR rates were 55.2, 22.8 and 28.8% with the three regimens respectively. Factors independently associated with SVR were HCV genotype 2 or 3, therapy with PEG-IFN, female gender and age. In treatment-naive patients with chronic hepatitis C, triple therapy with PEG-IFN alpha-2a, RBV and AMA produces higher SVR than dual or triple therapy with conventional IFN alpha-2a.
Asunto(s)
Amantadina/administración & dosificación , Hepacivirus/efectos de los fármacos , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/administración & dosificación , Polietilenglicoles/administración & dosificación , Ribavirina/administración & dosificación , Adolescente , Adulto , Anciano , Amantadina/efectos adversos , Biopsia con Aguja , Distribución de Chi-Cuadrado , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Hepatitis C Crónica/diagnóstico , Humanos , Inmunohistoquímica , Interferón alfa-2 , Interferón-alfa/efectos adversos , Masculino , Persona de Mediana Edad , Polietilenglicoles/efectos adversos , Probabilidad , Estudios Prospectivos , Proteínas Recombinantes , Ribavirina/efectos adversos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Método Simple Ciego , Estadísticas no Paramétricas , Resultado del Tratamiento , Carga ViralRESUMEN
Expert consensus recommends liver biopsy before therapy for chronic hepatitis C. A cost effectiveness analysis suggested that the best strategy in the management of patients was to treat without biopsy. We compared therapy in patients who did, or did not undergo biopsy. Hepatitis C virus (HCV)-positive patients (78) who did not agree to (n = 57) or with contraindications to liver biopsy (n = 21) (group A) were matched for age, sex and genotype with those who consented (group B). Before therapy (interferon/ribavirin for 12 months), a clinical diagnosis of chronic hepatitis, on the basis of standard biochemical and ultrasonographic parameters. The two groups showed similar baseline characteristics. A noninvasive, diagnosis of chronic hepatitis was made in 75.6% of group A, and in 83.3% of group B (P = 0.26). Concordance between clinical and histological diagnosis in group B amounted to 91%. End-of-therapy virological response was 52.6% in group A, and 57.7% in group B (P = 0.63). Sustained virological response was 41.0% [95% confidence interval (CI) 30.1-51.9] and 43.6% (95% CI 32.6-54.6) in the two groups (P = 0.87). Predictors of sustained response were noninvasive diagnosis of chronic hepatitis (P = 0.006), lack of portal hypertension (P = 0.037), platelets >10(5)/mm3 (P = 0.007), prothrombin >70% (P = 0.02), and genotype 2 or 3 (P < 0.0001). At multivariate analysis, genotype (P < 0.0001) and platelets (P = 0.004) maintained their predictive power. In most patients with HCV infection, virological clearance after therapy can be achieved irrespective of whatever a liver biopsy might show.
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Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/patología , Interferones/uso terapéutico , Hígado/patología , Ribavirina/uso terapéutico , Adulto , Biopsia , Quimioterapia Combinada , Femenino , Hepacivirus , Hepatitis C Crónica/virología , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
BACKGROUND/AIMS: To evaluate the therapeutic efficacy of interferon alpha-2b and lamivudine in combination compared to lamivudine monotherapy in patients with chronic hepatitis B. METHODS: One hundred and fifty-one patients were randomly assigned to receive either recombinant interferon alpha-2b (nine million units three times per week) and lamivudine (100 mg/daily per os) for 24 weeks or lamivudine alone (100 mg/daily per os) for 52 weeks. Patients were followed up for a further 48 weeks. RESULTS: Sustained HBeAg seroconversion with undetectable serum levels of HBV DNA was observed in 25 of 76 patients (33%) treated with the combination therapy and in 11 of 75 patients (15%) treated with monotherapy (P=0.014). Histological improvement defined as a reduction of at least two points in the inflammation score as compared with pretreatment score was observed in 35 of 76 patients (46%) treated with combination therapy and in 20 of 75 patients (27%) treated with monotherapy (P=0.021). Both therapeutic regimens were well tolerated. CONCLUSIONS: Six-month treatment with interferon alpha-2b and lamivudine in combination appeared to increase the rate of sustained HBeAg seroconversion compared to 1-year lamivudine monotherapy. However, the potential benefit of combining lamivudine and interferon should be investigated further in studies with different regimens of combination therapy.
Asunto(s)
Antivirales/administración & dosificación , Hepatitis B Crónica/tratamiento farmacológico , Interferón-alfa/administración & dosificación , Lamivudine/administración & dosificación , Adulto , Alanina Transaminasa/sangre , ADN Viral/análisis , Quimioterapia Combinada , Femenino , Antígenos de Superficie de la Hepatitis B/análisis , Virus de la Hepatitis B/clasificación , Virus de la Hepatitis B/genética , Hepatitis B Crónica/patología , Hepatitis B Crónica/virología , Humanos , Interferón alfa-2 , Lamivudine/uso terapéutico , Masculino , Persona de Mediana Edad , Mutación , Proteínas RecombinantesRESUMEN
BACKGROUND: In chronic hepatitis C the schedule of interferon (IFN), 3 MU thrice weekly (tiw) plus ribavirin (1000-1200 mg/daily) needs further evaluation, as IFN dosages >3 MU achieve better responses. AIMS: To compare the efficacy of 5 MU tiw of IFN with (96 patients) or without ribavirin (96 patients) for 12 months in naïve patients, to evaluate the effect of baseline features on the response to therapy, and to determine a reliable point in time during treatment to predict non-response. RESULTS: Sustained virologic response was 20.8% (95% CI 13-29) with IFN monotherapy and 54.2% (95% CI 44-64) with combination (P = 0.0001), the relapse rate 39.4% (95% CI 23-56) and 9% (95% CI 1-16) (P = 0.0007), and the combined rate of sustained biochemical and virologic response 22.7% (95% CI 14-31) and 60.5% (95% CI 50-71) (P = 0.0001), respectively. Patients given combination therapy were more likely to respond regardless of baseline features. Apart from genotype non-1, predictive factors for IFN monotherapy were ineffective in predicting response to combination therapy. Using logistic regression analysis, IFN-ribavirin was the strongest predictor of response (X2 = 21.3; P = 0.0001). Viral persistence at month 3 of therapy was a more accurate predictor than aminotransferase values for non-response to IFN monotherapy but not to combination therapy (positive predictive values of 98 and 82%, respectively). CONCLUSION: In this study, 5 MU of IFN combined with a standard dose of ribavirin has yielded the highest rate of sustained response reported to date. Further dose finding studies are warranted.
Asunto(s)
Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Interferones/uso terapéutico , Ribavirina/uso terapéutico , Adulto , Anciano , Alanina Transaminasa/sangre , Antivirales/efectos adversos , Quimioterapia Combinada , Femenino , Hepacivirus/genética , Hepatitis C Crónica/sangre , Hepatitis C Crónica/virología , Humanos , Interferones/efectos adversos , Masculino , Persona de Mediana Edad , Pronóstico , ARN Viral/sangre , Ribavirina/efectos adversosRESUMEN
The aim of this study was to compare, in an open-label study, the efficacy and safety of a combination of interferon (IFN) and amantadine (AMA) with that of IFN alone in previously untreated patients with chronic hepatitis C. A total of 200 patients were randomized to 6 MU of IFN-alpha2a 3 times per week, with 200 mg of AMA daily (n = 99) or to an identical dose of interferon alpha2a (n = 101). Patients were treated for 12 months and observed for 6 months' posttreatment. At the completion of treatment, 28.7% of patients in the monotherapy group and 45.5% in the combination group had a virologic response (P =.014). At 6 months' posttreatment, a sustained virologic response was observed in 16.8% (95% CI: 9-23) of patients with IFN alone versus 29.3% (95% CI: 19-37) of patients who were treated with combination therapy (P =.036). In each of the 2 treatments, genotype was the only predictive parameter for a sustained response. At the logistic regression analysis, therapy and genotype were the only 2 parameters with an independent predictive value. In the combination group, at examination of month 3, hepatitis C virus (HCV)-RNA status had a 97.6% (95% CI: 93-102) positive predictive value and a 50% (95% CI: 37-63) negative predictive value for a sustained virologic clearance. A substantial proportion of naïve patients with chronic hepatitis C have an end-of-treatment and end-of-follow-up virologic and biochemical response to a combination of IFN and AMA. This new treatment appears safe and well tolerated.
Asunto(s)
Amantadina/uso terapéutico , Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Interferones/uso terapéutico , Adulto , Anciano , Alanina Transaminasa/sangre , Amantadina/efectos adversos , Antivirales/efectos adversos , Quimioterapia Combinada , Femenino , Genotipo , Hepacivirus/genética , Hepatitis C Crónica/sangre , Hepatitis C Crónica/virología , Humanos , Interferones/efectos adversos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , ARN Viral/análisis , SeguridadRESUMEN
PURPOSE: To assess the efficacy of interferon alpha-2b and ribavirin in combination in the treatment of patients with chronic hepatitis C who had either failed to respond to therapy with interferon alpha (nonresponders), or who had relapsed after interferon therapy (relapsers). SUBJECTS AND METHODS: Four hundred patients with chronic hepatitis C (200 nonresponders and 200 relapsers) were randomly assigned in equal numbers to receive either subcutaneous administration of recombinant interferon alpha-2b (3 million units three times per week) and ribavirin (1,000 to 1,200 mg/daily orally) or interferon alpha-2b alone (6 million units three times per week). Both ribavirin and interferon alpha-2b were given for 24 weeks. The patients were then followed for an additional 24 weeks. RESULTS: At the end of the treatment period, normalization of serum alanine aminotransferase levels and absence of hepatitis C virus RNA were seen in 21% of nonresponders and in 39% of relapsers who were treated with interferon alpha-2b and ribavirin, compared with 5% of nonresponders (P = 0.001) and 9% of relapsers treated with interferon alpha-2b alone (P <0.001). At the end of follow-up, 14% of nonresponders and 30% of relapsers treated with the combination therapy had a sustained response, compared with 1% of nonresponders (P = 0.001) and 5% of relapsers treated with interferon alpha alone (P <0.001). CONCLUSIONS: A 24-week course of treatment with interferon alpha-2b and ribavirin offers a chance of sustained response, whereas retreatment with interferon alpha-2b alone does not give satisfactory results. The role of long-term therapy in inducing prolonged remission remains to be explored.
Asunto(s)
Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Ribavirina/uso terapéutico , Adolescente , Adulto , Quimioterapia Combinada , Ensayo de Inmunoadsorción Enzimática , Femenino , Hepatitis C Crónica/diagnóstico , Humanos , Immunoblotting , Interferón alfa-2 , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Proteínas Recombinantes , Recurrencia , Insuficiencia del Tratamiento , Resultado del TratamientoRESUMEN
Several factors suggest that endogenous benzodiazepines and gamma-amino-butyric acid may be involved in pathophysiology of hepatic encephalopathy (HE). Contrasting opinions exist on the therapeutic efficacy of flumazenil in the treatment of HE. This study was planned to assess the efficacy of flumazenil by a double-blind, placebo-controlled, crossover design in a large and selected population of cirrhotic patients in stage 4a HE admitted to intensive care units over a 4-year period. Out of 236 patients selected for the study, 132 received flumazenil, whereas 131 patients received placebo. Improvement of the neurological score was documented in 31 patients (23%) of flumazenil group and in two patients (1.5%) of placebo group (p < 0.001) during the first study period, whereas during the crossover period, improvement of the neurological score was documented in seven patients (5.3%) of the flumazenil group and in none of the placebo group (p = 0.022). Improvements in EEG tracings were observed in 44 patients (33.3%) of flumazenil group and in five patients (3.8%) of placebo group (p < 0.001) during the first study period; during the crossover period, improvements in EEG tracings were observed in 10 patients (7.5%) of the flumazenil group and in two patients (1.5%) of the placebo group (p = 0.040). The presence of benzodiazepines was detected in the serum of three responders and in two non-responders. The presence of diazepam and NN-desmethyl diazepam was documented in two responders; prior intake of synthetic diazepam was later confirmed in these patients. The results of our study suggest that flumazenil is beneficial only in a selected subset of cirrhotic patients with severe HE; the applicability of this treatment to unselected patients with hepatic coma or to cirrhotic patients with less severe HE still remains to be determined.
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Ansiolíticos/antagonistas & inhibidores , Antídotos/uso terapéutico , Flumazenil/uso terapéutico , Moduladores del GABA/uso terapéutico , Encefalopatía Hepática/tratamiento farmacológico , Encefalopatía Hepática/etiología , Cirrosis Hepática/complicaciones , Adulto , Ansiolíticos/efectos adversos , Ansiolíticos/sangre , Estudios Cruzados , Método Doble Ciego , Electroencefalografía , Femenino , Escala de Coma de Glasgow , Encefalopatía Hepática/inducido químicamente , Humanos , Italia , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
OBJECTIVE: The aim of the study was to assess the efficacy of interferon (IFN)-alpha-2b and ribavirin in combination in the treatment of chronic hepatitis C (CHC) patients unresponsive to a previous treatment with IFN-alpha-2b alone. METHODS: We conducted a randomized study in 303 CHC patients. One hundred fifty-two patients received subcutaneous administration of recombinant IFN-alpha-2b (3 MU thrice weekly) and ribavirin (1000-1200 mg/daily per os), whereas 151 received IFN-alpha-2b alone (6 MU thrice weekly). Both ribavirin and IFN-alpha-2b were given for 24 wk, regardless of treatment response. Alanine aminotransferase (ALT) levels and HCV RNA titer were checked during the treatment period and for a further 24 wk. RESULTS: Normal ALT levels were observed in 64.5% of the patients treated with IFN-alpha and ribavirin and in 22.6% of the patients treated with IFN-alpha alone. In the group of patients receiving IFN-alpha and ribavirin HCV RNA was not detectable in 40% of patients responders and remained undetectable in 44.2% of sustained responders. In the group of patients receiving IFN-alpha alone HCV RNA was not detectable in 24.2% of patients responders and remained not detectable in 33.3% of sustained responders. CONCLUSIONS: A 24-wk treatment course with IFN-alpha and ribavirin given to patients with a previous lack of response to IFN-alpha alone offers a chance of a sustained biochemical and virological response, at least in a subset of such patients. The role of long-term therapy in inducing prolonged remission still remains to be explored.
Asunto(s)
Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Ribavirina/uso terapéutico , Adulto , Antivirales/administración & dosificación , Antivirales/efectos adversos , Relación Dosis-Respuesta a Droga , Combinación de Medicamentos , Femenino , Hepatitis C Crónica/patología , Humanos , Interferón alfa-2 , Interferón-alfa/administración & dosificación , Interferón-alfa/efectos adversos , Masculino , Persona de Mediana Edad , Proteínas Recombinantes , Retratamiento , Ribavirina/administración & dosificación , Ribavirina/efectos adversos , Resultado del TratamientoRESUMEN
The rationale for use of benzodiazepine receptor antagonists is based on the so-called benzodiazepine pathogenetic hypothesis of hepatic encephalopathy (HE). To assess the efficacy of flumazenil, a specific benzodiazepine receptor antagonist, in a large and selected population of cirrhotic patients with severe HE, we conducted a double-blind, placebo-controlled, cross-over trial on 527 cirrhotic patients with HE grade III and IVa admitted to Intensive Care Units over a 5-year period; among them, 265 (132 of grade III and 133 of grade IVa) received flumazenil, whereas 262 (130 of grade III and 132 of grade IVa) received placebo. Treatment was begun within 15 minutes of randomization; the response to treatment was assessed by neurological score and by continuous electroencephalographic (EEG) recordings. Improvement of the neurological score was documented in 17.5% of grade III patients treated with flumazenil and in 14.7% of grade IVa patients, compared, respectively, with 3.8% and 2.7% of the patients of both groups treated with placebo. Improvements in EEG tracings were observed in 27.8% of grade III patients and in 21.5% of grade IVa patients, compared, respectively, with 5% and 3.3% of the patients of both groups treated with placebo. Benzodiazepines were detected in the serum of 10 patients (4 in grade III group and 6 in grade IVa group). Flumazenil is beneficial only in a selected subset of cirrhotic patients with severe HE; the applicability of this treatment to unselected patients with severe HE still remains to be determined.
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Flumazenil/uso terapéutico , Moduladores del GABA/uso terapéutico , Encefalopatía Hepática/complicaciones , Encefalopatía Hepática/tratamiento farmacológico , Cirrosis Hepática/complicaciones , Adulto , Anciano , Benzodiazepinas/sangre , Estudios Cruzados , Método Doble Ciego , Femenino , Flumazenil/efectos adversos , Moduladores del GABA/efectos adversos , Encefalopatía Hepática/clasificación , Humanos , Italia , Masculino , Persona de Mediana Edad , Sistema Nervioso/efectos de los fármacos , Sistema Nervioso/fisiopatología , Resultado del TratamientoRESUMEN
Although resistance has developed among Gram-positive pathogens to penicillins, cephalosporins, aminoglycosides, quinolones and macrolides, the glycopeptides seem to remain largely unaffected. However, the recent emergence and range of glycopeptide resistance in enterococci, well documented in the USA but not in the rest of the world, have prompted this European surveillance study. The European Glycopeptide Resistance Survey was undertaken in 1995 in 9 countries and involved 70 microbiological centres. The primary aims of the survey were as follows: (i) to perform a microbiological quality assurance assessment to evaluate the ability of participating laboratories to correctly identify the strains and assess their glycopeptide susceptibility; and (ii) to accurately determine the level of glycopeptide resistance among staphylococci, streptococci and enterococci in European hospitals. The in vitro activity of several other antibiotics was assessed on strains isolated from the Italian centres. In total, 7078 Gram-positive isolates were collected in Europe, and national coordinators used the National Committee for Clinical Laboratory Standards (NCCLS) agar dilution reference method to successfully retest 96% of these. According to mode minimum inhibitory concentrations (MICs), teicoplanin activity was similar to that of vancomycin against Staphylococcus aureus. In general, the range of MICs for teicoplanin was wider than that for vancomycin against coagulase-negative staphylococci. Against Enterococcus spp. and Streptococcus spp., teicoplanin was 4 times more active than vancomycin. The greatest number of glycopeptide refractory organisms was evident among enterococci; resistance was observed to be approximately 10 times more frequent in Enterococcus faecium than in E. faecalis. The results from the Italian isolates were similar to those from the overall study. In particular, teicoplanin was 2- to 8-fold more active than vancomycin against the majority of the enterococci. The incidence of enterococcal resistance was lower in Italy (0.6% for teicoplanin and 0.9% for vancomycin) than in Europe (1.7% for teicoplanin and 2.3% for vancomycin). This extensive survey confirms that teicoplanin is more active than vancomycin against enterococci and streptococci, and that both display similar potency against staphylococci.