False synergy between vancomycin and β-lactams against glycopeptide-intermediate Staphylococcus aureus (GISA) caused by inappropriate testing methods

ABSTRACTThe combination of vancomycin and β-lactams is often considered synergistic and has been recommended for the treatment of glycopeptide-intermediate Staphylococcus aureus (GISA) infections. In this study, the combination of vancomycin or teicoplanin with different β-lactams was tested. When using NaCl 4% w/v, for better expression of heterogeneous resistance to β-lactams, with a longer (48-h) incubation period and a higher (107 CFU/mL) inoculum, the association of vancomycin with β-lactams was antagonistic. However, a synergistic effect was observed for teicoplanin under the same conditions

Etude comparative sur les performances et l'ergonomie de nébuliseurs dans la mucoviscidose

National audienceThis study had, as its aim, to lest twelve nebulizers (6 jet, 6 ultrasonic) which are used in the treatment of cystic fibrosis. Devices were connected to a respirator in order to mimic the Ventilation of a child and of an adult suffering from cystis fibrosis. Three medications : tobramycine, colistine and amiloride were nebulised. The volume of the recommended solution varied between 1.5 and 13 ml according to the manufacturer. During a Session of ten minutes the ultrasonic nebulizer delivered an inhaled volume which was significantly greater than the jet (2.72+-0.98 ml vs 1.22+-0.59 ml, p <0.0001) for the three drugs. Regarding granulometry, the fraction of particles between 0.5 and 5 um, was higher with ultrasonic than with pneumatic nebulizer for tobramycine (67.1+-10.7 vs 55.5+-]1.5 %. p <0.001) and amiloride (66.4+-S1.2 % vs 58. l +-15%, p <0.05 %). The Variation of concentration due to nebulisation were independent of the type of apparatus but influenced by the drug since concentration was increased for tobramycine (+10.5+-18.6 %) and amiloride (+13.4+-8/9 %). In summary the effective fraction resulting from the inhalable fraction, from granulometry and from changes in concentration was significantly greater for ultrasonic than for jet nebrulizer (17.3+-6.7 % vs 9.7+-9.6 %, p <0.001). This study underlines the great variability of the performance of aerosols generators and therefore the need for an accurate evaluation of nebulizer performances in order to prescribe the best nebulizer/drug association in clinical practice.Cette étude avait pour but de tester douze appareils d'aérosols (six pneumatiques, six ultrasoniques) utilisés dans le traitement de la mucoviscidose. Les appareils étaient connectés à un respirateur afin de simuler la ventilation d'un enfant et d'un adulte atteints de mucoviscidose. Trois médicaments : tobramycine, colistine, amiloride étaient nébulisés. Les volumes de solution préconisés variaient entre 1,5 et 13 ml selon les fabricants. Au cours d'une séance de 10 min, les nébuliseurs ultrasoniques délivrent un volume inhalable significativement plus important que les pneumatiques (2.72+-0.98 ml vs l.22-t0,59 ml, p <0.0001) pour les trois médicaments. La fraction déposable, c'est-à-dire avec une granulométrie comprise entre 0,5 et 5 µm, est plus élevée avec les ultrasoniques qu'avec les pneumatiques pour la tobramycine (67.1+-10,7 % vs 55.5+-11.5 %, p <0,001) et l'amiloride (66.4+-9.2 % vs 58.1+-15 %, p <0,05 %). Les variations de concentration dues à la nébulisation sont indépendantes du type d'appareil, mais influencées par le médicament : augmentation de concentration pour la tobramycine (+!0,5+-I8,6 %) et l'amiloride (+13,4+-8,9 %). Au total, la fraction efficace qui résulte à la fois de la fraction inhalable, de sa granulométrie et des variations de concentration est significativement supérieure pour les ultrasoniques que pour les pneumatiques (17.3+-6,7 % vs 9,7+-9.6 %, p <0,001). Cette étude souligne la grande variabilité des performances des appareils d'aérosols, ainsi que la nécessite d'avoir des tests fiables avant l'utilisation en clinique afin de prescrire la meilleure combinaison appareil/médicament

Etude comparative sur les performances et l'ergonomie de nébuliseurs dans la mucoviscidose

National audienceThis study had, as its aim, to lest twelve nebulizers (6 jet, 6 ultrasonic) which are used in the treatment of cystic fibrosis. Devices were connected to a respirator in order to mimic the Ventilation of a child and of an adult suffering from cystis fibrosis. Three medications : tobramycine, colistine and amiloride were nebulised. The volume of the recommended solution varied between 1.5 and 13 ml according to the manufacturer. During a Session of ten minutes the ultrasonic nebulizer delivered an inhaled volume which was significantly greater than the jet (2.72+-0.98 ml vs 1.22+-0.59 ml, p <0.0001) for the three drugs. Regarding granulometry, the fraction of particles between 0.5 and 5 um, was higher with ultrasonic than with pneumatic nebulizer for tobramycine (67.1+-10.7 vs 55.5+-]1.5 %. p <0.001) and amiloride (66.4+-S1.2 % vs 58. l +-15%, p <0.05 %). The Variation of concentration due to nebulisation were independent of the type of apparatus but influenced by the drug since concentration was increased for tobramycine (+10.5+-18.6 %) and amiloride (+13.4+-8/9 %). In summary the effective fraction resulting from the inhalable fraction, from granulometry and from changes in concentration was significantly greater for ultrasonic than for jet nebrulizer (17.3+-6.7 % vs 9.7+-9.6 %, p <0.001). This study underlines the great variability of the performance of aerosols generators and therefore the need for an accurate evaluation of nebulizer performances in order to prescribe the best nebulizer/drug association in clinical practice.Cette étude avait pour but de tester douze appareils d'aérosols (six pneumatiques, six ultrasoniques) utilisés dans le traitement de la mucoviscidose. Les appareils étaient connectés à un respirateur afin de simuler la ventilation d'un enfant et d'un adulte atteints de mucoviscidose. Trois médicaments : tobramycine, colistine, amiloride étaient nébulisés. Les volumes de solution préconisés variaient entre 1,5 et 13 ml selon les fabricants. Au cours d'une séance de 10 min, les nébuliseurs ultrasoniques délivrent un volume inhalable significativement plus important que les pneumatiques (2.72+-0.98 ml vs l.22-t0,59 ml, p <0.0001) pour les trois médicaments. La fraction déposable, c'est-à-dire avec une granulométrie comprise entre 0,5 et 5 µm, est plus élevée avec les ultrasoniques qu'avec les pneumatiques pour la tobramycine (67.1+-10,7 % vs 55.5+-11.5 %, p <0,001) et l'amiloride (66.4+-9.2 % vs 58.1+-15 %, p <0,05 %). Les variations de concentration dues à la nébulisation sont indépendantes du type d'appareil, mais influencées par le médicament : augmentation de concentration pour la tobramycine (+!0,5+-I8,6 %) et l'amiloride (+13,4+-8,9 %). Au total, la fraction efficace qui résulte à la fois de la fraction inhalable, de sa granulométrie et des variations de concentration est significativement supérieure pour les ultrasoniques que pour les pneumatiques (17.3+-6,7 % vs 9,7+-9.6 %, p <0,001). Cette étude souligne la grande variabilité des performances des appareils d'aérosols, ainsi que la nécessite d'avoir des tests fiables avant l'utilisation en clinique afin de prescrire la meilleure combinaison appareil/médicament

In vitro antibacterial activity of ceftobiprole against clinical isolates from French teaching hospitals: proposition of zone diameter breakpoints

International audienceThe aims of this study were to determine the in vitro activity profile of ceftobiprole, a pyrrolidinone cephalosporin, against a large number of bacterial pathogens and to propose zone diameter breakpoints for clinical categorisation according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) minimum inhibitory concentration (MIC) breakpoints. MICs of ceftobiprole were determined by broth microdilution against 1548 clinical isolates collected in eight French hospitals. Disk diffusion testing was performed using 30μg disks according to the method of the Comité de l'Antibiogramme de la Société Française de Microbiologie (CA-SFM). The in vitro activity of ceftobiprole, expressed by MIC (MICs for 50% and 90% of the organisms, respectively) (mg/L), was as follows: meticillin-susceptible , 0.25/0.5; meticillin-resistant (MRSA), 1/2; meticillin-susceptible coagulase-negative staphylococci (CoNS), 0.12/0.5; meticillin-resistant CoNS, 1/2; penicillin-susceptible , ≤0.008/0.03; penicillin-resistant , 0.12/0.5; viridans group streptococci, 0.03/0.12; β-haemolytic streptococci, ≤0.008/0.016; , 0.25/1; , 64/128; Enterobacteriaceae, 0.06/32; , 4/16; , 0.5/64; , 0.03/0.12; and , 0.25/0.5. According to the regression curve, zone diameter breakpoints could be 28, 26, 24 and 22mm for MICs of 0.5, 1, 2 and 4mg/L respectively. In conclusion, this study confirms the potent in vitro activity of ceftobiprole against many Gram-positive bacteria, including MRSA but not , whilst maintaining a Gram-negative spectrum similar to the advanced-generation cephalosporins such as cefepime. Thus ceftobiprole appears to be well suited for the empirical treatment of a variety of healthcare-associated infections