[In vitro activity of doripenem and other carbapenems against Pseudomonas aeruginosa]. / Actividad comparativa in vitro de doripenem y de otros carbapenemes frente a Pseudomonas aeruginosa.

Doripenem, a new carbapenem, has shown to be more active against Pseudomonas aeruginosa than other carbapenems. The activity of doripenem, imipenem and meropenem was evaluated against 93 P. aeruginosa isolates, by agar dilution and disk diffusion methods. MIC50 and MIC90, were as follows (microg/ml): doripenem, 2 and 4; meropenem, 2 and 8; and imipenem, 4 and 8, respectively. Doripenem MICs were 1 to 3 dilutions lower (i.e. more active) than those for imipenem in 82% of the isolates. In comparison with meropenem, doripenem was 1 to 3 dilutions more active in 50% of the isolates. Forty-nine percent of isolates showed the same MIC for both antibiotics. Resistance percentages for both methods were (dilution/diffusion): imipenem = 7.5%/49.5% and meropenem = 3.2%/9.7%. As the CLSI has not established cut off values for doripenem yet, resistance rates for this antibiotic were estimated by considering (a) the same cut off values for imipenem/meropenem set up by the CLSI, and (b) those suggested by Brown et al. In case (a), resistance rates would be 1.1%/2.2% whereas in case (b) 1.1%/17.2% for agar dilution and disk diffusion, respectively. In scenarios where resistance to carbapenem is based on mechanisms other than carbapenemases, doripenem has a promising future for treating P. aeruginosa infections.

Actividad comparativa in vitro de doripenem y de otros carbapenemes frente a Pseudomonas aeruginosa / In vitro activity of doripenem and other carbapenems against Pseudomonas aeruginosa

Según estudios previos, el nuevo carbapeneme doripenem sería más activo frente a Pseudomonas aeruginosa en comparación con otros carbapenemes. En este estudio evaluamos la actividad in vitro del doripenem, el meropenem y el imipenem frente a 93 aislamientos de P. aeruginosa mediante los métodos de dilución en agar y de difusión con discos. Las CIM50 y CIM90 de los carbapenemes fueron (μg/ml): imipenem, 4 y 8; meropenem, 2 y 8; doripenem, 2 y 4, respectivamente. El doripenem fue 1 a 3 diluciones más activo que el imipenem para un 82% de los aislamientos. Comparado con el meropenem, el doripenem fue, 1-3 diluciones más activo frente a un 50% de los aislamientos, mientras que en el 49% la CIM fue la misma. Los porcentajes de resistencia según los métodos de dilución y de difusión fueron: imipenem = 7,5%/49,5% y meropenem = 3,2%/9,7%. Para el doripenem, estos valores variaron según los puntos de corte (PC) que se consideraron: 1,1%/2,2% usando el PC del CLSI para el imipenem y el meropenem, o 1,1%/17,2% según los PC sugeridos por Brown et al. El método de difusión presentó un elevado porcentaje de errores menores en la categorización de los aislamientos respecto de la dilución en agar, lo que sobrestimó la resistencia. El doripenem mostró muy buena actividad frente a P. aeruginosa, superior a la del imipenem y al menos equiparable a la del meropenem, por lo que puede considerarse una interesante opción para el tratamiento de infecciones por esta bacteria.

Doripenem, a new carbapenem, has shown to be more active against Pseudomonas aeruginosa than other carbapenems. The activity of doripenem, imipenem and meropenem was evaluated against 93 P. aeruginosa isolates, by agar dilution and disk diffusion methods. MIC50 and MIC90 were as follows (μg/ml): doripenem, 2 and 4; meropenem, 2 and 8; and imipenem, 4 and 8, respectively. Doripenem MICs were 1 to 3 dilutions lower (i.e. more active) than those for imipenem in 82% of the isolates. In comparison with meropenem, doripenem was 1 to 3 dilutions more active in 50% of the isolates. Forty-nine percent of isolates showed the same MIC for both antibiotics. Resistance percentages for both methods were (dilution/diffusion): imipenem = 7.5%/49.5% and meropenem = 3.2%/9.7%. As the CLSI has not established cut off values for doripenem yet, resistance rates for this antibiotic were estimated by considering (a) the same cut off values for imipenem/meropenem set up by the CLSI, and (b) those suggested by Brown et al. In case (a), resistance rates would be 1.1%/2.2% whereas in case (b) 1.1%/17.2% for agar dilution and disk diffusion, respectively. In scenarios where resistance to carbapenem is based on mechanisms other than carbapenemases, doripenem has a promising future for treating P. aeruginosa infections.

Activity of gatifloxacin compared to those of seven agents against bacteria recovered from outpatients with respiratory tract infection.

The in vitro activity of gatifloxacin and levofloxacin, ciprofloxacin, penicillin, ampicillin, ampicillin-sulbactam, ceftriaxone and clarithromycin was evaluated against 173 S. pneumoniae strains (128, penicillin-susceptible strains; 32, intermediate penicillin- resistant strains and 13, penicillin-resistant strains), 163 H. influenzae strains (128, beta-lactamase non-producer; 35, beta-lactamase producers), 111 M. catarrhalis (9, beta-lactamase non-producer; 102, beta-lactamase producers), 95 Streptococcus pyogenes and 116 S. aureus strains (96, methicillin-susceptible; 20, methicillin-resistant) recovered from outpatients with respiratory tract infection. Based upon the MICs at which 50% and 90% of the isolates were inhibited we concluded that gatifloxacin proved to be the most active antibiotic against respiratory pathogens, including all the penicillin-resistant pneumococci and H. influenzae or M. catarrhalis producing beta-lactamase. Furthermore, their MICs against S. pneumoniae and methicillin-resistant S. aureus were lower than those of levofloxacin and ciprofloxacin.Therefore, this new fluoroquinolone displayed in vitro features that make it suitable for treating community-acquired respiratory tract infections.

Comparative in vitro bactericidal activity between cefepime and ceftazidime, alone and associated with amikacin, against carbapenem-resistant Pseudomonas aeruginosa strains.

Fifteen unique isolates of carbapenem-resistant Pseudomonas aeruginosa were selected for time-kill studies to assess the bactericidal activity of cefepime (CFP) and ceftazidime (CZD) (at 4 and 16 microg/mL), alone and associated with amikacin (AMK) (4 microg/mL). CFP proved more active than CZD (p < 0.05, Student's t test). Bactericidal activity after 24-h incubation was only achieved by the combination of CFP (16 microg/mL) plus AMK. The higher in vitro activity of cefepime over that of ceftazidime against imipenem-resistant P. aeruginosa strains highlights the differences of these drugs beyond Enterobacterspp. and Staphylococcus aureus.