Federico Nicola

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, Students 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.

A Pharmacodynamic Model to Support a 12-Hour Dosing Interval for Amoxicillin/Sulbactam, a Novel Oral Combination, in the Treatment of Community-Acquired Lower Respiratory Tract Infections

Abstract We evaluated, by time-kill studies, the pharmacodynamics of amoxicillin/sul-bactam (AMX/SUL, 875 mg/125 mg), a novel oral combination, against the major respiratory pathogens in 12 volunteers receiving a single dose. The sera corresponding to 50% of a 12-h dosing interval displayed either bactericidal or inhibitory activity against both a penicillin-susceptible and a penicillin-intermediate Streptococcus pneumoniae strain (penicillin MIC of 0.03 and 0.25 μg/ml, respectively), as well as against a β-lactamase-positive Moraxella catarrhalis and a β-lactamase-negative Haemophilus influenzae strain. Both the peak samples and those corresponding to 4 h after dose (i.e. 33% of a 12-h dosing interval) proved active against both a penicillin-resistant S. pneumoniae (MIC, 2 μg/ml) and a β-lactamase-positive H. influenzae strain. The AMX-SUL formulation evaluated in this study showed pharmacodynamic features that support clinical trials to assess its efficacy in the treatment of lower respiratory tract infections with a 12-h dosing interval regimen.

Rationale for Treating Community-Acquired Lower Respiratory Tract Infections with Amoxicillin/Sulbactam Combination Through Pharmacodynamic Analysis in the Setting of Aminopenicillin-Resistant Organisms

Abstract In order to establish a rationale for treating community-acquired lower respiratory tract infections, we assess here the pharmacodynamics of amoxi-cillin/sulbactam, 500mg/500mg, a formulation marketed in Argentina since 1988 and currently available in 17 countries, against the major pathogens, in comparison with that of a novel formulation (875mg/125mg, see J Chemother 2000; 12: 223-227). In time-kill studies, both bactericidal and inhibitory activity were seen in the 1.5- and 6-h sera, obtained from 12 volunteers after a single oral dose, against both a penicillin-susceptible and an -intermediate Streptococcus pneumoniae strain, as well as against Moraxella catarrhalis and a β-lactamase-negative Haemophilus influenzae strain. Only the 1.5-h sera proved bactericidal against a penicillin-resistant S. pneumoniae strain (MIC, 2 μg/ml) and a β-lactamse-positive H. influenzae isolate. This study suggests that amoxicillin/sulbactam (500mg/500mg) is still a suitable option for treating community-acquired lower respiratory tract infections, allowing a b.i.d. dosing schedule. Caution should be taken with pneumonia caused by β-lacta-mase-positive H. influenzae or penicillin-resistant (MIC >2 μg/ml) S. pneumoniae isolates. Either shorter dosing intervals (t.i.d.) or a higher amoxicillin content in the formulation (i.e. 875 mg) may be required in these situations.

An ex-vivo pharmacodynamic study comparing bactericidal activity of amoxicillin/sulbactam, azithromycin, doxycycline and levofloxacin against Streptococcus pneumoniae.

Abstract We designed a 4-way crossover, Ex-Vivo pharmacodynamic study to compare the bactericidal rate of amoxicillin/sulbactam (AMX-SUL), azithromycin (AZM), doxycycline (DOX) and levofloxacin (LVX) against Streptococcus pneumoniae ATCC 49619. Six volunteers were randomized to receive alternatively a single tablet of the above drugs. Venous blood samples were obtained immediately before and at 2, 4 and 6 h after dose to perform time-kill studies and to determine antibiotic levels in serum. AMX-SUL was the only drug showing bactericidal activity with the sera obtained at every time after dose, as defined by a ≥ 3-log10 cfu/ml decrease in the viable cell counts compared to the original inoculum after a 24-h incubation. AZM was only inhibitory at 2h after dose (i.e. a 1.3-log10 cfu/ml decrease in the viable cell counts) and proved bactericidal at 4 and 6 h post-dose. LVX proved bactericidal with the 2-h serum, was only inhibitory with the 4-h serum (e.g. a 1.5- log10 cfu/ml decrease) and was unable to avoid bacterial growth at 6 h post-dose. Bacterial growth was observed with DOX at every time after dose. This study may shed light on the understanding of breakthrough pneumococcal bacteremia during the course of oral therapy with AZM in patients with community-acquired pneumonia (CAP), as well as the increasing treatment failures observed with LVX, and the selection of bacterial resistance during therapy reported with both drugs. It also provides the basis for a “warning signal” on the use of oral DOX and confirms the efficacy of AMX-SUL.

Criterios de ensayo, interpretación e informe de las pruebas de sensibilidad a los antibióticos en los bacilos gram negativos no fermentadores de importancia clínica: recomendaciones de la Subcomisión de Antimicrobianos de la Sociedad Argentina de Bacteriología, Micología y Parasitología Clínicas, Asociación Argentina de Microbiología

This document contains the recommendations for antimicrobial susceptibility testing of the clinically relevant non-fermenting gram-negative bacilli (NFGNB), adopted after conforming those from international committees to the experience of the Antimicrobial Agents Subcommittee members and invited experts. This document includes an update on NFGNB classification and description, as well as some specific descriptions regarding natural or frequent antimicrobial resistance and a brief account of associated resistance mechanisms. These recommendations not only suggest the antimicrobial drugs to be evaluated in each case, but also provide an optimization of the disk diffusion layout and a selection of results to be reported. Finally, this document also includes a summary of the different methodological approaches that may be used for detection and confirmation of emerging b-lactamases, such as class A and B carbapenemases.