New strategies to overcome antimicrobial resistance in Streptococcus pneumoniae with β-lactam antibiotics

Abstract

The worldwide epidemic of antibiotic resistance in Streptococcus pneumoniae appears to advance inexorably and the measures taken to date to contain its progression have not been successful. Consideration should be given to the complex relationship between antibiotic consumption and resistance to the drug administered and also to other agents in the same and other antibiotic groups. We propose an integrated triple strategy that maximizes the use of the current antibiotic arsenal and is designed to curb the spread of resistance in S. pneumoniae. There are three main parts to this strategy: (i) reduction of prescribing, with particular emphasis on those drugs whose consumption has been shown to correlate strongly with resistance; (ii) development of new formulations or dosing schedules of those drugs whose pharmacodynamic parameters are better suited to cope with highly resistant strains; and (iii) encouragement of the use of antibiotics with the maximal capability of bacterial eradication. We believe such a strategy would reduce the spread of resistance both in the current ecological situation and in the post-pneumococcal vaccination era to come. Of all current antibiotics amoxicillin meets the above requirements, and seems to be the least ecologically disturbing oral antibiotic with regard to resistance in S. pneumoniae.

Geographical and Ecological Analysis of Resistance, Coresistance, and Coupled Resistance to Antimicrobials in Respiratory Pathogenic Bacteria in Spain

“…Up to 62% of these penicillin-resistant isolates were susceptible to conventional amoxicillin-clavulanate. This proportion is likely to increase due to the higher activity of new amoxicillin-clavulanate formulations (1,5,10,14) with a probable susceptibility breakpoint of at least 4 g/ ml, although this breakpoint has not been approved by National Committee for Clinical Laboratory Standards or the Food and Drug Administration yet.…”

“…In S. pneumoniae, the high prevalence of resistance to penicillin (1,9), and the constant rise of resistance to macrolides (9) considerably limit the therapeutic options for the different conditions. Although amoxicillin has usually displayed an optimal activity against S. pneumoniae, with MICs one or two dilutions lower than that of penicillin, in recent years a worrisome number of articles have reported the spread of clones with increased MICs for amoxicillin and/or presenting MICs higher for amoxicillin than for penicillin (22).…”

Sensibilidad antibiótica y recomendaciones de tratamiento para Streptococcus pneumoniae

“…Las recomendaciones actuales en los casos de otitis media aguda por Streptococcus pneumoniae son altas dosis de amoxicilina, 80-100 mg/Kg/día 28,29 . En los casos de neumonía se considera adecuado el tratamiento bien con penicilina G parenteral o amoxicilina oral (3 dosis de 1 g) 23,29 , excepto en los casos de neumonía grave, paciente inmunocomprometido o mala evolución clínica en que se postulan otras alternativas como: cefotaxima, levofloxacino, imipenem o clindamicina 30,31 .…”

“…En los casos de neumonía se considera adecuado el tratamiento bien con penicilina G parenteral o amoxicilina oral (3 dosis de 1 g) 23,29 , excepto en los casos de neumonía grave, paciente inmunocomprometido o mala evolución clínica en que se postulan otras alternativas como: cefotaxima, levofloxacino, imipenem o clindamicina 30,31 . En la bacteriemia por neumococo el tratamiento de elección sigue siendo un betalactámico oral o parenteral, especialmente altas dosis de amoxicilina que se ha comprobado eficaz en neumococos con resistencia parcial a penicilina 29 . Finalmente la combinación de altas dosis de cefotaxima (225-300 mg/Kg/día) o ceftriaxona (100 mg/Kg/día) más vancomicina (60 mg/Kg/día) se mantiene como primera opción en los casos de sospecha de meningitis neumocócica 29 .…”

“…En la bacteriemia por neumococo el tratamiento de elección sigue siendo un betalactámico oral o parenteral, especialmente altas dosis de amoxicilina que se ha comprobado eficaz en neumococos con resistencia parcial a penicilina 29 . Finalmente la combinación de altas dosis de cefotaxima (225-300 mg/Kg/día) o ceftriaxona (100 mg/Kg/día) más vancomicina (60 mg/Kg/día) se mantiene como primera opción en los casos de sospecha de meningitis neumocócica 29 . Una vez conocida la sensibillidad del Streptococcus pneumoniae aislado, el tratamiento antibiótico se modificará en función de la misma, reduciendo la dosis del betalactámico si el aislamiento es sensible o cambiando de antibiótico si la resistencia así lo aconseja.…”