Eletters

Topic:

Review Series
Pneumonia research to reduce childhood mortality in the developing world
J. Anthony G. Scott, W. Abdullah Brooks, J.S. Malik Peiris, Douglas Holtzman, E. Kim Mulhollan
J. Clin. Invest. 2008; 118(4):1291

New breakpoints to define resistance to penicillin among pneumococcal pneumonia strains

Cristiana M. Nascimento-Carvalho | nascimentocarvalho@hotmail.com

Other authors: 2Fernando Ferrero and 3Maria R. A. Cardoso

1Federal University of Bahia School of Medicine, Salvador, Brazil. 2Hospital General de Niños Pedro de Elizalde, Buenos Aires, Argentina. 3University of São Paulo, Faculty of Public Health, São Paulo, Brazil.

Published on July 7, 2008

The comprehensive review by Scott et al. (1), addressing the globally important problem of childhood community-acquired pneumonia (CAP), informed that the impact of antimicrobial resistance on the management of childhood CAP remains unclear. Streptococcus pneumoniae has been recognized as the most common bacterial agent of CAP and the prevalence of disease caused by penicillin resistant S. pneumoniae has increased worldwide (2). Therefore, an urgent issue is whether penicillin is effective to treat pneumococcal pneumonia caused by penicillin resistant strains. In 1995, a South African study showed that the rate of improvement was similar when 78 children with pneumococcal pneumonia caused by either penicillin sensitive S. pneumoniae or intermediate resistant strains were treated with ampicillin or an equivalent β-lactam agent: 93% of children infected with susceptible strains responded and 88% of those infected with intermediate resistant strains responded (OR=1.9; 95%CI: 0.3-15.9) (3). In 1999, a study conducted in Uruguay and Argentina enrolled 75 patients with pneumococcal pneumonia treated with penicillin or ampicillin and there was no significant difference in mortality between the 52 patients infected with penicillin-susceptible S. pneumoniae and the 23 patients infected with highly penicillin-resistant strains (penicillin minimal inhibitory concentration [MIC] ≥2μg/mL) (RR=1; 95%CI: 0.8-1.1)(4). Another study, carried out in Latin America, has been published recently and the authors concluded that high-level S. pneumoniae penicillin resistance was not associated with failure to response to treatment with penicillin among children with pneumococcal pneumonia, meaning that penicillin remains the drug of choice for the treatment of children with severe pneumonia, when administrated at a dose of 200,000 units/kg/day, in areas where highly penicillin-resistant pneumococcal strains are present (MIC<2μg/mL) (5). The study in Latin America was a prospective, multicenter investigation conducted among 236 children and the analysis was adjusted for confounding variables, there was no co-morbidity, and the patients were admitted with disease of the same severity. Therefore, the sample size was appropriate and the results are valid for the general population. In 2008, the U.S. Clinical and Laboratory Standards Institute adopted new penicillin MIC breakpoints for cases of pneumonia (6). The new breakpoints define susceptible strains as responsive to penicillin MIC <2μg/mL, whereas the old breakpoints defined susceptible strains as those with penicillin MIC <0.06μg/mL. The upward shift of the breakpoints was to parallel results in vitro with treatment effectiveness in vivo. So, one must conclude that currently, the evidence points to penicillin as effective for the treatment of pneumococcal pneumonia if the causative pneumococcal strain has a penicillin MIC of <2μg/mL. However, continuous research is necessary to monitor the evolution of pneumococcal MIC and penicillin effectiveness when the penicillin MIC is over 2μg/mL.

References

  1. Scott, J.A., Brooks, W.A., Peiris, J.S., Holtzman, D., and Mulholland, K. 2008. Pneumonia research to reduce childhood mortality in the developing world. J. Clin. Invest. 118:1291–1300.
  2. Chetty, K., and Thomson, A.H. 2007. Management of community-acquired pneumonia in children. Paediatr. Drugs 9:401–411.
  3. Friedland, I.R. 1995. Comparison of the response to antimicrobial therapy of penicillin-resistant and penicillin-susceptible pneumococcal disease. Pediatr. Infect. Dis. J. 14:885–890.
  4. Deeks, S.L., et al. 1999. Risk factors and course of illness among children with invasive penicillin-resistant Streptococcus pneumoniae. The Streptococcus pneumoniae Working Group. Pediatrics 103:409–413.
  5. Cardoso, M.R., et al. 2008. Penicillin resistant pneumococcus and risk of treatment failure in pneumonia. Arch. Dis. Child. 93:221–225.
  6. CLSI. 2008. Performance Standards for Antimicrobial Susceptibility Testing; Sixteenth Informational Supplement. Wayne, USA: CLSI/NCCLS.


    7. Copyright © 2008, The American Society for Clinical Investigation.