Review article
Clinical relevance of antimicrobial resistance in the management of pneumococcal community-acquired pneumonia

https://doi.org/10.1016/j.lab.2004.02.002Get rights and content

Abstract

Streptococcus pneumoniae remains the most common bacterial cause of community-acquired pneumonia, and these infections are associated with significant morbidity and mortality worldwide. A major concern is the increasing incidence of antibiotic resistance among pneumococcal isolates, which, in the case of certain of the antibiotic classes, has been associated with treatment failure. Yet despite multiple reports of infections with penicillin-resistant pneumococcal isolates, no cases of bacteriologic failure have been documented with the use of penicillin or ampicillin in the treatment of pneumonia caused by penicillin-resistant pneumococci. Current prevalence and levels of penicillin resistance among pneumococal isolates in most areas of the world do not indicate a need for substantial treatment changes with regard to the use of the penicillins. For infections with penicillin-sensitive strains, penicillin or an aminopenicillin in a standard dosage will still be effective for treatment. In the cases of strains with intermediate resistance, β-lactam agents are still considered appropriate treatment, although higher dosages are recommended. Infections with isolates of high-level penicillin resistance should be treated with alternative agents such as the third-generation cephalosporins or the new antipneumococcal fluoroquinolones. In the case of the cephalosporins, pharmacodynamic/pharmacokinetic parameters help predict which of those agents are likely to be successful, and the less active agents should not be used. Debate continues in the literature with regard to the impact of macrolide resistance on the outcome of pneumococcal pneumonia, with some investigators providing evidence of an “in vivo–in vitro paradox,” referring to discordance between reported in vitro resistance and clinical success of macrolides/azalide in vivo. However, several cases of macrolide/azalide treatment failure have been documented, and many clinicians recommend that these agents not be used on their own in areas with a high prevalence and levels of macrolide/azalide resistance. However, evidence is emerging to show beneficial effects on outcome with combination therapy, especially that of a β-lactam agent and a macrolide given together to sicker, hospitalized patients with pneumococcal pneumonia. In an attempt to prevent the emergence of resistance, it has been recommended by some that the new fluoroquinolones not be used routinely as first-line agents in the treatment of community-acquired pneumonia; instead, they say, these agents should be reserved for patients who are allergic to the commonly used β-lactam agents, for infections known to be or suspected of being caused by highly resistant strains, and for patients in whom initial therapy has failed.

Section snippets

Antibiotic resistance in the community

Bacterial resistance in community-acquired respiratory-tract infections is a serious problem that is increasing at an alarming rate throughout the world, affecting all age groups.7, 8, 9, 10 Streptococcus pneumoniae, one of the main organisms associated with resistance in respiratory-tract infections, has developed multiple resistance mechanisms, and resistant strains, including multidrug-resistant ones, have spread to several regions of the world (Table I). 7, 11 The definitions of antibiotic

Penicillin resistance

Until 1967, all clinical isolates of the pneumococcus were considered uniformly sensitive to penicillin.21 Since that time, reports have appeared regularly in the literature documenting isolates with varying degrees and spectra of antibiotic resistance.22 Many reviews and several studies have been published describing the association between antibiotic resistance and the outcome of pneumococcal pneumonia.22 Although many reports have shown no differences in the outcomes of these infections, an

Evaluation of the consequences of antibiotic resistance

Despite the rapid increase in the prevalence and levels of antimicrobial resistance that have been documented among the isolates that commonly cause community-acquired pneumonia, relatively few controlled studies have revealed clinical failures or increased morbidity and mortality as consequences of this resistance.19, 75 Several reasons have been proposed to explain this discrepancy.19 First, even with the appropriate treatment of relatively mild infections with antibiotic-susceptible

Empiric antibiotic prescribing suggestions in the era of antibiotic resistance

Initial antibiotic therapy of community-acquired pneumonia is of necessity empiric; these infections are severe, with residual mortality, and evidence is beginning to suggest that the outcome of infection is improved by the early initiation of appropriate antibiotic therapy to which the causative organism(s) is susceptible. Because the causative organism is unknown at the outset of an infection, the initial antibiotic therapy is therefore “best guess,” intended to cover the most likely

Conclusions

It is important for the clinician attending a patient with community-acquired pneumonia to be fully aware of the rates of antimicrobial resistance among common respiratory-tract pathogens, such as the pneumococcus, in their communities and, particularly, in their own areas of practice. They should have a thorough knowledge of and search for risk factors for possible infection with antibiotic-resistant isolates.75 Because prior antibiotic exposure is thought to be a major risk factor for

References (93)

  • T Bauer et al.

    Streptococcus pneumoniae in community-acquired pneumonia. How important is drug resistance?

    Med Clin North Am

    (2001)
  • R.G Finch et al.

    A critical assessment of published guidelines and other decision-support systems for the antibiotic treatment of community-acquired respiratory tract infections

    CMI

    (2002)
  • R.C Moellering

    The continuing challenge of lower respiratory tract infections

    Clin Infect Dis

    (2002)
  • Pankey GA. Introduction. In: Ochsner clinic symposium on resistance and the use and misuse of antimicrobial therapy....
  • World Health Organization. WHO global strategy for containment of antimicrobial resistance. Available at:...
  • US Department of Health and Human Sciences. A USA public health action plan to combat antimicrobial resistance....
  • Centers for Disease Control and Prevention. CDC/National Center for Infectious Diseases website on antimicrobial...
  • Schrag SJ, Beall B, Dowell S. Resistant pneumococcal infections: the burden of disease and challenges in monitoring and...
  • J Garau

    Clinical failuresthe tip of the iceberg?

    Respir Med

    (2001)
  • K Cartwright

    Pneumococcal disease in western Europeburden of disease, antibiotic resistance and management

    Eur J Pediatr

    (2002)
  • R.A Bonomo

    Resistant pathogens in respiratory tract infections in older people

    J Am Geriatr Soc

    (2002)
  • Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Approved standard (ed 6)....
  • D.M Musher et al.

    A fresh look at the definition of susceptibility of Streptococcus pneumoniae to β-lactam antibiotics

    Arch Intern Med

    (2001)
  • R Austrian et al.

    Pneumococcal bacteremia, with special reference to bacteremic pneumococcal pneumonia

    Ann Intern Med

    (1964)
  • M Henry et al.

    Drug-resistant Streptococcus pneumoniae in community-acquired pneumonia

    Curr Infect Dis Reports

    (2003)
  • M.J Fine et al.

    Prognosis and outcomes of patients with community-acquired-pneumonia. A meta-analysis

    JAMA

    (1996)
  • D.R Feikin et al.

    Mortality from invasive pneumococcal pneumonia in the era of antibiotic resistance, 1995-1997

    Am J Public Health

    (2000)
  • R Pallares et al.

    Resistance to penicillin and cephalosporin and mortality from severe pneumococcal pneumonia in Barcelona, Spain

    N Engl J Med

    (1995)
  • K.P Klugman

    Bacteriological evidence of antibiotic failure in pneumococcal lower respiratory tract infections

    Eur Respir J

    (2002)
  • K.P Klugman et al.

    Streptococcus pneumoniae respiratory tract infections

    Curr Opin Infect Dis

    (2001)
  • I.R Friedland

    Comparison of the response to antimicrobial therapy of penicillin-resistant and penicillin-susceptible pneumococcal disease

    Pediatr Infect Dis J

    (1995)
  • T.Q Tan et al.

    Clinical characteristics and outcome of children with pneumonia attributable to penicillin-susceptible and penicillin-nonsusceptible Streptococcus pneumoniae

    Pediatrics

    (1998)
  • E.-H Choi et al.

    Clinical outcome of invasive infections by penicillin-resistant Streptococcus pneumoniae in Korean children

    Clin Infect Dis

    (1998)
  • H Watanabe et al.

    A comparative clinical study of pneumonia by penicillin-resistant and -sensitive Streptococcus pneumoniae in a community hospital

    Respirology

    (2000)
  • S Ewig et al.

    Pneumonia acquired in the community through drug-resistant Streptococcus pneumoniae

    Am J Respir Crit Care Med

    (1999)
  • J.P Metlay et al.

    Impact of penicillin susceptibility on medical outcomes for adult patients with bacteremic pneumococcal pneumonia

    Clin Infect Dis

    (2000)
  • G.S Turett et al.

    Penicillin resistance and other predictors of mortality in pneumococcal bacteremia in a population with high human immunodeficiency virus seroprevalence

    Clin Infect Dis

    (1999)
  • W.A Craig

    Pharmacokinetic/pharmacodynamic parametersrationale for antibacterial dosing of mice and men

    Clin Infect Dis

    (1998)
  • G.L Drusano et al.

    Relevance of pharmacokinetics and pharmacodynamics in the selection of antibiotics for respiratory tract infections

    J Chemother

    (1997)
  • J.F Moroney et al.

    Clinical outcomes of bacteremic pneumococcal pneumonia in the era of antibiotic resistance

    Clin Infect Dis

    (2001)
  • S.L Kaplan et al.

    Outcome of invasive infections outside the central nervous system caused by Streptococcus pneumoniae isolates nonsusceptible to ceftriaxone in children treated with beta-lactam antibiotics

    Pediatr Infect Dis J

    (2001)
  • P.J Chesney et al.

    Occurrence of Streptococcus penumoniae meningitis during vancomycin and cefotaxime therapy of septicemia in a patient with sick cell disease

    Pediatr Infect Dis J

    (1995)
  • S.F Dowell et al.

    Failure of treatment of pneumonia associated with highly resistant pneumococci in a child

    Clin Infect Dis

    (1999)
  • F.J Caballero-Granado et al.

    Cefuroxime efficacy in treatment of bacteremic pneumonia due to penicillin-resistant and cefuroxime-resistant Streptococcus pneumoniae

    Antimicrob Agents Chemother

    (1996)
  • V.L Yu et al.

    An international prospective study of pneumococcal bacteremiacorrelation with in vitro resistance, antibiotics administered, and clinical outcome

    Clin Infect Dis

    (2003)
  • R Leclercq et al.

    Resistance to macrolides and related antibiotics in Streptococcus pneumoniae

    Antimicrob Agents Chemother

    (2002)
  • Cited by (53)

    • Antimicrobial resistance in clinical isolates of Streptococcus pneumoniae in a tertiary hospital in Kuwait, 1997-2007: Implications for empiric therapy

      2010, Journal of Infection and Public Health
      Citation Excerpt :

      The in vitro/in vivo paradox with macrolide group of antibiotics, referring to discordance between reported in vitro resistance and clinical success, has been documented in respiratory infections. Macrolides are commonly prescribed for the management of community-acquired pneumonia in outpatients, with the newer generation macrolides (clarithromycin and azithromycin) often used as monotherapy [21]. However, the high prevalence of erythromycin resistance (37.7%) in S. pneumoniae with predominance of highly resistant strains (MIC ≥64 mg/l) observed in this study is of concern for empiric therapy of community-acquired pneumonia because therapeutic failure with these agents has been reported [18], and many clinicians caution against using these agents as monotherapy in areas with high prevalence of resistance [21].

    View all citing articles on Scopus

    The author has acted on the advisory board of pharmaceutical companies marketing antibiotics (Abbott, Aventis, and Bristol-Meyers Squibb), has been reimbursed for lectures sponsored by pharmaceutical companies (Pfizer, Abbott, Bristol-Meyers Squibb, and Glaxo-Smith Kline), and has attended conferences sponsored by pharmaceutical companies (Bristol-Meyers Squibb, Aventis, and Pfizer).

    View full text