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July 2020

Review of the epidemiology and patterns of antibiotic resistance in community-acquired pneumonia (CAP) 1

Introduction

Community-acquired pneumonia (CAP) is a major indication for antibiotic use. The epidemiology of CAP is changing, and geographical differences exist in the aetiology of bacterial CAP. This review provides an update on the prevalence and patterns of antibiotic resistance of bacterial CAP around the world.

Key points

Epidemiology

  • The incidence of CAP requiring hospitalisation in adults increases with increasing age, with various comorbid conditions identified as risk factors.
    • With ageing populations and growing numbers with comorbid conditions, the potential healthcare burden of CAP is substantial.
  • Globally, Streptococcus pneumoniae remains the leading causative pathogen.
    • Other common pathogens include Haemophilus influenzae, Mycoplasma pneumoniae, Staphylococcus aureus, Legionella pneumophila and Klebsiella pneumonia, but prevalence varies geographically and across patient populations.
  • Atypical bacteria such as Chlamydophila pneumoniae and Coxiella burnetiid have been reported in some countries.

Streptococcus pneumoniae

  • Despite widespread vaccination against pneumococcal disease, S. pneumoniae remains the most important bacterial cause of CAP.
  • Nevertheless, the rate of multi-drug resistance has declined in the US alongside reductions in non-susceptibility to penicillin and ceftriaxone while nonsusceptibility to erythromycin has increased.
  • Susceptibility to ceftaroline, levofloxacin, tigecycline, and linezolid remains high and stable.

Haemophilus influenzae

  • Although ampicillin remains the first-line drug of choice for H. influenzae infections, 10–20% of strains in Europe and the US are ß-lactamase producers.
  • Across Europe, Asia Pacific and Latin America, recent data show high rates of H. influenzae susceptibility to ceftriaxone, merepenem and amoxicillin-clavulanate.
  • However, resistance or reduced susceptibility to various agents (ß-lactams, cephems, carbapenems) is increasingly reported and heterogeneous resistance to carbapenems is emerging.

Mycoplasma pneumoniae

  • In the absence of a cell wall, M. pneumoniae is not intrinsically susceptible to ß-lactams or glycopeptides; thus, macrolides have been the first-line drug of choice.
  • Macrolide resistance varies widely with prevalence reports of <5% in Italy and Australia to up to 85% in China.
  • Alternative options include tetracyclines and fluoroquinolones, which retain high activity against macrolide-resistant strains.

Staphylococcus aureus

  • From the Sentry Surveillance Study (2015–2017):
    • Oxacillin resistance varied from 32% in Asia Pacific to 24% in Latin America and 22% and 15% in Western and Eastern Europe, respectively;
    • Ceftaroline susceptibility ranged from 94% in Asia Pacific to 100% in Eastern Europe;
    • Among methicillin-resistant S. aureus (MRSA) isolates, ceftaroline susceptibility was lowest in Asia Pacific (81%);
    • All isolates were susceptible to linezolid, tigecycline, and vancomycin.

Enterobacteriaceae, including Klebsiella pneumoniae

  • Extended spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae, especially carbapenemase-producing strains, are a serious concern.
  • CAP isolates with ESBL-producing Enterobacteriaceae have been reported at a frequency of 0.5% for Escherichia coli and 0.2–0.5% for K. pneumoniae.
  • Rapidly increasing rates of carriage in the community of ESBL-producing E. coli and K. pneumoniae point to a growing potential to cause CAP in the future.

Legionella pneumophila

  • Antibiotics that concentrate intracellularly, such as macrolides, fluoroquinolones, and rifampicin comprise the mainstay of treatment against this intracellular pathogen.
  • 10–13% of respiratory clinical isolates are fluoroquinolone resistant and resistance to rifampicin has been reported; clarithromycin and cotrimoxazole remain effective.

Chlamydophila pneumoniae

  • C. pneumoniae is susceptible to antibiotics that target DNA and protein synthesis, including tetracyclines, macrolides, and quinolones – these options have remained largely unchanged.

Conclusions

The significant burden of CAP is set to increase with ageing populations and growing rates of comorbidity. Globally, common bacterial pathogens are the causative agents of CAP in general although geographical variations exist. With increasing rates of antibiotic resistance, surveillance is important to guide appropriate antibiotic prescribing.

Reference:

  1. Ho J, Ip M. Antibiotic-resistant community-acquired bacterial pneumonia. Infect Dis Clin North Am. 2019;33(4):1087-1103.

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