Bacterial respiratory tract infections or RTIs are very common. Treatment is invariably empiric, requiring an appropriate antimicrobial active against the most likely pathogens: Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus and Streptococcus pyogenes. Atypical pathogens such as Chlamydophila (Chlamydia) pneumoniae, Mycoplasma pneumoniae and Legionella pneumophila may also need to be covered. Empirical choice is now further complicated by antimicrobial resistance. Global (excluding Europe) rates of non-susceptibility to penicillin among Streptococcus pneumoniae isolates range from 19.7% in Canada to greater than 50% in South Africa, Saudi Arabia, Hong Kong, Taiwan, South Korea and Japan. In spite of re-evaluation of interpretative breakpoints, non-susceptibility to amoxicillin was observed in excess of 10% of isolates in the USA, South Africa, Hong Kong and South Korea.
In Europe, penicillin non-susceptibility among isolates of Streptococcus pneumoniae varies widely. Countries bordering the Mediterranean and some eastern countries have the highest rates (peaking at 64.4% in France). Non-susceptibility to amoxicillin is generally below 5%, except in Spain, France and Greece.
Macrolide resistance is evolving rapidly with rates in excess of 25% among Streptococcus pneumoniae isolates in the USA, Mexico, and South Africa, and greater than 70% in South Korea, Hong Kong, Japan and Taiwan. In Europe, prevalence exceeds 25% in Belgium, Spain, France, Italy, Greece, Hungary and the Slovak Republic.
Tetracycline and, especially, trimethoprim-sulfamethoxazole resistance among isolates of Streptococcus pneumoniae is now found at high prevalence around the world. The highest rates are in East Asia.
Multi-drug resistance – erythromycin plus tetracycline and trimethoprim-sulfamethoxazole with or without reduced susceptibility to penicillin – is a growing concern. Rates in excess of 10% have been observed in the USA, Mexico, South Africa, Saudi Arabia and Western Russia, with more than 50% of isolates multi-drug resistant in Hong Kong, Taiwan and South Korea.
In Europe, the prevalence of multi-drug resistance in Streptococcus pneumoniae exceeds 10% in Spain, France, Greece, Hungary and the Slovak Republic.
In contrast, resistance to the fluoroquinolone levofloxacin among isolates of Streptococcus pneumoniae remains extremely low worldwide, despite its widespread use for many years.
Exceptionally, a fluoroquinolone-resistant strain of the Spain －23F-1 serotype in Hong Kong was found in approximately 10% of isolates of Streptococcus pneumoniae.
Macrolide resistance has been observed at rates in excess of 10% of Streptococcus pyogenes isolates in many countries and in excess of 30% of isolates in Hong Kong, South Korea, Portugal and the Slovak Republic. Tetracycline resistance is also established with rates in excess of 10% worldwide. By contrast, the vast majority of isolates of Streptococcus pyogenes remain susceptible to levofloxacin worldwide.
Prevalence of beta-lactamase production among Haemophilus influenzae isolates varies globally from less than 10% in South Africa, Japan and Western Russia to greater than 20% in the USA, Mexico, Hong Kong, Taiwan and South Korea, with a particularly high prevalence in France at 30.6%. Levofloxacin exhibits highly potent activity against Haemophilus influenzae with only very rare strains recognised as clinically resistant.
The potency of levofloxacin against Haemophilus influenzae as measured by an MIC50/MIC90 of 0.015mg/l greatly exceeds that of the macrolides/ketolides which are characterised by mode MIC in the range of 1-8 mg/l.
Levofloxacin’s antibacterial spectrum includes potent activity against the atypical bacterial respiratory tract pathogens Chlamydophila (Chlamydia) pneumoniae, Mycoplasma pneumoniae and Legionella pneumophila.
Empirical treatment of RTIs has been complicated by the emergence of significant resistance to many antimicrobials. Levofloxacin remains active against the majority of isolates of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pyogenes and atypical pathogens, and new data continues to be reported on the best therapeutic strategies to treat RTIs.