Acquired multidrug resistance in Str. pneumoniae has become a worldwide health problem, with increasing incidence of resistance to β-lactams, macrolides, lincosamides and tetracyclines in most parts of the world in the last three decades. The MIC of penicillin for sensitive strains of pneumococci is <0.01 mg/L; the first penicillin-resistant isolates, reported in 1967 from Papua New Guinea, showed ‘low-level’ resistance with MICs of up to 1 mg/L, but in 1977 pneumococci were isolated in South Africa showing ‘high-level’ resistance with penicillin MICs of >1 mg/L. High-level penicillin resistance has so far been confined to a few serotypes, whereas low-level resistance is now found in nearly all the common serotypes. There is a wide geographical variation in the prevalence of penicillin-resistant pneumococci, even between regions of a particular country.
The resistance of Str. pneumoniae to fluoroquinolones is due to chromosomal mutations in the DNA gyrase (gyrA and gyrB) and topoisomerase IV (parC and parE) and/or active efflux. Both mechanisms have so far been reported at low prevalence (<1%) in a majority of countries but with higher frequency in China (4–14%), Japan (0.5–6%) and Italy (6%). This is a cause for concern, given the usefulness of newer generation fluoroquinolones for the treatment of lower respiratory tract infections.
Respiratory and bloodstream infections with strains of pneumococci showing low- to moderate-level penicillin resistance (MIC <4.0 mg/L) can be treated with high doses of penicillin, amoxicillin or cephalosporins as there is no firm evidence that this level of penicillin resistance is associated with increased risk of treatment failure.