What is the role of medications in the treatment of pneumococcal infection?

Updated: Jun 08, 2020
  • Author: ; Chief Editor: John L Brusch, MD, FACP  more...
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Antibiotics are the mainstay of treatment in S pneumoniae infections. Until the 1970s, essentially all pneumococcal isolates were sensitive to easily achievable levels of most commonly used antibiotics, including penicillins, macrolides, clindamycin, cephalosporins, rifampin, vancomycin, and trimethoprim-sulfamethoxazole. Beginning in the 1990s, many pneumococcal isolates in the United States showed decreased susceptibility to penicillin and other commonly used antibiotics. Continued increases in these isolates have led to the need for re-establishment of susceptibility standards.

As of 2007, isolates of drug-resistant S pneumoniae have become increasingly common worldwide. The CDC, as well as many state health departments, maintain a population-based surveillance system (the ABC system) that investigates the epidemiology and susceptibility patterns of invasive pneumococcal infections in the United States. In 2017, 4.1% and 2.1% of the isolates obtained showed intermediate or resistant susceptibility patterns to penicillin and cefotaxime, respectively. One hundred percent of the isolated were susceptible to vancomycin. [98] The prevalence of resistance varies greatly among countries, states, counties, and within populations in particular cities and may be as high as 30%-40% in some locations. [99, 100] Resistance rates are generally higher in most European countries, as well as in Hong Kong and Thailand. [101, 102]

The mechanism of pneumococcal resistance to penicillin and cephalosporins is through alteration in the molecular cell wall targets, penicillin-binding proteins (PBPs). Mutations that alter the PBPs result in decreased affinity for binding to these agents, rendering them less effective. This type of resistance can be overcome if the antibiotic concentration at the site of infection exceeds the MIC of the organism for 40%-50% of the dosing interval.

Penicillin-resistant pneumococci are often resistant to multiple additional classes of antibiotics, including other penicillin derivatives, cephalosporins, sulfonamides, trimethoprim-sulfamethoxazole (through amino acid changes), macrolides (through methylation or via an efflux pump), quinolones (through decreased permeability, efflux pumps, and alteration of enzymes), and chloramphenicol (through inactivating enzymes). Resistance is obtained as part of a cassette of genetic information, or a transposon, that encodes resistance to multiple antibiotics.

Resistance rates of pneumococcal isolates in the United States to trimethoprim-sulfamethoxazole, tetracycline, and the macrolides are relatively high. Some isolates (< 10% in the United States) that are resistant to macrolides are also resistant to clindamycin.

Vancomycin-resistant pneumococcal isolates have not been reported in the United States. The phenomenon of tolerance (survival but not growth in the presence of a given antibiotic) has been observed, but its clinical relevance is unknown. Any strain with an in vitro MIC greater than 1 µg/mL to vancomycin should be immediately reported to the state health department and arrangements made for confirmatory testing at the CDC.

In the United States, most pneumococcal isolates remain susceptible to fluoroquinolones. In certain countries and specific populations in whom the use of "respiratory fluoroquinolones" is more prevalent (eg, nursing homes), an increase in resistance to these agents has been seen. [30, 31, 47]

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