Mycoplasma pneumoniae: Susceptibility and Resistance to Antibiotics

Cécile Bébéar; Sabine Pereyre; Olivia Peuchant


Future Microbiol. 2011;6(4):423-431. 

In This Article

Active Antibiotics

Since mycoplasmas lack a cell wall, the number of antibiotics that can be used for treating mycoplasmal infections is limited. Antibiotics with potential activity against mycoplasmas and used in clinical practice include the tetracyclines, MLSK antibiotics and fluoroquinolones.[8,9] These drugs achieve high intracellular concentrations in mammalian cells and are thereby able to reach the intracellular mycoplasmas. Only the fluoroquinolones and ketolides have a potential bactericidal action. All three classes have the advantage of being active against other bacteria that may be associated with mycoplasmas in respiratory and genital tract infections. Other antibiotics such as aminoglycosides and chloramphenicol may also show activity against mycoplasmas but are only rarely used.

Antibiotic treatment of M. pneumoniae infections will generally cure the patients with a reduction in fever and respiratory symptoms duration.[1] Macrolides are the treatment of choice of M. pneumoniae infections, but tetracyclines and fluoroquinolones are also effective.[6,8]

Macrolide–Lincosamide–Streptogramin–Ketolide Group

The antibiotics constituting the MLSK group inhibit protein synthesis at the ribosome level and are bacteriostatic except the streptogramin combinations and ketolides. Chemical footprinting and x-ray crystallography demonstrated direct binding of MLSK to specific nucleotides in domains II and V of 23S rRNA. MICs of the main antimicrobials belonging to the MLSK group are presented in Table 1 and are the lowest against M. pneumoniae, compared with those of other antibiotic classes. Azithromycin and ketolides (telithromycin, cethromycin and CEM-101) have better activity in vitro against M. pneumoniae while lincosamides, particularly lincomycin, have modest activity (Table 1). In a recent study, the new investigational ketolide CEM-101 demonstrated the greatest potency against 36 isolates of M. pneumoniae with a MIC90 of 0.000125 µg/ml, fourfold and eightfold higher than that of azithromycin and telithromycin, respectively.[15] Furthermore, CEM-101 maintained good in vitro activity against two macrolide-resistant isolates of M. pneumoniae, with MICs of 0.5 µg/ml, while the azithromycin and telithromycin MICs increased to 32 µg/ml for the two isolates.

Overall, macrolides are the drug of choice for the treatment of M. pneumoniae infections in children or when tetracyclines or fluoroquinolones are contraindicated.


Fluoroquinolones target the type II topoisomerases, DNA gyrase and topoisomerase IV, which are essential for bacterial DNA replication. The first members of the fluoroquinolone class, such as ofloxacin and ciprofloxacin were followed by new agents, like levofloxacin and moxifloxacin. Newer fluoroquinolones show an enhanced activity against all the human mycoplasmas studied including M. pneumoniae, compared with the older ones (Table 1). However MICs of all fluoroquinolones are higher than those of macrolides and related antibiotics. Recently, the new investigational quinolone derivative RD-03 was shown to be as active as azithromycin against 61 strains of M. pneumoniae with a MIC90 of 0.016 µg/ml.[16]

The newest fluoroquinolones are an interesting alternative in the treatment of respiratory or extrarespiratory M. pneumoniae infections, particularly in the treatment of disseminated infections in immunocompromised patients because of their bactericidal activity in vitro.[9] They are increasingly used for empiric treatment of respiratory tract infections in adults, since they are active against most of the community-acquired respiratory tract pathogens, such as atypicals (mycoplasmas, chlamydiae, legionellae) and pneumococci.


Tetracyclines and the related glycylcyclines inhibit bacterial protein synthesis. They exert bacteriostatic activity by binding to the ribosomal 30S subunit, composed of 16S rRNA and several ribosomal proteins. The major tetracycline binding site is located in a pocket formed by some residues of helix 34 and 31 in 16S rRNA.[17] Tetracyclines are the first-line treatment of mycoplasmal urogenital infections, but they are also indicated in the treatment of infections owing to M. pneumoniae in adults.[2] Glycylcyclines have been designed to overcome resistance to earlier tetracyclines mediated by efflux and ribosomal protection.[18]

MIC ranges of tetracycline, doxycycline, minocycline and the glycylcycline tigecycline against M. pneumoniae, are given Table 1. Tigecycline is as active as tetracyclines against tetracycline-susceptible strains of M. pneumoniae.[12]

Peptide Deformylase Inhibitors

A new class of antimicrobials that inhibit the peptide deformylase, a bacterial enzyme that acts in the early stages of polypeptide synthesis, was evaluated in vitro against human mycoplasmas including M. pneumoniae.[19] The investigational peptide deformylase inhibitor studied, LBM415, was highly active against all isolates of M. pneumoniae (MIC90; 0.001 µg/ml), rivaling those of macrolides. However, minimal bactericidal concentrations and time-killing assays indicated that this compound was bacteriostatic.[19]


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