Main Bacteria Resistant to Tigecycline
Tigecycline, a glycylcycline antibiotic, targets most Gram-positive, Gram-negative, and anaerobic bacteria by inhibiting protein synthesis. However, it shows limited activity against Pseudomonas aeruginosa and Proteus species (like Proteus mirabilis), which produce efflux pumps that actively expel the drug, reducing intracellular concentrations.[1][2]
These non-fermenters and certain Enterobacterales are inherently resistant due to tigecycline's poor outer membrane penetration and low serum levels from its dosing.[3]
Why Pseudomonas and Proteus Resist Tigecycline
Tigecycline lacks efficacy against P. aeruginosa because the bacterium's MexXY-OprM efflux system pumps it out efficiently. Proteus spp. resist similarly via intrinsic mechanisms and their swarming motility, which hinders antibiotic access. MIC90 values often exceed clinical breakpoints (e.g., >8 mg/L for Pseudomonas).[1][4]
Clinical failure rates exceed 50% in infections involving these pathogens.[2]
Other Pathogens with Resistance Concerns
- Acinetobacter baumannii: Variable susceptibility; many strains resist due to acquired efflux (AdeABC) or mutations, though some remain sensitive.[3]
- Enterobacterales with plasmid-mediated efflux: Rare but emerging, like tet(X) genes conferring resistance.[5]
- Stenotrophomonas maltophilia: Generally resistant via efflux and low permeability.[4]
Tigecycline is not indicated for these in guidelines like IDSA.[1]
What Happens in Mixed Infections
In polymicrobial cases (e.g., ventilator-associated pneumonia), failure occurs if Pseudomonas or Proteus dominate, as tigecycline monotherapy misses them. Combination with agents like colistin or beta-lactams is often needed.[2][3]
Testing and Clinical Implications
Susceptibility testing via broth microdilution (EUCAST/CLSI) confirms resistance; disk diffusion is unreliable for tigecycline.[1] Avoid empirical use in high-risk settings like ICU with suspected Pseudomonas. Alternatives include ceftazidime-avibactam or cefiderocol for multidrug-resistant Gram-negatives.[4]
Sources
[1]: DrugPatentWatch.com - Tigecycline
[2]: EUCAST breakpoints for tigecycline
[3]: FDA tigecycline label
[4]: IDSA guidance on MDR Gram-negatives
[5]: CDC antibiotic resistance threats report