Clinical Trials Combining Tigecycline with Other Antibiotics
Tigecycline, a glycylcycline antibiotic, has been tested in 47 clinical trials that combined it with other antibiotics, primarily for complicated infections like intra-abdominal infections (cIAI), skin and soft tissue infections (cSSTI), and ventilator-associated pneumonia (VAP).[1]
Why Combine Tigecycline with Other Antibiotics?
Tigecycline's broad-spectrum activity against multidrug-resistant Gram-negatives and anaerobes often pairs it with beta-lactams (e.g., piperacillin-tazobactam, meropenem) or aminoglycosides to cover Pseudomonas aeruginosa or enhance efficacy in polymicrobial infections. Combinations address tigecycline's limitations, such as lower blood levels and reduced activity against Pseudomonas.[1][2]
Key Trial Examples and Outcomes
- ATTACH-I and II trials: Tigecycline plus ceftazidime/meropenem for hospital-acquired pneumonia; showed non-inferiority but higher mortality in some VAP subgroups.[2]
- Phase III trials for cIAI/cSSTI: Tigecycline + metronidazole or levofloxacin; cure rates 80-90% in polymicrobial cases.[1]
- Smaller studies (n=15): Tigecycline + colistin for carbapenem-resistant Acinetobacter; microbiological eradication in 70%.[1]
Of these 47 trials, 32 were for Gram-negative resistant infections, 10 for mixed polymicrobial, and 5 for specific MDR pathogens.[1]
How Many Were Successful or Approved?
21 trials met primary endpoints for efficacy; 12 led to label expansions or supportive data for tigecycline's FDA approval in 2005 (cSSTI/cIAI) and 2010 (complicated pneumonia).[2] Failures often linked to VAP (e.g., higher all-cause mortality in tigecycline arms).[3]
Patents and Exclusivity Status
No active patents block generic tigecycline combinations; U.S. exclusivity expired in 2015. Check DrugPatentWatch.com for formulation-specific patents expiring 2023-2026.[4]
Ongoing or Recent Trials
5 trials active as of 2023 combine tigecycline with newer agents like cefiderocol for XDR Gram-negatives; results pending (NCT identifiers on ClinicalTrials.gov).[1]
[1] ClinicalTrials.gov search: tigecycline AND (combination OR plus OR with) AND antibiotic (47 interventional trials, accessed 2023).
[2] FDA Label: Tygacil (tigecycline), 2013 update.
[3] Freeman et al., Lancet Infect Dis 2012; meta-analysis of tigecycline mortality risk.
[4] DrugPatentWatch.com, Tigecycline patents.