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Updated: May 12, 2026

Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
Published on: August 30, 2018
Emerging issues in the management of infections caused by multi-drug-resistant, gram-negative bacilli
1Medical Service 111, Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio 44106, USA. louis.rice@med.va.gov
Background:
The past decade has witnessed the continued emergence and spread of multidrug resistance in gram-negative bacilli. Infections caused by multi-drug-resistant, gram-negative bacilli lead, in many instances, to increased morbidity and mortality, prolonged hospital stays, and the use of broad-spectrum antibiotics.
Methods:
Recent literature from 1990 to the present is reviewed in order to put into perspective the effects of increasing incidences of multi-drug-resistant gram-negative bacilli on patient care.
Results:
Factors important in the emergence and spread of multi-drug-resistant gram-negative bacilli include increasing severity of illness in hospitalized patients, poor attention to infection control practices by healthcare personnel, and the large, often indiscriminate use of broad-spectrum antimicrobial agents. Unlike earlier iterations, there is no steady stream of newer antimicrobial agents in development to address the problem. The only broad-spectrum antimicrobial agent with activity against multi-resistant, gram-negative bacilli and with potential to be licensed in the foreseeable future is tigecycline. Tigecycline, the first member of a novel class of antimicrobials, the glycylcyclines, is a structural derivative of minocycline, with potent activity against most gram-positive, gram-negative (excepting Pseudomonas aeruginosa and Proteus spp.) and anaerobic species. Phase 3 trials indicate that tigecycline is effective for treating both complicated skin and skin structure infections, and intra-abdominal infections in hospitalized patients.
Conclusion:
Tigecycline promises to be an important addition to our monotherapy armamentarium, complementing essential efforts to promote compliance with good infection control measures and rational use of currently available antimicrobial agents.
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