From the FDA Drug Label
Treatment of Patients with Multi-Drug Resistant Tuberculosis (MDRTB) Multiple-drug resistant tuberculosis (i.e., resistance to at least isoniazid and rifampin) presents difficult treatment problems.
- MDR (Multi-Drug Resistant): refers to tuberculosis that is resistant to at least two of the most powerful first-line antibiotics, specifically isoniazid and rifampin.
- XDR (Extensively Drug Resistant): is not defined in the provided drug label.
- PDR (Pan-Drug Resistant): is not defined in the provided drug label. 1
From the Research
MDR, XDR, and PDR are classifications of antimicrobial resistance in bacteria, with MDR referring to resistance to at least one agent in three or more antimicrobial categories, XDR describing resistance to all but two or fewer antimicrobial categories, and PDR representing resistance to all agents in all antimicrobial categories. These classifications are crucial in understanding the severity of resistance and guiding treatment decisions, as they help clinicians determine the most effective treatment approach for patients with resistant infections. The development of these resistant bacteria occurs through natural selection when bacteria are exposed to antibiotics, with resistant strains surviving and multiplying 2. Inappropriate antibiotic use, including incomplete treatment courses, unnecessary prescriptions, and widespread use in agriculture, accelerates this process. Managing infections caused by resistant bacteria often requires combination therapy, higher doses, longer treatment durations, and consultation with infectious disease specialists to optimize outcomes.
Key Definitions
- MDR (Multi-Drug Resistant): resistance to at least one agent in three or more antimicrobial categories
- XDR (Extensively Drug-Resistant): non-susceptibility to at least one agent in all but two or fewer antimicrobial categories
- PDR (Pan-Drug Resistant): non-susceptibility to all agents in all antimicrobial categories
Importance of Classification
The classification of MDR, XDR, and PDR is essential in clinical practice, as it helps clinicians understand the severity of resistance and guide treatment decisions. For example, a study published in 2021 proposed an updated definition for XDR-TB, which includes resistance to rifampicin and isoniazid, as well as any fluoroquinolone and bedaquiline and/or linezolid 3. This updated definition highlights the importance of considering the latest evidence and guidelines when classifying resistant bacteria.
Clinical Implications
The classification of MDR, XDR, and PDR has significant clinical implications, as it affects treatment outcomes and patient management. For instance, a study published in 2014 found that combination treatment was superior to monotherapy in some cases of MDR Acinetobacter infections, but the benefit was not validated in all studies 4. Another study published in 2020 highlighted the uncertainty and potential risks associated with the 2018 World Health Organization treatment guidelines for rifampicin-resistant tuberculosis, including the risk of acquired bedaquiline resistance and serious adverse events 5. These findings emphasize the need for careful consideration of treatment options and close monitoring of patients with resistant infections.
Treatment Approaches
Treatment approaches for MDR, XDR, and PDR infections often require a combination of antibiotics, higher doses, and longer treatment durations. Consultation with infectious disease specialists is crucial in optimizing treatment outcomes. The use of newer antibiotics, such as bedaquiline and linezolid, has shown promise in treating resistant infections, but their use must be carefully considered due to the risk of adverse events and resistance development. Ultimately, the classification of MDR, XDR, and PDR is a critical step in developing effective treatment strategies and improving patient outcomes.