MD Conference Express ICAAC 2011 - (Page 24)

n O T H E R N E W S The Conundrum of MDR-TB and Combination Therapy Written by Rita Buckley Cases of multidrug-resistant tuberculosis (MDR-TB), defined as TB that is resistant to isoniazid (INH) and rifampin (RMP) and extremely (or extensively) drug-resistant TB [ie, TB that is not only resistant to INH/RMP, but also to quinolone and capreomycin (cyclic peptide) or an aminoglycoside (amikacin or kanamycin)], are increasing. MDR complicates therapy and results in lower success rates and higher mortality, especially in HIV coinfected patients. George L. Drusano, MD, University of Florida, Gainesville, Florida, USA, discussed the conundrum of MDR-TB and combination therapy and ways to address it. According to Dr. Drusano, combination therapy generally suppresses resistance (Table 1). [Drusano GL et al. mBio 2010]. However, when drugs have vastly different half-lives (eg, rifampin and moxifloxacin) and one induces error-prone replication (as with moxifloxacin), resistance can develop with drug holidays (Figure 1) [Drusano GL et al. mBio 2011]. “If we wish to shorten therapy,” he said, “we have to suppress resistance, pay attention to schedule, and find combinations that are not only antagonistic but, hopefully, synergistic.” Table 1. Resistance Suppression: Log-Phase. Regimen 600 mg rifampin QD 800 mg moxifloxacin QD 100 mg rifampin QD + 100 mg moxifloxacin QD 24.2 AUC/MIC Ratio of Free: Rifampin 168.2 177.2 21.5 Moxifloxacin Failure Failure Success Resistance Suppression Figure 1. Resistance Emergence in Drug Holidays. A. (A) Control 7/7 Arms (B) Moxi 10.85+Rif 4.064 ug*h/mg (7/7) B. (C) Moxi 14.60+Rif 7.040 ug*h/mg (7/7) 7/7 Arms (D) Moxi 18.35+Rif 10.016 ug*h/mg (7/7) Peer-Reviewed Highlights from the 9 8 7 6 5 4 3 2 1 0 10 Log CFU/mL Log CFU/mL 0 10 20 Time (days) 30 8 6 4 2 0 0 10 20 Time (days) 30 51st ICAAC 5/7 Arms (A) Control (B) Moxi 10.85+Rif 4.064 ug*h/mg (5/7) (C) Moxi 14.60+Rif 7.040 ug*h/mg (5/7) 5/7 Arms (D) Moxi 18.35+Rif 10.016 ug*h/mg (5/7) 9 8 7 6 5 4 3 2 1 0 10 Log CFU/mL Log CFU/mL 0 10 20 Time (days) 30 8 6 4 2 0 0 10 20 Time (days) 30 Moxi=moxifloxacin; Rif=rifampin. Reproduced with permission from G. Drusano, MD. 24 November 2011 www.mdconferencexpress.com  http://www.mdconferencexpress.com http://www.icaac.org/ http://www.mdconferencexpress.com

Table of Contents for the Digital Edition of MD Conference Express ICAAC 2011

MD Conference Express ICAAC 2011
Contents
Infectious Disease Genomics
Emerging Resistance Among Gram-Negative Pathogens
Procalcitonin-Guided Antibiotic Therapy In Patients with Lower Respiratory Tract Infections
Combination Therapy with Flucytosine Improves Survival in AIDS-Related Cryptococcal Meningitis
CXA-201 Effective Against Common ICU Pathogens
Tigecycline Plus Standard Therapy Is More Effective For Treating Infections in Febrile Neutropenic Cancer Patients
Interventions Aimed at Reducing MRSA BSIs Led to Decreased Rates of Nosocomial MSSA BSIs
Is the Effectiveness of aP Vaccine in Pre-Adolescents Insufficient?
TMC435 Effective in the Treatment of HCV Genotype 1 Infection
HIV
Vaccines
Antibiotic Resistance
Drug Discovery
The Conundrum of MDR TB and Combination Therapy
New Drugs to Treat MDR Pathogens
Immunizations in Reproductive Health
Why Can’t Microbes Just Get Along?
The Role of Adjunctive Steroids in the Treatment of Bacterial Meningitis
Human and Animal Viruses Share “One World” and Emerging Zoonotic Infections Continue to Threaten

MD Conference Express ICAAC 2011

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