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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EA novel approach to treat drug-resistant microorganisms is antimicrobial photodynamic therapy (PDT), which is under investigation in animal models. PDT involves applying light from a laser, light-emitting diode, or other light source to an infected area that has been sprayed with a pathogen-penetrating photosensitizing agent.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EParasitic Infections\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EBacterial Infections\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EEmerging Therapies\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EA novel approach to treat drug-resistant microorganisms is antimicrobial photodynamic therapy (PDT), which is under investigation in animal models in the lab of Michael R. Hamblin, PhD, Wellman Center for Photomedicine, Massachusetts General Hospital Boston, Massachusetts, USA. PDT involves applying light from a laser, light-emitting diode, or other light source to an infected area that has been sprayed with a pathogen-penetrating photosensitizing agent. The combination of photosensitizer and light results in the generation of cytotoxic reactive oxygen species, which kills bacteria or fungi instantly (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E). \u201cThere has never been a single pathogen discovered that is resistant to photodynamic therapy,\u201d Dr. Hamblin said.\u003C\/p\u003E\u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/11\/12\/21\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Mechanisms of Action of Antimicrobial Photodynamic Therapy.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-303676212\u0022 data-figure-caption=\u0022Mechanisms of Action of Antimicrobial Photodynamic Therapy.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/11\/12\/21\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/11\/12\/21\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/11\/12\/21\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/12451\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-3\u0022 class=\u0022first-child\u0022\u003EMechanisms of Action of Antimicrobial Photodynamic Therapy.\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EReproduced with permission from M. Hamblin, MD.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-4\u0022\u003EPDT is safe for human tissue, because the photosensitizing agents penetrate bacteria quickly and take longer to affect eukaryotic cells. It is inexpensive and versatile and involves minimal training for staff and patients. Dr. Hamblin cites a further advantage in treating infections, such as traumatic infections and burns, since systemic antibiotics have trouble reaching damaged tissue. PDT has a broad therapeutic range, including viruses and parasites, and can reach pathogens in biofilms. In addition, Dr. Hamblin projects that PDT may be useful in the treatment of otitis media, necrotizing fasciitis, bacterial cystitis, gastric \u003Cem\u003EH. pylori\u003C\/em\u003E, sinusitis, or any infection where dye and light can be infused.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003ETwo interesting areas of PDT research are: (1) the pursuit of ideal photosensitizing agents, such as bacteriochlorins and porphycenes, and (2) assessing the effects of PDT in animal models of infection with bioluminescent organisms. Decreasing bioluminescence (correlating with decreased colony-forming units) and improved survival have been seen with burns in mouse models [Dai et al. \u003Cem\u003EVirulence\u003C\/em\u003E 2001], soft tissue [Gad et al. \u003Cem\u003EPhotochem Photobiol Sci\u003C\/em\u003E 2004], and sepsis across a range of pathogens, including MRSA [Dai et al. \u003Cem\u003ELasers in Surg and Med\u003C\/em\u003E 2010], \u003Cem\u003EE. coli, Pseudomonas, Acinetobacter\u003C\/em\u003E [Dai et al. \u003Cem\u003EAntimicrob Agents Chemother\u003C\/em\u003E 2009], \u003Cem\u003ES. aureus\u003C\/em\u003E [Gad et al. \u003Cem\u003EPhotochem Photobiol Sci\u003C\/em\u003E 2004], and \u003Cem\u003ECandida\u003C\/em\u003E [Dai et al. \u003Cem\u003EAntimicrob Agents Chemother\u003C\/em\u003E 2011]. PDT may also stimulate wound healing.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EScott F. Singleton, PhD, University of North Carolina, Chapel Hill, North Carolina, USA, is leading a team of researchers in the development of novel antibacterial adjunct agents that inhibit bacterial enzymes that are involved in DNA repair. Their current focus is a RecA inhibitor to combine with and potentiate the effect of DNA-damaging antibiotics. RecA protein of \u003Cem\u003EEscherichia coli\u003C\/em\u003E and other anabolic enzymes are upregulated by intracellular stress that is induced by antibiotic treatment and enable bacteria to survive [Kohanski MA et al. \u003Cem\u003ENature Rev Microbiol\u003C\/em\u003E 2010]. Furthermore, bacteria that are deficient in ReA show increased susceptibility to fluouroquinolones, aminoglycosides, trimethoprim, some \u03b2-lactams, and other agents [Thi TD et al. \u003Cem\u003EJ Antimicrob Chemother\u003C\/em\u003E 2011; Lui et al. \u003Cem\u003EAntimicrob Agents Chemother\u003C\/em\u003E 2010].\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003ELead candidate compound BRITE-345133, discovered by a collaborative effort between Dr. Singleton\u0027s lab and Dr. Li-An Yeh\u0027s lab at North Carolina Central University, is an allosteric inhibitor of RecA\u0027s ATPase activity. BRITE-345133 has been shown to potentiate \u003Cem\u003EE. coli\u003C\/em\u003E killing by ciprofloxacin (\u003Ca id=\u0022xref-fig-2-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F2\u0022\u003EFigure 2\u003C\/a\u003E), which translates into a dose-dependent reduction in ciprofloxacin MIC. An added benefit of RecA inhibition and improved bacterial killing is suppression of resistance emergence. New RecA inhibitors with improved physiochemical and activity spectra are under development.\u003C\/p\u003E\u003Cdiv id=\u0022F2\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/11\/12\/21\/F2.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022RecA Inhibitor BRITE-345133 Augments Bacterial Killing by Ciprofloxacin in vitro.             \u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-303676212\u0022 data-figure-caption=\u0022\u0026amp;lt;div xmlns=\u0026amp;quot;http:\/\/www.w3.org\/1999\/xhtml\u0026amp;quot;\u0026amp;gt;RecA Inhibitor BRITE-345133 Augments Bacterial Killing by Ciprofloxacin \u0026amp;lt;em\u0026amp;gt;in vitro.\u0026amp;lt;\/em\u0026amp;gt;             \u0026amp;lt;\/div\u0026amp;gt;\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 2.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/11\/12\/21\/F2.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/11\/12\/21\/F2.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 2.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/11\/12\/21\/F2.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/12452\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 2.\u003C\/span\u003E \n            \u003Cp id=\u0022p-8\u0022 class=\u0022first-child\u0022\u003ERecA Inhibitor BRITE-345133 Augments Bacterial Killing by Ciprofloxacin \u003Cem\u003Ein vitro.\u003C\/em\u003E\n            \u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-2\u0022\u003EReproduced with permission from J. Singleton, MD.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-9\u0022\u003ETerry Roemer, PhD, Merck Infectious Disease Research, Kenilworth, New Jersey, USA, presented his work on chemical genetic interaction networks that are aimed at uncovering targets for resensitization of methicillin-resistant \u003Cem\u003ES. aureus\u003C\/em\u003E (MRSA) to \u03b2-lactam antibiotics. Plasmid-based antisense interference is a technique that impairs transcription and translation of a targeted protein and has the potential to restore the susceptibility of MRSA to \u03b2-lactam antibiotics. A wide array of genes that are involved in \u03b2-lactam tolerance processes, including early- and late-stage peptidoglycan synthesis, cell division, and cell wall biogenesis, are potential antisense targets in MRSA [Lee et al. \u003Cem\u003EChem Biol.\u003C\/em\u003E In press 2011]. Dr. Roemer shared data regarding the development of small-molecule inhibitors to resistance targets that have been identified on genetic potentiation maps, including PC190723, a novel antistaphylococcal agent that targets a component of cell division initiation, FtsZ [Haydon DS et al. \u003Cem\u003EScience\u003C\/em\u003E 2008].\u003C\/p\u003E\u003Cp id=\u0022p-10\u0022\u003EDavid Shlaes, MD, Anti-Infectives Consulting, Stonington, Connecticut, USA, offered hope in the battle against microbial resistance in the form of new \u03b2-lactamase inhibitor combinations, focusing on tazobactam, clavulanic, and a newer class of agents\u2014avibactam (formerly called NXL-104) and MK-7655.\u003C\/p\u003E\u003Cp id=\u0022p-11\u0022\u003EPipeline agents to watch include CXA-201, a 2-to-1 combination of a new cephalosporin (CXA-101) and tazobactam. CXA-201 demonstrates good activity against strains of \u003Cem\u003EP. aeruginosa\u003C\/em\u003E with diverse resistance mechanisms [Cabot G et al. ICAAC 2010] but is less active against other gram-negative pathogens, particularly those that produce extended-spectrum \u03b2-lactamases (ESBLs) [Sader HS et al. \u003Cem\u003EAntimicrob Agents Chemother\u003C\/em\u003E 2011].\u003C\/p\u003E\u003Cp id=\u0022p-12\u0022\u003EA 4-to-1 combination of ceftazidime and avibactam is in development for use in complicated intraabdominal abscess (IAI) and urinary tract infections (UTIs) and is expected to enter Phase 3 by early 2012. This compound shows strong activity against \u003Cem\u003EE. coli, Klebsiella\u003C\/em\u003E species, and \u003Cem\u003EEnterobacter\u003C\/em\u003E species, including ESBL-producing strains [Sader HS et al. ICAAC 2010]. The addition of avibactam also improves ceftazidime\u0027s activity against \u003Cem\u003EPseudomonas\u003C\/em\u003E strains with various resistance mechanisms [Eurofins Medinet Study #5006\u201308]. In a prospective trial for the treatment of UTI, similar efficacy was demonstrated for ceftazidime\/avibactam compared with imipenem, and a greater proportion of ceftazidime-resistant \u003Cem\u003EE. coli\u003C\/em\u003E responded favorably to ceftazidime\/avibactam compared with imipenem (86% and 80%, respectively) [Vazquez JA et al. ECCMID 2011].\u003C\/p\u003E\u003Cp id=\u0022p-13\u0022\u003EOther combinations of interest include a 1-to-1 combination of ceftaroline and avibactam that is in Phase 2 for complicated UTI and a triple combination of imipenem, cilastatin, and MK7655 that is in Phase 1. Dr. Shlaes concluded by emphasizing that he hopes drugmakers will heed the call to develop a compound, such as aztreonam (or other monobactam base agents) and avibactam (or MK7655), which should retain activity against gram-negative pathogens that bear NDM-1 or other metallo-\u03b2-lactamases.\u003C\/p\u003E\u003Cp id=\u0022p-14\u0022\u003EAccording to Joyce Sutcliffe, PhD, Tetraphase Pharmaceuticals, Watertown, Massachusetts, USA, \u003Cem\u003EStreptomyces\u003C\/em\u003E that grew on stored grain supplied ancient cultures with naturally occurring tetracycline. The 1940s and 1950s saw the development of legacy and semisynthetic tetracyclines with great oral bioavailability, and now, a technique, called total synthesis, in which the right- and left-hand segments are designed in total and then connected together, has made possible the development of new classes of tetracyclines, including 8-aminomethyl, penta\/polycyclic, and 7,9 disubstituted analogs. Dr. Sutcliffe presented information on several promising agents that are in development, including orally active compounds that are effective against multidrug-resistant gram-positive and gram-negative pathogens.\u003C\/p\u003E\u003Cp id=\u0022p-15\u0022\u003EPTK0796 is a new C-9-aminomethyl minocycline analog that has shown efficacy against \u003Cem\u003ES. aureus, E. faecalis\u003C\/em\u003E, and \u003Cem\u003EE. coli\u003C\/em\u003E in mouse models of infection [McKenney D et al. ICAAC 2003]. It is under development for intravenous and oral use in humans. PTK0796 is in Phase 2\/3 development for skin and skin structure infections, with plans to study it in community-acquired pneumonia.\u003C\/p\u003E\u003Cp id=\u0022p-16\u0022\u003EThe 8-aminomethyl tetracycline class demonstrates activity that is comparable with tigecycline against key gram-negative pathogens, including ESBL-producing strains. From this class, TP-2758 has broad-spectrum activity, including excellent coverage of MRSA and gram-negatives, excluding \u003Cem\u003EPseudomonas\u003C\/em\u003E, and has entered Phase 1 clinical trials as an oral formulation. Other notable pipeline tetracyclines include TP-834, a pentacycline that is in development against MRSA community-acquired pneumonia, and TP-434, a 7,9 disubstituted analog with broad spectrum activity against aerobes, anaerobes, gram-positives, and gram-negatives except \u003Cem\u003EPseudomona\u003C\/em\u003Es. TP-434 is currently in Phase 2 for treating complicated IAI.\u003C\/p\u003E\u003Cp id=\u0022p-17\u0022\u003EStuart Johnson, MD, Loyola University Medical Center, Maywood, Illinois, USA, discussed a new option in the treatment of \u003Cem\u003EClostridium difficile\u003C\/em\u003E infections (CDIs). Approved in May 2011, fidaxomicin, a narrow-spectrum, nonabsorbed bactericidal RNA polymerase inhibitor that is effective against \u003Cem\u003EC. difficile\u003C\/em\u003E, is the first FDA-approved agent for use in the treatment of CDI in 25 years, making it one of two approved CDI therapies, along with vancomycin. Vancomycin use is complicated by a greater-than-20% recurrence rate for CDI and has the potential to select for vancomycin-resistant strains in the gut [Kelly and LaMont. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2008].\u003C\/p\u003E\u003Cp id=\u0022p-18\u0022\u003EIn two large, multicenter, double-blinded, randomized Phase 3 trials, fidaxomicin (200 mg BID) was shown to be noninferior to vancomycin (125 mg 4\u00d7\/day) for clinical cure\u201488% versus 86%, respectively\u2014in the modified intent-to-treat population. Notably, fidaxomicin treatment was associated with reduced rates of CDI recurrence compared with vancomycin (15% vs 25%; p=0.005) in the first trial [Louie TJ et al. \u003Cem\u003ENew Engl J Med\u003C\/em\u003E 2011]. Adverse events were similar between the two drugs, and results were similar in the second study.\u003C\/p\u003E\u003Cp id=\u0022p-19\u0022\u003EThe mechanism by which fidaxomicin prevents recurrence may be related to suppression of \u003Cem\u003EEnterobacteria\u003C\/em\u003E overgrowth in the gut [Tannock GW et al. \u003Cem\u003EMicrobiol\u003C\/em\u003E 2010].\u003C\/p\u003E\u003Cp id=\u0022p-20\u0022\u003EIn a separate analysis of the combined Phase 3 trials of fidaxomicin- and vancomycin-treated patients, the use of concomitant antibiotics with CDI treatment was a risk factor for prolonged duration of diarrhea [Mullane KM et al. \u003Cem\u003EClin Infect Dis\u003C\/em\u003E 2011]. This is consistent with what is known about risk factors for CDI, including antibiotic use and alterations of gastrointestinal microbiota. The adverse effect of concomitant antibiotic use on cure and recurrence rates was significantly (p\u0026lt;0.05) more prominent among vancomycin-treated patients. Vancomycin and fidaxomicin performed similarly against infections with epidemic strain BI\/NAP1\/027 [Patrella L. et al. ICAAC 2011].\u003C\/p\u003E\u003Cp id=\u0022p-21\u0022\u003ELooking to the future, Dr. Johnson suggested that CDI prevention strategies include immunotherapy and more effective probiotics.\u003C\/p\u003E\u003Cp id=\u0022p-22\u0022\u003EWith tremendous increases in the incidence of tuberculosis (TB) infection due to the HIV epidemic and the emergence of multidrug-resistant TB (MDR-TB), antituberculosis drug development has resurfaced as a major priority. Citing 2010 World Health Organization data, William Burman, MD, University of Colorado, Denver, Colorado, USA, said that a 55% increase globally in new MDR-TB cases has occurred in the past decade, with 440,000 new cases occurring each year, most of which remain undiagnosed.\u003C\/p\u003E\u003Cp id=\u0022p-23\u0022\u003ETreatment of MDR-TB takes 18 to 24 months, is very expensive, and has high rates of side effects. Therefore, there is a critical need for new agents for MDR-TB.\u003C\/p\u003E\u003Cp id=\u0022p-24\u0022\u003EThe most advanced pipeline agent in this area is TMC207 (bedaquiline). Bedaquiline is an ATPase synthetase inhibitor with good activity against MDR-TB and has the advantage of having no activity against bacterial pathogens.\u003C\/p\u003E\u003Cp id=\u0022p-25\u0022\u003ESince it interacts with rifampin, bedaquiline was evaluated as an add-on agent to optimized background therapy (excluding rifampin) in a prospective trial among patients with MDR-TB. Treatment substantially reduced (by 50%) time to sputum culture conversion (\u003Ca id=\u0022xref-fig-3-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F3\u0022\u003EFigure 3\u003C\/a\u003E) and was well tolerated [McNeeley DF et al. IUATLD 2010]. A FDA application is planned for 2012 for accelerated approval as an MDR treatment.\u003C\/p\u003E\u003Cdiv id=\u0022F3\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/11\/12\/21\/F3.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Time to Sputum Culture Conversion Among Patients with MDR-TB Treated with Optimized Background Therapy plus Placebo or TMC207.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-303676212\u0022 data-figure-caption=\u0022Time to Sputum Culture Conversion Among Patients with MDR-TB Treated with Optimized Background Therapy plus Placebo or TMC207.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 3.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/11\/12\/21\/F3.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/11\/12\/21\/F3.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 3.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/11\/12\/21\/F3.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/12454\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 3.\u003C\/span\u003E \n            \u003Cp id=\u0022p-26\u0022 class=\u0022first-child\u0022\u003ETime to Sputum Culture Conversion Among Patients with MDR-TB Treated with Optimized Background Therapy plus Placebo or TMC207.\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-3\u0022\u003EReproduced with permission from W. Burman, MD.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2011 MD Conference Express\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/11\/12\/21.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nzmxdp\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzmxdp\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}