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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/cdn\/css\/http\/css_Xg7z6oCTVgud_Q0huYz9x9iiD5H_2YPSJ5z2ZViSWdY.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\u003EMultidrug-resistant lung infections are increasingly common in vulnerable patient populations, including patients with tuberculosis and cystic fibrosis and the critically ill. This article discusses new approaches to the diagnosis and management of antibiotic-resistant pulmonary pathogens, including the use of first-line combination antibiotic therapy and novel drug delivery.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ELower Respiratory Infections\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDrug Resistance\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EPulmonary Genomics\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EMultidrug-resistant lung infections are increasingly common in vulnerable patient populations, including patients with tuberculosis and cystic fibrosis and the critically ill. In this session, chaired by Samuel M. Moskowitz, MD, Massachusetts General Hospital, Boston, MA, USA and Keertan Dheda, MBChB, PhD, University of Cape Town, Cape Town, South Africa, presenters discussed new approaches to the diagnosis and management of antibiotic-resistant pulmonary pathogens, including the use of first-line combination antibiotic therapy and novel drug delivery.\u003C\/p\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EEmerging Multidrug-Resistant Pathogens\u003C\/h2\u003E\n         \u003Cp id=\u0022p-3\u0022\u003EGram-negative bacteria are increasingly resistant to conventional antibiotics, including beta-lactams, fluoroquinolones, and aminoglycosides. Multidrug-resistant gram-negative bacteria thrive in part because of mobile genes on plasmids that spread readily through bacterial populations. The widespread and inappropriate use of nonprescription antibiotics, particularly the carbapenems, increases the numbers of drug-resistant bacterial clones through selective pressure.\u003C\/p\u003E\n         \u003Cp id=\u0022p-4\u0022\u003EOne recent example is the bla\u003Csub\u003ENDM-1\u003C\/sub\u003E gene, which encodes New Delhi metallo-beta-lactamase-1 (NDM-1), an enzyme that is expressed by \u003Cem\u003EEnterobacteriaceae\u003C\/em\u003E and confers resistance to a broad range of beta-lactam antibiotics. \u003Cem\u003EEnterobacteriaceae\u003C\/em\u003E, particularly \u003Cem\u003EEscherichia coli\u003C\/em\u003E and \u003Cem\u003EKlebsiella pneumoniae\u003C\/em\u003E, are among the most common causes of serious nosocomial and community-associated bacterial infections. NDM-1 was first detected in 2008 in a \u003Cem\u003EK. pneumoniae\u003C\/em\u003E isolate that was recovered from a Swedish patient in a hospital in New Delhi, India, and has since been detected in \u003Cem\u003EE. coli\u003C\/em\u003E and \u003Cem\u003EK. pneumoniae\u003C\/em\u003E isolates in India, Pakistan, Bangladesh, and the United Kingdom [Kumarasamy KK et al. \u003Cem\u003ELancet Infect Dis\u003C\/em\u003E 2010].\u003C\/p\u003E\n         \u003Cp id=\u0022p-5\u0022\u003EThe sudden and widespread presence of NDM-1-encoding plasmids suggests an alarming new mechanism for antimicrobial resistance. Without aggressive infection control measures, the medical community may face multidrug-resistant \u003Cem\u003EEnterobacteriaceae\u003C\/em\u003E that cause common respiratory infections, resulting in treatment failures and substantial increases in health care costs.\u003C\/p\u003E\n         \u003Cp id=\u0022p-6\u0022\u003EExtensively drug-resistant tuberculosis (XDR-TB) is another multidrug-resistant pathogen that has thrived as a result of inappropriate antibiotic use. XDR-TB is resistant to established first-line drugs (isoniazid and rifampin) as well as second-line therapy with fluoroquinolones and at least one injectable agent (amikacin, kanamycin, or capreomycin). Super XDR-TB is a subtype of XDR-TB that is resistant to all known classes of anti-TB medications. In a study of South African patients with XDR-TB, 68% had isolates that were resistant to all available drugs, leaving no effective treatment options for these patients [Shah NS et al. \u003Cem\u003EEmerging Infect Dis\u003C\/em\u003E 2011]. These findings highlight the importance of expanded drug susceptibility testing for second- and third-line drugs to improve diagnosis and guide treatment for patients with multidrug-resistant TB.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-2\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EManagement of Multidrug-Resistant Infections\u003C\/h2\u003E\n         \u003Cp id=\u0022p-7\u0022\u003EExperience in managing well-characterized respiratory infections may provide insight on the optimal management of emerging multidrug-resistant pathogens. \u003Cem\u003EPseudomonas aeruginosa\u003C\/em\u003E is a major cause of ventilator-associated pneumonia (VAP). In a multicenter, retrospective study of 183 patients with VAP and positive respiratory cultures for \u003Cem\u003EP. aeruginosa\u003C\/em\u003E, initial treatment with antibiotic monotherapy provided poor protection against resistance compared with combination therapy with meropenem\/levofloxacin. Moreover, patients who received inappropriate antibiotic therapy had a significantly higher risk of in-hospital mortality compared with patients who received at least one antibiotic with in vitro activity against \u003Cem\u003EP. aeruginosa\u003C\/em\u003E (72.5% vs 23.1%; p\u0026lt;0.05) [Garnacho-Montero J et al. \u003Cem\u003ECrit Care Med\u003C\/em\u003E 2007]. These findings underscore the importance of initial combination therapy to increase the likelihood of effective therapy and reduce the risk of death, at least until antimicrobial susceptibility can be confirmed and patients can be switched safely to monotherapy.\u003C\/p\u003E\n         \u003Cp id=\u0022p-8\u0022\u003EThe Procalcitonin to Reduce Patients\u0027 Exposure to Antibiotics in Intensive Care Units (PRORATA) trial was designed to evaluate the effects of reduced antibiotic exposure, through improved diagnosis or shorter treatment duration, on the risk of antimicrobial resistance [Bouadma L et al. \u003Cem\u003ELancet\u003C\/em\u003E 2010]. The PRORATA trial included 620 adult patients with bacterial infections who were expected to be in the intensive care unit (ICU) for at least 3 days. Patients were randomly assigned to antibiotic therapy that was guided by standard clinical parameters (n=319) or by serum procalcitonin (PCT) levels (n=311). In the PCT group, patients discontinued antibiotic therapy when PCT level reached an absolute value of \u0026lt;0.5 \u03bcg\/L or a relative value of \u0026lt;80% of peak pretreatment level. The primary endpoints were mortality at 28 and 60 days and number of days without antibiotics by Day 28.\u003C\/p\u003E\n         \u003Cp id=\u0022p-9\u0022\u003EOverall mortality was similar in the PCT and control groups at Day 28 and at Day 60 (\u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E). However, patients in the PCT group had significantly more days without antibiotics than those in the control group (14.3 vs 11.6 days; p\u0026lt;0.0001). Thus, PCT-guided treatment reduced mean antibiotic use in critically ill patients, with no apparent adverse outcomes on survival. Reducing cumulative antibiotic exposure through biomarker-directed therapy is a promising option for easing selective pressure toward antibiotic resistance in this highly vulnerable patient population. Additional prospective studies are needed to confirm the safety and efficacy findings of the PRORATA trial before this practice is widely implemented.\u003C\/p\u003E\n         \u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/12277\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/12277\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/12277\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\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 1.\u003C\/span\u003E \n               \u003Cp id=\u0022p-10\u0022 class=\u0022first-child\u0022\u003EPRORATA Trial: Biomarker-Directed Therapy in Critically Ill Patients.\u003C\/p\u003E\n            \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-12\u0022\u003EBetter delivery of antibiotics to the deep lung may also reduce the risk of multidrug resistance. In a Phase 3 trial, 100 patients with gram-negative VAP were randomly assigned to receive adjunctive nebulized colistimethate sodium (CMS) or nebulized placebo every 12 hours in addition to systemic antibiotic therapy. Patients who received adjunctive CMS had significantly more favorable microbiological outcomes than those in the control group (60.9% vs 38.2%; p=0.03) [Rattanaumpawan P et al. \u003Cem\u003EJ Antimicrob Chemother\u003C\/em\u003E 2010].\u003C\/p\u003E\n         \u003Cp id=\u0022p-13\u0022\u003EIn summary, multidrug resistance, especially among gram-negative bacilli, has emerged as a major factor that affects outcomes in patients with respiratory infections. To combat this looming public health crisis, there is an urgent need for health care providers to apply evidence-based strategies to improve infection control and reduce selective antibiotic pressure in patients with suspected bacterial infections.\u003C\/p\u003E\n      \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\/4\/18.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_openurl.js?nzn2xq\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_tables.js?nzn2xq\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}