MD Conference Express ICAAC 2011 - (Page 7)

America, and Asia by people who have had contact with medical facilities in the Indian subcontinent [Kumarasamy KK et al. Lancet ID 2010]. NDM-1 is often coded by plasmids that can spread readily among bacteria and is commonly produced together with rRNA methylases that confer aminoglycoside resistance. Some Gm pathogens with NDM enzymes have near-complete resistance— susceptible only to colistin, with or without moderate susceptibility to fosfomycin and tigecycline [Kumarasamy KK et al. Lancet ID 2010]. The dissemination of NDM-1 in parts of India is striking, with one survey revealing a 5% to 7% prevalence among Enterobacteriaceae species in Mumbai [Deshpande P et al. Clin Infect Dis 2010]. Multiresistant bacteria carriage rates among healthy individuals is facilitating the spread and repeated introduction into hospitals, and is a critical subject of international interest. Separate studies have shown gastrointestinal tract colonization by ESBL E. coli in 13% of job applicants in Saudi Arabia [Kadar et al. ICHE 2007] and in nursing home residents in Northern Ireland (40%) and Italy (64%) [Rooney PJ et al. JAC 2009; March A et al. CMI 2010]. A prospective study in Sweden revealed that one quarter of previously uncolonized individuals became colonized with ESBL E. coli during travel, with the highest rates of colonization associated with travel to East Asia (29%) and India (88%) [Tangden T et al. AAC 2010]. NDM-carrying bacteria were shown to inhabit the gut of 27% of inpatients and 14% of outpatients in military hospitals in Pakistan [Perry et al. JAC 2011]. The molecular basis of proliferating resistance among Gm bacteria is more complex than previously thought. Potent bacterial strains, such as sequence type (ST) 131 E. coli serotype 025 [Uchida et al. IJAA 2010; Guenther S et al. JAC 2010] and ST258 K. pneumoniae [Woodford N et al. FEMS Micro Revs 2011], play a pivotal role. E. coli ST131 commonly hosts plasmids that encode CTX-M-15 ESBL and has been instrumental in their international dissemination, while ST258 K. pneumoniae is playing a similar role in the spread of KPC carbapenemases. However, ST131 E. coli may also carry other ESBL types, including CTX-M-3 (Belfast) and CTX-M-14 (Far East), or may have no ESBL. Deeper analysis shows that the plasmids that carry β-lactamase genes are remarkably dynamic and are constantly in flux. The dominant E. coli ST131 variant in the UK (‘Strain A’) typically contains a complex CTX-M-15 plasmid, EK499, which is a fusion between two parent plasmids, one of which (pEK516) resembles, but is not identical to those that commonly host CTX-M-15 internationally [Woodford N et al. AAC 2009]. Moreover, although CTX-M-3—prevalent in E. coli ST131 from Belfast—differs from CTX-M-15 by only 1 amino acid, the plasmids that encode CTX-M-3 and CTX-M-15 are completely different. In the case of NDM, the encoding gene has transferred swiftly among plasmids that belong to diverse incompatibility groups, though the mechanism of transfer is unclear. Prof. Livermore suggests that this genetic fluidity among bacteria is perhaps “the finest but most disturbing evidence of evolution we shall ever see.” The emergence of carbapenem resistance is beginning to drive the use of nonconventional antibiotics, such as colistin, tigecycline, and fosfomycin, but none of these is ideal, and some resistance is beginning to emerge, even to colistin [Kontopoulou K et al. JHI 2010]. In addition, current pipeline agents represent incomplete solutions. Avibactam, a new β-lactamase inhibitor, inhibits KPC but not metallo-β-lactamases, and while CXA-201 (cephalosporin CXA101+tazobactam) evades ESBLs and has very good anti-Pseudomonas activity, it lacks activity against carbapenemase producers [Livermore DM et al. AAC 2011; Livermore DM. JAC 2010]. Aging populations, shifting world economies, and inadequate sanitation add to an already complex problem of emerging resistance. The elderly, who form a growing percentage of the population, are more vulnerable to infections, and economic growth in India and China is greatly increasing access to sophisticated medicine and modern antibiotics, often in settings where infection control and regulation of antibiotic use are weak. These are the perfect conditions to drive the selection of resistance, illustrated by the ESBL rates. In India, the lack of public health infrastructure is a tremendous concern. A recent study by the Health Board of the Delhi Municipal Council found that 18% of tap water samples were contaminated with fecal bacteria and that hundreds of millions lack access to a flush toilet [UN News Center 2010]. Improving sanitation here to prevent the spread of resistant bacteria is as important as it was in the US in the early twentieth-century in preventing the spread of classical infectious diseases. Development of new anti-Gm antibiotics is urgently needed and hinges on overcoming three challenges. First, discovery of agents that are capable of permeating the Gm cell wall and evading efflux is a key scientific challenge. Second, the regulatory pathway needs to confirm efficacy and safety, but has become too complex and often fails to test antibiotics in the types of patients or settings where they are most likely to be used. The third, and key economic challenge, is the likely return of antibiotic development. Short-term agents for acute infection do not generate the long-term income. These and other challenges must be confronted in order to effectively halt the spread of resistant Gm pathogens. Official Peer-Reviewed Highlights from the 51st ICAAC 7 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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