MD Conference Express ICAAC 2011 - (Page 6)
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F E A T U R E
Emerging Resistance Among Gram-Negative Pathogens: State of the Challenge
Written by Noelle Lake, MD
In the 1980s, antimicrobial resistance among gramnegative (Gm) pathogens seemed to be under control, with the availability of a growing anti-Gm armamentarium, including oxyimino-cephalosporins, fluoroquinolones, and carbapenems. Multiple treatment options were available in most infections and, while resistance to older antibiotics was common, it was caused by a relatively few stable mechanisms—TEM-1 β-lactamase, for example, accounted for over 90% of ampicillin resistance in E. coli. What is more, the residents of India and China—a third of the world’s population—had yet to experience large-scale exposure to modern medicine, modern antibiotics, and their consequences. Much has since changed, and physicians are now facing unprecedented clinical challenges due to the growing proliferation of multidrug-resistant Gm pathogens. David L iver more, PhD, Antibiotic Resistance Monitoring and Reference Laboratory, London, United Kingdom (UK), described current epidemiological, mechanistic, and demographic trends that are related to this worldwide epidemic. E. coli is a crucially important Gm pathogen, causing 80% of urinary tract infections, and is the most frequent Gm agent of bacteremia. For 20 years, E. coli was among the most susceptible Gm bacteria to modern antibiotics, but, over the past decade it has joined Enterobacter, Klebsiella, and Pseudomonas. According to recent data from the European Antimicrobial Resistance Surveillance Network (EARS-net), increasing proportions of E. coli bloodstream isolates are nonsusceptible to fluoroquinolones and cephalosporins. In Italy, for example, rates of fluoroquinolone resistance among E. coli bloodstream isolates jumped from between 1% and 5% to between 25% and 50% from 2001 to 2009 [http://www.ecdc.europa.eu]. These Southern European resistance rates pale in comparison to those observed in South and East Asia. According to a 2007 survey, E. coli isolates from intraabdominal infections in China and India, 50% and 80% respectively, carried extendedspectrum β-lactamases (ESBLs), rendering them resistant to modern oxyimino-generation cephalosporins [Hawser SP et al. AAC 2009]. It is striking that resistance to thirdgeneration cephalosporins among E. coli in India and China is now more prevalent than ampicillin resistance in E. coli in Sweden or Norway—countries that are known for their low antibiotic use and resistance. The accumulation of resistance to fluoroquinolones and cephalosporins in E. coli and related species is clinically
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important, and is dramatically supported by a 2007 metaanalysis by Schwaber and Carmeli [JAC 2007], who found that patients with bacteremia due to ESBL-containing pathogens had increased mortality rates compared with those with non-ESBL strains (pooled RR, 1.85; 95% CI, 1.39 to 2.47; p<0.001). The difference was attributed to delayed effective treatment, with many of the ESBL-producing strains resistant to the physician’s choice of empiric therapy. Early use of carbapenems, which are stable to ESBLs, might seem a logical solution to this problem; however, diverse carbapenemases are starting to emerge among Gms [Patel G et al. Expert Rev Anti Infect Ther 2011]. These include the VIM and NDM metallo and the KPC and OXA-48 nonmetallo types. EARS-net data reveal that although most European countries still have very low rates of carbapenem nonsusceptibility (<1% in Klebsiella bacteremia isolates across the continent), resistance is widespread in Greece, where rates among Klebsiella species reached 40% in 2005 and 50% by 2009. A major shift in carbapenemase type also occurred in Greece. The initial problem was the spread of plasmids that encoded VIM metallo-βlactamases among Klebsiella strains, but this has now been supplanted by the problem of a single Klebsiella strain with a nonmetallo ‘KPC’ carbapenemase that is spreading nationally [http://www.ecdc.europa.eu; Vatopoulos A Eurosurv 2008; Giakkoupi P et al. Eurosurv 2009]. Outbreaks of Klebsiella that produce the KPC carbapenemase were first noted in the United States (US) in 2005, but in addition to dissemination in the US, Israel and Greece, there are now growing clusters elsewhere in Europe, South America, and East Asia [Bratu S et al. Arch Int Med 2005; Nordmann P et al. Lancet ID 2009]. Pathogens that produce another carbapenemase, OXA48, are resistant to carbapenems but are susceptible to cephalosporins (unless they also have ESBLs), a pattern that is not always recognized by automated systems and therefore often missed. OXA-48 carbapenemase has spread from Turkey, where it has been recorded since 2000, into North Africa and Europe, while similar enzymes have been recorded in India and South America [Benouda et al. Ann Trop Med Para 2010; Moquet et al. EID 2011; Cuzon et al. IJAA 2010; Cuzon et al. AAC 2008; Cuzon et al. AAC 2011; Goern et al. IJAA 2011; Matar et al. CMI 2008; Carrer et al. AAC 2010; Carrer et al. AAC 2008; Poirel et al. AAC 2011; Castanheira et al. AAC 2011]. NDM-1 carbapenemase is prevalent in India and Pakistan and has repeatedly been exported to Europe, North
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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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