The Continuing Plague of Extended-spectrum β-lactamase–producing Enterobacteriaceae Infections

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Key points

  • The continued spread of extended-spectrum β-lactamase (ESBL) infections is correlated with shifts in medical care.

  • The overuse and misuse of prolonged 'prophylactic' courses of antimicrobials is a modifiable independent predictor for ESBL acquisition.

  • Agriculture and food products might have an additional role in dissemination of ESBL-producing organisms in community settings.

  • Emergence of a new class of ESBL enzymes, the CTX-Ms, might have resulted the epidemiologic evolution of human ESBL

The emergence of extended-spectrum β-lactamases

The incremental growth in resistance to β-lactam agents (eg, penicillins and cephalosporins) among Enterobacteriaceae is a worrisome trend. β-Lactams are among the oldest and safest therapeutics.9, 10 Given susceptible isolates, they are potent bacteriocidic agents.11 In addition, well-controlled data on their clinical efficacy against Enterobacteriaceae are readily available because of their extended years of usage.1, 12 Owing to their safety, tolerability, potency, and (usually) low price,

Worldwide prevalence of extended-spectrum β-lactamases

Overall, the rates and types of ESBL-producing Enterobacteriaceae infections have increased dramatically in the past 30 years; however, distinct geographic patterns and institutional variation do exist.17, 31 Huge surveillance programs are periodically reporting the prevalence of ESBLs among offending pathogens from all over the world.32, 33 Database from 2004 to 2006 illustrated for example, that the rates of ESBL production in Latin America was 44% among K pneumoniae and 13.5% among E coli

The historic evolution of TEM- and SHV-types extended-spectrum β-lactamases–producing Enterobacteriaceae infections

Third-generation (extended-spectrum) cephalosporins were introduced to clinical practice in the early 1980s.40, 41 In many institutions, they were prescribed in high volumes and with very little regulation.42 These agents were safe, potent, accessible, relatively cheap, and extremely effective against a wide array of human pathogens.43, 44 In many facilities, they became the backbone of empiric regimens for various indications.45 Frequently, administration of these broad-spectrum agents was

The CTX-M–producing E coli outbreak in nonhospital settings

After the reports of increased incidence of ESBL infections in nonhospital settings among patients with none of the known “traditional” risk factors (ie, associated with health care exposures), molecular investigations revealed that a change in ESBL types might be related to this epidemiologic shift.28, 48, 69, 71, 73, 75, 76, 82, 83, 84, 85, 86, 87, 88, 89, 90 As mentioned, K pneumoniae was the main isolate harboring ESBL genes (most often blaTEM and blaSHV types) during the 1990s.10 However,

The clonal expansion of a specific blaCTX-M–producing E coli strain in the community

After the recognition that CTX-Ms might be related in part to the epidemiologic shift in ESBL human infections and its dissemination into community settings, advanced investigational molecular techniques soon revealed the predominance of a specific E coli clone producing mainly blaCTX-M15 enzymes on at least 3 continents.137, 138 This successful clone was classified as (1) sequence type (ST) 131 per multilocus sequence typing71, 75, 137, 139, 140, 141, 142, 143; (2) phylogenetic group B2

What are the predictors for extended-spectrum β-lactamases–producing Enterobacteriaceae infections acquired outside of the hospital settings?

Many risk factor analyses pertaining to ESBLs acquired outside the hospital settings have been published from diverse geographic settings using various definitions.62, 63, 134, 153, 154, 155, 156, 157, 158, 159 The debate on how best to define “community-onset infections” is beyond the scope of this paper and is reviewed in detail elsewhere.8 The risk factors analyses that were published up until 2008 were nicely summarized by Pitout and Laupland.28 However, this was before the magnitude of the

What is the isolated impact of extended-spectrum β-lactamase acquisition on patients' clinical outcomes?

In a matched case–case-control analysis (ie, the preferred methodology to study the epidemiology of MDROs178, 179), patients with ESBL infections have been shown to experience worse clinical outcomes compared with patients with susceptible Enterobacteriaceae, and compared with uninfected controls.72, 79, 81, 180, 181, 182 In a metaanalysis looking at the impact of ESBL-production on mortality, comprising 16 studies conducted from 1996 to 2003, there was a significant rise in mortality among

Treatment options for extended-spectrum β-lactamases–producing Enterobacteriaceae infections in hospital settings

Despite being prevalent pathogens, both in hospital and community settings, no prospective randomized controlled trials have ever been conducted addressing the most efficacious therapy for ESBL-producing Enterobacteriaceae infections. The efficacy of some of the antimicrobial classes are reviewed in these sections.8

Treating extended-spectrum β-lactamase infections in ambulatory settings

ESBLs have become prevalent in “the community” of many regions worldwide, particularly since the spread of the ESBL-producing E coli ST131 strain.139, 149, 176 In ambulatory settings, DAAT is probably even more common than in acute care hospitals,8 and it probably impact patients’ outcomes, although controlled data on this issue are lacking.8 Some mild to moderate ESBL infections could probably be managed outside the hospital settings29, 222; however, oral therapeutics that possess potential

Future perspective

Antimicrobial resistance is a worldwide prevalent iatrogenic complication of modern medical care. ESBL-producing Enterobacteriaceaeare are one of the most common features of this complication. These infections are prevalent both in health care settings and in the community. Appropriate therapy is frequently delayed in these patients, who experience worse clinical outcomes as a result. Moreover, no prospective randomized controlled trials have ever been conducted in this field and there are

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  • Cited by (0)

    D. Marchaim had received in the past payments for lectures and a research grant from Merck (all not related to this paper).

    Funding: This study was not supported financially by any external source.

    Conflicts of Interest: No potential conflicts of interest.

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