Chest
Volume 119, Issue 2, Supplement, February 2001, Pages 391S-396S
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Hospital-Acquired Infections: Realities of Risks and Resistance
Evolution and Clinical Importance of Extended-Spectrum β-Lactamases

https://doi.org/10.1378/chest.119.2_suppl.391SGet rights and content

In the process of evolution, bacteria have acquired well-developed mechanisms of resistance to an extensive array of hostile substances. This time-tempered system of defense is so intricate and adaptable that contemporary medicine has been hard-pressed to maintain an advantage. In this article, the processes responsible for bacterial resistance to extended-spectrum cephalosporins are reviewed. Particular emphasis is placed on the extended-spectrum β-lactamases that have emerged to provide bacteria with formidable resistance to modern drugs. Avoidance of this problem requires limitations on extended-spectrum cephalosporin usage. While carbapenems are clearly the treatment of choice for infections caused by these pathogens, empirical use of β-lactam/β-lactamase inhibitors such as piperacillin/tazobactam has been associated with reduction in the prevalence of cephalosporin resistance.

Section snippets

β-Lactam Resistance

Beginning with the introduction of penicillin half a century ago, the β-lactams have remained the largest antibiotic class of clinical relevance, comprising four major families: the penicillins, cephalosporins, carbapenems, and monobactams.45 These antibiotic classes continue to be the objects of directed chemical modifications in order to modulate their antimicrobial activity (Fig 1).

Three principal mechanisms cause resistance to β-lactams6: (1) a reduction in the affinity of the drug targets

Origin of Extended-Spectrum β-Lactamases

ESBLs find their origins in genes that are already present in many bacteria. Approximately 25 to 30% of E coli, for instance, are resistant to ampicillin, in most cases as a result of their possessing a plasmid carrying the TEM-1 β-lactamase gene.14 Similarly, one study suggests that virtually all Klebsiella species carry an SHV-1-like β-lactamase gene on their chromosome.15 Various mechanisms, whether involving alterations in the promoter or translocation of the gene to a plasmid, can mediate

Treatment of K pneumoniae Outbreaks

The literature dealing with responses to ESBL-expressing K pneumoniae is not extensive, but from several documented accounts, a definite pattern is beginning to emerge. While there is evidence that these organisms can spread from hospital to hospital (making infection-control measures relevant to their containment), their emergence is first and foremost a response to the use of antibiotics (specifically, extended-spectrum cephalosporins such as ceftazidime and ceftriaxone).17 Consequently, an

Dr. Joseph Lynch

How often do plasmid-mediated resistances get transferred to other Enterobacteriaceae besides K pneumoniae? How widespread is fluoroquinolone resistance, and is it increasing?

Dr. Louis Rice

There are many plasmids capable of being transferred. In vitro, they are readily transferred to E coli and many other species. While Klebsiella is by far the most common source, they have also been found in E coli, as well as species of Proteus, Salmonella, Serratia, and Enterobacter. The fluoroquinolone correlation

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  • Cited by (37)

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      Several studies have noted a reduction in clinical effect against ESBL-producing bacteria with some β-lactam agents despite testing susceptible in vitro, whereas other studies have shown good clinical outcome with β-lactam–β-lactamase-inhibitor combinations.13,51 This is widely believed to occur as a result of the so-called inoculum effect that occurs when the minimum inhibitory concentration of the antibiotic rises (ie, the antibiotic looses activity) with the increasing size of the inoculum (or number) of bacteria tested.52 This effect has been described for cephalosporins, β-lactam–β-lactamase-inhibitor combinations (eg, piperacillin-tazobactam), and to a lesser extent with the quinolones.53

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