Chest
Hospital-Acquired Infections: Realities of Risks and ResistanceEvolution and Clinical Importance of Extended-Spectrum β-Lactamases
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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CEPTAZ® [manufacturer's prescribing information]
FORTAZ® [manufacturer's prescribing information]
Cited by (37)
Treatment of severe infections caused by ESBL or carbapenemases-producing Enterobacteriaceae
2023, Medicina IntensivaExtended-spectrum β-lactamase-producing Enterobacteriaceae: an emerging public-health concern
2008, The Lancet Infectious DiseasesCitation Excerpt :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
Infectious pathogens, pathogenesis, antimicrobial therapy, antimicrobial resistance, and surveillance measures
2020, Antimicrobial Resistance: Opportunities and Challenges