Concise review for cliniciansEmerging Issues in Gram-Negative Bacterial Resistance: An Update for the Practicing Clinician
Section snippets
Why Should We Be Concerned?
Antimicrobial resistance should concern clinicians for several important reasons. First, treatment options are limited and sometimes nonexistent. Among the Enterobacteriaceae (eg, Escherichia coli, Klebsiella, and Enterobacter), the extended-spectrum β-lactamases (ESBLs) mediate resistance to the first- through fourth-generation cephalosporins. The more recently developed carbapenemases, such as Klebsiella pneumoniae carbapenemases (KPCs) and New Delhi metallo-β-lactamases (NDMs), also
What Are the Mechanisms of β-Lactam Resistance in GNB?
The mechanisms of resistance in GNB seem daunting, partly because of the alphabet soup and the somewhat arbitrary nature of β-lactamase nomenclature. A basic understanding, however, is necessary to appreciate the epidemiology, treatment options, and infection control implications. Several important definitions are reviewed in Table 1. The Ambler classification system classifies β-lactamases into 4 groups (class A, B, C, and D) on the basis of their amino acid sequences and their active site (
Why Are ESBL and CPGNB Often Resistant to Other (Non–β-Lactam) Drug Classes?
Plasmids encoding β-lactamases often carry other antibiotic-resistance genes, for example, enzymes that modify antibiotic targets (eg, ribosomal RNA methylation conferring high-level aminoglycoside resistance), or antibiotics themselves (eg, acetyltransferases modifying quinolones and aminoglycosides). Plasmids can also encode various efflux pumps that extrude not only β-lactams but also quinolones, aminoglycosides, and tetracyclines.16
Who Is at Risk for Acquiring Resistant GNB?
Risk factors for acquiring ESBL and CPGNB include prior and recent antibiotic use, residence in long-term acute care facilities, admission to an intensive care unit, presence of indwelling medical devices or wounds, poor functional status, increased age, solid organ or stem cell transplant, and receipt of health care in or travel to endemic areas.17 In addition, resistance to a particular antibiotic may not necessarily be associated with exposure to antibiotics from the same class but may
How Are Infections With Resistant GNB Diagnosed?
Diagnosis of infection is via culture of clinical specimens with bacterial identification and susceptibility testing. Most isolates have a susceptibility pattern with a typical ESBL or CPGNB phenotype (Table 3).19 Confirmatory testing for ESBL or carbapenemase production can be performed for infection control purposes but is not currently routinely recommended by the Clinical Laboratory Standards Institute. The CPGNB isolates may sometimes test susceptible (using clinical breakpoints) to one or
What Is the Optimal Treatment of Infections With Resistant GNB?
Definitive therapy should always be guided by susceptibility testing. Expert consultation with an infectious disease specialist is recommended. Carbapenems are the treatment of choice for invasive or high-inoculum infections caused by ESBL and AmpC producers. For CPGNB, treatment options are even more limited. Often the polymyxin (colistin or polymyxin B), tigecycline, and sometimes select aminoglycosides are the only active agents (Table 2 and Table 3). The polymyxins are limited by
How Are Resistant Gram-Negative Infections Prevented?
A proactive approach to combating antimicrobial resistance should take place on the prescriber and local level and on the regional or national and international level.
Conclusions
Antimicrobial resistance, in particular resistant GNB, is a formidable threat to human health. Although the climate for the development of novel, active agents against CPGNB has improved somewhat in recent years, and indeed several new agents are in the pipeline, these agents will most certainly not be a panacea. A holistic approach must be embraced, including continued health care professional education, attention to infection control, adoption of new technologies and algorithms in screening,
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