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This online tutorial series "Quality Improvement: Tool Time" reinforces practical application of tools and competencies acquired during the live activity. Each Tool is a combination of faculty commentary on essentials in clinical practice, links to relevant scientific publications, and a printable handout that will serve as a reminder. Please select the topic:
  1. Ensuring Quality of Care†
  2. †††††††††††††
  3. Optimizing Vancomycin for MRSA Infections
  4. ††††††
  5. Selecting Appropriate Therapy for ESBL- and KPC-Producers
  6. ††††††
  7. Dosing Strategies for MDR P. aeruginosa/A. baumannii Infections
  8. ††††††
  9. Adjusting Antimicrobial Regimens for Efficacy and Safety
  10. ††††††

Selecting Appropriate Therapy for ESBL- and KPC-Producers

ESBL-Producers
Extended-spectrum β-lactamase-producing Enterobacteriaceae (namely Klebsiella pneumoniae and Escherichia coli) present a growing challenge in hospitals as they exhibit resistance to penicillins, cephalosporins, and monobactams. They are commonly resistant to other antimicrobial classes as well, including fluoroquinolones and aminoglycosides. Infections caused by ESBL-producing bacteria are associated with a greater length of stay, hospital costs, and mortality.[1]

Dr. Richard Drew discusses . . .

Treatment Strategies for Infections due to ESBL-Producing Enterobacteriaceae [2,3]
Carbapenems
  • Preferred agents (almost uniform in vitro susceptibility)
  • Clinical experience: extensive
  • Resistance: rare, though multiple mechanisms identified
Tigecycline
  • Clinical data: limited
  • Breakpoints: not established for ESBL-producers
  • Urinary penetration: limited
3rd-generation cephalosporins

Avoid as monotherapy for confirmed
ESBL-producers

Cefepime and piperacillin/tazobactam

Unreliable

Aminoglycosides and fluoroquinolones
  • Resistance: higher likelihood
  • Some gentamicin-susceptible strains resistant to tobramycin/amikacin

KPC-Producers
KPC-producing Enterobacteriaceae (also known as carbapenemase-resistant Enterobacteriaceae, or CRE) represent the latest in the evolution of β-lactam resistance. They exhibit resistance to the carbapenemsóconsidered the last line of defense against these pathogens. Another concern is that carbapenemase-resistance genes are commonly present on plasmids that are easily transferable between bacterial species. KPC-producing bacteria, first evident on the US East coast, are gradually spreading across the US. Hospitals will have to take special precautions to isolate and prevent the spread of this dangerous pathogen. [4]

Optimal treatment for infections caused by KPC-producing bacteria is largely unknown. Some agents have shown limited success, though no agent has consistently demonstrated the ability to attain successful outcomes. [2,3]

Dr. Richard Drew discusses . . .

Treatment Strategies for Infections due to KPC-producing Enterobacteriaceae [2,3]
Tigecycline
  • Not active against P. aeruginosa
  • Clinical data: limited
  • Concerns: low serum concentrations, adverse events
Colistin
  • Optimal dosing: unknown
  • Clinical data: limited
  • Concerns: neurotoxicity and nephrotoxicity
Aminoglycosides
  • Data primarily with combination therapy
  • Concern: nephrotoxicity
  • Serum concentration monitoring: needed
Ampicillin-sulbactam
  • β-lactamase inhibitor component active against select strains; not active against KPC-3
  • Optimal dosing: unknown

References

  1. SchwaberMJ, Navon-Venezia S, Kaye KS, Ben-Ami R, Schwartz D, Carmeli Y. Clinical and economic impact of bacteremia with extended-spectrum-β-lactamase-producing Enterobacteriaceae. Antimicrob Agents Chemother. 2006;50:1257-1262. Click here for complete article
  2. Paterson DL, Bonomo RA. Extended-spectrum β-lactamases: a clinical update. Clin Microbiol Rev. 2005;18:657-686. Click here for complete article
  3. American Thoracic Society and Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005;171:388-416. Click here for complete article
  4. Centers for Disease Control and Prevention. Guidance for control of infections with carbapenem-resistant or carbapenemase-producing Enterobacteriaceae in acute care facilities. MMWR. 2009;58:256-260. Click here for complete article

Suggested Reading
Sidjabat HE, Silveira FP, Potoski BA, et al. Interspecies spread of Klebsiella pneumoniae carbapenemase gene in a single patient. Clin Infect Dis. 2009;49:1736-1738. Click here for abstract
This case study report illustrates the ability of carbapenem-resistance genes to transfer between bacterial species and spread resistance. A 44-year-old transplant recipient experienced multiple episodes of tissue rejection and infection and was eventually admitted to the hospital for bacteremia. Over a 5-month period, 5 ertapenem-resistant isolates involving 3 different bacterial species were identified. Molecular analysis revealed that the gene originated in K. pneumoniae and then transferred to E. coli and finally S. marcescens. The MICs were typically above 32 μg/mL for each carbapenem tested.

Kohner PC, Robberts FJ, Cockerill FR III, Patel R. Cephalosporin MIC distribution of extended-spectrum-β-lactamase- and pAmpC-producing Escherichia coli and Klebsiella species. J Clin Microbiol. 2009;47:2419-2425. Click here for complete article
This study determined the MICs of several cephalosporins for 264 isolates of K. pneumoniae and E. coli. Many isolates determined to be ESBL-producers were susceptible to cephalosporins based on the standard CLSI breakpoints. This study was used to support the lowering of cephalosporin breakpoints to prevent the use of a cephalosporin for infections caused by ESBL-producing bacteria.

Munoz-Price LS, Hayden MK, Lolans K, et al. Successful control of an outbreak of Klebsiella pneumoniae carbapenemase-producing K. pneumoniae at a long-term acute care hospital. Infect Control Hosp Epidemiol. 2010;31:341-347.
Click here for abstract

This article describes the effectiveness of an infection control intervention bundle for preventing the horizontal spread of KPC-producing K. pneumoniae during an outbreak at a long-term acute care facility. Prior to implementation of the bundle approach, a point prevalence screen showed that 21% of the patients (8 of 39) were colonized with KPC-producing bacteria. The interventions included daily 2% chlorhexidine gluconate baths for patients, enhanced environmental cleaning, surveillance cultures at admission, serial point prevalence cultures, isolation precautions, and training of personnel. Following the implementation of the bundle, the prevalence of KPC-producing organisms was reduced to 0%.