What is the recommended treatment approach for efflux pump-mediated colistin resistance in Klebsiella?

From the Guidelines

The recommended treatment approach for efflux pump-mediated colistin resistance in Klebsiella typically involves combination therapy rather than monotherapy, with a common strategy being the use of colistin in combination with other antimicrobials such as carbapenems or tigecycline. This approach is supported by recent guidelines and studies, including those from the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) 1. The use of combination therapy is thought to be beneficial in targeting multiple bacterial mechanisms simultaneously, thereby increasing the chances of successful treatment.

Some key considerations in the treatment of efflux pump-mediated colistin resistance in Klebsiella include:

• The use of colistin in combination with other antimicrobials, such as carbapenems (e.g. meropenem 1g IV every 8 hours) or tigecycline (e.g. 100mg IV loading dose followed by 50mg IV every 12 hours) 1
• The potential addition of efflux pump inhibitors, such as phenylalanine-arginine beta-naphthylamide (PAβN), to restore colistin susceptibility by blocking the efflux pumps
• The importance of regular monitoring of renal function during treatment due to colistin's nephrotoxicity potential 1
• The need for antimicrobial susceptibility testing to guide the final selection of antibiotics and ensure optimal efficacy against the specific resistant strain

It is worth noting that the evidence for specific combination therapies is still limited, and more research is needed to determine the most effective approaches for treating efflux pump-mediated colistin resistance in Klebsiella. However, based on current guidelines and studies, combination therapy with colistin and other antimicrobials appears to be a reasonable approach, with the specific choice of antibiotics depending on the individual patient's circumstances and the results of antimicrobial susceptibility testing 1.

From the Research

Efflux Pump-Mediated Colistin Resistance in Klebsiella

• Efflux pump-mediated colistin resistance is a significant concern in the treatment of Klebsiella pneumoniae infections, as it can lead to reduced susceptibility to colistin, a last-resort antibiotic 2, 3.
• Studies have identified several mechanisms contributing to colistin resistance in Klebsiella pneumoniae, including the overexpression of efflux pumps, such as the RND-type efflux pump H239_3064 3.
• The CrrB protein has been shown to play a crucial role in regulating the expression of efflux pumps, including H239_3064, and mutations in the crrB gene can lead to increased colistin resistance 2, 3.
• Combination therapy with antibiotics other than colistin and carbapenems may be an effective approach to treating infections caused by colistin-resistant Klebsiella pneumoniae, particularly in patients with septic shock 4.

Treatment Approaches

• The combination of colistin and tigecycline has been shown to be effective against extended-spectrum β-lactamase-producing Klebsiella pneumoniae isolates, including those with carbapenem resistance 5.
• However, the use of colistin in combination with other antibiotics, such as carbapenems, may not be effective against colistin-resistant Klebsiella pneumoniae, and alternative combination therapies should be considered 4.
• Efflux pump inhibitors may be a potential therapeutic strategy to combat efflux pump-mediated colistin resistance in Klebsiella pneumoniae, although further research is needed to explore this approach.

Prevalence and Epidemiology

• Efflux pump-mediated colistin resistance has been reported in diverse clones of Klebsiella pneumoniae from various environments, including aquatic environments 6.
• The prevalence of efflux pump-mediated colistin resistance in Klebsiella pneumoniae is a concern, as it can limit the effectiveness of colistin as a treatment option for infections caused by this bacterium 2, 3.