Treating infections that caused by Carbapenem-resistant Enterobacteriaceae (CRE)

 Treating infections caused by Carbapenem-resistant Enterobacteriaceae (CRE) presents significant challenges due to limited treatment options and the potential for adverse outcomes. CRE are Gram-negative bacteria that have acquired resistance to carbapenem antibiotics, which are often considered last-line therapies for multidrug-resistant infections. Here's an overview of the treatment strategies for CRE infections, along with relevant references:

  1. Antibiotic Susceptibility Testing:

    • Antibiotic susceptibility testing is essential to guide treatment decisions for CRE infections. Testing helps identify which antibiotics are still effective against the specific strain of CRE.
    • Reference: Tamma, P. D., & Simner, P. J. (2018). Phenotypic detection of carbapenemase-producing organisms from clinical isolates. Journal of Clinical Microbiology, 56(11), e01140-18.

  2. Combination Therapy:

    • Combination antibiotic therapy, using two or more antibiotics with synergistic activity against CRE, is often recommended to improve treatment efficacy and reduce the risk of resistance development.
    • Combinations may include agents such as polymyxins (colistin or polymyxin B), tigecycline, aminoglycosides, and newer β-lactam/β-lactamase inhibitor combinations (e.g., ceftazidime-avibactam).
    • Reference: Tzouvelekis, L. S., Markogiannakis, A., Psichogiou, M., Tassios, P. T., & Daikos, G. L. (2012). Carbapenemases in Klebsiella pneumoniae and other Enterobacteriaceae: an evolving crisis of global dimensions. Clinical Microbiology Reviews, 25(4), 682-707.

  3. Polymyxin Therapy:

    • Polymyxins (colistin or polymyxin B) are often used as last-resort treatments for CRE infections. They disrupt the bacterial cell membrane and are effective against many multidrug-resistant Gram-negative bacteria, including CRE.
    • However, polymyxin therapy is associated with significant nephrotoxicity and neurotoxicity, limiting its use to severe or refractory infections.
    • Reference: Nation, R. L., Li, J., Cars, O., Couet, W., Dudley, M. N., Kaye, K. S., ... & Tsuji, B. T. (2015). Framework for optimisation of the clinical use of colistin and polymyxin B: the Prato polymyxin consensus. The Lancet Infectious Diseases, 15(2), 225-234.

  4. Tigecycline Therapy:

    • Tigecycline, a glycylcycline antibiotic, is often used as part of combination therapy for CRE infections. It has broad-spectrum activity against many multidrug-resistant organisms, including CRE.
    • However, tigecycline has limitations, including reduced efficacy in bloodstream infections and concerns about increased mortality rates.
    • Reference: Doi, Y., Potoski, B. A., Adams-Haduch, J. M., Sidjabat, H. E., Pasculle, A. W., & Paterson, D. L. (2008). Simple disk-based method for detection of Klebsiella pneumoniae carbapenemase-type β-lactamase by use of a boronic acid compound. Journal of Clinical Microbiology, 46(12), 4083-4086.

  5. Novel Agents and Combination Regimens:

    • Research efforts are focused on developing novel antibiotics and combination regimens to combat CRE infections. This includes exploring alternative β-lactam/β-lactamase inhibitor combinations, novel siderophore-conjugated antibiotics, and other innovative approaches.
    • Clinical trials are underway to evaluate the efficacy and safety of new antibiotics and combination therapies for CRE infections.
    • Reference: Bassetti, M., Peghin, M., & Pecori, D. (2017). The management of multidrug-resistant Enterobacteriaceae. Current Opinion in Infectious Diseases, 30(6), 666-675.

  6. Infection Control Measures:

    • In addition to antibiotic therapy, implementing strict infection control measures, including hand hygiene, contact precautions, environmental cleaning, and surveillance cultures, is essential to prevent the spread of CRE within healthcare facilities.
    • Reference: Schwaber, M. J., & Carmeli, Y. (2017). An ongoing national intervention to contain the spread of carbapenem-resistant Enterobacteriaceae. Clinical Infectious Diseases, 68(3), 341-346.

Treating infections caused by Carbapenem-resistant Enterobacteriaceae requires a multifaceted approach that includes antibiotic stewardship, combination therapy, infection control measures, and ongoing research into novel treatment options. Collaboration among healthcare providers, researchers, and policymakers is essential for effective management of CRE infections and reducing the spread of antimicrobial resistance

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