Is it time to move away from polymyxins?: evidence and alternatives
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REVIEW
Is it time to move away from polymyxins?: evidence and alternatives Rajeev Soman 1 & Yamuna Devi Bakthavatchalam 2 & Abinaya Nadarajan 3 & Hariharan Triplicane Dwarakanathan 4 & Ramasubramanian Venkatasubramanian 5 & Balaji Veeraraghavan 2 Received: 5 August 2020 / Accepted: 25 September 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Increasing burden of carbapenem resistance and resultant difficult-to-treat infections are of particular concern due to the lack of effective and safe treatment options. More recently, several new agents with activity against certain multidrug-resistant (MDR) and extensive drug-resistant (XDR) Gram-negative pathogens have been approved for clinical use. These include ceftazidimeavibactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, plazomicin, and cefiderocol. For the management of MBL infections, clinically used triple combination comprising ceftazidime-avibactam and aztreonam is hindered due to nonavailability of antimicrobial susceptibility testing methods and lack of information on potential drug-drug interaction leading to PK changes impacting its safety and efficacy. Moreover, in several countries including Indian subcontinent and developing countries, these new agents are yet to be made available. Under these circumstances, polymyxins are the only last resort for the treatment of carbapenem-resistant infections. With the recent evidence of suboptimal PK/PD particularly in lung environment, limited efficacy and increased nephrotoxicity associated with polymyxin use, the Clinical and Laboratory Standards Institute (CLSI) has revised both colistin and polymyxin B breakpoints. Thus, polymyxins ‘intermediate’ breakpoint for Enterobacterales, P. aeruginosa, and Acinetobacter spp. are now set at ≤ 2 mg/L, implying limited clinical efficacy even for isolates with the MIC value 2 mg/L. This change has questioned the dependency on polymyxins in treating XDR infections. In this context, recently approved cefiderocol and phase 3 stage combination drug cefepime-zidebactam assume greater significance due to their potential to act as polymyxin-supplanting therapies. Keywords Carbapenem . Colistin . Polymyxin B . Cefiderocol . Cefepime-zidebactam
Introduction Antimicrobial resistance, especially in clinically important Gram-negative pathogens, has reached a critical level, with the emergence of resistance to almost all the available antibiotics. Gram-negative resistance is generally mediated by betalactamases, target site modifications, efflux pumps, or decreased permeability due to porin channel mutations. Very
* Balaji Veeraraghavan [email protected] 1
Department of Infectious Diseases, Jupiter Hospital, Pune, India
2
Department of Clinical Microbiology, Christian Medical College, Vellore, Tamil Nadu 632 004, India
3
Department of Surgery, Christian Medical College, Vellore, India
4
Department of Orthopaedics, Christian Medical College, Vellore, India
5
Department of Infectious Diseases, Apollo Hospitals, Chennai, India
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