Emerging therapies and diagnostic innovations for multidrug-resistant infections in kidney allograft recipients: Challenges and future directions

Abstract

Multidrug-resistant (MDR) bacterial infections are a major cause of morbidity, mortality, and graft loss in kidney transplant recipients, who are particularly vulnerable due to intensive immunosuppression, frequent healthcare exposure, and recurrent antibiotic use. The rising prevalence of resistance among key uropathogens and bloodstream isolates has outpaced the development and uptake of transplant-specific diagnostic and therapeutic strategies. This mini-review synthesizes contemporary evidence on MDR gram-negative and gram-positive infections in kidney allograft recipients, focusing on extended-spectrum beta-lactamase-producing Enterobacterales, carbapenem-resistant Enterobacterales, difficult-to-treat Pseudomonas aeruginosa, carbapenem-resistant Acinetobacter baumannii, vancomycin-resistant Enterococci, methicillin-resistant Staphylococcus aureus, and Clostridioides difficile infection. We outline epidemiology, risk factors, and clinical impacts on patient and graft outcomes, including the association of recurrent urinary tract infection and MDR bloodstream infection with reduced estimated glomerular filtration rate, increased hospitalization, and higher death-censored graft failure. The article highlights advances in rapid molecular diagnostics (such as polymerase chain reaction, matrix-assisted laser desorption/ionization-time of flight, and syndromic panels) that shorten time to organism and resistance detection, enabling earlier optimization and de-escalation of antimicrobial therapy. Emerging agents - including novel beta-lactam/beta-lactamase inhibitor combinations, siderophore cephalosporins, and investigational boronate beta-lactamase inhibitors - are discussed, emphasizing nephrotoxicity profiles, drug-drug interactions with calcineurin inhibitors, and evidence gaps in transplant populations. We also review the evolving roles of phage therapy, monoclonal antibodies, vaccines, and therapeutic drug monitoring (including area under the curve/minimum inhibitory concentration-guided vancomycin dosing and cautious reuse of aminoglycosides) in this high-risk cohort. Finally, we propose a pragmatic stewardship framework tailored to kidney transplant units, integrating individualized perioperative prophylaxis, avoidance of unnecessary treatment of asymptomatic bacteriuria, early device removal, and minimization of broad-spectrum exposure to limit MDR selection and Clostridioides difficile infection. A transplant-specific approach that combines rapid diagnostics, rational deployment of new antimicrobials, and rigorous stewardship is essential to improve survival and preserve allograft function in the era of MDR infections after kidney transplantation.

Keywords: Kidney transplantation; Multidrug-resistant bacterial infections; Kidney allograft recipients; Urinary tract infection; Bloodstream infection; Antimicrobial stewardship; Novel antimicrobial agents; Molecular rapid diagnostics; Therapeutic drug monitoring

Core Tip: Multidrug-resistant bacterial infections are now a leading threat to survival and long-term graft function after kidney transplantation. This mini-review synthesizes current data on multidrug-resistant epidemiology, risk factors, and outcomes in kidney transplant recipients, and highlights emerging tools, such as rapid molecular diagnostics, novel β-lactam/β-lactamase inhibitor combinations, siderophore cephalosporins, and individualized perioperative antibiotic strategies. A kidney transplant-specific antimicrobial stewardship framework is proposed to balance timely, effective therapy with preservation of allograft function and containment of resistance.