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

Table 2 Preferred and alternative agents for multidrug-resistant pathogens in kidney transplant: Dosing, key toxicities, and transplant-specific caveats

Pathogen	Preferred agents	Alternative agents	Dosing/administration	Key toxicities and transplant caveats
Extended-spectrum beta-lactamase-Enterobacterales	Cystitis/pyelonephritis (if susceptible): Trimethoprim-sulfamethoxazole, ciprofloxacin, or levofloxacin. If resistant/toxic or non-urinary source: Ertapenem, meropenem, or imipenem-cilastatin	Pyelonephritis/complicated urinary tract infections: Aminoglycosides	Duration: Short course (6-10 days) may be comparable to longer courses (11-21 days) for complicated urinary tract infections	Aminoglycosides: Use restricted by potential nephrotoxicity. Step-down: Lack of oral options (due to fluoroquinolone/trimethoprim-sulfamethoxazole co-resistance) impedes shortening intravenous duration
Carbapenem-resistant Enterobacterales	Pyelonephritis: Ceftazidime-avibactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, cefiderocol. Klebsiella pneumoniae carbapenemase-producers: Meropenem-vaborbactam, ceftazidime-avibactam, imipenem-cilastatin-relebactam. MBL-producers (e.g., new Delhi metallo-β-lactamase): Ceftazidime-avibactam + aztreonam or cefiderocol (monotherapy)	Pyelonephritis/complicated urinary tract infections: Aminoglycosides. Klebsiella pneumoniae carbapenemase. Alternative: Cefiderocol		Nephrotoxicity: Polymyxins and aminoglycosides limited by nephrotoxicity. Novel agents (ceftazidime-avibactam, etc.) have low nephrotoxicity risk. Calcineurin inhibitor interactions: Novel agents have limited interaction with tacrolimus, but imipenem-relebactam + cyclosporine increases neurotoxicity risk
DTR Pseudomonas aeruginosa	Beta-lactam susceptible (non-carbapenem): Piperacillin-tazobactam, ceftazidime, cefepime, or aztreonam (preferred over carbapenems). Carbapenem-resistant (non-MBL): Ceftolozane-tazobactam (drug of choice if carbapenemase negative), ceftazidime-avibactam, imipenem-relebactam. MBL-producers: Cefiderocol	MBL-producers: Ceftazidime-avibactam + aztreonam; polymyxins (poor efficacy/toxicity); cefepime-zidebactam (salvage)	Traditional beta-lactams: High-dose extended-infusion suggested	Resistance: Pseudomonas aeruginosa can develop resistance during therapy; close monitoring required. Polymyxins: Poor data due to toxicity
Carbapenem-resistant Acinetobacter baumannii	Combination therapy: Sulbactam-durlobactam + carbapenem (imipenem-cilastatin or meropenem)	Alternative combination: High-dose ampicillin-sulbactam + at least one other agent (polymyxin B, minocycline, tigecycline, or cefiderocol)	Ampicillin-sulbactam: High-dose (total daily dose of 9 g sulbactam component)	Strategy: Combination therapy suggested due to limited single-agent data
Vancomycin-resistant Enterococci	Vancomycin-resistant Enterococci faecium urinary tract infection: Daptomycin monotherapy. Vancomycin-resistant Enterococci endocarditis: Daptomycin + ampicillin	In-vitro synergy (clinical efficacy to be explored): Fosfomycin + daptomycin or amoxicillin		Renal preservation: Daptomycin + ampicillin is an aminoglycoside-sparing therapy to protect renal function
Clostridioides difficile	Preferred: Oral vancomycin or fidaxomicin	Recurrent Clostridioides difficile infection: Fecal microbiota transplantation	Oral vancomycin: 125 mg four times daily	Fidaxomicin: Lower recurrence rate than vancomycin. Fecal microbiota transplantation: Efficacy/safety in solid organ transplant comparable to immunocompetent individuals
Methicillin-resistant Staphylococcus aureus	Preferred: Vancomycin	Alternatives: Daptomycin (if intolerance, persistent bacteremia, or minimum inhibitory concentration > 1 μg/mL); teicoplanin; ceftaroline; ceftobiprole	Vancomycin: Target serum trough 15-20 μg/mL. Continuous infusion preferred	Vancomycin: Continuous infusion reduces odds of acute kidney injury by 53%. Monitor area under the curve/minimum inhibitory concentration to reduce nephrotoxicity. Daptomycin: Monitor creatine kinase (myopathy risk). Novels: Ceftaroline/ceftobiprole have minimal interactions with calcineurin inhibitors

MBL: Metallo-β-lactamase.