On March 12, 2026, the global community marks the 21st World Kidney Day, with the theme “Kidney Health for All: Caring for People, Protecting the Planet.”
For patients with end-stage kidney disease, kidney transplantation represents a life-changing treatment that can restore quality of life and offer a “second chance.” However, transplantation success is only the beginning of a long journey. Lifelong immunosuppressive therapy—while essential for preventing rejection—also exposes recipients to a significant risk: infection.Infections have become the second leading cause of death after cardiovascular disease among kidney transplant recipients. Achieving a delicate balance between anti-rejection therapy and infection prevention to ensure long-term graft and patient survival remains a major challenge in clinical practice.
Major Challenges in Infection Prevention and Control in Kidney Transplant Recipients
1. A Unique Host: High Infection Risk Under Immunosuppression
Kidney transplant recipients require long-term use of immunosuppressive agents, including calcineurin inhibitors and antimetabolites, which suppress T-cell function and significantly reduce the body’s ability to clear pathogens such as bacteria, viruses, and fungi.
As a result, these patients are not only more susceptible to common infections but also at increased risk of opportunistic infections.
2. Complex Pathogens: Prevalence of Multidrug-Resistant Organisms
Multiple factors contribute to infection risk in kidney transplant recipients, including:
Donor-derived infections
High-dose immunosuppressive therapy
Use of broad-spectrum antibiotics
Invasive medical procedures
Infections in this population are characterized by bacterial pathogens as the predominant cause, followed by viral and fungal infections, as well as other opportunistic pathogens.
Kidney transplant recipients are also a high-risk group for Pneumocystis jirovecii pneumonia (PJP), particularly during the first six months after transplantation and following intensified anti-rejection therapy.
A German transplant cohort study reported that among 804 kidney transplant recipients, bacteria accounted for 66.4% of infections (645/972), followed by viruses (28.9%) and fungi (4.7%).
Among bacterial infections, Gram-negative bacteria predominated. The most common pathogens included:
Escherichia coli
Klebsiella pneumoniae
Pseudomonas aeruginosa
Acinetobacter species
In China, carbapenem resistance rates among transplant recipients are significantly higher than those observed in the general population.
Examples include:
Carbapenem-resistant Klebsiella pneumoniae: 39.7% (200/504)
Carbapenem-resistant E. coli: 6.1% (21/347)
Carbapenem-resistant Acinetobacter baumannii (CRAB): 59.9% (106/177)
Carbapenem-resistant Pseudomonas aeruginosa (CRPA): 35.5% (49/138)
Infections caused by multidrug-resistant (MDR) bacteria pose a serious threat, with mortality rates reaching up to 40.4%.
3. Diagnostic and Therapeutic Challenges
Immunosuppression often masks classical symptoms and inflammatory markers of infection, leading to delayed diagnosis.
Treatment decisions are also complicated by the need to consider:
Nephrotoxicity of anti-infective drugs
Drug interactions with immunosuppressants
Potential impact on graft function
These factors significantly narrow the therapeutic window for antimicrobial treatment.
Anti-Infective Treatment Strategies
Given the complexity of infections in kidney transplant recipients, a multilayered treatment strategy is required.
1. Rapid and Accurate Diagnosis
When severe infection caused by multidrug-resistant Gram-negative bacteria is suspected, guidelines recommend performing rapid pathogen identification and resistance enzyme detection alongside conventional culture and susceptibility testing.
Recent advances in rapid diagnostics include:
Multiplex polymerase chain reaction (PCR)
Metagenomic next-generation sequencing (mNGS)
Resistance mechanisms can also be identified through molecular and protein-based assays.
2. Precision Therapy Based on Resistance Mechanisms
According to the Chinese Clinical Guidelines for Multidrug-Resistant Bacterial Infections in Kidney Transplantation (2023), treatment strategies should be tailored according to resistance profiles.
ESBL-producing Enterobacterales (ESBL-E)
Severe infection: carbapenems preferred
Mild-to-moderate infection: β-lactam/β-lactamase inhibitor combinations
Carbapenem-resistant Enterobacterales (CRE)
Treatment depends on the type of carbapenemase:
KPC or OXA-48 positive:
first-line ceftazidime–avibactam
Metallo-β-lactamase (MBL) positive:
ceftazidime–avibactam + aztreonam
Alternative options may include:
Polymyxin-based combination therapy
Tigecycline or eravacycline (for non-bloodstream and non-UTI infections)
Multidrug-resistant Pseudomonas aeruginosa
If susceptible to non-carbapenem β-lactams, these agents are preferred and should be administered via prolonged infusion at high doses.
For difficult-to-treat resistant strains, ceftazidime–avibactam or polymyxin-based combination therapy may be used.
Carbapenem-resistant Acinetobacter baumannii (CRAB)
Recommended regimen:
High-dose sulbactam (6–9 g/day)
combined with at least one active agent such as:
Cefoperazone
Polymyxin B
Eravacycline
Tigecycline
Minocycline
Fosfomycin and rifampin are not recommended in CRAB combination therapy.
Stenotrophomonas maltophilia
Combination therapy with two agents is recommended, chosen from:
Minocycline / tigecycline / eravacycline
Levofloxacin
Trimethoprim-sulfamethoxazole (TMP-SMX)
MRSA (Methicillin-resistant Staphylococcus aureus)
Therapeutic options include:
Linezolid
Daptomycin
Vancomycin
Teicoplanin
These may be used alone or combined with agents such as fosfomycin or rifampin.
VRE (Vancomycin-resistant Enterococcus)
Recommended treatment includes:
Oxazolidinones
or
High-dose daptomycin
Nephrotoxicity Management
When antibiotics are used in kidney transplant recipients, clinicians must carefully balance benefits and risks, especially with nephrotoxic agents such as:
Aminoglycosides
Polymyxins
Vancomycin
Therapeutic drug monitoring should guide dosing whenever possible, while renal injury biomarkers (serum creatinine, urine protein, cystatin C) should be closely monitored.
Drug doses should be adjusted according to creatinine clearance or estimated glomerular filtration rate (eGFR).
Emerging Antimicrobial Agents
As antimicrobial resistance continues to rise, new antibiotics are becoming increasingly important.
In 2025, several new agents were approved in China, including:
Aztreonam–avibactam
Imipenem derivatives
Telavancin
In January 2026, the siderophore cephalosporin cefiderocol was approved in China for the treatment of complicated urinary tract infections (cUTI) caused by susceptible Gram-negative pathogens.
Cefiderocol: Mechanism and Antibacterial Spectrum
Cefiderocol uses a siderophore-mediated iron transport mechanism to penetrate the outer membrane of Gram-negative bacteria.
It demonstrates strong in vitro activity against carbapenem-resistant Gram-negative organisms, including:
Klebsiella pneumoniae
Escherichia coli
Pseudomonas aeruginosa
Acinetobacter baumannii
Stenotrophomonas maltophilia
Clinical Evidence
The APEKS-cUTI international multicenter trial demonstrated that cefiderocol achieved non-inferiority to imipenem–cilastatin in microbiological eradication and clinical response.
The CREDIBLE-CR study further confirmed its efficacy in infections caused by carbapenem-resistant pathogens.
A multicenter retrospective study (CEFI-ID) including 114 immunocompromised patients with multidrug-resistant Gram-negative infections—many with hematologic malignancies or solid organ transplants—also demonstrated promising outcomes.
Role in Empirical Therapy
A 2025 systematic review suggested that cefiderocol may be a promising option for empirical therapy in critically ill patients at high risk for MDR Gram-negative infections, due to its broad activity and stability against multiple β-lactamases.
This may be particularly relevant in kidney transplant recipients with a high risk of MDR infection.
Considerations in Clinical Use
Despite its promise, cefiderocol should be used cautiously. Key considerations include:
Uncertain optimal role in Acinetobacter infections
Potential emergence of resistance
Unclear preference for monotherapy versus combination therapy
Treatment decisions should therefore be guided by pathogen identification, resistance patterns, and local epidemiology.
Comprehensive Management Strategies
Effective infection prevention after kidney transplantation requires multidisciplinary management.
Individualized Immunosuppression
During infection treatment, clinicians must balance the risks of infection and rejection by adjusting immunosuppressive therapy appropriately.
Typically:
Reduce or discontinue antimetabolites first
Adjust calcineurin inhibitors under therapeutic monitoring
Carefully control corticosteroid dosage
Individualized Duration of Therapy
Urinary tract infections in kidney transplant recipients generally require longer treatment courses than in the general population.
For other infections, duration should be determined based on:
Clinical symptoms
Laboratory markers
Microbiological findings
Imaging results
Infection site
Immunosuppressive status
Emerging Therapies
Bacteriophage therapy remains under investigation but may provide a future option for refractory multidrug-resistant infections after transplantation.
Multidisciplinary Collaboration
Optimal management requires a multidisciplinary team including:
Transplant surgeons
Infectious disease specialists
Clinical pharmacists
Microbiologists
Nephrologists
Such collaboration ensures comprehensive, individualized care throughout the patient journey.
Conclusion
Preventing and managing infections after kidney transplantation is a complex clinical challenge requiring a careful balance between immunosuppression and infection control.
By integrating:
Rapid diagnostic technologies
Mechanism-based precision antimicrobial therapy
Individualized immunosuppression adjustment
Innovative treatment approaches
clinicians can better protect both graft function and patient survival, ultimately helping kidney transplant recipients achieve long-term, high-quality survival and advancing the vision of “Kidney Health for All.”
Prof. Lei Liu
