Should Keytruda Be Held With Infections?
Keytruda (pembrolizumab) should be temporarily discontinued during active infections until clinical resolution is achieved, particularly when systemic immunosuppression (corticosteroids) is required for immune-related adverse events, as this combination significantly increases opportunistic infection risk.
Risk of Infections During Pembrolizumab Therapy
Infections occur in approximately 45.7% of patients receiving pembrolizumab-based therapies for NSCLC, with 14.8% experiencing two or more infections during treatment 1.
Infected patients demonstrate significantly worse outcomes, including increased ED visits (33.3% vs. 19.7%), hospitalizations (78.4% vs. 40.1%), ICU admissions (23.4% vs. 3.8%), and reduced median overall survival (11.53 vs. 21.03 months) compared to non-infected patients 1.
Patients requiring anti-infective therapy at ICI initiation have a 3.32-fold increased risk of subsequent infections (OR 3.32,95% CI: 1.26-8.76) 1.
When to Hold Pembrolizumab
Active Bacterial Infections
Temporarily discontinue pembrolizumab during active bacterial infections until symptom resolution 2.
Maintain dosing during prophylactic antibiotic therapy, but hold during active treatment of documented infections 2.
For patients with moderate to severe infections, particularly those requiring hospitalization or ICU admission, pembrolizumab should be withheld until clinical improvement is documented 1.
Opportunistic Infections During Immunosuppression
When treating immune-related adverse events (particularly pneumonitis) with high-dose corticosteroids, maintain heightened suspicion for opportunistic infections including nocardiosis, which can develop rapidly in this setting 3.
A documented case of severe pulmonary nocardiosis occurred in a patient treated with high-dose corticosteroids for pembrolizumab-associated pneumonitis, requiring ECMO support 3.
The combination of ICI therapy plus corticosteroid treatment for immune-related adverse events creates dual immunosuppression, substantially elevating infection risk beyond either agent alone 3.
Fungal Infections
Temporarily discontinue pembrolizumab during active fungal infections until symptom resolution 2.
Resume therapy only after appropriate antifungal treatment has been initiated and clinical improvement documented 2.
Viral Infections
For COVID-19: Temporarily discontinue until clinical resolution together with RT-PCR clearance 2.
For influenza: Hold therapy if confirmed infection present; treat according to standard guidelines before resuming 2.
For herpes zoster reactivation: Discontinue if patient experiences reactivation; resume after appropriate antiviral therapy and clinical improvement 2.
When Pembrolizumab Can Be Maintained
Continue pembrolizumab during prophylactic antimicrobial therapy without active infection 2.
Patients receiving trimethoprim-sulfamethoxazole prophylaxis for Pneumocystis jirovecii can continue pembrolizumab without interruption 2.
During treatment of asymptomatic microbial colonization (not active infection), pembrolizumab may be continued 2.
Criteria for Resuming Therapy
Clinical resolution of infection symptoms (fever resolution, normalization of vital signs, improvement in inflammatory markers) 2.
Completion of appropriate antimicrobial therapy course or transition to suppressive therapy if indicated 2.
For severe infections requiring ICU admission, ensure hemodynamic stability and resolution of organ dysfunction before restarting 1.
Document negative cultures or appropriate microbiologic clearance when applicable (particularly for COVID-19, tuberculosis, or other specific pathogens requiring clearance documentation) 2.
Special Considerations
Immune-Related Adverse Events Mimicking Infection
Cytokine release syndrome (CRS) can occur even more than two years after pembrolizumab initiation, presenting with fever and severe fatigue that mimics infection 4.
When fever and systemic symptoms occur without clear infectious source despite thorough workup (imaging, cultures), consider immune-related CRS as differential diagnosis 4.
CRS responds to corticosteroids (prednisolone 1 mg/kg/day), whereas continuing antibiotics alone without addressing the immune-mediated component leads to clinical deterioration 4.
Prophylaxis Recommendations
Universal Pneumocystis jirovecii prophylaxis is recommended for all patients on pembrolizumab with trimethoprim-sulfamethoxazole, dapsone, or atovaquone 2.
Screen for latent tuberculosis, hepatitis B/C, and consider helminthic infection screening in patients from endemic regions before initiating therapy 2.
Ensure influenza and COVID-19 vaccination of patients and close contacts 2.
Common Pitfalls to Avoid
Failing to distinguish between immune-related adverse events and true infections: Both can present with fever, constitutional symptoms, and radiographic abnormalities 4, 3.
Continuing pembrolizumab during active infection treatment, particularly when concurrent immunosuppression is required, substantially increases morbidity and mortality risk 3, 1.
Inadequate infectious workup before initiating corticosteroids for presumed immune-related adverse events: This can mask underlying infections and lead to rapid progression of opportunistic pathogens 3.
Resuming pembrolizumab too early before adequate antimicrobial therapy and clinical stabilization, risking infection recurrence or progression 2.
Not recognizing that patients with ECOG >1 at ICI initiation have 5.79-fold increased infection risk (OR 5.79,95% CI: 1.72-19.47), warranting more aggressive infection prevention strategies 1.