From the Guidelines
In a patient with metastatic pancreatic cancer on chemotherapy presenting with persistent fever, lymphopenia, elevated liver enzymes (AST > 5x ALT), and high CRP, empiric antimicrobial therapy with fluconazole 400mg daily for possible candidiasis or voriconazole 6mg/kg IV q12h for two doses, then 4mg/kg IV q12h if Aspergillus is suspected, should be considered while awaiting results of an expanded infectious workup. The most likely possibilities include opportunistic infections such as fungal infections (particularly Candida or Aspergillus), viral infections (CMV, HSV, VZV), or Pneumocystis jirovecii pneumonia, as suggested by the NCCN guidelines for prevention and treatment of cancer-related infections 1. Next steps should include:
- Expanded infectious workup with fungal serologies (beta-D-glucan, galactomannan)
- Viral PCR panels for CMV, EBV, HSV, and respiratory viruses
- Consideration of bronchoscopy with bronchoalveolar lavage to evaluate for PJP or fungal pneumonia The lymphopenia increases susceptibility to these opportunistic infections, and the chemotherapy further compromises immune function, as noted in the guidelines for prevention and treatment of cancer-related infections 1. The elevated alkaline phosphatase likely reflects bone metastases rather than cholangitis, but biliary sources of infection should still be considered given the pancreatic primary, and a thorough medication review is essential to identify potential drug-induced fever or hepatotoxicity from the chemotherapy regimen, as recommended by the NCCN guidelines 1. Given the high CRP and negative initial cultures, it is crucial to consider empiric treatment for possible infections while awaiting further diagnostic results, as the patient's immune-compromised state puts them at high risk for severe infections, as discussed in the guidelines for prevention and treatment of cancer-related infections 1.
From the Research
Possible Infectious Etiologies
- Pseudomonas aeruginosa infection, as suggested by the elevated CRP and AST > 5x ALT, which may indicate liver involvement or sepsis 2
- Other bacterial infections, such as those caused by gram-negative bacilli or methicillin-resistant Staphylococcus aureus (MRSA), which are common in hospitalized patients with compromised immune systems 2
Next Steps in Work-up
- Consider empiric antibiotic therapy, taking into account the patient's history of chemotherapy and absolute lymphopenia, as well as the potential for antibiotic-resistant bacteria 2
- Choose an antibiotic regimen that covers Pseudomonas aeruginosa, such as piperacillin-tazobactam, ceftazidime, or carbapenems, and consider the optimal dosing strategy, such as extended or continuous infusion 3, 4, 5
- Monitor the patient's response to treatment and adjust the antibiotic regimen as needed, based on culture and susceptibility test results 2
- Investigate other potential sources of infection, such as the urinary tract or lungs, and consider additional diagnostic tests, such as imaging studies or biopsies, if necessary 2
Considerations for Antibiotic Therapy
- Piperacillin-tazobactam may be a suitable option for treating Pseudomonas aeruginosa infections, especially when used in an extended-infusion dosing strategy 3, 4
- Carbapenems may be associated with a higher risk of developing resistant P. aeruginosa, and therefore may not be the first choice for empiric therapy 5
- Ceftazidime or piperacillin-tazobactam may be preferred over carbapenems for treating susceptible P. aeruginosa infections, due to the potential for carbapenem resistance 5