Cancer Therapy Advisor: What is your strategy for narrowing antibiotic therapy?

Dr Walsh: The initial empiric regimen of antibacterials may be followed by drug-resistant bacterial pathogens and those who are on antifungal prophylaxis may experience coverage breakthrough, in which case liposomal amphotericin B may be added.

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Patients who have undergone HCT are also at risk for cytomegalovirus, influenza, adenovirus, and various others, all of which can cause significant morbidity and excess mortality. Antiviral agents include oseltamivir for influenza, prophylactic ganciclovir or valganciclovir for cytomegalovirus, and acyclovir as prophylaxis or treatment for herpes simplex virus and varicella zoster virus.

Cancer Therapy Advisor: What are some special considerations for patients with renal or hepatic impairment?

Dr Walsh: These patients are already particularly fragile physiologically. They are less likely to be able to tolerate the infection because of the related physiological reserve associated with renal impairment or hepatic insufficiency.

For patients with renal impairment, we need to pay especially close attention to the management of the renally cleared antimicrobial agents. In that setting, we have to do careful therapeutic drug monitoring. The classic situation would be if we are using aminoglycosides and vancomycin.

If we overestimate, we can cause more renal impairment; if we underestimate, we may not be able to treat the infection adequately. Expert understanding the pharmacokinetics of these agents is critical to treating the infection without further compromising the kidney.

Nephrotoxic agents like liposomal amphotericin B should also be avoided in patient with renal impairment and an azole antifungal would be used instead; if a patient has hepatic impairment, the converse would apply. Clinicians should also be aware of drug-drug interactions.

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The classic case for drug-drug interactions is for vincristine, which is commonly used in patients with lymphoma, and triazole antifungals. These agents inhibit the metabolism of vincristine through the cytochrome P450 system, leading to higher exposure and increased risk for toxicity.

Dr Walsh: For the individual patient that suffers from these infections, having a broad differential diagnosis and a heightened awareness of these uncommon but lethal infections is absolutely critical for they occur much more commonly in patients with cancer and hematologic malignancies.