Preventing Antimicrobial Complications, Ensuring Stewardship in Cancer Care

This week, infectious disease specialists from different organizations are meeting in San Francisco for ID Week, an annual conference focused on many different infectious disease topics and their intersection with cancer, HIV, respiratory diseases, and more.

Read about the FDA's initiative to develop new antibiotics.

The purpose of the AML study was to evaluate whether IV anti-pseudomonal (IVPSA) antibiotics could be safely de-escalated or discontinued in high-risk AML patients with febrile neutropenia (FN) following implementation of a guideline.¹

Two abstracts presented results about what is needed to prevent complications in cancer care, one about patients with acute myeloid leukemia (AML) with prolonged neutropenia, and one examining the frequency of antimicrobial complications following initiation of palliative chemotherapy.

FN is among the most serious clinical complications in patients with cancer who are undergoing chemotherapy. Patients with neutropenia, or low neutrophil counts, are predisposed to serious and life-threatening infections because of their immune system’s impaired ability to mount inflammatory responses to bacteria, fungi, and yeast. Because fever is often the only sign of infection, the presence of both fever and neutropenia must be treated as a medical emergency. Mortality rates in patients with cancer and FN can range from 5% to 20%.

The Infectious Disease Society of America and the National Comprehensive Cancer Network guidelines recommend continuing IVPSA therapy until neutrophil recovery (ie, an absolute neutrophil count > 500 cells/mm³) is achieved in high-risk patients with AML and FN. The authors of the abstract wrote that the current practice should be re-evaluated given the emergence of multidrug resistant organisms and high rates of Clostridium difficile infection (CDI) in this population.

In their single-center, pre-post quasi-experimental study, 93 patients with AML receiving induction chemotherapy hospitalized between September 2015 to February 2018 were compared to a historical cohort of patients admitted before implementation of the guideline. The primary outcome was the incidence of suspected or documented bacterial infection after antibiotic de-escalation in the intervention group (or meeting criteria for de-escalation in the historical control group).

Secondary outcomes included the incidence of CDI, IVPSA Days of Therapy (DOTs), hospital length of stay (LOS), and mortality. Patients in the intervention group were evaluated for antibiotic de-escalation on day 5 of FN and antibiotics were discontinued if patients were afebrile, hemodynamically stable, and without evidence of infection irrespective of their ANC (or de-escalated to fluoroquinolone prophylaxis in relapsed/refractory disease).

In clinically stable patients with suspected or documented bacterial infection, antibiotics were continued for a defined duration per indication as outlined in the guideline.

Patients in the intervention group had similar clinical outcomes and lower rates of CDI and IVPSA DOTs. In high-risk AML patients with FN, an antibiotic de-escalation guideline reduced the incidence of CDI and IVPSA antibiotic DOTs without adversely affecting clinical outcomes, the authors wrote.

In another study, the authors identified patients with advanced cancer patients aged ≥ 65 years started on palliative chemotherapy from January 2016 to September 2017 at Yale New Haven Hospital. Complications with and without antimicrobials were assessed during first hospitalizations until death or March 2018. Differences were compared with x² tests.

Of 2680 patients started on palliative chemotherapy, 1181 had ≥1 hospitalization. Median age was 74 years and 856 (72%) had solid tumors. Median time to hospitalization from starting palliative chemotherapy was 77 days (range 1 to 580) and length of stay was 4 days (range 1 to 50).

During first hospitalization, 158 (13%) died or were discharged to hospice. Overall, 493 (42%) died. Palliative chemotherapy often included FOLFIRINOX (n=257), FOLFOX (n=239), or pembrolizumab (n=210). During first hospitalizations, patients given antimicrobials more likely incurred nephrotoxicity, hepatotoxicity, or C. difficile infection within 7 days of use than patients not given antimicrobials.

The authors wrote that antimicrobial complications are common in advanced cancer patients on palliative chemotherapy. and that increased stewardship and alignment of infection treatment with goals of care are needed.

References

1 Alegria W, Marini BL, Perissinotti AJ, Bixby D, Gregg K, Nagel J. Febrile Neutropenia antibiotic de-escalation study in acute myeloid leukemia patients with prolonged neutropenia. Presented at ID Week 2018; October 4, 2018; San Francisco, California. Abstract 253.

2 Datta R, Doyle M, Quagliarello V, Sanft T, Juthani-Mehta M. Frequency of antimicrobial complications following initiation of palliative chemotherapy in advanced cancer patients. Presented at ID Week 2018; October 4, 2018; San Francisco, California. Abstract 249.