Antimicrobial Agents in Neutropenic Cancer Patients 

Updated: Jul 27, 2017
  • Author: Alexandre Chan, PharmD, MPH, FCCP, BCPS, BCOP; more...
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Recommendations

Guidelines for the use of antimicrobial agents in neutropenic cancer patients have been issued by the following organizations:

  • Infectious Disease Society of America (IDSA) [1]
  • American Society of Clinical Oncology (ASCO) [2]

Infectious Disease Society of America

IDSA recommendations for risk assessment are as follows:

  • Risk stratification is required to determine the management of patients with fever and neutropenia
  • The Multinational Association for Supportive Care in Cancer (MASCC) scoring system can be used for a formal assessment of risk; a MASCC score <21 indicates high risk
  • Results of risk assessment should guide decisions on the route of antibiotic therapy (oral vs. IV), its duration, and the choice of inpatient or outpatient care

Widely accepted indications of high risk include either or both of the following:

  • Chemotherapy-related neutropenia that is expected to be prolonged (duration >7 days) and profound (absolute neutrophil count [ANC] <100 cells/μL
  • Significant medical  co-morbid  conditions (eg, hypotension, pneumonia, new-onset abdominal pain, neurologic changes)

Patients at low risk include those whose period of neutropenia is anticipated to last 7 days or less or who have no or few co-morbidities

Recommended tests and procedures for the initial assessment include the following:

  • Complete blood cell count (CBC) with differential
  • Serum creatinine and blood urea nitrogen (BUN)
  • Electrolyte levels
  • Hepatic transaminase enzymes
  • Total bilirubin
  • At least two sets of blood cultures
  • Cultures from suspected infection sites
  • Chest radiograph in patients with respiratory manifestations

IDSA recommendations for prophylaxis are as follows:

  • Antibiotic prophylaxis is not routinely recommended for low-risk patients who are expected to remain neutropenic for <7 days
  • Fluoroquinolone prophylaxis should be considered for high-risk patients if the ANC is expected to be ≤100/μL for longer than 7 days
  • Of the fluoroquinolines, levofloxacin and ciprofloxacin have been most extensively evaluated and are considered largely equivalent, but levofloxacin is preferred for patients at increased risk for oral mucositis-related invasive viridans  group streptococcal infection
  • Candida prophylaxis should be given to all patients at substantial risk (eg, those undergoing induction chemotherapy for acute leukemia or allogeneic hematopoietic stem cell transplantation [HSCT]); fluconazole, itraconazole, voriconazole, posaconazole, micafungin, and  caspofungin are all equally preferred agents
  • Herpes simplex virus (HSV)–seropositive patients should receive acyclovir prophylaxis
  • Yearly influenza vaccination with inactivated vaccine is recommended
  • Myeloid colony-stimulating factors should be considered for patients at ≥20% risk for fever and neutropenia

IDSA recommendations for treatment are as follows:

  • All patients with fever and neutropenia should be given immediate empiric antibiotic therapy that covers both gram-positive and gram-negative pathogens
  • An oral fluoroquinolone plus amoxicillin/clavulanate (or clindamycin, for those with penicillin allergy) should be given for empiric therapy unless fluoroquinolone prophylaxis was used before fever developed
  • Vancomycin or other agents active against aerobic gram-positive cocci are not recommended as part of the initial antibiotic regimen except for specific clinical indications (eg, suspected catheter-related infection, skin or soft-tissue infection, pneumonia, hemodynamic instability)
  • Selected low-risk patients may be treated as outpatients and/or with oral antibiotics
  • High-risk patients require inpatient treatment with an IV anti-pseudomonal β-lactam agent (eg, cefepime), a carbapenem (meropenem or imipenem-cilastatin), or piperacillin-tazobactam for empiric antibiotic therapy
  • Afebrile neutropenic patients who have symptoms suggestive of infection should be treated as high-risk patients
  • Antibiotic treatment should continue for at least the duration of neutropenia (until ANC exceeds 500 cells/μL), or longer if clinically necessary
  • Empirical antifungal coverage should be considered in high-risk patients with no identified fever source who have persistent fever after 4–7 days of broad-spectrum antibiotics

Additions to initial empirical therapy may be considered for patients at risk for infection with antibiotic-resistant organisms, as follows:

  • Methicillin-resistant Staphylococcus aureus (MRSA) – Vancomycin, linezolid, or
  • daptomycin
  • Vancomycin-resistant enterococcus (VRE) –  Linezolid or daptomycin
  • Extended-spectrum beta-lactamase (ESBL)–producing gram-negative bacteria – A carbepenem
  • Carbapenemase-producing  organisms (eg, Klebsiella pneumoniae carbapenemase [KPC]) – polymyxin-colistin  or tigecycline

American Society of Clinical Oncology

In 2012, ASCO also released guidelines for antimicrobial prophylaxis and outpatient management of fever and neutropenia in adult cancer patients. On topics where the ASCO and IDSA guidelines overlap, there are no significant differences between the two organizations’ recommendations. The ASCO guidelines include the following additional recommendation [2] :

  • No evidence of clinical benefit has been found for footwear exchange, protected environments, respiratory or surgical masks, neutropenic diet, or nutritional supplements