Guidelines for the Initial Evaluation and Management of the Febrile Neutropenic Patient
ABSTRACT & COMMENTARY
Source: Hughes WT, et al. 1997 guidelines for the use of antimicrobial agents in neutropenic patients with unexplained fever. Clinics Infect Dis 1997;25:551-573.
The infectious disease society of america (IDSA) has just published new guidelines for the evaluation of fever in neutropenic cancer patients and has made recommendations for antimicrobial use in this high-risk population. These guidelines represent an update from the 1990 recommendations by the same organization. Given that these patients are often sent directly to the ED, it is imperative that the emergency physician realize and practice state-of-the-art initial management of this group.
The IDSA defined fever as a single oral temperature of higher than 38.3°C (101°F) or a temperature higher than 38.0°C (100.4°F) over at least one hour. Rectal thermometers should be avoided in these patients. Neutropenia was defined as a neutrophil count of less than 500 or less than 1000 with predicted decline to less than 500. At a minimum, the evaluation should include cultures of blood from peripheral and central catheter sites (at least two sets), cultures of skin lesions and diarrheal stools, chest radiograph, complete blood count, urinalysis (with urine culture sent if abnormal or patient symptomatic), electrolytes, renal function, and liver transaminases.
Patients with neutrophil counts less than or equal to 500 are at considerable risk for infection. With documented fever, 48-60% of this population will have an established or occult infection, and, in patients with neutrophil counts below 100, 16-20% will become bacteremic. Organisms most responsible for infection and bacteremia include aerobic Gram-positive cocci (in particular, coagulase-negative staphylococci, viridans streptococci, or S. aureus) and aerobic Gram-negative rods (E. coli, Klebsiella pneumoniae, or Pseudomonas aeruginosa). Careful search of the most commonly infected sites is required. These sites include the periodontium, pharynx, lower esophagus, perineum, anus, lung, bone marrow aspiration sites, the eye (funduscopic evaluation), tissue around the nails, and vascular catheter access sites. In the absence of visible disease, routine cultures of the throat, anus, nares, CSF, and urine are not recommended.
Antimicrobial therapy should be instituted empirically in the febrile neutropenic cancer patient; in the past, there was some controversy regarding use of mono vs. dual antibiotic therapy. The most recent literature suggests that monotherapy with ceftazidime or imipenem/cilastatin can be considered standard of care. Quinolones are not recommended for routine initial therapy. Dual therapy with an aminoglycoside plus an anti-pseudomonal penicillin offers some enhanced synergy but with the added risk of nephrotoxicity and ototoxicity.
It is important to recognize that the regimens above provide inadequate coverage of Gram-positive organisms, particularly in the era of growing antimicrobial resistance. If Gram-positive infection is suspectedfor example, a catheter or catheter-tunnel infection, or in the hypotensive patientempiric addition of vancomycin is recommended. The IDSA panel recommends vancomycin plus ceftazidime in this group of patients.
COMMENT BY KATHERINE L. HEILPERN, MD
The new IDSA guidelines are well-written and geared to the primary care physician and emergency physician. There is far more detail than I included in the abstract, but most of it pertains to the patient’s course once hospitalized. Of importance in the ED is recognition of these patients, prompt laboratory confirmation of the total neutrophil count, placement of the patient in an enclosed room away from other ill patients, a careful history, and a physical examination. Because of the paucity of actual and/or functioning white blood cells, pyuria may be absent and chest radiographs may not reveal an infiltrate. Even in the absence of fever, profoundly neutropenic patients (i.e., neutrophil counts < 500) with signs or symptoms suggesting infection should get a full work-up and empiric broad-spectrum antibiotics.
Cultures should be obtained quickly with the first dose of antibiotics instituted in the ED. This is not a time to wait for the routine admission orders. In a user-friendly fashion, the IDSA has also clarified the use of antimicrobials. Monotherapy with good antipseudomonal coverage is easy for both the practitioner and the patient. Empiric vancomycin should be reserved for patients on quinolone prophylaxis, those known to be colonized with resistant Gram-positive organisms, obvious catheter infection, severe mucositis, or hypotension. Febrile neutropenic patients may look less ill than they actually are and require our quick and accurate decision-making.
Reasonable empiric antibiotic coverage for the neutropenic cancer patient without an obvious source includes:
a. ciprofloxacin.
b. cefotaxime.
c. vancomycin.
d. ceftazidime.
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