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388 Part V: Therapeutic Principles Chapter 24: Treatment of Infections in the Immunocompromised Host 389

TABLE 24–1. Coverage and Side Effects of Drugs Used as Empiric Therapy (Continued)
Drug Category Drug Brand Name Activity Toxicity
Echinocandin Caspofungin Cancidas Aspergillus, Candida, mucormycosis ‡
Micafungin Mycamine Aspergillus, Candida, mucormycosis ‡
Anidulafungin Eraxis Aspergillus, Candida, mucormycosis ‡
Oxazolidinone Linezolid Zyvox Staphylococci (including MRSA), Enterococ- Thrombocytopenia, anemia,
cus (including VRE), streptococci small risk of serotonin syndrome
with concomitant SSRIs, mito-
chondrial side effects with pro-
longed use
Lipopeptide Daptomycin Cubicin Staphylococci (including MRSA), Enterococ- Creatinine kinase elevation
cus (including VRE), streptococci

Ampho-B, amphotericin B; CHF, congestive heart failure; CMV, cytomegalovirus; HSV, herpes simplex virus; LFT, liver function test; SSRI, selective
serotonin reuptake inhibitor; VRE, vancomycin-resistant Enterococcus; VZV, varicella-zoster virus.
*Ceftazidime has less activity than cefepime against methicillin-sensitive Staphylococcus aureus and viridans streptococci.
† Levofloxacin has more reliable activity against viridans streptococci than ciprofloxacin.
‡ Echinocandins are commonly used in combination with amphotericin in the treatment of mucormycosis, but are not used as monotherapy.

with glucocorticoids. Cure is difficult to achieve regardless of the reg- in the prevention of bacterial infection during neutropenia. Instrumen-
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imen used and mortality is high. 101 tation should be avoided whenever possible. Intravenous access sites
Indwelling catheter infections are another important consider- should be carefully maintained. In addition, systemic antibiotics are
ation in persistent fever after hematologic recovery. Diagnosing catheter currently widely used as prophylaxis against Gram-negative infections
infections remains a major challenge, and the use of catheter-sparing in neutropenic patients.
diagnostic techniques should be considered, as the need to remove cath- The use of prophylactic antibiotics reduces the number of
eters is patient and organism dependent. Coagulase-negative Staphylo- Gram-negative infections and all-cause mortality in high-risk patients
coccus spp. are most commonly isolated and are generally amenable who are expected to have prolonged, severe neutropenia and is rec-
to catheter-sparing treatment. If the catheter is to be retained, a 10- to ommended in these patients. By contrast, the use of antibiotic pro-
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14-day course of antibiotics is recommended. If a tunnel infection is phylaxis in lower-risk patients expected to have a shorter duration of
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present, successful therapy is less likely without catheter removal. neutropenia is of much less certain benefit, and is not recommended
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Gram-negative, S. aureus, and fungal infections of the cath- in most cases. Several studies show a reduction in mortality in high-
eter usually necessitate its removal. This may be followed, if necessary, risk patients given prophylactic antibiotics, but the contribution of this
by insertion of a new catheter at a different site once blood cultures practice to the emergence of drug-resistant pathogens must be taken
have cleared. Antibiotic therapy for at least 14 days is recommended. into account when deciding whether to employ it. 112,113 Furthermore,
Chlorhexidine and silver-impregnated central venous catheters may although the agents used for this purpose are generally safe, the risk
prevent bloodstream infections in neutropenic patients. Catheter of drug toxicity must also be taken into consideration. Adverse events
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infections and their management are reviewed in detail elsewhere. 102 associated with antibiotic prophylaxis include drug fever, rash, and
worsening of cytopenias. Infection with C. difficile is a potentially seri-
OUTPATIENT THERAPY ous risk of prophylaxis. Incidence of C. difficile infection is high in
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Twenty years ago, treatment of the febrile neutropenic patient outside stem cell transplant recipients, and patients who receive high-risk anti-
of the hospital would have been unthinkable. Economic pressures, cou- biotics including fluoroquinolones more frequently acquire infection
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pled with the widespread availability of home infusion services and with this organism. This potential complication deserves strong con-
more potent oral antibiotics, have made outpatient therapy an option sideration, as drug-resistant, hypervirulent strains of this organism have
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for some of these patients. 107 become more prevalent over the last several years.
Outcomes among patients with neutropenic fever treated as outpa- The fluoroquinolones, particularly ciprofloxacin and levoflox-
tients seem to be comparable to those observed in hospitalized patients, acin, have received considerable attention for their ability to prevent
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provided the patients are selected properly and appropriate monitoring Gram-negative infections in neutropenic patients. Ciprofloxacin has
can be ensured. Suitable candidates for home therapy include patients more activity against Pseudomonas, whereas levofloxacin is more active
who are expected to have a short duration of neutropenia and who have against Gram-positive organisms. Unfortunately, indiscriminate use of
few comorbidities. 108,109 Individuals who remain febrile, who require these agents in the community, as well as prophylactic use, has led to
multiple antibiotics, or who are unreliable are not candidates for home a greatly increased prevalence of quinolone-resistant Gram-negative
therapy. Rigorous family education is crucial for a successful outcome. organisms. Up to 85 percent of Gram-negative isolates from patients with
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febrile neutropenia are resistant to quinolones, and quinolone prophy-
PREVENTION OF INFECTIONS laxis has resulted in an increased incidence of quinolone-resistant viri-
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dans streptococci. Prophylactic use also eliminates these agents from
Bacterial Infections therapeutic use in the same patient. For these reasons, some centers
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In view of the high mortality rate associated with infections in neutro- abandoned the use of prophylactic quinolones in certain patients. 120–122
penic patients, preventive measures remain a priority. Careful attention These studies consistently showed a decrease in fluoroquinolone resis-
to sterile technique and personal hygiene is of the utmost importance tance in isolates from neutropenic patients. While some studies have

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