Page 879 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

610 PART 5: Infectious Disorders

TABLE 68-3 Antimicrobial Therapy Used for Therapy in Febrile Neutropenic Patients β-Lactam Antibiotics Typical Dosing
β-Lactam Antibiotics Typical Dosing Voriconazole 6 mg/kg IV q12 h day 1, then 4 mg/kg q12 h IV,
Ticarcillin + clavulanic acid 200-300 mg/kg per day IV in 4-6 divided doses or 200-300 mg PO q12 h
Piperacillin + tazobactam 200-300 mg/kg per day IV in 3-4 divided doses Posaconazole 200 mg q8 h PO
Cefoperazone 2 g q12 h IV Echinocandin antifungal agents
Ceftriaxone 2 g q24 h IV Caspofungin 70 mg IV day 1, then 50 mg per day IV
Ceftazidime 2 g q8 h IV Micafungin 100 mg q24 h IV
Anidulafungin 200 mg IV day 1, then 100 mg q24 h IV
Cefepime 2 g q8 h IV
Other antifungal agents
Imipenem/cilastatin 500 mg q6 h IV
5-Fluorocytosine 150 mg/kg per day PO in 4 divided doses
Meropenem 1 g q8h IV
Terbinafine 250 mg q8 h PO
Aminoglycosides
HSV, herpes simplex virus; IV, intravenously; kg, kilogram; PO, orally; TMP-SMX, trimethoprim-sulfa-
Gentamicin 1.5-2 mg/kg q8 h IV
methoxazole; VZV, varicella-zoster virus.
Netilmicin 1.5-2.0 mg/kg q8 h IV
Tobramycin 1.5-2 mg/kg q8 h IV
β-lactam antibacterial agent was designed to provide a broad spectrum
Amikacin 7.5 mg/kg q12 h IV of antibacterial activity, achieve bactericidal serum concentrations, exert
Fluoroquinolones a synergistic antibacterial effect, and prevent emergence of resistance.
Ciprofloxacin 400 mg q12 h IV Such combinations have been recommended in the published guide-
lines by the Infectious Diseases Society of America, 65,120,136 the National
500-750 mg q12 h PO Comprehensive Cancer Network, 205,206 and the Infectious Diseases
118
Levofloxacin 500-750 mg q24 h PO/IV Working Party of the German Society of Hematology and Oncology
207
Norfloxacin 400 mg q12 h PO but not the Spanish guidelines. The choice of aminoglycoside must be
based on bacterial susceptibility patterns, availability of serum amino-
Moxifloxacin 400 mg Q12 h PO/IV glycoside concentration monitoring, and drug cost.
Macrolides A large randomized controlled trial (N = 733) compared piperacillin/
116
Erythromycin 0.5-1.0 g q6 h IV tazobactam to piperacillin/tazobactam plus amikacin. The primary
outcome was defervescence of all signs and symptoms of infection
Azithromycin 500 mg IV/PO day 1, then 250 mg IV/PO q24 h
without modification of the initial antibacterial regimen. Response
Glycopeptides was observed in 49% monotherapy versus 53% combination recipients
Vancomycin 1.0 g q12 h IV or 30 mg/kg IV q24 h (p = 0.2). The response rates in single pathogen gram-positive bactere-
mias were low (27% and 32%, respectively) because of the high propor-
Teicoplanin 800 mg IV day 1, then 400 mg IV q24 h
tion of coagulase-negative staphylococcal bacteremias. In contrast, the
Dalbavancin 1 g IV day 1, then 500 mg IV q7days response rates for streptococcal and enterococcal bacteremias between
Other antibacterial agents the two groups were significantly higher (60% and 71%, respectively,
p = 0.7). The response rates for single gram-negative bacteremias were
TMP-SMX 10-20 mg/50-100 mg/kg per day in also similar (36% and 34%, respectively; p = 0.9). The aminoglycoside
4 divided doses
failed to enhance the response rates in any circumstance. The overall
Metronidazole 500 mg q8 h IV/PO mortalities in the monotherapy and combination therapy groups were
Linezolid 600 mg q12 h IV/PO 4% and 6%, respectively (p = 0.2).
Two systematic reviews of the literature have examined the safety
Daptomycin 4-6 mg/kg/24 hours IV
and efficacy of β-lactam plus aminoglycoside combinations in febrile
Antiviral agents neutropenic patients in comparison to monotherapy. 160,208 Furno et al
Acyclovir HSV: 400 mg 5 times daily, or 5 mg/kg q8 h IV reviewed 4795 heterogeneously treated febrile neutropenic episodes
from 29 randomized controlled clinical trials comparing monotherapy
VZV: 800 mg 5 times daily PO, or 10 mg/kg q8 h IV
(ceftazidime, 9 trials; cefepime, 2 trials; cefoperazone, 1 trial; imipenem/
Valacyclovir HSV: 500 mg q12 h PO cilastatin, 9 trials; meropenem, 4 trials; ciprofloxacin, 2 trials; ofloxacin,
VZV: 1000 mg q8 h PO 2 trials) and aminoglycoside-based combination therapy. The pooled
odds ratios for overall treatment failure and for treatment failure in
Famciclovir HSV: 500 mg q12 h PO
bloodstream infections were significant at 0.88 and 0.70, respectively,
VZV: 750 mg q24 h or 500 mg q12 h PO demonstrating fewer failures in the monotherapy groups. Paul et al
160
Ganciclovir 5 mg/kg q12 h IV examined 7807 febrile neutropenic patients entered into 47 randomized
controlled trials comparing β-lactam monotherapy to β-lactam plus
Valganciclovir 900 mg q12 h PO
aminoglycoside combination therapy. The main outcome was overall
208
Polyene antifungal agents mortality. While there was no significant difference in overall mortal-
Amphotericin B deoxycholate 0.5-1.0 mg/kg per day IV ity (7.8% vs 9.1% for monotherapy and combination therapy, respec-
tively; RR 0.85; p = 0.08), there were fewer failures among β-lactam
Amphotericin B lipid complex 5 mg/kg per day IV
monotherapy recipients. Monotherapy recipients had fewer adverse
208
Liposomal amphotericin B 3-5 mg/kg per day IV events overall and less nephrotoxicity. On the basis of these analyses,
208
Triazole antifungal agents β-lactam plus aminoglycoside combinations appear to offer no advan-
Fluconazole 200-400 mg IV/PO q day tages over broad-spectrum β-lactam-based monotherapy. Further, the
combination regimens present significant disadvantages with respect to
Itraconazole 200-400 mg PO q day
toxicity and costs related to drug monitoring and administration.

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