Medication Summary
Because patients with neutropenic enterocolitis have often received numerous courses of antibiotics previously for other indications, a specific agent or regimen cannot be recommended, and the decision must be made on an individual basis. However, a few possible choices of antibiotics and antifungals are listed below. The author favors a combination of amikacin plus imipenem or cefepime/ceftazidime plus metronidazole in addition to vancomycin.
Consider adding antifungal agents if clinical improvement does not occur with antibiotics.
Antibiotics
Class Summary
Empiric broad-spectrum antibiotics are recommended to cover potential primary or secondary infectious causes of neutropenic enterocolitis and to control sepsis. The antibiotics should cover aerobic and anaerobic enteric organisms, including Clostridium species, because anecdotal reports reveal an association between Clostridium septicum and neutropenic enterocolitis.
Metronidazole (Flagyl)
Synthetic antibacterial with good activity against gram-negative anaerobes, including Bacteroides species, and gram-positive anaerobes, including Clostridium species.
Cefepime (Maxipime)
Fourth-generation cephalosporin with good gram-negative coverage. Similar to third-generation cephalosporins but has better gram-positive coverage. Covers pseudomonads.
Ceftazidime (Ceptaz, Fortaz)
Semisynthetic, broad-spectrum, third-generation cephalosporin covering predominantly gram-negative aerobes, including pseudomonads. Provides poor coverage against gram-positive organisms and anaerobes.
Ceftriaxone (Rocephin)
Semisynthetic, broad-spectrum, third-generation cephalosporin covering gram-negative aerobes and anaerobes, including Bacteroides and Clostridium species. Not reliable for coverage against pseudomonads.
Ticarcillin and clavulanate (Timentin)
Antipseudomonal penicillin plus beta-lactamase inhibitor that provides coverage against most gram-positive organisms, most gram-negative organisms, and most anaerobes.
Piperacillin and tazobactam (Zosyn)
Antipseudomonal penicillin plus beta-lactamase inhibitor. Inhibits biosynthesis of cell wall mucopeptide and is effective during the stage of active multiplication.
Vancomycin (Vancocin, Lyphocin)
Tricyclic glycopeptide indicated for the treatment of suspected or confirmed serious infection with methicillin-resistant staphylococci, an entity not uncommonly observed in patients who are severely ill and in the intensive care setting.
To avoid toxicity, the current recommendation is to assay vancomycin trough levels after the third dose, drawn 0.5 h before the next dosing. Use creatinine clearance to adjust dose in patients diagnosed with renal impairment.
Imipenem and cilastatin (Primaxin)
Potent broad-spectrum combination antibiotic consisting of a thienamycin class of antibiotic and cilastatin, which is an inhibitor of renal dipeptidase. Coverage includes gram-negative aerobes and anaerobes.
Amikacin (Amikin)
For gram-negative bacterial coverage of infections resistant to gentamicin and tobramycin. Effective against Pseudomonas aeruginosa.
Irreversibly binds to the 30S subunit of bacterial ribosomes. Blocks the recognition step in protein synthesis and causes growth inhibition. Use the patient's IBW (ideal body weight) for dosage calculation.
Gentamicin (Garamycin)
Water-soluble aminoglycoside antibiotic with good coverage against gram-negative aerobes. Used in conjunction with other antibiotics for broad-spectrum coverage in intra-abdominal infections. Coadministration with carbenicillin or piperacillin provides synergistic effects against most strains of Pseudomonas aeruginosa. Follow each regimen by at least a trough level drawn on the third or fourth dose (0.5 h before dosing). May draw a peak level 0.5 h after 30-min infusion.
Tobramycin (Nebcin)
Used in bone and skin structure infections caused by Staphylococcus aureus, P aeruginosa, Proteus species, Escherichia coli, Klebsiella species, and Enterobacter species. Indicated in the treatment of staphylococcal infections when penicillin or potentially less toxic drugs are contraindicated and when bacterial susceptibility and clinical judgment justifies its use.
Antifungal Agents
Class Summary
Consider adding antifungal agents if no clinical improvement occurs with broad-spectrum antibiotics. Amphotericin B is the preferred agent because non-albicans candidemia is more likely to be present and is usually fluconazole resistant. Consider liposomal amphotericin B if the infection is refractory to conventional amphotericin or in patients with renal failure.
Amphotericin B (Amphocil, Fungizone)
Produced by a strain of Streptomyces nodosus. Can be fungistatic or fungicidal. Binds to sterols, such as ergosterol, in the fungal cell membrane, causing intracellular components to leak, with subsequent fungal cell death.
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Neutropenic enterocolitis. Ulcerative oral mucositis lesion on the lateral and ventral surfaces of the tongue.
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Neutropenic enterocolitis. Colonic pseudomembranes of pseudomembranous colitis. Photographs courtesy of Eric M. Osgard, MD.
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Neutropenic enterocolitis. Frontal abdominal radiograph in a patient with proved pseudomembranous colitis. Note the nodular haustral thickening, most pronounced in the transverse colon.
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Neutropenic enterocolitis. Perforated appendicitis with abscess; computed tomography scan. Note the appendicolith (arrow) and air within the abscess. The terminal ileum lies anterior to the appendiceal abscess, and inflammatory change is noted in its wall, which appears thickened (open arrow).
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Neutropenic enterocolitis. Plain abdominal radiograph in a 44-year-old man known to have a long history of ulcerative colitis. The patient presented with an acute exacerbation of symptoms. Image shows thumbprinting in the region of the splenic flexure of the colon.
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Typhlitis. Marked asymmetric cecal wall thickening (arrow) in a 64-year-old patient whose status is postchemotherapy for lymphoma.
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Typhlitis. Marked circumferential cecal and ascending colon wall thickening (large arrows) with mild pericolonic inflammatory stranding (small arrows).
