Typhlitis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Synonyms and keywords: neutropenic colitis; neutropenic enterocolitis; cecitis

Overview

Typhlitis occurs in neutropenic patients undergoing treatment for a malignancy, most frequently patients with acute leukemia who are receiving chemotherapy. It has also been reported in patients with aplastic anemia, lymphoma, or acquired immunodeficiency syndrome and after kidney transplantation. Typhlitis is characterized by edema and inflammation of the cecum, the ascending colon, and sometimes the terminal ileum. The inflammation can be so severe that transmural necrosis, perforation, and death can result. The mechanism of the condition is not known, but it is probably due to a combination of ischemia, infection (especially with cytomegalovirus), mucosal hemorrhage, and perhaps neoplastic infiltration. Treatment consists of bowel rest, total parenteral nutrition, antibiotics, and aggressive fluid and electrolyte replacement.

CT

• Cecal distention and circumferential thickening of the cecal wall
• Inflammatory stranding of the adjacent mesenteric fat is a common finding.
• Detection of complications such as pneumatosis, pneumoperitoneum, and pericolic fluid collections is important because they indicate a need for urgent surgical management.

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Causes

Life Threatening Causes

Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated.

Causes by Organ System

Cardiovascular	No underlying causes
Chemical/Poisoning	No underlying causes
Dental	No underlying causes
Dermatologic	No underlying causes
Drug Side Effect	Doxorubicin Hydrochloride, Sulfasalazine
Ear Nose Throat	No underlying causes
Endocrine	No underlying causes
Environmental	No underlying causes
Gastroenterologic	No underlying causes
Genetic	No underlying causes
Hematologic	No underlying causes
Iatrogenic	No underlying causes
Infectious Disease	No underlying causes
Musculoskeletal/Orthopedic	No underlying causes
Neurologic	No underlying causes
Nutritional/Metabolic	No underlying causes
Obstetric/Gynecologic	No underlying causes
Oncologic	No underlying causes
Ophthalmologic	No underlying causes
Overdose/Toxicity	No underlying causes
Psychiatric	No underlying causes
Pulmonary	No underlying causes
Renal/Electrolyte	No underlying causes
Rheumatology/Immunology/Allergy	No underlying causes
Sexual	No underlying causes
Trauma	No underlying causes
Urologic	No underlying causes
Miscellaneous	No underlying causes

Causes in Alphabetical Order

• Clofarabine
• Doxorubicin Hydrochloride

Treatment

Medical Therapy

• 1. Community-acquired infection in adults

• 1.1. Mild-to-moderate severity (perforated or abscessed appendicitis and other infections of mild-to-moderate severity):

• 1.1.1. Single agent:

• Preferred regimen (1): Cefoxitin 2 g IV q6h
• Preferred regimen (2): Ertapenem 1 g IV q24h
• Preferred regimen (3): Moxifloxacin 400 mg IV q24h
• Preferred regimen (4): Tigecycline 100 mg initial dose, THEN 50 mg IV q12h
• Preferred regimen (5): Ticarcillin-clavulanic acid 3.1 g IV q6h; FDA labeling indicates 200 mg/kg/day in divided doses every 6 h for moderate infection

• 1.1.2. Combination:

• Preferred regimen (1): Cefazolin 1–2 g IV q8h AND Metronidazole 500 mg IV q8–12 h OR 1500 mg q24h
• Preferred regimen (2): Cefuroxime 1.5 g IV q8h AND Metronidazole 500 mg IV q8–12 h OR 1500 mg q24h
• Preferred regimen (3): Ceftriaxone 1–2 g IV q12–24 h AND Metronidazole 500 mg IV q8–12 h OR 1500 mg q24h
• Preferred regimen (4): Cefotaxime 1–2 g IV q6–8 h AND Metronidazole 500 mg IV q8–12 h OR 1500 mg q24h
• Preferred regimen (5): Ciprofloxacin 400 mg IV q12h AND Metronidazole 500 mg IV q8–12 h OR 1500 mg q24h
• Preferred regimen (6): Levofloxacin 750 mg IV q24h AND Metronidazole 500 mg IV q8–12 h OR 1500 mg q24h

• 1.2. High risk or severity (severe physiologic disturbance, advanced age, or immunocompromised state):

• 1.2.1. Single agent:

• Preferred regimen (1): Imipenem-cilastatin 500 mg IV q6h OR 1 g q8h
• Preferred regimen (2): Meropenem 1 g IV q8h
• Preferred regimen (3): Doripenem 500 mg IV q8h
• Preferred regimen (4): Piperacillin-tazobactam 3.375 g IV q6h

• 1.2.2. Combination:

• Preferred regimen (1): Cefepime 2 g q8–12 h AND Metronidazole 500 mg IV q8–12 h or 1500 mg q24h
• Preferred regimen (2): Ceftazidime 2 g q8h AND Metronidazole 500 mg IV q8–12 h or 1500 mg q24h
• Preferred regimen (3): Ciprofloxacin 400 mg q12h AND Metronidazole 500 mg IV q8–12 h or 1500 mg q24h
• Preferred regimen (4): Levofloxacin 750 mg q24h AND Metronidazole 500 mg IV q8–12 h or 1500 mg q24h
• Note: Antimicrobial therapy of established infection should be limited to 4–7 days, unless it is difficult to achieve adequate source control. Longer durations of therapy have not been associated with improved outcome.

• 2. Health Care–Associated Complicated Intra-abdominal Infection

• 2.1. Less than 20% Resistant Pseudomonas aeruginosa, Extended-spectrum B-lactamase-producing Enterobacteriaceae, Acinetobacter, or other multidrug resistant gram-negative bacilli:

• Preferred regimen (1): Meropenem 1 g IV q8h AND Piperacillin-tazobactam 3.375 g IV q6h AND Ceftazidime 2 g IV q8h AND Metronidazole 500 mg q8–12 h or 1500 mg q24h
• Preferred regimen (2): Imipenem-cilastatin 500 mg IV 6 h OR 1 g q8h AND Piperacillin-tazobactam 3.375 g IV q6h AND Ceftazidime 2 g IV q8h AND Metronidazole 500 mg IV q8–12 h or 1500 mg q24h
• Preferred regimen (3): Doripenem 500 mg IV q8h AND Piperacillin-tazobactam 3.375 g IV q6h AND Ceftazidime 2 g IV q8h AND Metronidazole 500 mg IV every 8–12 h or 1500 mg q24h
• Preferred regimen (4): Meropenem 1 g IV q8h AND Piperacillin-tazobactam 3.375 g IV q6h AND Cefepime 2 g IV q8–12 h AND Metronidazole 500 mg q8–12 h or 1500 mg q24h
• Preferred regimen (5): Imipenem-cilastatin 500 mg IV q6h OR 1 g q8h AND Piperacillin-tazobactam 3.375 g IV q6h AND Cefepime 2 g IV q8–12 h AND Metronidazole 500 mg IV q8–12 h or 1500 mg q24h
• Preferred regimen (6): Doripenem 500 mg IV q8h AND Piperacillin-tazobactam 3.375 g IV q6h AND Cefepime 2 g IV q8–12 h AND Metronidazole 500 mg IV q8–12 h or 1500 mg q24h

• 2.2. Extended-spectrum B-lactamase-producing Enterobacteriaceae:

• Preferred regimen (1): Meropenem 1 g IV q8h AND Piperacillin-tazobactam 3.375 g IV q6h AND Gentamicin 5–7 mg/kg IV q24h
• Preferred regimen (2): Meropenem 1 g IV q8h AND Piperacillin-tazobactam 3.375 g IV q6h AND Tobramycin 5–7 mg/kg IV q24h
• Preferred regimen (3): Meropenem 1 g IV q8h AND Piperacillin-tazobactam 3.375 g IV q6h AND Amikacin 15–20 mg/kg IV q24h
• Preferred regimen (4): Imipenem-cilastatin 500 mg IV q6h OR 1 g q8h AND Piperacillin-tazobactam 3.375 g IV q6h AND Gentamicin 5–7 mg/kg IV q24h
• Preferred regimen (5): Imipenem-cilastatin 500 mg IV q6h OR 1 g q8h AND Piperacillin-tazobactam 3.375 g IV q6h AND Tobramycin 5–7 mg/kg IV q24h
• Preferred regimen (6): Imipenem-cilastatin 500 mg IV q6h OR 1 g q8h AND Piperacillin-tazobactam 3.375 g IV q6h AND Amikacin 15–20 mg/kg IV q24h
• Preferred regimen (7): Doripenem 500 mg IV q8h AND Piperacillin-tazobactam 3.375 g IV q6h AND Gentamicin 5–7 mg/kg IV q24h
• Preferred regimen (8): Doripenem 500 mg IV q8h AND Piperacillin-tazobactam 3.375 g IV q6h AND Tobramycin 5–7 mg/kg IV q24h
• Preferred regimen (9): Doripenem 500 mg IV q8h AND Piperacillin-tazobactam 3.375 g IV q6h AND Amikacin 15–20 mg/kg IV q24h

• 2.3. Pseudomonas aeruginosa with more than 20% resistant to ceftazidime:

• Preferred regimen (1): Meropenem 1 g IV q8h AND Piperacillin-tazobactam 3.375 g IV q6h AND Gentamicin 5–7 mg/kg IV q24h
• Preferred regimen (2): Meropenem 1 g IV q8h AND Piperacillin-tazobactam 3.375 g IV q6h AND Tobramycin 5–7 mg/kg IV q24h
• Preferred regimen (3): Meropenem 1 g IV q8h AND Piperacillin-tazobactam 3.375 g IV q6h AND Amikacin 15–20 mg/kg IV q24h
• Preferred regimen (4): Imipenem-cilastatin 500 mg IV q6h OR 1 g q8h AND Piperacillin-tazobactam 3.375 g IV q6h AND Gentamicin 5–7 mg/kg IV q24h
• Preferred regimen (5): Imipenem-cilastatin 500 mg IV q6h OR 1 g q8h AND Piperacillin-tazobactam 3.375 g IV q6h AND Tobramycin 5–7 mg/kg IV q24h
• Preferred regimen (6): Imipenem-cilastatin 500 mg IV q6h OR 1 g q8h AND Piperacillin-tazobactam 3.375 g IV q6h AND Amikacin 15–20 mg/kg IV q24h
• Preferred regimen (7): Doripenem 500 mg IV q8h AND Piperacillin-tazobactam 3.375 g IV q6h AND Gentamicin 5–7 mg/kg IV q24h
• Preferred regimen (8): Doripenem 500 mg IV q8h AND Piperacillin-tazobactam 3.375 g IV q6h AND Tobramycin 5–7 mg/kg IV q24h
• Preferred regimen (9): Doripenem 500 mg IV q8h AND Piperacillin-tazobactam 3.375 g IV q6h AND Amikacin 15–20 mg/kg IV q24h

• 2.4.Methicillin-resistant Staphylococcus aureus (MRSA):

• Preferred regimen: Vancomycin 15–20 mg/kg IV q8–12 h
• Note: Antimicrobial therapy of established infection should be limited to 4–7 days, unless it is difficult to achieve adequate source control. Longer durations of therapy have not been associated with improved outcome.

• 3. Community-acquired infection in pediatric patients

• 3.1. Single agent:

• Preferred regimen (1): Ertapenem 3 months to 12 years 15 mg/kg bid (not to exceed 1 g/day) Every 12 h, older than 13 years 1 g/day Every 24 h OR
• Preferred regimen (2): Meropenem 60 mg/kg/day q8h
• Preferred regimen (3): Imipenem-cilastatin 60–100 mg/kg/day IV q6h
• Preferred regimen (4): Ticarcillin-clavulanate 200–300 mg/kg/day IV of ticarcillin component q4–6 h
• Preferred regimen (5): Piperacillin-tazobactam 200–300 mg/kg/day IV of piperacillin component q6–8 h

• 3.2.Combination:

• Preferred regimen(1): Ceftriaxone 50–75 mg/kg/day q12–24 h, AND Metronidazole 30–40 mg/kg/day q8h
• Preferred regimen(2): Cefotaxime 150–200 mg/kg/day q6–8 h, AND Metronidazole 30–40 mg/kg/day q8h
• Preferred regimen(3): Cefepime 100 mg/kg/day q12h, AND Metronidazole 30–40 mg/kg/day q8h
• Preferred regimen(4): Ceftazidime 150 mg/kg/day q8 h, AND Metronidazole 30–40 mg/kg/day q8h
• Preferred regimen(5): Gentamicin 3–7.5 mg/kg/day q2–4 h, AND Metronidazole 30–40 mg/kg/day q8h ± Ampicillin 200 mg/kg/day q6h
• Preferred regimen(6): Gentamicin 3–7.5 mg/kg/day q2–4 h, AND Clindamycin 20–40 mg/kg/day q6–8 h ± Ampicillin 200 mg/kg/day q6h
• Preferred regimen(7): Tobramycin 3.0–7.5 mg/kg/day q8–24 h, AND Metronidazole 30–40 mg/kg/day q8h ± Ampicillin 200 mg/kg/day q6h
• Preferred regimen(8): Tobramycin 3.0–7.5 mg/kg/day q8–24 h, AND Clindamycin 20–40 mg/kg/day q6–8 h ± Ampicillin 200 mg/kg/day q6h
• Note: Antimicrobial therapy of established infection should be limited to 4–7 days, unless it is difficult to achieve adequate source control. Longer durations of therapy have not been associated with improved outcome.