Version May 2024
INTRODUCTION — Neutropenic enterocolitis is a life-threatening, necrotizing enterocolitis occurring primarily in neutropenic patients [1]. Other terms that have been used to describe this syndrome include "necrotizing enterocolitis" and "ileocecal syndrome." Neutropenic enterocolitis occurs most commonly in individuals with hematologic malignancies who are neutropenic and have breakdown of gut mucosal integrity as a result of cytotoxic chemotherapy. "Typhlitis" (from the Greek word "typhlon," or cecum) describes neutropenic enterocolitis of the ileocecal region; we prefer the more inclusive term "neutropenic enterocolitis," since other parts of the small and/or large intestine are often involved.
The pathogenesis, clinical manifestations, diagnosis, management, and prognosis of neutropenic enterocolitis are reviewed here.
Other infectious complications of chemotherapy-induced neutropenia are discussed separately:
●(See "Overview of neutropenic fever syndromes".)
●(See "Diagnostic approach to the adult cancer patient with neutropenic fever".)
●(See "Risk assessment of adults with chemotherapy-induced neutropenia".)
●(See "Fever in children with chemotherapy-induced neutropenia".)
PATHOGENESIS — The pathogenesis of neutropenic enterocolitis is incompletely understood and likely involves a combination of factors, including mucosal injury by cytotoxic drugs or other means, profound neutropenia, and impaired host defense to invasion by microorganisms [2]. The microbial infection leads to necrosis of various layers of the bowel wall. The cecum is usually affected, and the process often extends into the ascending colon and terminal ileum [3]. The predilection for the cecum is possibly related to its distensibility and its diminished vascularization relative to the rest of the colon.
Gross and histologic examinations may reveal bowel wall thickening, discrete or confluent ulcers, mucosal loss, intramural edema, hemorrhage, necrosis, perforation, and depletion of inflammatory cells (neutrophils) [4]. Various bacterial and/or fungal organisms are often seen infiltrating the bowel wall. Polymicrobial infection is frequent. (See 'Microbiology' below.)
Only rarely are inflammatory or leukemic infiltrates identified [3].
MICROBIOLOGY — As noted above, various bacterial and/or fungal organisms, including gram-negative bacilli, gram-positive cocci, anaerobes (eg, Clostridium septicum), and Candida spp, are often seen infiltrating the bowel wall, and polymicrobial infection is frequent. Bacteremia or fungemia is also common; pathogens include Pseudomonas aeruginosa, Escherichia coli, Klebsiella spp, viridans group streptococci, enterococci, Bacteroides spp, Clostridium spp, and Candida spp [5]. Recovery of Clostridium septicum from the bloodstream has been associated with a fulminant course and a high mortality rate [6].
Candida spp are the most common cause of fungal bloodstream infection in patients with neutropenic colitis; various Candida species have been detected in such patients, including C. albicans, C. tropicalis, C. glabrata, C. krusei, and C. guilliermondii [5,7]. Less commonly detected fungi include Aspergillus, Cryptococcus neoformans, and Trichosporon spp.
RISK FACTORS AND INCIDENCE — Neutropenic enterocolitis was originally reported in children who underwent induction chemotherapy for acute leukemia [8]. It has subsequently been described in children and adults with acute leukemia (especially acute myeloid leukemia), lymphoma, multiple myeloma, myelodysplastic syndromes, aplastic anemia, acquired immunodeficiency syndrome, cyclic or drug-induced neutropenia, and after immunosuppressive therapy for solid malignancies and transplants [2,3,5,9-13]. In one study, mucositis (odds ratio [OR] 31), hematopoietic cell transplantation (OR 59), and receipt of chemotherapy in the previous two weeks (OR 13) were significantly associated with the occurrence of neutropenic enterocolitis in pediatric patients with cancer [14]. (See "Acute myeloid leukemia: Overview of complications".)
Rare reports have described it in otherwise healthy nonneutropenic adults following ingestion of food contaminated with C. perfringens type A [15,16].
The true incidence of neutropenic enterocolitis is unknown. In studies from the early 1990s, histologic findings of neutropenic enterocolitis were reported in up to 46 percent of childhood leukemia cases at autopsy [3,17], with only one-third of patients being diagnosed before death in one study [3]. In a 2007 report, it was diagnosed in 3.5 percent of 317 episodes of severe neutropenia among individuals >16 years of age [18]. The frequency of neutropenic enterocolitis appears to be increasing with the widespread use of cytotoxic agents, which cause gastrointestinal mucositis [5]. Examples of such agents include the taxanes (docetaxel, paclitaxel), cytarabine, idarubicin, vinorelbine, fluorouracil, capecitabine, cyclophosphamide, ifosfamide, cisplatin, and carboplatin. (See "Management of acute chemotherapy-related diarrhea", section on 'Neutropenic enterocolitis'.)
Pre-existing bowel abnormalities (eg, diverticulitis, tumor infiltration, previous surgery) may also increase the risk of necrotizing enterocolitis following chemotherapy [5]. Prior episodes of neutropenic enterocolitis appear to increase the risk of episodes during chemotherapy-induced neutropenia.
CLINICAL MANIFESTATIONS
Signs and symptoms — Neutropenic enterocolitis must be considered in any severely neutropenic patient (absolute neutrophil count <500 cells/microL) who presents with fever and abdominal pain. The location of abdominal pain depends upon the location of the neutropenic colitis and is often in the right lower quadrant. Symptoms, including fever, frequently appear during the third week (median 17 days) after receiving cytotoxic chemotherapy, at a time when neutropenia is most profound [5,19]. Additional symptoms may include abdominal distension, cramping, tenderness, nausea, vomiting, watery or bloody diarrhea, and frank hematochezia [3,5,17]. Paralytic ileus may occur but is uncommon [5]. Peritoneal signs and shock suggest the possibility of bowel wall perforation. Stomatitis and pharyngitis, suggesting the presence of widespread mucositis, may be present.
Patients may remain febrile until recovery from neutropenia, independent of antimicrobial therapy [5]. Patients developing neutropenic enterocolitis during chemotherapy are prone to develop this complication again during subsequent treatments. (See 'Subsequent chemotherapy' below.)
Imaging — Computed tomography (CT) is the preferred imaging modality since it appears to have a lower false-negative rate of diagnosis (15 percent) than does ultrasound (23 percent) or plain radiographs of the abdomen (48 percent) [20]. In a study that included 53 patients with neutropenic enterocolitis, CT findings included bowel wall thickening (100 percent), mesenteric stranding (51 percent), bowel dilatation (38 percent), mucosal enhancement (28 percent), and pneumatosis (21 percent) (image 1 and picture 1) [21]. Although findings frequently involved the right colon (in 75 percent), imaging abnormalities were limited to the cecum in only 28 percent of patients.
Plain films of the abdomen are nonspecific, but, occasionally, a fluid-filled, distended cecum with dilated adjacent small bowel loops, thumbprinting, or localized pneumatosis intestinalis is seen (image 2) [17]. Plain films are useful for detecting free air.
DIAGNOSIS — Neutropenic enterocolitis is usually diagnosed by detection of the characteristic computed tomography (CT) findings in neutropenic patients presenting with fever and abdominal pain and tenderness (image 1). All patients suspected of having neutropenic colitis should undergo abdominal CT scanning (picture 1). Both oral and intravenous (IV) contrast should be given, when feasible. However, oral contrast is sometimes not tolerated in patients with severe gastrointestinal tract symptoms, and IV contrast is typically avoided in patients with renal insufficiency. (See 'Imaging' above.)
In addition to CT scanning, blood and stool cultures and Clostridioides difficile toxin assays should be performed.
Barium enema is hazardous in the presence of potentially necrotic bowel, since it can cause perforation [22]. Similarly, colonoscopy is relatively contraindicated in the presence of neutropenia and thrombocytopenia, and air insufflation may precipitate cecal perforation. In those very few patients who underwent colonoscopic examination, mucosal irregularity with nodularity, ulcerations, and hemorrhagic friability, as well as a mass-like lesion mimicking carcinoma, have been described [23,24].
DIFFERENTIAL DIAGNOSIS — Neutropenic enterocolitis, especially when it involves the right lower quadrant, can mimic acute appendicitis, and distinguishing between the two is important due to their different management [25]. Acute lower gastrointestinal bleeding should suggest neutropenic enterocolitis instead of appendicitis [3]. Computed tomography is usually helpful in the differentiation of neutropenic enterocolitis from appendicitis, appendiceal abscess, and C. difficile colitis [21,26,27]. (See 'Diagnosis' above.)
In addition to neutropenic enterocolitis, appendicitis, and C. difficile colitis, several other entities can cause gastrointestinal signs and symptoms in patients with chemotherapy-induced neutropenia, including the following [5,26]:
●Graft-versus-host disease (GVHD) – GVHD can complicate allogeneic hematopoietic cell transplantation (HCT). Some patients with gastrointestinal tract GVHD will also have skin and/or liver involvement. GVHD typically occurs after engraftment, whereas neutropenic enterocolitis usually presents before engraftment. (See "Clinical manifestations, diagnosis, and grading of acute graft-versus-host disease".)
●Cytomegalovirus (CMV) colitis – Among patients with chemotherapy-induced neutropenia, CMV colitis is most likely to occur in HCT recipients. (See "Approach to the diagnosis of cytomegalovirus infection", section on 'Gastrointestinal disease'.)
●Norovirus infection – Although in immunocompetent hosts norovirus causes a self-limited gastroenteritis, in immunocompromised hosts it can cause a severe and/or prolonged diarrheal illness that can mimic neutropenic enterocolitis or GVHD or coexist with these entities. (See "Norovirus".)
●Ischemic colitis – Ischemic colitis occurs most commonly in older adult patients and involves the left side of the colon most often. (See "Colonic ischemia".)
●Ogilvie's syndrome (colonic pseudoobstruction) – Ogilvie's syndrome is a disorder characterized by gross dilatation of the cecum and right hemicolon (although occasionally extending to the rectum) in the absence of an anatomic lesion that obstructs the flow of intestinal contents. It is usually associated with an underlying disease, such as trauma, infection (eg, pneumonia, sepsis), myocardial infarction, congestive heart failure, surgery, or neurologic diseases. (See "Acute colonic pseudo-obstruction (Ogilvie's syndrome)", section on 'Clinical manifestations'.)
●Cholangitis – Acute cholangitis is a syndrome characterized by fever, jaundice, and abdominal pain that develops as a result of stasis and infection in the biliary tract. (See "Acute cholangitis: Clinical manifestations, diagnosis, and management", section on 'Clinical manifestations'.)
●Cholecystitis – Acute cholecystitis refers to a syndrome of right upper quadrant pain, fever, and leukocytosis associated with gallbladder inflammation that is usually related to gallstone disease. (See "Acute calculous cholecystitis: Clinical features and diagnosis", section on 'Clinical manifestations'.)
MANAGEMENT — A general approach to patients with neutropenic enterocolitis can be suggested, although care should be individualized. In patients without complications (ie, peritonitis, perforation, or severe bleeding), nonsurgical management with bowel rest, nasogastric suction, intravenous (IV) fluids, nutritional support, blood product support (packed red blood cells and fresh frozen plasma as needed), and broad-spectrum antibiotics is a reasonable initial approach [20,22,28].
Although surgery is typically avoided in neutropenic and thrombocytopenic patients, surgical intervention is recommended in patients with free perforation or another process that cannot be controlled medically (eg, persistent bleeding despite correction of coagulopathy and cytopenias). (See 'Surgery' below.)
Antimicrobial therapy — The antimicrobial regimen should target likely pathogens as well as pathogens that have been detected from the patient's bloodstream. No trials have been performed evaluating the efficacy of different regimens in patients with neutropenic enterocolitis. The regimen should include agents that are active against Pseudomonas aeruginosa, Escherichia coli, other enteric gram-negative bacilli, and anaerobes. In severely ill patients, we also include an agent with activity against enterococci. (See "Treatment of enterococcal infections".)
The choice of regimen should be made based upon the individual patient's recent antimicrobial exposure and microbiology data, as well as local epidemiology and resistance patterns [5]. The dosing of most of the following antibacterial agents must be reduced for renal dysfunction (all but metronidazole).
Suggested regimens — We suggest one of the following empiric regimens for patients with neutropenic enterocolitis, provided that the patient does not have bacteremia with an organism that is resistant to the following agents [29]. The following doses are intended for patients with normal renal function. Most of the following agents (with the exception of metronidazole) must be adjusted for renal dysfunction.
●Piperacillin-tazobactam (for adults: 4.5 g IV every six hours; for infants <9 months: 80 mg/kg of piperacillin component IV every eight hours; for infants and children ≥9 months and ≤40 kg: 100 mg/kg of piperacillin component IV every eight hours; for children >40 kg: 3 g of piperacillin component IV every six hours or 4 g of piperacillin component IV every six to eight hours; the maximum daily dose of the piperacillin component is 16 g/day)
●Cefepime (for adults: 2 g IV every eight hours; for children: 50 mg/kg IV every eight hours up to a maximum of 2 g per dose) PLUS metronidazole (for adults: 500 mg IV every eight hours; for children: 30 to 40 mg/kg IV per day in divided doses every six to eight hours, maximum daily dose 1500 mg/day).
We reserve the carbapenems for patients who are allergic to the other options or who are infected or colonized with an organism that is resistant to the other recommended agents (eg, extended-spectrum beta-lactamase–producing Enterobacteriaceae). Generally, we select either imipenem or meropenem because of their broad spectrum of activity (ie, spectrum includes antipseudomonal activity). Doses may need adjustment for renal dysfunction.
●Imipenem (for adults: 500 mg IV every six hours; for children: 25 mg/kg IV every six hours up to a maximum of 1 g per dose for infants older than one month of age and children)
●Meropenem (for adults: 1 g IV every eight hours; for children ≥3 months of age: 20 mg/kg IV every eight hours up to a maximum of 1 g per dose).
Antibiotic coverage for C. difficile should be added if pseudomembranous colitis has not been excluded. (See "Clostridioides difficile infection in adults: Treatment and prevention" and "Clostridioides difficile infection in children: Treatment and outcome", section on 'Severe disease'.)
Fungemia and fungal invasion of the bowel can occur. As a result, an antifungal agent should be started in neutropenic patients with protracted fever (>72 hours) despite broad-spectrum antibiotics. We favor an antifungal agent with activity against fluconazole-resistant Candida spp as well as Aspergillus spp. Examples of appropriate antifungal agents include voriconazole and amphotericin B formulations. (See "Management of candidemia and invasive candidiasis in adults" and "Treatment and prevention of invasive aspergillosis".)
Duration and transition to an oral regimen — Antimicrobial therapy should be continued until well after recovery from neutropenia and until the patient has experienced resolution of the signs and symptoms of neutropenic enterocolitis (fever, abdominal pain and tenderness). In patients who have clinical resolution following recovery from neutropenia and who did not have signs of severe disease on abdominal computed tomography (CT; perforation, abscess) at the time of diagnosis, we continue antimicrobial therapy for 14 days following recovery from neutropenia. In patients who have ongoing or worsening signs and symptoms following recovery from neutropenia or who had concerning findings on CT (perforation, abscess) at the time of diagnosis, repeat CT scanning should be performed and the appropriate duration of therapy should be determined with the input of an infectious diseases specialist. If there is evidence of a contained perforation, a longer duration of therapy is required. If there is evidence of an abscess, a longer duration of therapy should be given and drainage should be considered.
For patients who are doing well clinically and who did not have bacteremia requiring parenteral antibiotics (eg, a pathogen that cannot be treated with an oral fluoroquinolone) around the time of diagnosis of neutropenic enterocolitis, we typically switch to an oral regimen following recovery from neutropenia. Namely, if the patient has been afebrile for at least two days and the absolute neutropenic count is >500 cells/microL with a consistent increasing trend, IV antibiotics may be stopped and replaced with an oral regimen [30]. (See "Treatment of neutropenic fever syndromes in adults with hematologic malignancies and hematopoietic cell transplant recipients (high-risk patients)", section on 'Duration'.)
For adults in whom it is appropriate to give an oral regimen, we give ciprofloxacin (750 mg orally twice daily) plus metronidazole (500 mg orally every 8 hours). An alternative regimen is amoxicillin-clavulanate (875 mg of the amoxicillin component orally every 12 hours). Amoxicillin-clavulanate does not have activity against Pseudomonas aeruginosa, so it should not be used when this organism has been detected.
For children in whom it is appropriate to give an oral regimen, we typically use amoxicillin-clavulanate, but ciprofloxacin plus metronidazole can be used for those who require coverage against Pseudomonas and in those who cannot take amoxicillin-clavulanate. The dosing of amoxicillin-clavulanate for children ≥3 months of age and <40 kg is 45 mg/kg per day of the amoxicillin component in two divided doses, not to exceed 875 mg per dose. For children ≥40 kg, the dose is 875 mg of the amoxicillin component orally every twelve hours. The dosing of ciprofloxacin for children is 20 to 30 mg/kg per day orally in divided doses every 12 hours, not to exceed 1500 mg/day. The dosing of metronidazole for children is 30 to 40 mg/kg orally per day in divided doses every six to eight hours, not to exceed 1500 mg/day.
In some studies of fluoroquinolones in children, an increased incidence of reversible adverse events involving joints or surrounding tissues has been observed, but no compelling published evidence supports the occurrence of sustained injury to developing bones or joints in children treated with available fluoroquinolones [31,32]. The risks and benefits should be considered if a fluoroquinolone is prescribed in a child younger than 18 years of age. (See "Fluoroquinolones", section on 'Tendinopathy' and "Fluoroquinolones", section on 'Children'.)
In patients who had bacteremia in the setting of neutropenic enterocolitis, following recovery from neutropenia we continue to use a regimen that is appropriate for the pathogen detected from the bloodstream. Some patients (ie, those with an infection caused by an organism that is resistant to the oral regimens suggested above) will require ongoing parenteral therapy after recovery from neutropenia in order to treat the organism isolated from the bloodstream.
Supportive therapy — As noted above, bowel rest, nasogastric suction, intravenous fluids, nutritional support, and blood product support (packed red blood cells, platelets, and fresh frozen plasma as needed) are the key components of supportive therapy [20,22,28]. Anticholinergic, antidiarrheal, and opioid agents should be avoided since they may aggravate ileus.
Other possible treatments such as selective decontamination of the digestive tract, enteral nutrition (for maintaining structural and functional integrity of the gut), glutamine (for maintaining gut integrity and local and systemic immune function), and granulocyte transfusions as a means of reducing the incidence or duration of neutropenic enterocolitis are of unproven benefit but deserve further study [2,33].
As noted above, patients developing neutropenic enterocolitis during chemotherapy are prone to develop this complication again during subsequent treatments. Sufficient time should be allowed for complete healing. (See 'Subsequent chemotherapy' below.)
Granulocyte colony-stimulating factor — In severely ill patients, it is reasonable to give granulocyte colony-stimulating factor (G-CSF) in an attempt to accelerate leukocyte recovery since normalization of the neutrophil count may hasten the containment and healing of bowel lesions [5,9,34,35]. However, the use of G-CSF in patients with neutropenic enterocolitis remains controversial because it has not been adequately studied for this condition. In addition, some authors have raised a theoretical risk of reduced integrity of the bowel wall in the setting of an augmented inflammatory response during myeloid reconstitution [5]. A general discussion of G-CSF in patients with neutropenic fever is presented separately. (See "Use of granulocyte colony stimulating factors in adult patients with chemotherapy-induced neutropenia and conditions other than acute leukemia, myelodysplastic syndrome, and hematopoietic cell transplantation", section on 'Neutropenic fever'.)
Surgery — Surgery is often avoided in neutropenic and thrombocytopenic patients, given concerns about the risk of infection, poor wound healing, and bleeding. However, surgical intervention is recommended for those with perforation with free air in the peritoneum, persistent gastrointestinal bleeding despite correction of coagulopathy and cytopenias, clinical deterioration during close observation and serial examinations, or development of another indication for surgery (eg, appendicitis) [36]. In one retrospective study involving 74 pediatric patients with neutropenic enterocolitis, the presence of bowel obstruction, pneumatosis, and a greater percentage of large bowel involvement were associated with a higher likelihood of surgical intervention [37]. A surgeon may be tempted not to resect edematous bowel without apparent severe inflammation or gangrene. The caveat is that diffuse mucosal necrosis may be present underneath unimpressive serosal inflammation [2]; incomplete removal of all necrotic tissue uniformly results in death.
Subsequent chemotherapy — Following episodes of neutropenic enterocolitis, subsequent rounds of chemotherapy should generally be delayed until full recovery has occurred [5]. If surgery is performed, further chemotherapy should be delayed until the surgical site has healed.
OUTCOMES — Initial reports of patients with neutropenic enterocolitis described mortality rates between of 50 percent or higher [38]. Most deaths are attributed to transmural bowel necrosis, perforation, and sepsis. More recently, early recognition and progress in management have reduced mortality substantially, although no large series have been published. In a case-control study that included 42 children with neutropenic enterocolitis between 1995 and 2005, all 42 children survived [14].
Patients developing neutropenic enterocolitis during chemotherapy are prone to develop this complication again during subsequent treatments.
SUMMARY AND RECOMMENDATIONS
●Definition − Neutropenic enterocolitis is a life-threatening, necrotizing enterocolitis occurring primarily in neutropenic patients. Other terms that have been used to describe this syndrome include "typhlitis," "necrotizing enterocolitis," and "ileocecal syndrome." (See 'Introduction' above.)
●Pathogenesis − The pathogenesis of neutropenic enterocolitis is incompletely understood. It probably involves a combination of factors, including mucosal injury by cytotoxic drugs or other means, profound neutropenia, and impaired host defense to invasion by microorganisms. The microbial infection leads to necrosis of various layers of the bowel wall. The cecum is usually affected, and the process often extends into the ascending colon and terminal ileum. (See 'Pathogenesis' above.)
●Microbiology − Various bacterial and/or fungal organisms, including gram-negative bacilli, gram-positive cocci, anaerobes (eg, Clostridium septicum), and Candida spp, are often seen infiltrating the bowel wall, and polymicrobial infection is frequent. Bacteremia or fungemia is also common, usually with enteric organisms such as Pseudomonas or yeasts such as Candida. (See 'Microbiology' above.)
●Epidemiology − Neutropenic enterocolitis was originally reported in children who underwent induction chemotherapy for acute leukemia. It has subsequently been described in children and adults with acute leukemia (especially acute myeloid leukemia), lymphoma, multiple myeloma, myelodysplastic syndromes, aplastic anemia, acquired immunodeficiency syndrome, cyclic or drug-induced neutropenia, and after immunosuppressive therapy for solid malignancies and transplants. (See 'Risk factors and incidence' above.)
●Clinical manifestations − Neutropenic enterocolitis must be considered in the differential diagnosis of any severely neutropenic patient (absolute neutrophil count <500 cells/microL), who presents with fever and abdominal pain, usually in the right lower quadrant. Symptoms frequently appear during the third week after receiving cytotoxic chemotherapy, at a time when neutropenia is most profound and the patient is febrile. (See 'Clinical manifestations' above.)
●Diagnosis and imaging − Neutropenic enterocolitis is usually diagnosed by detection of the characteristic computed tomography (CT) findings in neutropenic patients presenting with fever and abdominal pain and tenderness. All patients suspected of having neutropenic colitis should undergo abdominal CT scanning. CT findings include bowel wall thickening, mesenteric stranding, bowel dilatation, mucosal enhancement, and pneumatosis. (See 'Diagnosis' above and 'Imaging' above.)
●Management − Patients without complicated neutropenic enterocolitis (ie, perforation or severe bleeding) should receive nonsurgical management with broad-spectrum antimicrobials, bowel rest, nasogastric suction, intravenous fluids, nutritional support, and blood product support (packed red blood cells and fresh frozen plasma as needed). Although surgery is typically avoided in neutropenic and thrombocytopenic patients, surgical intervention is recommended for those with free perforation or another process that cannot be controlled medically (eg, persistent bleeding despite correction of coagulopathy and cytopenias). (See 'Management' above.)
●Antimicrobial therapy − The antimicrobial regimen should target likely pathogens as well as pathogens that have been detected from the patient’s bloodstream. The regimen should include agents that are active against Pseudomonas aeruginosa, Escherichia coli, other enteric gram-negative bacilli, and anaerobes. (See 'Antimicrobial therapy' above.)
●Antimicrobial selection − We suggest one of the following empiric regimens for patients with neutropenic enterocolitis provided that the patient does not have bacteremia with an organism that is resistant to the following agents (Grade 2C):
•Cefepime plus metronidazole
An antipseudomonal carbapenem (imipenem or meropenem) can also be used, but we reserve these agents for patients who are allergic to the other options or who are infected or colonized with an organism that is resistant to the other recommended agents (eg, extended-spectrum beta-lactamase–producing Enterobacteriaceae).
An antifungal agent should be started in neutropenic patients with protracted fever (>72 hours) despite broad-spectrum antibiotics. We favor an antifungal agent with activity against fluconazole-resistant Candida spp as well as Aspergillus spp. Examples of appropriate antifungal agents include an echinocandin for Candida species and voriconazole or amphotericin B formulations for both yeasts and molds. (See 'Suggested regimens' above.)
●Duration of treatment − Antimicrobial therapy should be continued until well after recovery from neutropenia and until the patient has experienced resolution of the signs and symptoms of neutropenic enterocolitis (fever, abdominal pain and tenderness). In patients who have clinical resolution following recovery from neutropenia and who did not have signs of severe disease on CT (perforation, abscess) at the time of diagnosis, we continue antimicrobial therapy for 14 days following recovery from neutropenia. Such patients can usually be switched to an oral regimen following recovery from neutropenia. (See 'Duration and transition to an oral regimen' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Kieren Marr, MD, who contributed to an earlier version of this topic review.
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