Evaluation And Management Of The Febrile Patient

The differential diagnosis of fever in the HSCT recipient in the preengraftment period includes infectious and noninfectious causes, as summarized in Table 99.3. The differential diagnosis is guided by the presence or absence of localizing symptoms and physical findings and by the prior infectious disease history. Routine cultures of blood should be obtained, including through respective lumens of intravascular devices. In multilumen central venous catheters, infection may be confined to the inner surface of a single lumen. Cultures of urine, stool assays for C. difficile toxin, nasopharygeal specimens for direct fluorescent antibody testing for CRVs, and mouth cultures for HSV should be obtained as clinically indicated. Plain films of the chest may disclose an infiltrate even in the absence of respiratory symptoms and should be obtained. In patients with sinus symptoms, computed tomography of the sinuses is preferred to sinus plain films. In persistently febrile individuals and those at high risk for invasive aspergillosis, computed tomography of the chest should be performed in search of an occult infiltrate, even if the chest radiograph is normal. In those with a halo sign or cavitary infiltrate, both

Table 99.3 Common causes of fever in the HSCT recipient in the preengraftment period


Common pathogens


Intravascular devices



Staphylococci Viridans streptococci Gram-negative bacilli

Oral Mucositis, Esophagitis

Noninfectious Herpes simplex virus


Noninfectious Clostridium difficile


Mouth flora (aspiration)

Gram-negative bacilli Staphylococci Community respiratory viruses Aspergillus species

Intravascular device

Staphylococci Gram-negative bacilli Candida species

Noninfectious causes Drug fever Chemical aspiration Engraftment syndrome

suggestive of invasive pulmonary aspergillosis, bron-choscopy is indicated to establish a microbiologic diagnosis.

The selection of an empiric antimicrobial regimen should be guided by the suspected anatomic origin of the fever, by the pathogens suspected, and by local susceptibility profiles of institutional isolates. It is imperative to prospectively monitor and report to clinicians the antimicrobial susceptibility profiles of bacterial pathogens encountered within the institution and on the stem cell transplant unit, as this may impact on the selection of empiric antibacterial regimens and identify potential outbreaks.2 The recent change by the National Committee on Clinical Laboratory Standards in the breakpoint defining susceptibility of coagulase negative staphylococci to methicillin has led to the reclassification of >95% of coagulase negative staphylococci as methicillin-resistant. As these organisms are the most common cause of intravascular device-related bacteremia in HSCT recipients, this has resulted in increasing pressure to include vancomycin in empiric antibacterial regimens in febrile HSCT recipients. The emergence of vancomycin-resistant enterococci and vancomycin-intermediate and van-comycin-resistant Staphylococcus aureus31 has led, on the other hand, to recommendations to minimize indiscriminate vancomycin use.2 However, a recent single center study suggested that early empiric van-comycin administration with as little as two doses between days -7 and +7 dramatically reduced the incidence of viridans streptococcal bacteremia in HSCT recipients.32 Therefore, vancomycin may be included in the initial coverage of febrile HSCT recipients pending cultures, but its long-term empiric use in the absence of a microbiologic diagnosis or strong clinical indication is discouraged. Persistent fever despite antifungal prophylaxis with fluconazole or low-dose amphotericin should heighten concern about invasive fungal infection and prompt consideration of empiric antifungal therapy with higher dose amphotericin B or voriconazole.

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