Chapter 019. Fever of Unknown Origin
(Part 6)

Nosocomial FUO
(See also Chap. 125) The primary considerations in diagnosing nosocomial
FUO are the underlying susceptibility of the patient coupled with the potential
complications of hospitalization. The original surgical or procedural field is the
place to begin a directed physical and laboratory examination for abscesses,
hematomas, or infected foreign bodies. More than 50% of patients with
nosocomial FUO are infected. Intravascular lines, septic phlebitis, and prostheses
are all suspect. In this setting, the best approach is to focus on sites where occult
infections may be sequestered, such as the sinuses of intubated patients or a
prostatic abscess in a man with a urinary catheter. Clostridium difficile colitis may
be associated with fever and leukocytosis before the onset of diarrhea. In ~25% of
patients with nosocomial FUO, the fever has a noninfectious cause. Among these
causes are acalculous cholecystitis, deep-vein thrombophlebitis, and pulmonary
embolism. Drug fever, transfusion reactions, alcohol/drug withdrawal, adrenal
insufficiency, thyroiditis, pancreatitis, gout, and pseudogout are among the many
possible causes to consider. As in classic FUO, repeated meticulous physical
examinations, coupled with focused diagnostic techniques, are imperative.
Multiple blood, wound, and fluid cultures are mandatory. The pace of diagnostic
tests is accelerated, and the threshold for procedures—CT scans, ultrasonography,
111
In WBC scans, noninvasive venous studies—is low. Even so, 20% of cases of
nosocomial FUO may go undiagnosed.
Like diagnostic measures, therapeutic maneuvers must be swift and
decisive, as many patients are already critically ill. IV lines must be changed (and
cultured), drugs stopped for 72 h, and empirical therapy started if bacteremia is a
threat. In many hospital settings, empirical antibiotic coverage for nosocomial
FUO now includes vancomycin for coverage of methicillin-resistant
Staphylococcus aureus as well as broad-spectrum gram-negative coverage with

Ga scan may help
identify Pneumocystis pulmonary infection. FUO has an infectious etiology in
>80% of HIV-infected patients, but drug fever and lymphoma remain important
considerations. Treatment of HIV-associated FUO depends on many factors and is
discussed in Chap. 182.
Fever of Unknown Origin: Treatment
The focus here is on classic FUO. Other modifiers of FUO—neutropenia,
HIV infection, a nosocomial setting—all vastly affect the risk equation and dictate
therapy based on the probability of various causes of fever and on the calculated
risks and benefits of a guided empirical approach. The age and physical state of
the patient are factors as well: the frail elderly patient may merit a trial of
empirical therapy earlier than the robust young adult.
The emphasis in patients with classic FUO is on continued observation and
examination, with the avoidance of "shotgun" empirical therapy. Antibiotic
therapy (even that for tuberculosis) may irrevocably alter the ability to culture
fastidious bacteria or mycobacteria and delineate ultimate cause. However, vital-
sign instability or neutropenia is an indication for empirical therapy with a
fluoroquinolone plus piperacillin or the regimen mentioned above (see
"Nosocomial FUO"), for example. Cirrhosis, asplenia, intercurrent
immunosuppressive drug use, or recent exotic travel may all tip the balance
toward earlier empirical anti-infective therapy. If the PPD skin test is positive or if
granulomatous hepatitis or other granulomatous disease is present with anergy
(and sarcoid seems unlikely), then a therapeutic trial with isoniazid and rifampin
(and possibly a third drug) should be undertaken, with treatment usually continued
for up to 6 weeks. A failure of the fever to respond over this period suggests an
alternative diagnosis.
The response of rheumatic fever and Still's disease to aspirin and
nonsteroidal anti-inflammatory drugs (NSAIDs) may be dramatic. The effects of
glucocorticoids on temporal arteritis, polymyalgia rheumatica, and granulomatous
hepatitis are equally dramatic. Colchicine is highly effective in preventing attacks