The evaluation of fever in the ICU usually begins with a search for signs of infection, since approximately only half of febrile events in the ICU are due to infection and the majority of these infections are related to devices, for example, urinary catheters, endotracheal tubes, nasogastric tubes, or central venous catheters.10 The early removal of devices when they are no longer needed is a very cost-effective strategy for reducing ICU infections and many ICUs now utilize the daily goals checklists on interdisciplinary rounds to document the necessity for each device.
Blood cultures should be obtained from all ICU patients with a new fever when the clinical picture does not strongly suggest a noninfectious cause.8 In order to maximize the sensitivity of blood cultures for true bacteremia, guidelines from the American College of Critical Care Medicine and the Infectious Diseases Society of America8 emphasize that the blood cultures should be obtained prior to antibiotic initiation and that an adequate volume of blood should be instilled into the collection bottles (usually 20-30 mL per culture).27 Spacing out sets of blood cultures over time does not increase the yield. In order to avoid contamination, the blood cultures should be drawn only after proper hand washing and after sterilization of the intended site with an approved individually prepackaged chlorhexidine, alcohol, or iodine-based applicator.
CATHETER-ASSOCIATED BLOOD STREAM INFECTIONS
There has been an explosion in the use of central venous catheters in the ICU and with it an increase in risk of central line–associated bloodstream infection (CLABSI). Use of full barrier precautions, shorter duration of catheter use, use of antibiotic impregnated catheters, avoidance of femoral venous access, and care by a central-line team are factors associated with a lower risk of CLABSI.28 Measurement of the “differential time to positivity,” that is, the difference in time for blood cultures to become positive when they are drawn simultaneously through a central venous catheter and a peripheral vein, has been shown to have high sensitivity and specificity for catheter-related infection.29 When line sepsis is suspected, the line should be removed aseptically and 5cm of the line tip submitted for semiquantitative culture. Isolation of ≥15 colony-forming units (CFUs) on semiquantitative culture of the catheter tip correlates with true line-associated infection.30 Isolation of <15 CFUs usually represents contamination during removal. However, it is not recommended to routinely culture line tips upon removal from asymptomatic patients. In one epidemiologic study of intensive care unit-acquired bloodstream infections, multiple antibiotic-resistant organisms were uncommon suggesting it may be safer to use a more narrowed spectrum of antibiotics.31
Urine cultures are almost universally obtained during the evaluation of fever in a critically ill patient regardless of patient age, gender, and duration of catheter placement. However, urinary tract infections in the ICU occur almost exclusively in patients who have had indwelling urinary catheters for a long duration and the infections occur more frequently in females and in those patients who have received prior antibiotics.32 In an 18-month retrospective study of 510 trauma patients, the incidence of urinary tract infections was estimated to be only 16/1000 catheter days, and during the first 2 weeks of urinary catheter use, urinary tract infection was found to be an unlikely cause of either fever or leukocytosis.33
When clinically indicated, most ICU urinary cultures are obtained from an indwelling catheter because very few critically ill patients are candidates for clean catch, midstream specimens. When obtaining cultures from an indwelling catheter, it is paramount to adequately sterilize of the rubber port prior to sampling and to promptly process the specimen in less than 1 hour to prevent bacterial proliferation.8 Cultures should never be obtained from a collection bag. A better idea is to obtain the culture from an “in-and-out” straight catheterization because it avoids contamination of the specimen by bacteria adherent to the indwelling urinary catheter. In rare cases, an ultrasound-guided suprapubic tap can be obtained to avoid contamination from the highly colonized distal urethra.
In a retrospective review of patients undergoing major gynecologic surgery, 80% of patients who developed pneumonia had symptoms suggestive of the diagnosis,34 whereas obtaining a routine chest x-ray on all febrile patients yielded a finding of pneumonia in only 9% of cases. These data would suggest that chest radiography for the evaluation of fever in nonintubated post-op patients should be reserved for patients with signs and symptoms of pneumonia.
Although the performance of routine daily chest x-rays on stable, nonintubated patients in the ICU has a low diagnostic yield for pathology, it is often appropriate to obtain an on-demand chest x-ray in a critically ill, ventilated patient with fever.35,36 The incidence of ventilator-associated pneumonia (VAP) has been reported to range from 5% to 67% among mechanically ventilated patients37 with an attributable mortality of up to 10%.38 In practice, the diagnosis is most often made using readily available clinical variables (eg, characterization of secretions, chest x-ray appearance, body temperature, leukocyte count, culture, and measurement of the / ratio). However, it is clear that many intubated patients who meet these clinical criteria do not have VAP.39 Compared to a simple tracheal aspirate and culture, the use of invasive techniques, such as bronchoalveolar lavage, to definitively establish the diagnosis of VAP does not appear to reduce the use of antibiotics nor does it appear to improve clinical outcomes.40 The preferred approach when VAP is suspected is to initiate empiric broad-spectrum antibiotics using existing guidelines41 followed by rapid de-escalation of broad-spectrum antibiotics based on culture results.42
Most ICU patients will at some point have an endotracheal tube, a nasogastric tube, or a nasotracheal suctioning device. These indwelling tubes can cause mucosal trauma, introduce bacteria, and promote biofilm formation all of which increase the likelihood of infection and fever. Within 1 week of nasotracheal intubation and nasogastric tube placement, approximately 1/3 of patients will have purulent maxillary sinusitis, a rate approximately fourfold greater than that associated with oral placement.43 In one prospective study of febrile intubated patients, sinusitis was determined to be the sole cause or a contributing cause of fever in 30%.44 Because sinusitis is rarely associated with symptoms in the critically ill patient, it is seldom recognized as the source of fever. Although computed tomography is the gold standard for the diagnosis of sinusitis, its utility in the day-to-day management of patients is limited because of difficulties in transporting critically ill patients to the radiology suite. Ultrasonography of the maxillary sinuses is not as sensitive as CT, but it is very specific (∼95%), easy to learn, noninvasive, and repeatable.45
CLOSTRIDIUM DIFFICILE COLITIS
In many ICUs, C difficile colitis has replaced methicillin-resistant Staphylococcus aureus (MRSA) as the most common hospital-acquired infection.46 Most cases of antibiotic-associated diarrhea are unrelated to C difficile, but the association of fever, abdominal pain, or leukocytosis with diarrhea should suggest the diagnosis. In those patients who have received antibiotics within the past 30 days, up to three individual stool specimens may be required to confirm a positive toxin assay.47
Acalculous cholecystitis is a complication of critical illness that when it is untreated has a high mortality.48 Increased lithogenicity of bile and ischemia of the gallbladder wall leads to biliary stasis and the formation of bile salt sludge. Secondary infection and gangrene of the gallbladder are common sequelae. Acalculous cholecystitis is most commonly observed among patients with sepsis, severe trauma, or burns. The diagnosis should be suspected in any critically ill patient with fever and right upper quadrant pain or tenderness. Abdominal ultrasound and computed tomography are the most useful diagnostic tests. Gallbladder distension, thickening of the gallbladder wall, presence of pericholecystic fluid, and intraluminal slugging are highly suggestive of the diagnosis. Although hepatobiliary iminodiacetic scintigraphy (HIDA scan) is often used in the evaluation of calculous cholecystitis, its negative predictive value for acalculous cholecystitis has been reported to be poor (<25%) when the disease is suspected.49
The risk of surgical site infections (SSI) among postoperative inpatients ranges from 2% to 5%, while 75% of postoperative deaths are directly attributable to SSIs.50 When fever occurs more than 96 hours postoperatively, infection is the likely cause.8 A myriad of factors impact the risk of SSIs, for example, the anatomic location of the surgery (eg, facial wounds less commonly become infected), the degree of contamination of the surgical site, quality of the sterile technique, prior surgical trauma at the operative site, use of prophylactic antibiotics, the length of time required to achieve hemostasis, and the presence of preexisting comorbidities. SSIs may involve superficial skin structures or deeper subcutaneous tissues, organs, or implanted material. Empiric antibiotics are usually not as effective for management as is surgical drainage. Many SSIs are preventable. The Centers for Disease Controls has published a toolkit for hospitals to use to reduce SSIs.51 Use of appropriate antibiotic prophylaxis,52 preoperative control of remote infections, proper skin prepping, maintenance of normothermia postoperatively, proper wound dressings,53 and daily probing of the wound with a cotton-tipped applicator between loosely applied staples54 are associated with a reduced risk of SSI.