Catheter-Associated Bloodstream Infections
Catheter-associated bloodstream infections are one of the most common reasons for patients to have fever in the ICU. Central venous and arterial catheters are important tools for monitoring patients and delivering fluids, antibiotics, nutrition, and other therapies. Bacteria and yeast that colonize the skin of the patient or the hands of health care providers can easily gain access to the circulation via these devices. The risk of infection from these catheters is variable and depends on several factors such as length of the catheter, type of catheter such as arterial versus venous, tunneled versus nontunneled, technique of insertion, site of insertion, duration they have been in place, frequency of manipulation, patient population etc (Table 38–1). The highest risk is with short-term, noncuffed central venous catheters, in the range of 2 to 5 per 1000 catheter-days. There are several mechanisms, which may lead to the infection of an indwelling catheter. Skin pathogens can infect the catheter exit site or contaminate the catheter hub, leading to intraluminal catheter colonization and infection. Parenteral fluid, blood products, or intravenous medications can also be a source of infection. The catheter exit site should be inspected daily for evidence of erythema or pus; however these signs are absent in most cases with catheter-related bloodstream infection. Any expressible purulence or exudate should be sent for Gram stain and culture. Gram-positive organisms such as Staphylococcus aureus, coagulase-negative Staphylococcus, and Enterococcus species are commonly responsible for catheter-associated bloodstream infections. Increasingly these organisms have acquired resistance to beta-lactam antibiotics and even vancomycin. Many gram-positive organisms are also capable of forming biofilms which make them difficult to eradicate and removal of the central venous catheter is generally necessary for successful treatment of these infections.
Table 38–1Infectious causes of fever in the ICU. |Favorite Table|Download (.pdf) Table 38–1 Infectious causes of fever in the ICU.
Catheter-related bloodstream infection
Surgical site/wound infection
Soft tissue infections including necrotizing fasciitis and myonecrosis
Infected decubitus ulcer
Urinary tract infections
Clostridium difficile colitis
Gram-negative organisms are also important cause of catheter-associated bloodstream infections. Enterobacteriaceae such Escherichia coli, Klebsiella pneumoniae, and Enterobacter species are considered normal flora of the gastrointestinal (GI) tract; however they may colonize the hubs and tubing of central catheters and they may eventually be a cause of bacteremia. Pseudomonas aeruginosa is another important gram-negative organism that is often associated with nosocomial infection, including catheter-associated bacteremia. Because of the production of endotoxin gram-negative organisms are likely to trigger the release of cytokines that clinically manifest with signs of sepsis. In the hospital environment many gram-negative organisms have acquired multiple antibiotic resistance mechanisms. In addition to production of extended-spectrum beta-lactamase, several gram-negative species have also acquired carbapenemases that have made them resistant to the carbapenem class of antibiotics. The spread of these organisms within ICUs and throughout health care institutions more generally has been a particular challenge for infection control programs.
Candida bloodstream infections are also a common source of fever in the ICU. The use of central venous catheters to deliver total parenteral nutrition and empiric broad-spectrum antibacterial agents are important risk factors for Candida bloodstream infections. Catheter removal is of particular importance in the setting of fungemia as these infections are typically very difficult to eradicate when the infected catheter has not been removed. Candida albicans is frequently recovered from blood cultures in these patients; however increasingly nonalbicans species are responsible for these types of infection. Empiric therapy for Candida bloodstream infections should be guided initially by the severity of the infection as well as the epidemiology of Candida species as several nonalbicans species are resistant to fluconazole.
Pulmonary Infection Including Ventilator-Associated Pneumonia
Pneumonia is the second most common cause of infection acquired in the ICU and ventilator-associated pneumonia (VAP) is a common source of fever in the intubated patient. Between 10% and 25% of patients on mechanical ventilation will develop VAP during their ICU stay. Several factors increase the risk of patients in the ICU for developing pneumonia including endotracheal intubation and altered levels of consciousness associated with primary processes or with sedation for mechanical ventilation. Cough responses normally important as a host defense may be impaired by these and other factors, including age over 60, male gender, chronic lung disease, aspiration, acute respiratory distress syndrome (ARDS), sinusitis, nasogastric tube use, delayed extubation, continuous sedation, use of paralytic agents, and endotracheal cuff pressures less than 20 cm of H2O.
Nosocomial pathogens such as Pseudomonas and methicillin-resistant S aureus are more commonly associated with patients in the ICU. Precise microbiologic diagnosis is often challenging since obtaining an appropriate sputum sample or endotracheal aspirate is difficult in patients who are intubated. Organisms that colonize the airways may not reflect the true etiology of a lower respiratory tract infection in a patient with nosocomial pneumonia and sputum cultures should be interpreted with caution. High-quality sputum or bronchoalveolar lavage specimens with few squamous epithelial cells and many polymorphonuclear cells may be useful to guide antibiotic therapy. A higher-resolution study such as computerized tomography (CT) may be pursued if clinical suspicion is high enough and it may be helpful for detecting infiltrates in the posterior-inferior lung bases. Fiberoptic bronchoscopy with transbronchial biopsy may be especially useful for the detection of pathogens such as Pneumocystis jiroveci, Aspergillus species and other filamentous fungi, Nocardia, Legionella, cytomegalovirus (CMV), and Mycobacterium species. Thoracentesis can also be performed on patients with significant pleural effusions. Fluid should be sent for cell count, chemical analysis, and culture, especially if there is adjacent pulmonary infiltrate, suspicion of tuberculosis, or possible contamination of the pleural space due to surgery, trauma, or a fistula.
Catheterization of the bladder is a common practice in ICUs for several reasons including close monitoring of fluid balance. Urinary tract infection can be a cause of fever for patients in the ICU, particularly if there is some obstruction to urinary flow such as nephrolithiasis or ureteral blockage by tumor. Colonization of urinary catheters by resistant organisms such as vancomycin-resistant Enterococcus (VRE) is also very common in patients in the ICU and interpretation of urine cultures must be made with caution with this caveat in mind. It is important to distinguish between asymptomatic bacteriuria from a genuine urinary tract infection.
The frequent use of empiric systemic antibiotics puts many patients in the ICU at risk for C difficile infection. In patients with C difficile infection watery diarrhea is generally accompanied by marked leukocytosis; however some patients with toxic megacolon may also present with abdominal distension and reduced bowel sounds. The diagnosis can be confirmed with stool polymerase chain reaction (PCR) testing for C difficile toxin. If sigmoidoscopy is performed, pseudomembranes may also be noted, but stool assays are generally adequate for diagnosis. In addition to therapy with oral vancomycin or metronidazole, systemic antibiotics should be discontinued if possible. Stool transplant has emerged as a potentially useful therapy in particular for patients with refractory C difficile infection.
Central Nervous System Infections
Nosocomial meningitis is most commonly seen in hospitalized patients who have undergone neurosurgical procedures. When an infection is suspected in a febrile patient with an intracranial device, cerebrospinal fluid (CSF) should be obtained for analysis from the CSF reservoir. In patients with ventriculostomies who develop stupor or signs of meningitis, the catheter tip should be removed and cultured. CSF should be analyzed with Gram stain, cell count, protein, and glucose measurements. The most common organisms are S aureus and coagulase-negative staphylococci; however, Gram-negative organisms such as Pseudomonas and Klebsiella may also be responsible for CNS infections in this setting. Additional testing for tuberculosis, viral and fungal disease should be performed if there is a clinical suspicion of these less common organisms.
Surgical site infections can be important causes of fever in patients recovering from recent surgery. These infections will often present with erythema and purulence at a surgical site and eventually may lead to dehiscence of the wound. Prompt surgical debridement is generally required for patients with this etiology of fever. Deeper infections may also occur in particular in patients with recent bowel surgery where intraluminal organisms can leak into the peritoneum and cause abscesses. Evaluation with CT or direct examination in the operating room may be necessary for patients with abdominal or pelvic collections. Drainage of collections and correction of anastomotic leaks are generally required in addition to appropriate antibiotic therapy.
Sinusitis is a less frequent infectious cause of fever in the ICU. Most ICU patients have nasogastric tubes and endotracheal tubes which predispose them to nosocomial sinusitis. Other risk factors include facial fractures or nasal packing. The most common organisms causing nosocomial sinusitis are those that colonize the naso-oropharynx. Gram-negative bacilli (especially P aeruginosa) constitute 60% of the bacteria isolated from nosocomial sinusitis. Gram-positive cocci such as S aureus are also common, and many infections are polymicrobial. Diagnosis may be made supported by imaging such as CT scan or confirmed with puncture and aspiration of the involved sinuses for culture and susceptibility if invasive testing is warranted.