The use of long-term indwelling catheters has revolutionized medical care. Chemotherapy, as well as prolonged antimicrobial treatment and parenteral nutrition, can be given without repeated replacement of peripheral catheters. However, catheter infection remains a major cause of morbidity in these patients.
The most common mechanism of catheter infection is the colonization by bacteria at the insertion site with subsequent migration to the catheter tip. A less frequent cause of catheter infection is the hematogenous seeding of the catheter from a bacteremia originating at a separate site.
Consideration of catheter infection should be made in all patients with indwelling catheters presenting with fever. This is particularly true in patients who have signs of inflammation around the catheter itself. The evaluation of a febrile patient who has an indwelling catheter should always include the following:
Diagnosis of Catheter Infections
The hallmark of the diagnosis of catheter infection is a positive blood culture from the catheter. One of the challenges is that the blood culture may be positive in a patient with a catheter who has a catheter infection or has sepsis originating at a separate site. Furthermore, a bacteremia originating at another site may ultimately seed and infect that catheter.
Several methods have been proposed for the diagnosis of catheter infection:
A summary of the diagnostic methods for catheter infection is provided in Table 15.1.
TABLE 15.1. Diagnosis of Catheter Infections
Empiric Antibiotic Therapy
Depending on the clinical status of the patient, empiric therapy should be broad. Many clinicians, when faced with a potential catheter infection, include vancomycin (as coverage for coagulase-negative staphylococcus, S. aureus, methicillin-resistant S. aureus, and enterococcus). Some physicians who wish to limit the empiric use of vancomycin begin with semisynthetic penicillin such as nafcillin and resort to vancomycin only when a pathogen requiring vancomycin is documented. Because of the rapid mortality caused by gram-negative organisms, aggressive gram-negative coverage is usually begun. This often consists of a third-generation cephalosporin combined with an aminoglycoside. In patients who are severely ill, with decreased peripheral profusion and hypotension, empiric antifungal treatment may be started. The initial empiric therapy can always be reduced after culture results are available.
Treatment of Catheter Infections
There are two options for the treatment of catheter infections:
Organisms that infect catheters often produce a biofilm that causes the organism to adhere to the catheter. It has been shown that antibiotic concentration must be 100 to 1,000 times greater to kill bacteria residing within a biofilm. This explains the difficulty in treating infected catheters with antibiotic therapy alone.
Guidelines have recently been published by the Infectious Disease Society of America. This important document states that randomized trials regarding treatment of infected catheters are lacking; definitive recommendations therefore are often not available. Recommendations are based on a consensus from a panel of experts, taking into account a large amount of historical experience with catheter infections.
These guidelines are grouped according to the pathogens causing the catheter infection.
It is important to remember that a clinical or microbiological relapse following completion of antibiotics with the same pathogen in a patient in whom the catheter was retained, warrants immediate consideration for catheter removal, regardless of the pathogen.
Specific Pathogens of Catheter Infection
Coagulase-negative staphylococci are the most common cause of catheter infection. These bacteria may have lower virulence than other pathogens, and one can consider treatment with antibiotic therapy alone. The treatment is with oxacillin or nafcillin for methicillin-sensitive isolates and with vancomycin for organisms that are methicillin resistant. Some investigators believe that infection with coagulase-negative staphylococcus represents an infection with a heterogenous population of organisms; that is, the organisms involved in the infection may be both oxacillin sensitive and resistant. Thus, some clinicians use vancomycin for any coagulase-negative staphylococcus infection thought to require treatment. Treatment is for 10 to 14 days in patients in whom the catheter is retained.
The diagnosis of endocarditis in patients with S. aureus bacteremia remains controversial. In adults, transesophageal echocardiography (TEE) is routinely used to assess for vegetations. In patients who have had a prolonged course of bacteremia or have abnormalities on TEE, treatment with antibiotics is often given for 4 to 6 weeks.
In pediatrics, the use of TEE is limited, making the diagnosis of S. aureus endocarditis more difficult. Some clinicians, when faced with persistent bacteremia preceding or following catheter removal, make a presumptive diagnosis of endocarditis and consider a prolonged course of antibiotic therapy.
The gram-negative bacilli are increasingly causing catheter-related infections. No controlled studies have addressed definitively whether catheters infected by gram-negative bacilli must be removed. In some settings in which the patient is hemodynamically
stable, attempts with medical therapy alone can be tried. In patients who present with a septic picture, hypotension, or system failure, immediate catheter removal should be considered. A recent study examining gram-negative catheter infection in neonates found that the bacteremia was successfully treated with medical management in only 45% of cases; successful therapy was most likely to occur when there was only a single day's duration of bacteremia. Infection was rarely resolved in infants who had more prolonged bacteremia and bacteremia-associated thrombocytopenia, unless the catheter was removed.
Candida species are another major cause of morbidity and mortality in patients with catheter infections. Once a fungal catheter infection is documented, removal of the catheter is necessary. Retention of the catheter will only result in persistent fungemia, which can cause significant morbidity and even mortality.
Although minimal inhibitory concentration (MIC) breakpoints are not available for amphotericin B, breakpoints for candidal species to the azole class (e.g., fluconazole, itraconazole) are available. The Infectious Disease Society of America has recently published recommendations regarding the treatment of a variety of Candida species with antifungal agents. Infections with Candida albicans, Candida tropicalis, and Candida parapsilosis can usually be treated with fluconazole. Candida krusei and Candida glabrata are generally considered resistant to fluconazole and may have reduced sensitivity to amphotericin B, requiring either increased dosing of amphotericin B or the use of caspofungin. Candida lusitaniae is considered to be potentially resistant to amphotericin B. Current guidelines recognize that resistance patterns may change over time; testing for azole resistance may need to be increasingly used, particularly if faced with clinical or microbiological failure.
Duration of therapy for fungemia is a common question. Adequate therapy is desired because of the high risk for secondary spread to bone, kidneys, or cerebrospinal fluid. In the past, all fungemia was treated with a 6-week course of antifungal agents. Recently, efforts to determine which patients may be candidates for a shorter course of antifungal therapy have been made. Early catheter removal is essential. A vigorous search for secondary sites of infection by urine culture, urinalysis, funduscopic examination, and renal ultrasound are often recommended. If repeat blood cultures following catheter removal are negative and there is no evidence of a secondary infected site, many clinicians will administer 2 weeks of additional therapy following first negative culture. Secondary sites of infection needprolonged therapy (Table 15.2).
Routine Changes of Central Venous Catheters
Recently, several studies have examined the prevention of catheter-related bloodstream infections in the intensive care setting with scheduled replacement of these
catheters over guide wires. These studies have not shown a decrease in infection; there was actually an increased risk for mechanical complication when the catheters were replaced. The most current recommendation is that routine scheduling and changing of catheters does not prevent catheter-related bloodstream infections.
TABLE 15.2. Management of Catheter Infections by Specific Pathogens
Benjamin, DK, Miller W, Garges H, et al. Bacteremia, central catheters, and neonates: when to pull the line. Pediatrics2001;107(6):1272–1276.
Donowitz LG, Hendley JO. Short course amphotericin B therapy for candidemia in pediatric patients. Pediatrics 1995;95(6):888–891.
Gaur AH, Flynn PM, Giannini MA, et al. Difference in time to detection: a simple method to differentiate catheter-related from non-catheter related blood steam infection in immunocompromised pediatric patients. Clin Infect Dis 2003;37(4):469–475.
Haimi-Cohen Y, Shafinoori S, Tucci V, et al. Use of incubation time to detect in BACTEC 9240 to distinguish coagulase-negative staphylococcal contamination from infection in pediatric blood cultures. Pediatr Infect Dis J 2003;22:968–973.
Mermel LA, Farr BM, Sheretz RJ, et al. Guidelines for the management of intravascular catheter-related infections. Clin Infect Dis2001;32(9):1249–1272.
Nazemi KJ, Buescher ES, Kelly RE, et al. Central venous catheter removal versus in situ treatment in neonates with Enterobacteriaceae bacteremia. Pediatrics 2003;111(3):E269–274.