Managing bloodstream infections in patients who have short-term central venous catheters

Empiric antibiotic therapy for bloodstream infection from a short-term CVC

In order of prevalence, the four most common pathogens are coagulase-negative staphylococci, Staphylococcus aureus, Candida species, and enteric gram-negative bacilli.⁷

Gram-positive pathogens. A recent randomized clinical trial comparing vancomycin and linezolid (Zyvox) treatment for CVC-related bloodstream infections showed that 89 (57%) of 157 S aureus isolates and 95 (80%) of 119 coagulase-negative staphylococcal isolates were resistant to methicillin.⁸ Given the prevalence of gram-positive infections and the regularity of methicillin-resistant isolates, vancomycin should be started empirically in cases of suspected bloodstream infection related to short-term CVCs. In institutions where methicillin-resistant S aureus (MRSA) isolates regularly have a vancomycin minimum inhibitory concentration (MIC) of greater than 2 μg/mL, an alternative agent such as daptomycin (Cubicin) should be used.^9,10

Gram-negative pathogens. Infections due to resistant gram-negative pathogens have become more common in the past 10 years.^11,12 Prospective cohort studies have shown that resistant gram-negative infections and inadequate empiric antimicrobial therapy of bloodstream infections independently predict the risk of death.^13,14 Risk factors for resistant gram-negative infections include critical illness, neutropenia, prior antibiotic therapy, and femoral insertion of the CVC.^15–18 Patients with these risk factors should receive empiric antibiotic therapy for gram-negative bacilli.

No randomized controlled trial has been done to guide the choice of empiric gram-negative antibiotic coverage. The initial choice should be based on local antimicrobial patterns and susceptibility data and on the severity of the patient’s illness. Initial options include fourth-generation cephalosporins, carbapenems, or combined beta-lactam and beta-lactamase inhibitors. Patients with neutropenia, severe sepsis, or known multiple-drug-resistant gram-negative bacilli colonization or prior infection should receive empiric combination therapy with two different classes of antibiotics.

Candida. Risk factors for CVC-related bloodstream infections due to Candida species include total parenteral nutrition, prolonged use of broad-spectrum antibiotics, hematologic malignancy, solid organ or bone marrow transplantation, colonization with Candida species at multiple sites, and femoral catheter insertion. Empiric treatment with an echinocandin is recommended for patients with these risk factors. Fluconazole (Diflucan) can be substituted for an echinocandin in patients without azole exposure in the previous 3 months and in settings where the prevalence of Candida krusei and Candida glabrata is low.

PATHOGEN-SPECIFIC MANAGEMENT: RECOMMENDATIONS

Coagulase-negative staphylococci

Most patients with coagulase-negative staphylococcal infections have a benign clinical course.

Although no randomized trial has evaluated different treatment approaches, most experts recommend removing the catheter and giving a short course of antibiotics (ie, 5–7 days). Longer courses of antibiotics may be required for patients with endovascular hardware in place or persistent fever or bacteremia after catheter removal. The IDSA guidelines recommend 5 to 7 days of antibiotic therapy if the catheter is removed, and 10 to 14 days of systemic antibiotic therapy in combination with “antibiotic lock therapy” if the catheter is retained. Antibiotic lock therapy involves instilling a high concentration of an antibiotic to which the organism is susceptible into the catheter lumen and allowing it to dwell.

Not all patients are good candidates for antibiotic lock therapy, and neither are all organisms. In general, patients should be at low risk (immunocompetent, without hardware in place), and organisms should have a low risk of causing metastatic infection.

Staphylococcus lugdunensis can cause endocarditis and metastatic infections similar to those caused by S aureus and so should be managed similarly to S aureus.¹⁹

Staphylococcus aureus

Short-term CVCs infected with S aureus should be removed immediately. Removal of vascular catheters infected with S aureus has been associated with more rapid clinical response and higher cure rates compared with catheter retention.^20–23S aureus bacteremia results in hematogenous complications in 20% to 30% of patients, and failure to remove or a delay in removing the catheter increases the risk of complications.^21,24–27

There are no data from randomized clinical trials on the optimal duration of antibiotic therapy for S aureus bloodstream infections related to short-term CVCs. Traditionally, 4 weeks have been recommended out of concern for the risk of infective endocarditis,^28,29 and the IDSA recommends 4 to 6 weeks unless patients meet certain low-risk criteria.

Factors associated with a higher risk of hematogenous complications include the presence of a retained foreign body, an intravascular prosthetic device, retained catheter, immune suppression, diabetes, persistent bacteremia at 72 hours despite catheter removal and appropriate antibiotics, skin changes consistent with septic emboli, or evidence of endocarditis or suppurative thrombophlebitis on transesophageal echocardiography (TEE) or ultrasonography, respectively.^21,25–27 TEE is superior to transthoracic echocardiography and is most sensitive when performed 5 to 7 days after the onset of bacteremia.^28,30 Patients who have had the catheter removed and who do not have any of these risk factors, and in whom TEE performed 5 to 7 days after the onset of bacteremia is negative, can be considered for a shorter duration of therapy (but a minimum of 14 days).

Patients with catheters colonized with S aureus (ie, those with positive catheter-tip cultures and negative blood cultures) are at risk of subsequent bacteremia. This risk may be reduced with anti-staphylococcal therapy started within 24 hours of catheter removal.^31,32 Therapy should be continued for 5 to 7 days, and patients should be closely monitored for signs or symptoms of ongoing infection.

Oxacillin or nafcillin should be the first-line therapy for susceptible S aureus isolates. Vancomycin should be used to treat MRSA. Patients with MRSA isolates with a vancomycin MIC greater than 2 μg/mL should receive daptomycin or linezolid, depending on susceptibility data.

Enterococcal species

Up to 10% of nosocomially acquired bloodstream infections are due to enterococci, and many are related to intravascular catheters.^33,34 Although the risk of endocarditis as a complication of enterococcal CVC-related bloodstream infection is relatively low, estimated at 1.5% in a multicenter prospective study, enterococcal bacteremia lasting longer than 4 days has been independently associated with risk of death.^35,36 These observational data support routine removal of short-term CVCs infected with enterococci.

The choice of antibiotics for enterococcal infections depends on the susceptibility of the isolate. Sixty percent of Enterococcus faecium isolates and 2% of Enterococcus faecalis isolates are vancomycin-resistant, and reports of resistance to newer agents, including linezolid, have been published.^34,37,38 Ampicillin is the preferred antibiotic for treatment of ampicillin-susceptible enterococci. Vancomycin should be used if the pathogen is ampicillin-resistant and vancomycin-susceptible. Enterococci resistant to both ampicillin and vancomycin can be treated with linezolid or daptomycin, based on susceptibility data.

For combination therapy with an aminoglycoside, the data are mixed. Retrospective observational studies have shown no difference in outcomes in uncomplicated enterococcal bacteremia with combination therapy vs monotherapy.^39,40 However, in a large series of patients with enterococcal infections in which the catheter was retained, the combination of gentamicin and ampicillin was more effective than monotherapy.⁴¹

No controlled trial has been done to define the optimal duration of antibiotic therapy for enterococcal bloodstream infections related to short-term CVCs, but the IDSA recommends 7 to 14 days. If catheter salvage is attempted, concurrent antimicrobial lock therapy is recommended based on expert opinion. Catheters should be removed if complications arise (eg, insertion site or pocket infection, suppurative thrombophlebitis, sepsis, endocarditis, persistent bacteremia, metastatic infection). Signs and symptoms of endocarditis, persistent bacteremia, or the presence of a prosthetic heart valve should prompt evaluation with TEE.^42,43