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622 PART 5: Infectious Disorders

with vancomycin minimum inhibitory concentrations (MIC) of ≥2 mg/L Erythema, exudate, and focal tenderness at the exit site suggest,
may be prolonged, empirical daptomycin may be more appropriate in but do not prove, the presence of infection. A quantitative increase in
facilities with a high prevalence of MRSA with MICs of ≥2 mg/L. 486,487 bacterial colony counts in culture swabs from the exit site has been
Consideration for echinocandin-based anti-Candida coverage should associated with an increased probability that central venous catheter
be given for cancer patients, particularly for those with hematological infection is present. 471,472 Staphylococcus epidermidis and C jeikeium are
malignancies or who are HSCT recipients, with risk factors including the most commonly isolated colonizing microorganisms at the exit site
recent use of broad-spectrum antibacterial therapy or total parenteral and represent the most common etiologic agents of catheter sepsis in
nutrition, femoral CVC, or colonization by Candida spp at multiple cancer patients. 473,474 Catheter-related sepsis is suspected if bacteremia
sites. 272,488 Following removal of the CVC, the duration of treatment of or fungemia is present unassociated with any other site of suspected
uncomplicated candidemia (defined by absence of suppurative throm- infection. The predominant mechanism of infection appears to be
bophlebitis, or visceral infection such as endophalmitis) should be for at bacterial migration from the exit site along the outside surface of the
least 14 days following the first negative blood culture. 272,348,349 catheter. Suspected catheter exit-site infection, with or without bacte-
465
Current guidelines recommend catheter removal for certain CVC- remia, may be treated with antimicrobials without removing the line.
499
related bloodstream infections due to S aureus, gram-negative bacilli, Unless exit-site surveillance cultures dictate otherwise, the empirical
and Candida spp. 21,348 Coagulase-negative staphylococci (CoNS) have antibacterial therapy should include an agent such as vancomycin that
been the most common isolate from hospitalized patients with sus- is active against S epidermidis and C jeikeium in addition to S aureus
489
pected bloodstream infections and biofilm-producing CoNS have and streptococci. Infection of the subcutaneous tunnel site is more
been the leading cause of CRBSI. 490,491 The attributable mortality with difficult to control with antimicrobial agents alone and often requires
such infections is low. CVC retention among patients with CRBSI due to catheter removal. Catheter removal is also often recommended in the
348
CoNS has not been associated with treatment failure, but has been asso- setting of bacteremia due to more highly pathogenic organisms such as
492
ciated with a higher risk of recurrence. Accordingly, administration of S aureus, P aeruginosa, or Serratia marcescens, catheter-related funge-
antibacterial therapy for CoNS CRBSI with the CVC retained in situ has mia, or persistent catheter-related bacteremia that has not responded
been recommended. In general, CRBSI due to S aureus, gram-negative to appropriate antibacterial therapy. The differential time to positivity
bacilli, or opportunistic yeast in patients with severe sepsis, suppura- (ie, the time difference between the time that the blood culture from the
tive thrombophlebitis, or persistently positive blood cultures after peripheral site and central venous catheter site was obtained to the time
>72 hours of appropriate therapy should be managed with CVC the cultures became positive) of >2 hours has been used as a method for
removal and appropriate antimicrobial therapy. 348 predicting catheter-related infections. 65,466
CVC removal among candidemic patients has been advocated based
on clinical trial–driven observations of better outcomes; namely, higher
rates of treatment success (defined as resolution of signs and symptoms INFECTION PREVENTION IN THE NEUTROPENIC HOST
rapid mycological eradication, decreased rates of persistent and of recur- ■ ANTIBACTERIAL PROPHYLAXIS
of infection plus mycological eradication of the baseline pathogen), more
rent candidemia, and increased hospital survival. 355,397,398,493 The median Antibacterial chemoprophylaxis is used widely for preventing or modi-
time to eradication of Candida spp from blood cultures with or without fying the etiology of bacterial infection in patients for whom the
494
CVC removal has been reported to of the order of 5 days. Independent expected duration of neutropenia is longer than 7 days. 433,500-504 Oral
predictors for treatment failure in candidemic patients include use of cor- nonabsorbable antimicrobial regimens consisting of agents such as
ticosteroids, persistent severe neutropenia, increased severity of illness, aminoglycosides, vancomycin, polymyxin B, colistin, and oral nystatin
and older age. Survival is reduced in candidemic patients with persistent or amphotericin B have not been consistently effective for reducing the
severe neutropenia, increased severity of illness, and who are older. 494 incidence of febrile neutropenic episodes, documented superficial or
The onset of a new fever in ICU patients with indwelling CVCs poses invasive infection, or overall mortality. In addition, they are unpalatable
a difficult problem for critical care clinicians. 495,496 Fever is used as a sur- and costly. On the other hand, oral absorbable antibacterial regimens
rogate of the activity of infection. The observation of a relative brady- consisting of trimethoprim/sulfamethoxazole (TMP/SMX) or fluoro-
495
cardia in patients with temperatures of ≥38.9°C (the pulse-temperature quinolones including norfloxacin, ciprofloxacin, enoxacin, ofloxacin,
deficit) who are not receiving β-blocker therapy and who have a nega- levofloxacin, or perfloxacin have proved useful, though efficacy appears
tive chest radiograph suggests a drug fever. Single isolated temperature to be linked with compliance, personal hygiene, the spectrum of
497
505
elevations rarely indicate infection; rather, the most common associa- antimicrobial activity of the regimen, the cytotoxic potential of the
23
tion is with administration of blood products. 497 antineoplastic regimen, and the timing of the administration of the
96
Fever in critically ill patients with neurological or neurosurgical dis- regimen relative to the onset of the neutropenia-related risk for bacte-
ease is common and may have infectious or noninfectious causes. The rial infection. 23
latter include neuronal injury–driven release of endogenous pyrogens, Oral fluoroquinolones have shown a significant reduction in mor-
and the presence of blood in the cerebral parenchyma, ventricles, or bidity and mortality due to infection by aerobic gram-negative bacilli
subarachnoid space. 498 compared with TMP/SMX. 433,500 The trade-off for this appears to be an
Venous and arterial cannulae physically disrupt the integrity of the increase in the risk of infection due to gram-positive organisms such
skin and blood vessels, thus providing an avenue for ingress of bacteria as coagulase-negative staphylococci, Enterococcus spp, and viridans
or fungi colonizing the skin surfaces at the site of cannula placement. group streptococci. The presence of a tunneled indwelling central
Determinants of intravenous cannula infection include the type of venous catheter adds to the risk for infections due to coagulase-negative
506
cannula, the duration of use, the technique of skin preparation for staphylococci, whereas severe mucositis and periodontal disease
insertion, and the use of venotoxic infusates. The most common micro- appear to predispose to viridans streptococcal infection. 97,98,315,507 A
organisms causing intravenous site infection are gram-positive organ- syndrome of viridans streptococcal bacteremia has been recognized
isms (eg, Staphylococcus aureus), coagulase-negative staphylococci, and among high-dose cytarabine or HSCT recipients that is often associated
Corynebacterium jeikeium; gram-negative bacilli; and fungi such as with pulmonary infiltrates and hypotension. 97,508,509 The pathogenesis is
Candida species. Erythema, swelling, exudate, and focal tenderness at believed to involve severe cytotoxic therapy–induced intestinal mucosal
a peripheral intravenous catheter site should alert the clinician to these damage in the setting of severe prolonged neutropenia and GI luminal
etiologic possibilities. Suspect catheters should be removed promptly colonization by these organisms. Oral fluoroquinolone use tends to
510
and carefully using aseptic technique and submitted to the microbiology select for these microorganisms. The inconsistent susceptibility of
laboratory in a sterile, dry container for microbiologic evaluation. these organisms to penicillin G and the apparent need to modify the

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