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CHAPTER 68: Approach to Infection in Patients Receiving Cytotoxic Chemotherapy for Malignancy 621

hematological malignancies with a positive galactomannan test showed Nontunneled noncuffed CVCs, intended for short-term use, are
a 42% survival benefit in combination recipients. 448 positioned into the superior vena cava via a percutaneous insertion
Caspofungin is approved in the United States for the treatment of into the subclavian or internal jugular veins. Nontunneled CVC-related
invasive aspergillosis in patients refractory or intolerant of polyene- bloodstream infections have been reported as 2.6 to 2.9 per 1000 catheter-
based therapy. The initial experience in such patients demonstrated days. The most common bloodstream isolates from these devices
449
469
response rates of 50% in invasive pulmonary aspergillosis, 23% in include CoNS, S aureus, Candida spp, and enteric gram-negative bacilli. 470
disseminated aspergillosis, and 26% in neutropenic patients. Among Tunneled cuffed CVCs are intended for longer-term access and are
patients receiving caspofungin for empirical therapy of suspected fungal implanted through a surgically created tunnel under the skin to a vein—
infection in neutropenic patients and in whom invasive aspergillosis usually subclavian or internal jugular. The proximal end of the catheter
ultimately was determined to be the cause of the persistent fever, the projects from an exit site on the anterior chest wall. The catheter becomes
response rate was 42% compared to only 8% among liposomal ampho- anchored in place by a fibrous tissue reaction with the aid of a dacron cuff
tericin B recipients. 450 around the outside of the catheter located within the tunnel and provides
Amphotericin B lipid complex (ABLC) has been widely used in a barrier to the migration of microorganisms along the outside of the
patients with invasive fungal infections refractory to or intolerant of con- catheter. Erythema, exudate, and focal tenderness at the exit site suggest,
ventional amphotericin B deoxycholate. In a review of 556 such patients but do not prove, the presence of infection. A quantitative increase in
receiving ABLC on an emergency drug release program, the response bacterial colony counts in culture swabs from the exit site has been asso-
rate among 130 patients with invasive aspergillosis was 42%. A 47% ciated with an increased probability that central venous catheter infec-
451
response rate was reported in a historical controlled study of ABLC tion is present. 471,472 Staphylococcus epidermidis and C jeikeium are the
in 39 solid organ transplant recipients with invasive aspergillosis. most commonly isolated colonizing microorganisms at the exit site and
452
In a series of pediatric patients with invasive aspergillosis, a 56% represent the most common etiologic agents of catheter sepsis in cancer
response rate was reported. 453 patients. 473,474 Tunneled cuffed catheter-related bloodstream infections
Amphotericin B–related nephrotoxicity impacts morbidity, mortality, have been reported at rates of 1.5 to 1.7 per 1000 catheter-days. 469
and the cost of management. 454-456 The safety profiles in the published The use of the PICC lines has become popular for the management
literature of the lipid formulations of amphotericin B have been con- of cancer patients in the outpatient setting usually over the timeframe of
sistent in demonstrating advantages in reduced amphotericin B–related 6 weeks to 6 months. These devices are implanted into a peripheral vein
nephrotoxicity. 275,456 Even among patients with elevated serum creati- in the arm. The rates of PICC-related bloodstream infections in the out-
nine levels at the outset of ABLC therapy, the advantage persists. These patient setting have been reported as in the range of 0.4 to 1.2 per 1000
elevated serum creatinine levels have been observed to fall after the first catheter-days, whereas the rates for adult inpatients have been higher
475
week with continued administration of the drug. This reduction in at 1.0 to 3.2 per 1000 catheter-days. 469,475 PICCs are more vulnerable
451
elevated serum creatinine after the first week of therapy may occur even to thrombosis and malfunction. 476-479 In order of prevalence, the most
when initially normal serum creatinine levels rise within the first week common isolates from PICC-related bloodstream infections are CoNS,
of ABLC therapy. 455 facultatively anaerobic gram-negative enteric bacilli, S aureus, and afer-
The extended spectrum azoles are useful in the management of inva- mentative gram-negative bacilli such as P aeruginosa. 470
sive mold infections. Voriconazole proved to be superior to conventional Totally implantable venous access ports made of plastic or titanium
amphotericin B deoxycholate or other licensed antifungal therapy for are implanted underneath the skin in a surgically fashioned subcutane-
the management of invasive aspergillosis in a large multinational trial. ous pocket usually on the anterior chest wall. The catheter extending
457
The treatment effect was observed in hematopoietic stem cell transplant from the port reservoir is implanted into either the subclavian or inter-
recipients, neutropenic patients, proven or probable invasive aspergil- nal jugular veins. Ports-related bloodstream infection rates have been
losis, and pulmonary and extrapulmonary aspergillosis. significantly lower than for other types of CVCs, 0 to 0.1 per 1000 port
There is a high risk of infection relapse, in the range of 10% to 50% days in situ. 469,480 Port pocket infections suspected by tenderness, indura-
in cancer patients surviving an initial episode of invasive aspergillosis tion, and erythema of the soft tissues overlying the device, or by erosion
during subsequent cytotoxic treatments. 458-461 For this reason, many and necrosis of the overlying skin have a low event rates of 0.01 to 0.09
investigators recommend secondary prophylaxis with antifungal agents per 1000 port days. Bloodstream infections associated with ports have
480
such as the mold-active azoles for those with treated invasive fungal been reported at rates of 0.07 to 0.12 per 1000 port days in situ. 469,480,481
infection undergoing subsequent high-dose cytotoxic therapy. 21,65,445,462 The definitive diagnosis of catheter-related bloodstream infection
Voriconazole reduced this event rate to 6.7% in allogeneic HSCT recipi- (CRBSI) requires concordance in the bacterial isolate recovered from a
ents with previous proven/probable invasive fungal infection. 463 peripheral blood culture and the isolate grown from the catheter tip. In
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■ INDWELLING CENTRAL VENOUS ACCESS DEVICE INFECTIONS this situation, the catheter should be removed, though this is not always
possible in patients with limited venous access. Alternatively, paired and
Indwelling central venous catheters (CVCs) have long been recognized site-labeled blood cultures should be obtained from a peripheral vein
as a source of sepsis for critically ill cancer patients. This topic has been and from the hubs of the CVC lumens. 482-484 Quantitative blood cultures
the subject of numerous reviews. 348,464-466 CVC-related infections may are the most predictive for CRBSI; however, few clinical microbiology
be categorized as systemic, which include CVC-related bloodstream laboratories offer such testing. The differential time to positivity as a cri-
infections, or localized, which include skin and soft tissue infections terion for CRBSI requires that bacterial growth in a blood culture drawn
involving the exit site (the site from which the catheter egresses the from a CVC hub occur at least 2 hours before the growth is detected in
skin), tunnel site (the subcutaneous track extending from the exit site to blood cultures drawn from a peripheral vein.
the insertion site), insertion site (the site at which the catheter cannu- Empirical antibacterial therapy of suspected but unproven CRBSI
lates the vein), or the subcutaneous surgical pocket created for implant- should include combination antibacterial therapy targeting multidrug
able venous access ports systems. resistant gram-negative bacilli such as Pseudomonas aeruginosa as well as
There are four types of central venous access catheter devices com- S aureus and methicillin-resistant CoNS. The choice of the antibacte-
485
monly used in cancer patients: nontunneled CVCs, tunneled CVCs, rial agent for gram-negative bacilli should be based on local susceptibility
subcutaneous indwelling ports systems, and peripherally inserted patterns and upon the severity of the clinical syndrome. Methicillin-
210
central venous catheters (PICC). Infection rates related to these sites resistant CoNS are the most common pathogens causing CVC-related
are commonly expressed as a function of the number of days with infections. Accordingly, vancomycin for suspected CRBSI is recom-
the catheter in situ. These are usually expressed as infections per 1000 mended for health care facilities where methicillin-resistant CoNS and
catheter-days. 467,468 MRSA are prevalent. 21,348 Since vancomycin-driven clearance of MRSA

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