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600 PART 5: Infectious Disorders

• Botelho-Nevers E, Thuny F, et al. Dramatic reduction in infec-
tive endocarditis related mortality with a management based of less than 5 to 7 days. This pattern of neutrophil recovery influences
approach. Arch Intern Med. 2009;169(14):1290-1298. the natural history of febrile neutropenic episodes.
• Fayad G, Vincentelli A, Leroy G, et al. Impact of antimicro- • Febrile episodes during neutropenia are defined by an oral tempera-
bial therapy on prognosis of patients requiring valve surgery ture of ≥38.3°C (100°F) in the absence of other noninfectious causes
during active infective endocarditis. J Thorac Cardiovasc Surg. of fever such as administration of blood products or pyrogenic drugs
2014;147(1):254-258. (eg, cytotoxic therapy, amphotericin B), the underlying disease,
thromboembolic or thrombophlebitic events, or hemorrhagic events.
• Gouello J, Asfar P, et al. Nosocomial endocarditis in the intensive
care unit: an analysis of 22 cases. Crit Care Med. 2000;28:377-382. • A single neutropenic episode may be characterized by one or more
febrile episodes, of which one or more may represent infections.
• Lalani T, Cabell CH, et al. Analysis of the impact of early surgery
on in-hospital mortality of native valve endocarditis. Circulation. • Body sites most often associated with infection in the neutropenic
2010;121:1005-1013. patient are those associated with integumental surfaces (skin, upper
and lower respiratory tract, and upper and lower gastrointestinal tract).
• Mermel LA, Allon M, et al. Clinical practice guidelines for the
diagnosis and management of intravascular catheter-related infec- • Antibacterial prophylaxis with oral fluoroquinolone agents such as
tion: 2009 update by the infectious diseases society of America. ciprofloxacin or levofloxacin can reduce the frequency of febrile epi-
Clin Infec Dis. 2009;29:1-45. sodes and bacteremic events in patients with protracted neutropenia.
• O’Grady, Barie PS, et al. Guidelines for evaluation of new fever in • Patients undergoing remission induction for acute myeloid leuke-
critically ill adult patients: 2008 update from the American col- mia or bone marrow transplantation with a history of herpetic sto-
lege of critical care medicine and the infectious diseases society of matitis or who are IgG seropositive for herpes simplex virus (HSV)
America. Crit Care Med. 2008;36:1330-1349. are at risk for severe herpetic mucositis. Such patients should be
considered for oral nucleoside analogue-based antiviral prophylaxis.
• Pronovost P, Needham D, et al. An intervention to decrease
catheter related bloodstream infections in the ICU. N Engl J Med. • The recommended initial empirical antibacterial therapy for
2006;355(26):2725-2732. suspected infection in the febrile neutropenic patient is a broad-
spectrum antibacterial regimen of an antipseudomonal penicillin
• Safdar N, Fine JP, Maki DG. Meta-analysis: methods for diagnosing or carbapenem administered as a single agent (monotherapy).
intravascular device-related bloodstream infection. Ann Intern Additional initial antibacterial agents such as aminoglycosides,
Med. 2005;142:451-466. fluoroquinolones, or vancomycin may be indicated for the initial
• Wilson W, Taubert KA, et al. Prevention of infective endocarditis: management of severe sepsis/septic shock, pneumonia, or where
guidelines from the american heart association. Circulation. antimicrobial resistance is suspected.
2007;116:1736-1754. • The median time to defervescence for febrile neutropenic patients
at low- and high-risk for medical complications is 3 and 5 days,
respectively.
REFERENCES

Complete references available online at www.mhprofessional.com/hall INTRODUCTION
Critical care physicians are often called on to provide support for
patients with various inherited or acquired defects in host defense that
render them susceptible to potentially lethal infections. Patients with
CHAPTER Approach to Infection single host defense system defects (eg, congenital agammaglobulinemia)
are susceptible to encapsulated respiratory pathogens such as Strepto-
68 in Patients Receiving coccus pneumoniae that require opsonizing antibodies for clearance.
Cytotoxic Chemotherapy In contrast, cancer patients undergoing potentially curative high-
intensity myeloablative cytotoxic therapy acquire defects in multiple
for Malignancy host defense systems that lead to increased susceptibility to different
groups of pathogens normally contained and controlled by the absent
E. J. Bow or damaged systems.
The host immune response is mediated by the innate and adap-
tive defense systems. The former is mediated by pattern recognition
KEY POINTS receptors each with broad spectrum of specificities for genetically
• Risk of infection increases as the circulating absolute neutrophil conserved and stable antigenic characteristics of pathogenic micro-
1
count (ANC) declines below 1.0 and 0.5 × 10 /L. The greatest risk organisms. The latter, the adaptive immune system, is mediated by a
9
of bacteremic infection occurs when the ANC is <0.1 × 10 /L. diverse array of antigen receptors with random but narrow-spectrum
9
2
• Cytotoxic therapy for remission-induction therapy for acute myeloid specificities clonally distributed on B and T lymphocytes. Four broad
categories of defects in host defense are clinically relevant: disrup-
leukemia or conditioning therapy for bone marrow transplantation tion of the integumental surfaces, quantitative neutrophilic phagocyte
(high-risk patients) is associated with periods when the ANC is defects, diminished B-lymphocyte (humoral) function, and diminished
<0.1 × 10 /L for 14 to 21 days. The time to marrow recovery (ANC T-lymphocyte system function. A working knowledge of the sources
9
>0.5 × 10 /L) can vary from 21 to 42 days. of failure in these host defense systems is particularly important for
9
• Intermittent administration of cytotoxic therapy for solid tissue predicting the pathogens likely to be driving life-threatening infections.
malignancies or lymphoreticular malignancies (low-risk patients) is This, in turn, provides a basis for a rational approach to the choice of
often associated with a neutrophil nadir at 10 to 14 days from begin- antimicrobial therapy. This chapter reviews the approach to managing
ning treatment and with periods of neutropenia (ANC <0.5 × 10 /L) suspected or proven infection in patients with multiple defects in host
9
defense systems, with a particular emphasis on patients undergoing

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