Chapter 15 - The Immunocompromised Host - APIC Text Online

7/29/13 Chapter 15 – The Immunocompromised Host - | APIC Text Online
Chapter 15 – The
Immunocompromised Host
George F. Risi, Jr., MD, FACP, FIDSA, FSHEA

Infectious Disease Specialists, PC
Missoula, Montana
APIC recognizes and appreciates the contributions made to this chapter by prior authors.
Copyright © 2013 by the Association for Professionals in Infection Control and Epidemiology, Inc. (APIC)
All rights reserved. Intended for personal use only. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form
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ABSTRACT
Infectious diseases cause significant morbidity and mortality in immunocompromised patients. The
timing and specific type of infection is often predictable and may be preventable. This chapter
provides a practical overview of the broad topic of the immune compromised host and prevention of
infection, focusing on specific types of immune compromise and the types of infection associated with
them. Methods of augmenting host resistance are discussed, as well as techniques to avoid exposure to
potential pathogens. Topics have been chosen to include areas of care that differ from those of the
immune competent patient, including isolation, immunizations, augmentation of host resistance, and
antimicrobial prophylaxis. National practice guidelines are cited, when available, and, where no
consensus exists, practical recommendations based on available literature are provided. A systematic
approach to care of the immunocompromised host, tailored to the needs of each individual patient,
will reduce the risk of infection.
KEY CONCEPTS
Several categories of immune compromise exist, and some patients may have more than
one type.
Thorough history taking and detailed physical examination often reveal potential problems.
Host resistance to infection can often be augmented.
Avoidance of hospitalization is desirable, whenever feasible.
Consistent use of hand hygiene as well as standard and category-specific isolation
guidelines are the most important of all interventions.
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BACKGROUND
The immunocompromised host is a person with impairments in the body’s normal mechanisms of
defense against infection. A review of normal host defenses is beyond the scope of this chapter,
but references to recent discussions of the topic can be found in Supplemental Resources. Several
categories of host abnormality that are commonly associated with impaired resistance exist.
Within these broad categories, variations in immunologic function are recognized. The degree of
impairment may wax or wane with time and therapy. Comprehensive management of the
immunocompromised host entails all of the following elements: (1) recognition of the categories
of host defects that are associated with impaired resistance, (2) knowledge of the type of infection
to anticipate in each category of immune compromise, (3) the most common portals of entry for
opportunistic organisms, (4) the fact that clinical manifestations of illness may be different in the
immunocompromised host, and (5) an understanding of the broad array of modalities for
prevention of infection.
BASIC PRINCIPLES
Recognition and Characterization of the Immunocompromised Host
The immunocompromised host is an individual who has one or more defects in the body’s normal
defense mechanisms that predisposes him or her to infections, often life threatening, that would
otherwise not occur. These individuals continue to be at risk for common infections as well, but
these may pursue a more aggressive course than they might otherwise. The number and type of
immunocompromised hosts are constantly increasing for several reasons, including the aging of
the U.S. population, medical advances that have kept alive persons who previously would have
died of their underlying disease, pandemic infection by human immunodeficiency virus (HIV) and
hepatitis B (HBV) and C (HCV) viruses, homelessness and the resultant lack of basic hygiene and
good nutrition, the obesity epidemic, tobacco and recreational drug abuse, diminishing access to
primary care with resultant late diagnosis of diseases, and immigration of persons from
developing parts of the world where exotic and potentially immunocompromising infectious
agents are endemic.
The categories of host defects that are commonly associated with impaired resistance are listed in
Table 15-1.
Within these categories, broad variations in immunological function are recognized. Most patients
have abnormalities that may wax or wane with time and therapy. For this reason, the individual
patient’s risk of infection is best evaluated by defining his or her net state of
immunosuppression.1
Table 15-1. Categories of Host Defect That Are Associated With Impaired Resistance
I.Defects in the cutaneous barrier to invasion of endogenous or acquired organisms
A. Surgical incisions
B. Thermal or chemical burns
C. Traumatic injuries to the skin
D. Severe dermatologic conditions
1. Poorly controlled eczema or psoriasis
2. Scleroderma
3. Mycosis fungoides
4. Chronic fungal infections of the skin or nail beds
E. Indwelling intravenous lines, either temporary or long term
F. Injections, either legal/medicinal or illicit
G. Ulcers: decubitus, diabetic, vascular insufficiency, others
II. Mucous membrane barrier defects
A. Mucositis induced by irradiation or chemotherapy

B. Trauma to the head and neck
C. Smoking (tobacco, recreational drugs)
D. Inhalation injuries (heat, smoke, caustic chemicals, recreational drugs)
E. Poor oral hygiene
F. Erosions from nasogastric or endotracheal tubes or indwelling Foley catheters
G. Antacids, proton pump inhibitors, etc.
1. Decrease the number of ingested organisms necessary to cause gastrointestinal
disease, including Clostridium difficile
2. Allow a reservoir of bacteria to develop in the stomach, which can be regurgitated and
aspirated
III. Conditions that cause obstruction of a natural body passage
A. Tumors of the lung, gastrointestinal tract, pancreatic head, elsewhere

B. Foreign bodies: aspiration, endotracheal tubes
C. Renal stones, gallstones
D. Prostatic enlargement
E. Cystic fibrosis
IV. Abnormal number or function of granulocytes
A. Leukemia
B. Chemotherapy for malignant disease
C. Aplastic anemia
D. Granulocytopenia as an adverse drug reaction
E. Dysfunctional granulocytes despite normal numbers
1. Diabetes mellitus, especially if poorly controlled
2. Corticosteroid administration
3. Rheumatoid arthritis
4. Renal failure
5. Congenital disorders of phagocyte function: Chediak-Higashi syndrome, chronic
granulomatous disease, hypereosinophilic (Job) syndrome, others
V. Abnormalities of cell-mediated immunity
A. Bone marrow transplantation

B. Human immunodeficiency virus (HIV) infection
C. Chemotherapy for malignancy
D. Tumor necrosis factor inhibitors for rheumatologic disorders and Crohn’s disease
E. Aging
F. Hodgkin’s disease, non-Hodgkin’s lymphoma
G. Corticosteroid administration
H. Third trimester of pregnancy
I. Severe malnutrition
VI. Abnormalities of humoral immunity
A. Bone marrow transplantation

B. HIV infection
C. Chronic lymphocytic leukemia
D. Multiple myeloma and Waldenström’s macroglobulinemia
E. Aging
F. Childhood immunoglobulin deficiencies
G. Acquired hypogammaglobulinemia (common variable immunodeficiency)
VII. Patients with defects in multiple arms of immunity
A. Aging
B. Severe trauma
C. Alcoholism, chemical dependency
D. Malnutrition
E. Obesity
F. Splenectomy
G. Organ failure (cirrhosis, chronic renal failure with or without hemodialysis)
H. Spinal cord injury
I. High-dose corticosteroid administration
J. Chemotherapy
The net state of immunosuppression is determined by the interaction of several variables,

including: (1) host-defense defects caused by the disease process itself; (2) the type of
immunologic abnormality induced by a specific agent; (3) the dose, duration, and temporal
sequence of immunosuppressive therapy; (4) the presence or absence of neutropenia and/or
lymphopenia; (5) the state of humoral and cellular host defenses; (6) the integrity of the skin (to
include presence or absence of an indwelling intravenous catheter) and mucosal surfaces of the
body; (7) metabolic factors, such as malnutrition, uremia, hyperglycemia, and hepatic dysfunction;
(8) abnormalities of the reticuloendothelial system, most notably the absence of splenic function;
and (9) the presence or absence of immunomodulating infections, such as HIV, hepatitis viruses,
cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human herpesvirus 6 (HHV-6).1–3
Additional stressors include smoking,4 injecting drug use,5 obesity,6 and alcoholism.7,8 The net
state of immunosuppression not only determines the risk of infection, the type of infection to be
anticipated, and the need for prevention, but it also influences the degree of effectiveness of
intervention attempts.
Opportunistic Organisms That Most Often Cause Disease in the Immunocompromised Host
In the immune-intact individual, only a relative handful of pathogens are able to cause disease.
These have been called “true pathogens” and include, for example, such “classic” organisms as
influenza, Salmonella typhi, Yersinia pestis, Bacillus anthracis, and Corynebacterium diphtheriae.
Certain exotic diseases, such as the hemorrhagic fever viruses, fall into this category as well.9 As
the host becomes progressively more immunocompromised, progressively less virulent
organisms are able to become pathogenic. Thus, patients with major immune defects are subject
to a larger number and greater variety of infectious diseases. A recent survey identified 1407
currently recognized species of human pathogen, many of which have been described only
recently.10 It can be anticipated that this list will continue to enlarge as the result of such forces as
population growth, climate change, habitat destruction, or encroachment on wilderness habitats
that are reservoirs for animals that harbor novel infectious agents.11
Although the classic pathogens also cause disease in the immunocompromised host, often their
presentation is different than would be seen in the healthy individual.
Table 15-2 lists the organisms that are commonly considered opportunistic in the setting of
different types of immune compromise.
Opportunistic Organisms Encountered Internationally
Increasing numbers of individuals reside in the United States who were born in the developing
world. A variety of organisms that are uncommon in the United States are endemic in developing
countries and may be associated with worsening chronic disease or reactivation in the setting of
immunosuppression.12,13
Table 15-2. The Most Common Opportunistic Infections Associated With Specific Immune Deficits
I. Breaks in cutaneous integrity: invasion by skin flora organisms
A. Staphylococcus aureus, coagulase-negative species of Staphylococcus

B. Streptococcus pyogenes (group A beta-hemolytic Streptococcus)
C. Corynebacterium spp. (aka "diphtheroids")
D. Malassezia furfur, if lipid-containing intravenous infusions are being given
II. Defects in mucous membranes, with invasion by resident flora
A. Anaerobic bacteria (Bacteroides fragilis, Clostridium perfringens, C. septicum)

B. Aerobic Gram-negative bacilli
C. Candida spp. and Torulopsis glabrata
D. Enterococcus spp. and Streptococcus bovis
III. Obstruction of a natural body passage: overgrowth or invasion (or both) by resident flora
A. Lung: oral flora; if patient is hospitalized, nosocomial Gram negatives, Staphylococcus aureus,
including methicillin-resistant S. aureus
B. Biliary and pancreatic system: aerobic Gram-negative bacilli, Enterococcus, anaerobes
C. Colon: aerobic Gram-negative bacilli, anaerobes, Streptococcus bovis.
IV. Granulocytopenia (defined as absolute neutrophil count <500/mL)
A. Duration of 2 weeks or less: aerobic Gram-negative bacilli, S. aureus, and coagulase-negative

Staphylococci
B. Duration of more than 2 weeks: the above plus Candida spp., T. glabrata, Aspergillus spp.
V. Dysfunction of cell-mediated immunity
A. Bacteria: primarily intracellular pathogens

1. Listeria monocytogenes
2. Salmonella spp.
3. Mycobacterium spp., including M. tuberculosis
4. Nocardia (N. asteroides, others)
5. Legionella pneumophila, other species of Legionella
6. Rhodococcus equi
7. Pseudomonas pseudomallei
B. Fung
1. Cryptococcus neoformans
2. Candida spp. and T. glabrata
3. Coccidioides immitis
4. Histoplasma capsulatum
5. Penicillium marneffei
6. Pneumocystis jiroveci
C. Viruses
1. Herpes group, especially cytomegalovirus, herpes zoster
D. Protozoa
1. Toxoplasma gondii
2. Cryptosporidium spp. (C. parvum, others)
E. Helminths
1. Strongyloides stercoralis
VI. Splenectomy or humoral dysfunction-encapsulated bacteria
A. Streptococcus pneumoniae
B. Encapsulated strains (especially type B) of Haemophilus influenzae

C. Neisseria meningitidis
Internationally Acquired Infections That May Go Unrecognized for Prolonged Periods
Strongyloides stercoralis
Trematodes such as Schistosoma spp., Fasciola, Opisthorchis, Clonorchis, Paragonimus
Pseudomonas pseudomallei
Hydatid disease (Echinococcus spp.)
Trichinella spiralis
Tapeworms, especially Taenia solium
Nematodes (Onchocerca volvulus)
HTLV-1/2
Trypanosoma cruzi (Chagas disease)
The Source of the Infection May Be Endogenous, Exogenous, or Both
Isolation of a specific microorganism may at times allow its source of origin, either endogenous or
exogenous, to be deduced (Table 15-3). This is helpful in determining the optimal way to proceed
with individual patients. Note that organisms that arise from an endogenous source in one patient
may then be transmissible to healthcare workers or other patients.
Most Important Portals of Entry for Opportunistic Organisms
Skin
The skin is an important portal, especially for individuals with long-term venous access devices
and patients with major defects in skin integrity, such as burns. In one recent review of the
microbiology of burn wounds Staphylococcus aureus and Pseudomonas aeruginosa were the two
dominant organisms, representing 23% and 19% of all isolates from burn wounds, respectively.
The majority of the remainder of isolates fell into seven genera (Table 15-4).14 However,
microbiologic patterns differ among institutions and evolve over time. Mehta et al15 found
diminishing importance of Pseudomonas aeruginosa and Staphylococcus aureus in comparison of
isolates from 1997 to 2002 and from 2002 to 2005, with increasing prevalence of Acinetobacter,
Klebsiella, and other Gram-negative rods. Enterococcus may play a role in some centers.16 Thus, in
choosing empiric antibiotic regimens it is important to review the recent patterns from an
individual institution. Finally, the emergence of methicillin resistance among Staphylococcus aureus
has become a major concern for all institutions.17,18
Table 15-3. Sources of Opportunistic Infection
I. Opportunists that are more commonly (but not exclusively) endogenous
A. Mycobacterium tuberculosis (lung, lymphatics, others)

B. Coagulase-negative Staphylococci (skin)
C. Corynebacterium spp. (skin)
D. Enterococcus spp. and Streptococcus bovis (gastrointestinal tract)
E. Clostridium septicum (gastrointestinal tract)
F. Candida spp. and Torulopsis glabrata (oropharynx and gastrointestinal tract)
G. Coccidioides immitis (lung, liver, spleen, others)
H. Histoplasma capsulatum (lung, liver, spleen, others)
I. Malassezia furfur (skin)
J. Pneumocystis jiroveci (lungs, rarely elsewhere)
K. Toxoplasma gondii (central nervous system)
L. Herpes simplex and herpes zoster (skin and mucous membranes)
II. Opportunists that are more commonly (but not exclusively) exogenous
A. Clostridium difficile (hands of personnel, fomites)

B. Legionella pneumophila (tap water and air conditioning systems, spread by aerosols)
C. Rhodococcus equi (soil)
D. Aspergillus spp. (ventilation systems, especially during construction or demolition)
E. Zygomycetes (ubiquitous in the environment)
F. Rapidly growing mycobacteria such as M. fortuitum, M. chelonei (environmental sources)
G. Cryptosporidium (water supplies)
H. Viruses other than herpes group (hands, droplet nuclei, fomites occasionally)
III. Opportunists that can be either endogenous or exogenous
A. A. Aerobic Gram-negative bacilli

1. Endogenous from oropharynx and gastrointestinal tract
2. Exogenous from aerosols, contaminated food, fomites
B. Staphylococcus aureus
1. Endogenous as resident skin flora, nasal carriage
2. Exogenous from hands of personnel
Table 15-4. Bacteria and Fungi That Constituted 1830 Isolates Recovered From 1234 Burn
Wound Infections: NNIS System, CDC, 1980–1998
Pathogen Number of Isolates (%)

Staphylococcus aureus 420 (23)
Pseudomonas aeruginosa 353 (19.3)
Enterococcus spp. 202 (11)
Enterobacter spp. 176 (9.6)
Escherichia coli 131 (7.2)
Coagulase-negative staphylococci 78 (4.3)
Candida albicans 64 (3.5)
Serratia marcescens 64 (3.5)

Klebsiella pneumoniae 48 (2.6)
Others 294 (16)
Oropharynx
Hospitalization is associated with acquisition of nosocomial organisms within the oropharynx that
replace the normal flora.19, 20 The presence of a nasogastric tube changes the ecosystem of the
oropharynx, with increased prevalence of P. aeruginosa.21 Nasotracheal or orotracheal intubation
also predisposes to colonization with nosocomial organisms and leads to nosocomial pneumonia
due to blockage of sinus drainage, mechanical trauma to the mucosa, impaired swallowing of
secretions, adherence of bacteria to a foreign body, pooling of secretions around the cuff,
mucosal ischemia around the cuff, and impaired ciliary clearance and cough.22 From the
oropharynx affected by chemotherapy, thermal burn, or radiation, local invasion into the
bloodstream can occur by the members of the normal oropharyngeal flora (Table 15-3) or
nosocomial organisms.
Lung
The lung is the common portal of entry for Mycobacterium tuberculosis, Aspergillus spp., and
regionally important fungi, such as Coccidioides immitis, Histoplasma capsulatum, Penicillium
marneffei, and Paracoccidioides brasiliensis. Within the gastrointestinal tract, due to decreased acid
production, use of enteral feeding, and stress ulcer prophylaxis, the stomach becomes colonized
with bacteria, particularly Gram negatives.23 The contribution of this site as a potential source of
nosocomial pneumonia continues to be a topic of debate, with studies demonstrating from no role
to up to 15% of patients with pneumonia having the stomach as the source of pneumonia. 23
Gastrointestinal Tract
In the neutropenic host, the gastrointestinal tract is the most important source for bacteremia as
the result of transmigration across the mucosal barrier.24
Clinical Manifestations of Disease May Be Different in the Immunocompromised Host Versus the
Intact Host
The immunocompromised host may present with a very different clinical picture than the intact
host. The pace of disease may be much more rapid. This is especially true in the asplenic patient
presenting with bacterial infection and the neutropenic patient. Seemingly trivial problems may
rapidly become life threatening. Neutropenic patients have little purulence at the site of infection
and less obvious chest radiographic findings. Elderly patients may have confusion or incontinence
as their only manifestation of infection. Patients receiving corticosteroids may have diminished or
absent fever response. Patients who are sedated or have central nervous system dysfunction
perceive pain less well and are less able to articulate a problem to the examiner. Finally, the white
blood cell count may be in the normal or even low range but demonstrate an increased number
of immature (band) forms.
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PREVENTING INFECTION IN THE IMMUNOCOMPROMISED

HOST
Identify and Address Specific Problems Before the Patient Is Subjected to Immunocompromising
Procedures
A thorough history and a detailed physical examination are essential in the care of the
immunocompromised patient. Potential problems can be identified in a careful interview, which
may be supplemented with a printed questionnaire for consistency.
The patient may provide information about previous infections that imply specific types of
immune dysfunction (Table 15-2).
A complete listing of all medications should include all over-the-counter medications. In addition,
patients may seek dual services with traditional as well as alternative healthcare providers and
may be taking substances in the forms of teas, food additives, or pills that, although “natural,” may
still affect the immune system.25,26 These substances should also be noted on the intake form.
Birthplace and geographical areas of residence or extensive travel are important clues to
potential latent infections. Pet ownership; hobbies; and recreational activities, such as spelunking,
hiking and camping, and hunting or fishing may expose the patient to zoonotic infections. The
patient’s sexual history should be obtained, including the incidence of sexually transmitted
diseases and their treatments, as well as the history of drug use, including quantity of alcohol
consumption; oral, inhaled or injectable illicit substances; and misuse of prescription drugs.
Finally, a meticulous systems review and physical examination should be performed.
Routine lab work should include a complete blood count with differential, a chemistry panel that
includes a measurement of liver enzymes, renal function, and electrolytes. Nutritional status can
be assessed by calculation of the body mass index (weight in kg/square of the height in meters)
along with serum albumin, transferrin, and total lymphocyte count.
Patients requiring long-term venous access should have such devices placed well in advance of
any immunosuppressive therapy. Central venous access should be obtained using sterile
technique, including donning of masks, gowns, sterile gloves, and the use of a sterile drape.
Detailed recommendations regarding strategies to prevent central venous line-associated
bloodstream infections have recently been published.27 Two percent aqueous chlorhexidine
gluconate used as skin preparation has been shown to lower the incidence of bloodstream
infection compared with the use of either 10% povidone iodine or 70% alcohol.28 The use of
antiseptic- or antimicrobial-impregnated central venous catheters, use of chlorhexidine-
containing sponge dressings, and antimicrobial locks have all recently received favorable
recommendations for patients who are at high risk for severe sequelae from a central line-
associated bloodstream infection.27 Any needed dental work should be completed before therapy
is administered. Patients who smoke should be strongly encouraged to quit or at least reduce
their consumption4 because smoking can increase the severity of a variety of respiratory viral
illnesses and can exacerbate mucositis induced by chemotherapy or radiation. Any chronic skin,
scalp, or nail bed condition should be addressed and brought under control as much as possible
before rendering the immune system more compromised.
Potential recipients of solid organ transplant should be screened in advance of the transplant for
latent infection. The aims of such screening are fourfold29: (1) to determine the immune status of
the recipient against common pathogens that can be transmitted by transplants. This is because
established immunity against pathogens, such as cytomegalovirus, Toxoplasma gondii, and
possibly HBV, protects the recipient from severe sequelae of infection with these agents; (2) to
permit the allocation of organs from donors infected with a certain pathogen to recipients who
are already carriers of this agent, such as HCV infection; (3) to recognize and possibly treat
infections that can be expected to exacerbate or reactivate after immunosuppression, such as
tuberculosis, the endemic mycoses histoplasmosis and coccidioidomycosis, or parasites, such as
Strongyloides stercoralis; and (4) to avoid transplantation in patients with a poor prognosis after
transplantation, such as advanced HIV infection or colonization with multidrug-resistant bacteria.
Augmentation of Host Resistance
Gastric Acidity
Gastric acid is an important defense mechanism against bacterial pathogens and, in general,
should not be neutralized in an immunocompromised patient. With a normal gastric acid barrier,
the majority of ingested pathogens never reach the intestinal tract to cause disease. Neutralization
of this barrier may increase the susceptibility to and severity of a variety of bacterial and parasitic
diseases,30–37 including Clostridium difficile.38 In the hospitalized patient, the stomach can serve as
a reservoir for overgrowth of nosocomial Gram-negative bacteria when acidity is neutralized.23,39
These bacteria may serve as a reservoir for aspiration after regurgitation.23
Immunizations
Patients should be up to date on all routine immunizations.40 The Advisory Committee on

Immunization Practices (ACIP) divides patients with immunocompromising disorders into three
practical categories: group 1, patients with HIV infection; group 2, patients with severe
immunosuppression not caused by HIV; and group 3, patients with other conditions that cause
limited immune deficits, such as asplenia, renal failure, diabetes, and alcoholism. In general,
inactivated vaccines can be administered to patients in all three categories. Live virus vaccines are
generally contraindicated in all patients in group 2, in some patients in group 1, and in no patients
in group 3. The ACIP has recently published a recommended immunization schedule by age group
and medical condition.41
Herd immunity against Streptococcus pneumoniae has developed in regions of the United States
since introduction of the protein conjugate vaccine for children. This has resulted in marked
decreases in the rate of invasive pneumococcal disease among adults, including those with
immune compromise.42,43 The logical extension of these regional observations is to improve the
use of protein conjugate pneumococcal vaccines in children in other communities. The use of
conjugate pneumococcal vaccines in adults is an area of active research, with promising
preliminary results.44,45 Because the protective efficacy of influenza vaccination in the elderly
may be diminished,46 it becomes particularly important for those involved in their care or
residing in the same household to have been immunized.47
Vaccines will likely play an increasingly important role in disease prevention in the future. A
variety of investigational uses for vaccines are under study, including vaccination for S. aureus in
chronic hemodialysis patients48 and other populations,49 vaccination against P. aeruginosa
infections for hospitalized patients50 and for patients with cystic fibrosis,51,52 immunization
against the endotoxin of Gram-negative bacteria,53,54 and vaccination of trauma victims against
Klebsiella and Pseudomonas.55 Better protection for the immunocompromised patient will likely
require the development of more effective adjuvants as well.56,57
Immunization in Recipients of Transplanted Organs (Autologous or Allogeneic Bone Marrow

Transplants, Solid Organ Transplants)
Despite the burden of illness due to vaccine-preventable diseases in transplant recipients,

licensed vaccines remain underutilized. One reason for this may be concern that immunization
might trigger allograft rejection. Several recent studies have shown the lack of excess incidence of
rejection and the general safety of vaccinations in organ transplant recipients.58
In general, vaccines are more likely to be effective in persons whose immune system is
functioning normally than in a compromised host. The more compromised the host, the less
effective the vaccine is likely to be. For transplant patients of all types, therefore, it is desirable to
update all immunizations in advance of a transplant.59,60
Recipients of transplanted marrow or stem cells experience severe immunosuppression for

several months after transplantation. This immunosuppression occurs regardless of the type of
graft (autologous, syngeneic, or allogeneic), the underlying disease, the conditioning and
preparative regimens, and whether graft-versus-host disease (GVHD) develops. Even in the
absence of GVHD, reconstitution of a fully functioning immune system occurs slowly during the
course of several months to years. Thus, interest is considerable in modalities to prevent infection
during the period after transplantation. The literature supports the use of vaccinations, and
standard preparations can be used effectively. Poor responses to vaccination can be expected for
at least the first 6 months after transplantation. Detailed recommendations have recently been
published for immunization of hematopoietic stem cell transplant recipients.61 Recommendations
include the use of tetanus/diphtheria; Haemophilus influenzae type B; hepatitis B; 23 valent
Streptococcus pneumoniae vaccine; inactivated polio vaccine; annual influenza (beginning ≥6
months after transplantation); and at 24 months after transplant, use of varicella vaccine, as well
as measles, mumps, and rubella (MMR) vaccine (assuming no active GVHD or immunosuppressive
therapy).
Because of the ongoing use of immunosuppressive medications, solid organ transplant recipients
are at risk of life-threatening infections indefinitely. Specific vaccinations have been recommended
for these patients, to include pneumococcal, influenza, Neisseria meningitidis, and hepatitis A and
B. Also indicated are tetanus, diphtheria, and Haemophilus influenzae type B. The safety of live
attenuated vaccines is unknown. Some of them are absolutely contraindicated, including oral
polio, vaccinia, bacillus Calmette-Guerin, and live oral typhoid. Yellow fever vaccine is not
recommended.62 Varicella vaccine is not recommended. Specific vaccination recommendations for
solid organ transplant recipients have recently been published.60
Passive Immunization With Either Intramuscular or Intravenous Immune Globulin
The administration of preformed donor antibody by either the intramuscular or intravenous

route has a long-established role in the prevention of infection. It is indicated as postexposure
prophylaxis in susceptible patients exposed to such diseases as hepatitis A, hepatitis B, tetanus,
rabies, and varicella. Intravenous immune globulin (IVIG) has been used for the treatment of
primary and secondary antibody deficiencies for decades.63–65 Many other potential uses have
been investigated or are currently under investigation. Human trials of IVIG to prevent infections
in high-risk postoperative, trauma, and burn patients have been inconclusive.66,67 Similarly, IVIG-
based treatment and prophylactic strategies for bacterial sepsis have yielded inconsistent results.
A systematic review in 2002 concluded that current evidence is inconclusive regarding the clinical
benefit of adjunctive IVIG therapy for the treatment of sepsis and septic shock,68 but a meta-
analysis of studies performed between 1966 and 2006 demonstrated a survival benefit.69 Early
encouraging reports in treatment of recurrent sinopulmonary infection and low–birth-weight
infants70,71 have not been substantiated in larger clinical trials.72 IVIG is not generally
recommended for routine oncology patients but may be indicated in selected patients with
chronic lymphocytic leukemia and hematopoietic stem cell transplant recipients. The studies
performed in patients with chronic leukemia showed a reduction in infectious episodes occurring
in patients with less than 600 mg/dL of immunoglobulin G with monthly IVIG administration,
provided it was performed for a minimum of 6 months.73,74 Trials performed in hematopoietic
stem cell transplant recipients demonstrated that in the absence of hypogammaglobulinemia,
monthly administration of IVIG did not reduce late complications and might impair long-term
humoral recovery after transplantation.75 Because of the several controversies that still exist
regarding the use of IVIG in these populations, such as cost, availability of the product, and
appropriate doses, the suggestions of Egerer et al76 are reasonable: use of 250 to 400 mg/kg
every 4 weeks in patients with marked hypogammaglobulinemia and with more than two recent
severe infections.
IVIG is being used increasingly for a variety of infectious and noninfectious disorders, including
acute inflammatory disorders, hematologic disorders, autoimmune diseases, and
neuroimmunologic disorders.63 An expert panel has published consensus guidelines for the use
of therapeutic IVIG.77 The Food and Drug Administration (FDA) has approved the use of virus-
specific monoclonal antibodies against respiratory syncytial virus and cytomegalovirus.63
Granulocyte Transfusions
The transfusion of donor leukocytes to augment resistance in chemotherapy-induced neutropenia

was once commonly used. However, minimal benefit was gained, primarily because of the small
numbers of granulocytes that could be harvested from donors. In addition, adverse reactions
were common, including fever, alloimmunization, and transmission of CMV.78 For these reasons,
granulocyte transfusion became relatively uncommon.
Recent developments, including improved donor screening and use of colony-stimulating factors
to improve the harvest from donors, could lead to increased use of granulocyte transfusion in a
subset of the neutropenic population. The patients most likely to benefit from this would be those
with profound and sustained neutropenia or neutropenic patients with infection not responding
to antimicrobial therapy.79 However, a review of 66 observational studies of granulocyte
transfusions in neutropenic children (age, 1–18 years) performed over 30 years showed no
evidence of a positive benefit risk ratio.80 And a Cochrane review performed in 2003 found
inconclusive evidence from randomized controlled trials to either support or refute the use of
this modality. Heterogeneity between studies and methodological deficiencies presented
significant obstacles to their review. The authors concluded that “contemporary well designed
prospective trials are required to evaluate the efficacy of this intervention in these patient
populations and to establish definitively whether it has clinical benefit. In such studies, average
numbers of collected granulocytes for adults should be at least greater than 1 x 1010.”81 Because
of the short half-life of granulocytes, which necessitates daily transfusion; the technical difficulties;
and the discomfort to the donor of harvesting techniques, as well as improved chemotherapeutic
regimens and availability of colony-stimulating factors, it is unlikely this modality will become
commonly utilized, but it may be useful in selected patients.
Colony-Stimulating Factors
The colony-stimulating factors (CSFs), granulocyte colony-stimulating factor (GCSF, filgrastim),

pegylated GCSF (pegfilgrastim), and granulocyte/macrophage colony-stimulating factor (GMCSF,
sargramostim) have been evaluated for prophylactic use following the administration of
chemotherapy when neutropenia is anticipated. The limited data available do not demonstrate a
difference between the use of filgrastim or that of sargamostin.82 Pegfilgrastim has a prolonged
half-life, permitting either a single dose or once-weekly dosing versus daily dosing. The agent is
considered equivalent in efficacy to filgrastim.82 The American Society of Clinical Oncology (ASCO)
recently updated its guidelines for the use of these agents. The committee unanimously agreed
that reduction in febrile neutropenia is an important clinical outcome that justifies the use of CSFs,
regardless of the impact on other factors, when the risk of febrile neutropenia is approximately
20% or higher (unlikely with most commonly used regimens). Use of CSFs as primary prophylaxis
is recommended for patients who are at high risk for febrile neutropenia based on age, medical
history, disease characteristics, and myelotoxicity of the chemotherapeutic regimen. In addition,
the use of CSFs allows a modest to moderate increase in the dose density or dose intensity of
chemotherapeutic regimens.83
There is now a widespread consensus that prolonged filgrastim therapy represents the standard
of care for relatively rare primary neutropenic disorders, such as severe congenital neutropenia,
cyclic neutropenia, and symptomatic idiopathic neutropenia.63 The use of CSFs in the
nonneutropenic host to augment neutrophil function in established infection is a topic of great
interest; however, the results in clinical trials in humans have been modest or discouraging. In
community-acquired pneumonia, a double-blind trial of filgrastim versus placebo in 756 patients
showed no overall difference in mortality or length of hospitalization.84 However, the incidence of
adult respiratory distress syndrome was lower in the treatment group. In addition, in the
subgroup with multilobar disease, the incidence of empyema or organ failure was 5.8% in the
treatment group versus 17.1% in the placebo arm. Unfortunately, two subsequent trials of septic
patients with pneumonia failed to demonstrate reductions in either mortality or
complications.85,86 In a small study of severe foot infections in diabetics, more rapid healing was
reported in the group receiving filgrastim for 7 days than that receiving placebo.87 The use of
immunomodulatory agents is an area of active research, with several agents currently undergoing
trials to include macrophage CSF, type I interferons, gamma interferon, and interleukins 1, 2, 10,
and 12.63
Reduction of Exposure to Pathogens
Isolation and Hand Hygiene
In the majority of circumstances, standard isolation guidelines88 are sufficient for protection of
most immunocompromised hosts, if they are followed strictly and are accompanied by good hand
hygiene. Hand hygiene has been the focus of extensive research recently, summarized in the
Centers for Disease Control and Prevention’s (CDC’s) Guideline for Hand Hygiene in Health-Care
Settings.89,90 Compliance among healthcare workers with guidelines for isolation and hand
hygiene continues to pose a challenge.89–92 Adherence to published guidelines is especially
important when dealing with the immunocompromised host.
Reverse isolation has been extensively studied in the granulocytopenic patient. Most studies that
showed improved outcomes for patients in reverse isolation did not adequately control for other
variables. When careful hand hygiene is utilized and food and supplies are handled appropriately,
reverse isolation offers no additional benefit in reducing infection in the typical granulocytopenic
patient,93,94 so for the typical neutropenic patient, there no longer appears to be a role for this
modality.
Recent CDC Isolation Guidelines88 recommend the use of a protective environment for allogeneic
hematopoietic stem cell transplant patients. The need for such controls has been demonstrated in
studies of Aspergillus outbreaks associated with construction. Components of the protective
environment include such engineering designs as high-efficiency particulate air (HEPA) filtration
of incoming air, directional air flow with positive room air relative to the corridor, well-sealed
rooms to prevent flow of air from the outside, ventilation to provide more than 12 air changes
per hour, scrubbable surfaces rather than upholstery and carpet, and routinely cleaning crevices
and sprinkler heads.95
Prophylactic Antimicrobials
Patients at risk for development of pneumonia caused by Pneumocystis jiroveci should receive
prophylaxis with trimethoprim-sulfamethoxazole (TMP/SMX) for the duration of that risk.
Alternatives for allergic patients include dapsone or atovaquone by mouth and pentamidine given
by inhalation.
Multiple studies have demonstrated the efficacy of prophylactic antibiotic administration to

patients with neutropenia.96 However, the appropriateness of regular use of this modality has
been called into question for three reasons. First, antibiotic prophylaxis has not been shown to
consistently reduce mortality rates. Second, the potential exists for deleterious effects from
toxicity and fungal overgrowth. Third, use of antimicrobials has been shown to cause the
emergence of antibiotic-resistant bacteria.96–98 Thus, whereas the evidence for use of prophylaxis
would be enough to warrant an A-I recommendation (good evidence to support a

recommendation for use based on evidence from one or more properly randomized, controlled
trials), the guidelines for the past several years96,99 as well as recent textbooks100,101 have not
recommended the routine use of antimicrobials for prophylaxis against bacterial infection. Still,
the issue remains unsettled. Subsequent to publication of the 2002 IDSA guidelines96 a meta-
analysis of 95 randomized trials in afebrile neutropenic cancer patients of antibiotics versus
placebo found a decreased risk for death with only a nonsignificant increased risk for
colonization with resistant bacteria.102 On the other hand, a large, randomized, double-blind,
placebo-controlled comparison of levofloxacin from the time of initiation of chemotherapy until
neutrophil recovery failed to document a survival benefit.103 Not addressed in these trials is the
clear association with escalation in the rates of use of extended spectrum fluoroquinolones and
development of diarrhea caused by Clostridium difficile, particularly the new and more virulent
NAP1 strain.104 Thus, at this time it appears prudent to utilize antibiotic prophylaxis in a selected
and judicious fashion, rather than for all patients rendered neutropenic by chemotherapy.
Among those who might be more reasonable candidates for antibiotics include those whose
underlying disease or the nature or intensity of the chemotherapy place them at much higher risk
for infection. This includes patients whose chemotherapy will result in severe mucositis and
prolonged or profound neutropenia (<100 neutrophils/mm3). The use of certain drugs, such as
alemtuzumab and pentostatin; multiple myeloma treated with myelosuppressive chemotherapy;
and hematopoietic cell transplantation are also in this category.82 Finally, personal factors, such
as willingness to comply with prescribed prophylaxis, personal hygiene habits, and environmental
(hospital or home) circumstances, should be considered.96 If prophylaxis is considered, TMP/SMX
and fluoroquinolones have been studied the most extensively. Antibiotics, if given, should be
given for as short a period as possible.96
Antifungal drugs have similarly been employed as prophylaxis in neutropenic patients. In a meta-
analysis of 64 randomized trials, systemic antifungal prophylaxis was associated with a decrease
in all-cause mortality and invasive fungal infection mortality. However, for acute leukemia patients
the reduction in all-cause mortality was only borderline significant.105 Regarding which antifungal
agent to employ, Cornely et al106 compared fluconazole, itraconazole, and posaconazole in a
randomized multicenter trial of 602 patients with leukemia or myelodysplastic syndrome who
had prolonged neutropenia due to chemotherapy. Posaconazole was associated with significantly
fewer cases of invasive aspergillosis, and survival was significantly greater in the group receiving
this drug. However, serious adverse events, primarily gastrointestinal, were significantly higher in
the posaconazole group.106 Although these data suggest benefit, concerns similar to those with
antimicrobials of the development of drug resistance need to be taken into consideration. In
addition, the risk of invasive fungal infections is relatively low compared with that of bacterial
infections. For these reasons, antifungal prophylaxis should be considered on a case-by-case
basis with individual patients, taking into consideration the specific type of malignancy, the
intensity of chemotherapy, and patient comorbidities, such as age, mucositis, diabetes, and
smoking.82
Prevention of Healthcare-Associated Pneumonia
Recognition in advance of the patients who are at greatest risk for development of pneumonia is
critical to prevention. Intubation and mechanical ventilation alter first-line defenses. Therefore,
such patients are at the highest risk of development of nosocomial pneumonia. Other risk factors
are age older than 70 years; chronic lung disease; depressed consciousness; aspiration; chest
surgery; the presence of an intracranial pressure monitor or nasogastric tube; H2 blocker or
antacid therapy; transport from the intensive care unit (ICU) for diagnostic or therapeutic
procedures; previous antibiotic exposure, particularly to the third generation cephalosporins;
reintubation; hospitalization during the fall or winter; mechanical ventilation for acute respiratory
distress syndrome; and frequent ventilator circuit changes.107
Most cases of healthcare-associated pneumonia occur by aspiration of bacteria colonizing the

oropharynx or upper gastrointestinal tract of the patient. Factors that tend to increase the
colonization of the oropharynx include coma, hypotension, acidosis, azotemia, alcoholism,
diabetes mellitus, leukocytosis, leukopenia, pulmonary disease, nasogastric or endotracheal tubes,
and receipt of antimicrobials.19 The use of chlorhexidine, but not oral application of antibiotics for
topical antisepsis of the oropharynx, reduces the incidence of ventilator-associated
pneumonia.108,109 However, mortality was not improved.
Selective decontamination of the digestive tract has been studied extensively. This strategy aims to
decrease the incidence of pneumonia by preventing gastric colonization with nosocomial bacteria
and Candida spp. A variety of regimens have been utilized, including application of antibiotics
topically to the oropharynx, administration through a nasogastric tube, or systemic
administration. Whereas randomized trials and two meta-analyses suggest that this modality has
benefit in reducing nosocomial pneumonia,107 concerns about the emergence of resistant
bacteria has limited the popularity of selective digestive tract decontamination.110
Patients who are placed in a semirecumbent position have a lower incidence of hospital-
associated pneumonia than do patients who are supine.111 For intubated patients, drainage of
subglottic secretions limits the incidence of ventilator-associated pneumonia, particularly among
patients expected to require more than 72 hours of mechanical ventilation.112 Silver-coated
endotracheal tubes have been demonstrated to reduce the incidence of ventilator-associated
pneumonia in patients intubated for more than 24 hours. However, no differences were found in
the duration of intubation, duration of stay in the ICU, duration of hospitalization, or overall
mortality.107,113 The robustness of the findings was modest, and the trial was not blinded. In the
editorial review of this trial, it was suggested that the subset of intubated patients who are at very
high risk of developing early-onset ventilator-associated pneumonia may be the group to benefit
from this modality.114
The American Thoracic Society and the Infectious Disease Society of America in their most recent
guidelines emphasize the following modalities for prevention of nosocomial pneumonia: effective
infection prevention measures, including staff education, compliance with hand hygiene, and
isolation to reduce cross-contamination with multidrug-resistant organisms, surveillance of ICU
infections, avoidance of intubation and reintubation, body positioning in the semirecumbent
position, use of enteral rather than parenteral nutrition, daily lightening of sedation, use of either
sucralfate or H2 blockers if needed for stress ulcer prophylaxis, limitation of red blood cell
transfusion, and intensive insulin therapy to maintain serum glucose levels between 80 and 110
mg/dL in ICU patients.110
Water
Water is a reservoir and a source for healthcare-associated infections.115 Several commonly

encountered pathogens are able to replicate in tap water, including include aerobic Gram-
negative bacteria, such as Pseudomonas spp., Legionella spp., and nontuberculous mycobacteria.
The reservoirs of concern include drinking water, sinks, faucet aerators, showers, tubs, toilets,
dialysis water, ice and ice machines, flower vases (see following discussion), eyewash stations,
and dental unit water stations. Several examples are found in the literature of environmental
water reservoirs being associated with infection involving aerosolization from those sources,
including faucet aerators associated with Pseudomonas infections and shower heads associated
with legionellosis.116 Those of theoretical concern for infection in the immunocompromised host
include potable water, ice and ice machines, tubs for immersion, and in hospitals with high rates
of nosocomial Pseudomonas and Legionella spp. infections, faucet and shower aerators.115 Highly
immunocompromised patients (i.e., those who are utilizing some version of a neutropenic diet)
(see following discussion) should consider ingesting filtered or sterile water, use ice made from
the same source, and avoid immersion in tubs.
Food
Fresh fruits and vegetables carry several species of Gram-negative rods as part of their natural
flora.117,118 Shooter et al117 performed cultures on a variety of foods from eight hospitals in the
London area. Foods sampled included salads, cold meat, cold sweets, other cold foods, hot food,
and pureed food. A significant proportion of salads were found to carry P. aeruginosa, Escherichia
coli, and Klebsiella spp. Furthermore, the majority of positive cultures yielded greater than 1000
colonies per gram of food.117
Organisms colonizing fruits and vegetables have been shown to colonize the gastrointestinal tract
of neutropenic patients after ingestion119 and food has been implicated in both colonization and
invasion in immunocompromised patients.120 The neutropenic diet, also called the cooked food
diet or the low-bacterial diet, was devised to reduce the introduction of potentially pathogenic
bacteria into the gut by the restriction of certain foods, particularly uncooked fruits and
vegetables.121–123 This modality continues to be widely employed. Smith and Besser124 surveyed
400 hospitals associated with the Association of Community Cancer Centers regarding use of the
neutropenic diet. Among the 156 hospitals responding to the survey, 78% used some version of
the neutropenic diet. Most of these diets restrict fresh vegetables, fruits, and juices.124 Despite the
popularity of this diet, its effectiveness has not been rigorously evaluated, and many have begun
to question whether the existing evidence supports continued use of this intervention.125 This
becomes important because many components of the neutropenic diet would be appealing
choices for patients undergoing chemotherapy who may be experiencing nausea, altered taste
sensation, and mouth sores.125 Thus, the concern is that use of a neutropenic diet may contribute
to poor nutrition without providing any benefit to the patient. Historically, when a neutropenic
diet was combined with skin cleansing, topical and oral nonabsorbable antibiotics, and a laminar
airflow room, serious bacterial infections have been avoided.126 When the diet is studied alone,
there is mounting evidence of its lack of effectiveness. Moody et al127 performed a pilot study in
children comparing the neutropenic diet to safety guidelines approved by the FDA, which
emphasizes common sense and good hygiene advice. Among the 19 patients, the infection rates
were similar.127 A larger study performed in adults randomly assigned 153 patients to a diet
containing no raw fruits or vegetables to a diet containing these items. Twenty-nine percent of
patients in the cooked food group and 35% of patients in the raw food group developed a major
infection (p = .60); the time to major infection and survival time were similar in the two groups.
Fever of unknown origin occurred in 51% of the cooked food group and 35% of the raw food
group.128
The CDC, the Department of Health and Human Services, and the U.S. Department of Agriculture
(USDA) do not endorse the neutropenic diet in cancer patients with neutropenia.127 Instead, they
offer food safety guidelines that emphasize common sense, good hygiene, and clean water. The
recommendations include hand hygiene;, washing fruits and vegetables; cooking meat, fish, and
poultry to well done; reheating deli meats and hot dogs to steaming hot; and avoidance of
vegetable sprouts and rough skinned fruits, such as raspberries and strawberries. However,
broad elimination of raw, washed fresh fruits and vegetables is not a standard part of federal
guidelines.129, 130
Although a hospital kitchen occasionally may be the source of food contamination,120 agents of
gastroenteritis and hepatitis A are much more likely to be encountered in food purchased in a
restaurant.131 For hospitalized immunocompromised patients, restriction of food to controllable
sources where adherence to USDA guidelines is assured is advised. Bringing in food prepared in
the home should be done only with approval of the attending physician.
Plants and Fresh Flowers
It is well established that both potted plants132 and fresh flowers133,134 carry microbial flora that
are pathogenic for the immunocompromised host. Taplin and Merz133 detected gentamicin-
resistant Gram-negative rods in 23 of 75 vases tested in a burn unit and associated the removal of
these flowers with a decrease in wound colonization. Kates et al134 examined the microbial flora
of vase water from cut flowers obtained from hospital environments, restaurants, and flowers
grown in private gardens. A total of 41 different bacterial species were identified, including many
common nosocomial bacterial species. Overall, 90% of the isolated organisms were known as
causative agents of infection. High levels of resistance to multiple antimicrobi-als were found in
the organisms irrespective of their source, indicating that multiple-resistant microbial flora found
in vase water is indigenous to flowers, rather than originating from the healthcare environment.
The colony count of water from vases rose steadily over time. The authors postulated that the
hands of healthcare personnel becoming transiently colonized while changing vase water could
serve as a potential source for infection.134
Because of data such as these, most bone marrow transplant units do not allow flowers or live
plants to be brought into patients rooms.135 A recent study found that introducing fresh flowers
into the rooms of nonneutropenic, non-bone marrow transplant patients did not increase the
number of fungi isolated.136 The recommendations made by Kates are reasonable: ban flowers
from high-risk areas, such as cancer wards and burn units; designate the handling of flowers to
support staff with no patient contact or, when this is not feasible, wear gloves when handling
flowers; wash hands after contact with plant material; change the vase water at least every 48
hours; dispose of vase water into designated sinks that are not in the immediate environment of
the patient; and thoroughly disinfect vases after use.134 The immunocompromised patient should
strive to avoid direct contact with cut flowers or living potted plants of any type and should
perform hand hygiene with an alcohol-based gel if such contact occurs.
Visitors
The healthcare team should ensure that visitors are properly screened for infections and
instructed about the importance of proper infection prevention precautions, especially proper
handwashing in advance of interacting with the patient. All visitors should be instructed to follow
the same standard precautions as healthcare workers.88 Visitors who currently have a diagnosed
illness that is communicable by airborne, droplet nuclei, or contact routes or who have symptoms
of upper respiratory infection or diarrhea should be discouraged from visiting the patient. If
visitation does take place, appropriate precautions should be employed.88
Pediatric visitors may carry and transmit disease unknowingly,137 and thus it is advisable that
visitors younger than 12 years be permitted only with physician approval, even if they appear
healthy. Children should be screened for known illness or exposure in the previous 4 weeks to
varicella, rubella, rubeola, mumps, hepatitis A, group A streptococcal pharyngitis, pertussis, viral
respiratory infection, undifferentiated diarrhea, vomiting, fever, rash, or live virus immunization
(MMR, varicella or polio).138 Patients should perform hand hygiene with an alcohol-based hand
gel after interaction with any pediatric visitors.
Pets
The American Pet Product Manufacturer’s Association estimates that nearly 63% of American
households have at least one companion animal and that the total number of pets in the United
States is approximately 360 million. The majority of these continue to be dogs and cats, but
rabbits, birds and reptiles make up an increasing number of pets in the home.139 Forty-one
percent of dogs share their owner’s beds.140 The list of potential diseases transmitted to owners
from such traditional pets has included such agents as Campylobacter, Bartonella,
Cryptosporidium, Giardia, Salmonella, and Toxoplasma spp.141 In addition, there are nearly 40
bacteria that have been isolated from dog and cat bite wounds.142 An increasing number of
persons are obtaining nontraditional or exotic pets, including rodents, reptiles, prairie dogs,
nonhuman primates, ferrets, animals caught in the wild (raccoons, pigeons), and animals
imported, both legally and illegally, from foreign countries (i.e., Gambian pouch rats [Cricetomys
gambianus], African hedgehogs [Atelerix albiventris], sugar gliders [Petaurus breviceps], axolotls
[Ambystoma mexicanum], and others).139,141 Thus, to the list of potential infectious diseases
transmissible from pets to people must now be added such agents as, for instance, Escherichia coli
O157:H7,143 monkeypox,144 Cercopithecine herpesvirus,145 Francisella tularensis, Leptospira spp.
rabies, and Yersinia pestis,139 as well as diseases transmitted by the mites, fleas, and ticks
associated with some of these animals. Pet therapy has been advocated as psychologically
beneficial to hospitalized patients146,147 and to nursing home residents.148 There is a paucity of
literature on the true risk to immunocompromised patients of exposure to pets, and a survey of
20 pediatric oncology centers in the United Kingdom revealed that only 4 used either published
or locally developed guidelines regarding pet ownership.141 Potential transmission routes to
immunocompromised hosts include inhalation of infectious aerosols; contact with urine, saliva, or
feces; and bites or scratches. Common sense dictates the following: exotic pets or pets without a
known pedigree (i.e., may have been illegally imported) should not be allowed. Pets that are
allowed to visit a patient should be housebroken (i.e., no puppies or kittens), tame, docile, up to
date on all vaccinations, and pronounced disease free by a veterinarian. Pets should be kept
cleaned and brushed, and nails clipped short to minimize the risk of scratches. Patients should
perform hand hygiene after contact with pets of any kind (handwashing with antiseptic soap if
exposure has occurred to organic material, otherwise alcohol-based hand gels are acceptable).
Hand hygiene performance in children should be supervised. In addition, scratches and bites
should receive immediate attention, including disinfection, regardless of how trivial the injury
appears.
Certain circumstances raise particular concern regarding pet visitation. Patients who have had a
splenectomy are at high risk for invasive infection by Capnocytophaga canimorsus, a Gram-
negative bacterium that is part of the normal oral flora of dogs. Because pets can act as fomites
for the transmission of bacteria between patients, patients who are placed in contact isolation
should not be allowed to interact with animals. Some animals pose an unacceptable risk of
diseases, such as rabies in skunks, raccoons, and bats; Cercopithecine herpesvirus (B virus) in
Asian macaques; and Salmonella carriage in turtles, lizards, and snakes. These animals should be
excluded from the hospital and not be part of any pet therapy program. As a result of
asymptomatic urinary excretion of Leptospira spp. (dogs and others) and lymphocytic
choriomeningitis virus (LCM) (mice and hamsters), careful hand hygiene is necessary after
exposure to the urine of these animals. A recent series of organ transplant recipients contracted
LCM either from the organ donor or the environment of the organ donor. Seven of the eight
recipients died of the disease.149
Prophylaxis Against the Emergence of Endogenous Infections
A variety of organisms have the capacity to establish latency within the body once an infection has
been established. This establishment may occur with symptomatic clinical illness (i.e., primary
varicella, herpes simplex, others) or without clinical illness (i.e., M. tuberculosis, P. jiroveci). These
latent infections may reactivate during immune compromise. Table 15-5 lists the most important
microorganisms that establish latency, as well as their geographic distribution. Some agents can
be detected serologically (C. immitis, T. gondii) or by skin testing (M. tuberculosis). Under certain
circumstances, it is appropriate to offer prophylaxis against these infections to reduce the
incidence of their reactivation to cause clinical disease. For instance, HIV-infected individuals with
CD4 cell counts of less than 200/mL are recommended to receive prophylaxis against P. jiroveci.
Persons with previous exposure to M. tuberculosis undergoing treatment with tumor necrosis
factor inhibitors should receive prophylaxis with isoniazid.150
Table 15-5. Latent Organisms and Their Geographic Distribution
Organism Geographic Distribution
Mycobacterial
Worldwide, especially in urban centers and
M. tuberculosis
developing countries
M. avium complex
Ubiquitous in the environment
Fungal
Histoplasma
capsulatum
Coccidioides
Central river valleys of the United States
immitis
Desert Southwest
Blastomyces
Mississippi and Ohio River basins
dermatitidis
Worldwide
Pneumocystis
jirovecii Southeast Asia

Penicillium
marneffei
Bacterial
Pseudomonas
Southeast Asia, South Pacific
pseudomallei
Protozoal
Strongyloides
Tropics and the Southern United States
stercoralis
Worldwide
Toxoplasma gondii
Viral
Herpes group
Worldwide
viruses
Worldwide
JC papovavirus
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CONCLUSIONS
Care of the immunocompromised host poses tremendous challenges. Those challenges include
identification of compromised patients and determining their net state of immunosuppression,
anticipating the microbial pathogens of unique concern for their type of immune deficit,
augmenting their innate resistance to opportunistic infection, and early identification of infection
such that appropriate therapy can be instituted. The infection prevention issues include both
prevention of acquisition of potential pathogens as well as prevention of reactivated infection
from affecting other individuals. New therapies continue to evolve, and novel pathogens continue
to be discovered.10,151,152 Well-supported guidelines now exist for care of patients in a variety of
circumstances. Optimal approaches to other circumstances are yet to be defined completely,
leading to the need for extrapolation and the use of clinical experience. Effective methods for
overcoming such obstacles as emerging drug resistance and failure of healthcare workers to
adhere to basic hygiene techniques also are lacking. Cost-effectiveness and appropriate outpatient
locations for healthcare delivery are additional areas of study.
Treatment decisions often need to be made in situations where no formal guidelines exist. In such
situations, the recommendations discussed here are reasonable based on the literature that
exists. In the individual patient, these guidelines should be applied carefully, taking into
consideration the specific situation and the net state of immunosuppression of the patient. Careful
follow-up of the immunocompromised patient is important because infection can rapidly become
fulminant.
FUTURE TRENDS
Probiotics
The term probiotics refers to the medicinal use of viable organisms to cause beneficial effects on
a host. The Food and Agriculture Organization (FAO) of the United Nations and the World Health
Organization (WHO) have stated that there is adequate scientific evidence to indicate that there is
potential for probiotics to provide health benefits and that specific strains are safe for human
use.153 Whereas the comprehensive review of the literature by the FAO and WHO demonstrated a
relatively small number of areas in which probiotics have proven antidisease effects, preliminary
investigations have been promising for their use in enhancing mucosal immunity, treatment of
surgical wound infection, reduction in the incidence of certain malignancies, and reducing the
duration of diarrhea. Most studies have been small, and many have important methodologic
limitations. In addition, considerable differences exist in composition, dose, and biologic activity
among various commercial preparations, so comparison of results between studies is often
difficult or impossible. No probiotic is approved by the FDA. These may not always be benign
agents. A critically ill patient with diarrhea was given Saccharomyces boulardii as a probiotic and
developed invasive disease.154 Large, well-designed, multicenter controlled trials are needed to
clarify the role of different probiotics in different patient populations. The interested reader is
referred to the review by Reid et al,155 the online posting of the Working Group report of the FAO
and WHO,153 and a recent Clinical Infectious Diseases supplement156 for a discussion of the
potentials of this modality.
Vaccinations
Tremendous advances in vaccine technology have been made in the past decade, and although
many of these advances have been directed toward the traditional definition of a vaccine, namely
the prevention of an infectious disease, new technologies have extended the scope of vaccinations
to include treatment of established disease as well. Targets for vaccines outside the field of
infectious diseases continue to expand and now include cancer, addiction, cardiovascular disease,
gastrointestinal disease, autoimmune disease, prevention of drug toxicity, and fertility. The
implications of this line of research for the many kinds of immunocompromised patient are
significant. A detailed discussion of these issues provides fascinating reading.157
Irradiation of Food Products

Despite ongoing efforts of public health agencies and food growers, processors, and
manufacturers to reduce the risk of foodborne diseases, every year in the United States
foodborne diseases cause approximately 76 million illnesses, 225,000 hospitalizations, and 5000
deaths.158 A substantial portion of those illnesses are borne by immunocompromised patients.

Food irradiation or “cold pasteurization” of solid foods with low doses of rays, x-rays, and
electrons can effectively control bacterial and parasitic pathogens, even at extremely low levels of
contamination.158,159 Consumption of foods prepared in these ways has been shown to be
safe.159 The WHO has endorsed food irradiation, as have the CDC, the USDA, and the FDA. An
increasing list of foods has been approved by the FDA to undergo irradiation, including recently
spinach and lettuce, and there are approximately 60 commercial irradiation facilities available in
the United States.160 Food irradiation for the general public or for the immunocompromised host
has yet to be embraced fully. With efforts to educate the public about irradiation of food at the
grocery store level, consumer acceptability is likely to improve.161
Statins
Inhibitors of the enzyme HMG CoA reductase, commonly referred to as statins, have been utilized
for years to reduce cholesterol and lipid levels. Independent of their lipid-lowering abilities,
statins have been demonstrated to modulate the inflammatory response associated with
infection.162 Animal models demonstrated that the administration of a statin before a sepsis-
inducing insult reduces morbidity and improves survival.163 An observational cohort study of 361
consecutive patients admitted to an ICU with presumed or documented acute bacterial infection
demonstrated that severe sepsis developed in 19% of the group not taking statins and only 2.4%
of those who were receiving one.164 In the near future, randomized, controlled clinical trials will
define if statins have a role in preventing or reducing complications of infection.
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7/29/13 Chapter 15 – The Immunocompromised Host - | APIC Text Online

George F. Risi, Jr., MD, FACP, FIDSA, FSHEA

Recognition and Characterization of the Immunocompromised Host

I.Defects in the cutaneous barrier to invasion of endogenous or acquired organisms

II. Mucous membrane barrier defects

A. Mucositis induced by irradiation or chemotherapy

III. Conditions that cause obstruction of a natural body passage

A. Tumors of the lung, gastrointestinal tract, pancreatic head, elsewhere

IV. Abnormal number or function of granulocytes

V. Abnormalities of cell-mediated immunity

A. Bone marrow transplantation

VI. Abnormalities of humoral immunity

A. Bone marrow transplantation

VII. Patients with defects in multiple arms of immunity

The net state of immunosuppression is determined by the interaction of several variables,

Opportunistic Organisms Encountered Internationally

I. Breaks in cutaneous integrity: invasion by skin flora organisms

A. Staphylococcus aureus, coagulase-negative species of Staphylococcus

II. Defects in mucous membranes, with invasion by resident flora

A. Anaerobic bacteria (Bacteroides fragilis, Clostridium perfringens, C. septicum)

IV. Granulocytopenia (defined as absolute neutrophil count <500/mL)

A. Duration of 2 weeks or less: aerobic Gram-negative bacilli, S. aureus, and coagulase-negative

V. Dysfunction of cell-mediated immunity

A. Bacteria: primarily intracellular pathogens

VI. Splenectomy or humoral dysfunction-encapsulated bacteria

B. Encapsulated strains (especially type B) of Haemophilus influenzae

Internationally Acquired Infections That May Go Unrecognized for Prolonged Periods

The Source of the Infection May Be Endogenous, Exogenous, or Both

Most Important Portals of Entry for Opportunistic Organisms

Table 15-3. Sources of Opportunistic Infection

I. Opportunists that are more commonly (but not exclusively) endogenous

A. Mycobacterium tuberculosis (lung, lymphatics, others)

A. Clostridium difficile (hands of personnel, fomites)

III. Opportunists that can be either endogenous or exogenous

A. A. Aerobic Gram-negative bacilli

Pathogen Number of Isolates (%)

Serratia marcescens 64 (3.5)

PREVENTING INFECTION IN THE IMMUNOCOMPROMISED

Augmentation of Host Resistance

Patients should be up to date on all routine immunizations.40 The Advisory Committee on

Immunization in Recipients of Transplanted Organs (Autologous or Allogeneic Bone Marrow

Despite the burden of illness due to vaccine-preventable diseases in transplant recipients,

Recipients of transplanted marrow or stem cells experience severe immunosuppression for

Passive Immunization With Either Intramuscular or Intravenous Immune Globulin

The administration of preformed donor antibody by either the intramuscular or intravenous

The transfusion of donor leukocytes to augment resistance in chemotherapy-induced neutropenia

The colony-stimulating factors (CSFs), granulocyte colony-stimulating factor (GCSF, filgrastim),

Reduction of Exposure to Pathogens

Isolation and Hand Hygiene

Multiple studies have demonstrated the efficacy of prophylactic antibiotic administration to

would be enough to warrant an A-I recommendation (good evidence to support a

Prevention of Healthcare-Associated Pneumonia

Most cases of healthcare-associated pneumonia occur by aspiration of bacteria colonizing the

Water is a reservoir and a source for healthcare-associated infections.115 Several commonly

Plants and Fresh Flowers

Prophylaxis Against the Emergence of Endogenous Infections

Table 15-5. Latent Organisms and Their Geographic Distribution

Organism Geographic Distribution

jirovecii Southeast Asia

Irradiation of Food Products

deaths.158 A substantial portion of those illnesses are borne by immunocompromised patients.

8. Szabo G. Alcohol’s contribution to compromised immunity. Alcohol Health Res World

Professionals in Infection Control/Infectious Diseases Society of America. MMWR Recomm