Transcript infection

Pneumonia in Compromised
hosts
Dr. M. Shahparianpour
Compromised hosts
 Patients with damaged defense mechanisms, which leads to
severe, life-threatening infections. These conditions are:
 acute leukemia (granulocytopenia, changed normal flora, damaged barriers)
 lymphoma
 transplantation
 AIDS
 carcinoma, sarcoma (these stop the normal passage)
 myeloma, chronic lymphoid leukemia (decreased antibody function)
 severe trauma after an accident (damaged barriers)
 intravenous drug users (microorganisms pass directly into the blood
stream, decreased defense)
 any severe underlying disease
Main problems
 Any microorganism can cause infection
 Microorganisms with low virulence may
also be involved in severe infections
 Infections may present with unusual
symptoms
 Without a correct microbiological
diagnosis, it is too dangerous to treat the
patient
Case
 A 48-year-old male patient (horse breeders),, who had
undergone renal transplantation 6 month earlier,
was admitted to a surgical unit. The X-ray
examination revealed a cavitary infiltrate suspicious
of lung tumor.
 He had fever and a cough.
 A series of biopsies from the lung tissues and blood
culture samples (6 pairs of bottles during 3 days) were
taken.
 The histology did not confirm the suspicion of tumor.
Gram staining was carried out on the same samples .
Case (cont.)
 From all the blood culture bottles and from the tissue
samples, the same polymorphic Gram-positive coccobacilli
were cultured. Ziel-Nielsen staining showed them to be
slightly acid-fast.
 Following the susceptibility test results, the patient
received amoxicillin/clavulanic acid treatment for 2 weeks
and left the hospital.
 After 6 month, he visited the hospital with the same
symptoms. The same bacterium was isolated from his
blood culture.
 The same treatment was introduced for 6 weeks. Since then
the patient has been free of symptoms of infection.
Culture results obtained from the
blood and the tissue after 24 h
incubation
blood agar
Lövenstein-Jensen agar
Case (cont.)
What was the causative agent? Do you think it was a
usual pathogen?
Rhodococcus equi
This is an intracellular pathogen. What other
intracellular pathogens can cause, similar pulmonary
infection?
Multiple simultaneous pulmonary processes
are common.
These include infectious (eg, viral, bacterial,
fungal, parasitic), and noninfectious (eg,
pulmonary edema and malignancies) etiologies.
Routine chest radiography and sputum
sampling may fail to document these
concomitant diseases
Serologic testing
is not generally useful in the acute
management of immunocompromised
patients.
These patients often fail to generate a timely antibody
response to infection.
Microbiologic testing should include antigen detection or
nucleic acid detection-based assays as well as cultures
Biopsies with special histopathologic
stains (eg, for fungi or mycobacteria) and microbiologic
studies (eg, viral cultures, molecular assays) are often essential
epidemiology of infection
Awareness of the
in the community (eg, respiratory viruses, tuberculosis) and the
individual (eg, travel) often provide helpful clues
The incidence and severity of pneumonia vary with the
characteristics of the affected individual, including:
the nature of the immune
deficits
epidemiologic exposures
Aspiration remains an important source of
pulmonary infection in all compromised
patients.
Neutropenia is the most important
risk factor for pulmonary infection in
immunocompromised patients
No originating site of infection can be determined in
to 50 percent of febrile cancer patients
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common sources of infection in the febrile, neutropenic patient
with hematopoietic malignancy includes
the perineal and perirectal areas,
the urinary tract,
skin (including intravenous lines and wounds)
lungs.
However, pulmonary infections predominate
in series of all non-hematopoietic cancer
patients.
Nonmyeloablative conditioning was
designed to shorten the duration of
neutropenia and mucosal effects of
neutropenia, notably when coupled with
hematopoietic stem cell transplantation
(HSCT).
While the length of time a patient is
neutropenic has been shortened, the
occurrence of late infections after
nonmyeloablative conditioning, including
fungal infections, have been more common
than anticipated
Autoimmune and inflammatory
conditions:
Patients with hematopoietic malignancies, and
to a lesser extent, acquired deficiencies (eg,
glomerulonephritis with proteinuria or
Goodpasture's syndrome) may be susceptible to
opportunistic infections similar to those of cancer
or transplant patients.
Bacterial infections are of greater importance,
possibly related to deficiencies in opsonization
and phagocytosis
Corticosteroid
individuals receiving the equivalent of 15
to 20 mg of prednisone per day for
more than three weeks were at
increased risk particularly for P.
carinii/jirovecii pneumonia (PCP)
steroid-sparing strategies
calcineurin inhibitors sirolimus,
costimulatory blockade, and antibody
therapies (both antilymphocyte and antitumor necrosis factor [TNF]
preparations) with concomitant infectious
complications.
anti-TNF antibodies
for rheumatoid arthritis, Crohn's disease,
and GVHD has been associated with
activation of
latent tuberculosis,
cryptococcosis,
aspergillosis,
other intracellular organisms
ETIOLOGY OF PULMONARY
INFILTRATES
Infectious
 Conventional bacteria
 Fungi
 Viruses
 Pneumocystis carinii/jirovecii
 Nocardia asteroides
 Mycobacterium tuberculosis
 Mixed infections
37 percent
14 percent
15 percent
8 percent
7 percent
1 percent
20 percent
Mixed infections
combinations of
respiratory viruses,
CMV,
Aspergillus spp
gram-negative bacilli
are common in neutropenic hosts and after HSCT
CMV
most common after HSCT, as viral reactivation in
seropositive individuals after the completion of
prophylaxis (late infection)
This contrasts with the risk of CMV pneumonitis in
solid organ transplantation which is greatest in
seronegative recipients of seropositive organs
Noninfectious
Noninfectious etiologies for pulmonary infiltrates are
common in immunocompromised patients, including
pulmonary embolus,
tumor,
radiation pneumonitis,
atelectasis with pulmonary edema,
drug allergy or toxicity,
pulmonary hemorrhage.
Often, the resolution of fever in response to a trial of
antibiotics is the only suggestive evidence that
infection was present.
mimics of infection
 Alveolar proteinosis
 pulmonary infarction
 primary connective tissue/collagen vascular
diseases
 pulmonary-renal syndromes
 Sarcoidosis
 Acute respiratory distress syndrome
 Transfusion-associated leukoagglutinin reactions
Radiation-induced injury
Clinically apparent injury due to radiation
therapy can occur acutely or more than six
months after the initial exposure to a
dose of over 2000 rads.
Vascular damage, mononuclear infiltrates,
and edema are seen histologically at three to
12 months
Drug-induced injury
Acute, drug-induced lung disease may also
reflect hypersensitivity to chemotherapeutic
agents or to sulfonamides
Drug toxicity may be related to the cumulative
dose of the agent
Synergistic toxicity for the lung is seen with a
variety of chemotherapeutic agents and radiation
INITIAL
EVALUATION OF
THE PATIENT
Recognition that infection is present in the
immunocompromised hosts is often delayed because the usual signs
of infection are missing
due to the muted
inflammatory response
Many infections are recognized only when
fever, clinical symptoms (eg, cough, pleurisy, confusion),
unexplained hypotension, or radiologic abnormalities develop after
immune suppression or neutropenia is
reversed
The first decision to make in an immunocompromised
patient with possible infection is whether or not
hospital admission is appropriate.
Any sign of invasive infection in
immunocompromised patients requires at least a
brief hospitalization (one to three days) with a
careful evaluatio n
Certain subgroups of patients are highly susceptible
to infection
 Aggressive tumors (eg, new leukemia or lymphoma or with
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uncontrolled metastatic cancer)
Recent HSCT recipients and allogeneic HSCT recipients with
significant degrees of graft-versus-host disease (GVHD)
Recent infections, especially due to CMV, or with known
colonization with fungi or resistant bacteria
Absolute neutrophil count (ANC) below 500/microL, and
especially those below 100/microL, or those in whom the ANC
is falling rapidly or expected to fall below 100/microL
High dose corticosteroid therapy or recent intensification of
immune suppression
Patients with a history of frank rigors or hypotension
splenectomized patients with fever
The initial evaluation for immunocompromised patients with
fever with or without pulmonary findings should include:
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Rapid assessment of vital signs including oxygen saturation
Complete blood count with differential
Electrolytes, blood urea nitrogen and creatinine
Blood cultures (minimum of two with at least one peripheral and
one from any indwelling catheter)
Urine sediment examination and culture
Sputum for Gram's stain, fungal smears, and cultures
Imaging of the lungs (chest radiography or whenever possible, chest
computed tomographic [CT] scanning) and imaging of any
symptomatic site (eg, abdomen)
Perineal exam to exclude perirectal infection
The presence or absence of hypoxemia can assist
in the differential diagnosis of pulmonary infiltrates in
immunocompromised patients.
Hypoxemia with an elevation in lactic dehydrogenase
and minimal radiographic findings are common in P.
carinii/jirovecii infection,
the absence of hypoxemia with pulmonary consolidation
is more common in nocardiosis, tuberculosis, and
fungal infections until late in the course of disease
DIAGNOSIS
Historical clues
 Travel and employment: Exposures to mycobacteria, endemic fungi (eg, H.
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capsulatum, Coccidioides immitis), R. equi (horse breeders), or C.
neoformans (spelunkers and pigeon breeders), or exposure to soil (eg,
Aspergillus spp. or Nocardia spp. in gardeners)
Prolonged duration of neutropenia (higher risk for gram-negative
infection, Aspergillus or Fusarium sp.)
Past history of frequent antimicrobial exposure (increased risk for
organisms with resistance to various antimicrobials used previously)
Potential or witnessed aspiration (risk for anaerobic infection)
Presence of potential pulmonary pathogens in prior cultures particularly
molds (Aspergillus, Fusarium), Pseudomonas, or Stenotrophomonas
Cardiac abnormalities (endocarditis), indwelling catheters or
intravascular clot (bacteremic seeding of the lungs)
Metastatic tumor particularly intrathoracic malignancies
Diabetes with sinopulmonary infection (Zygomycosis [more commonly
called mucormycosis])
Chest radiograph
 A focal or multifocal consolidation of acute onset will
probably be caused by a bacterial infection.
 subacute to chronic progression are more commonly due
to fungal, tuberculous, or nocardial infections.
 Large nodules are usually a sign of fungal or nocardial
infection in this patient population, particularly if they are
subacute to chronic in onset.
 Subacute disease with diffuse abnormalities, either of
the peribronchovascular type or miliary micro nodules, are
usually caused by viruses (especially CMV), P.
carinii/jirovecii, or rejection in the lung transplant
patient
 The presence of cavitation suggests a necrotizing
infection which can be caused by fungi, Nocardia,
mycobacteria, and certain gram-negative bacilli
(most commonly Klebsiella pneumoniae and
Pseudomonas aeruginosa
 The appearance of invasive pulmonary aspergillosis is
heterogeneous with patchy infiltrates, nodules,
cavitation and pleural-based wedge-shaped lesions
most common.
 In neutropenic patients, the initial appearance may be
pleural-based lesions with surrounding attenuation
(the "halo sign") followed by cavitating nodules
("air-crescent sign") after the return of neutrophils.
The depressed inflammatory response of the
immunocompromised transplant patient
may greatly modify or delay the appearance of a
pulmonary lesion on radiograph, especially if
neutropenia is present.
fungal invasion, which excites a less exuberant inflammatory
response than does bacterial invasion, will often be very slow
to appear on conventional chest radiography
Chest CT
CT frequently reveals abnormalities
even when the chest radiograph is
negative or has only subtle findings
 Cavitary CT lesions are suggestive of infections
with mycobacteria, Nocardia, Cryptococcus, Aspergillus,
and some gram-negative bacilli (Pseudomonas,
Klebsiella).
 Rapidly expanding pulmonary lesions
with cavitation and/or hemorrhage are
associated with the zygomycetous fungi (eg, Mucor),
especially in diabetics.
 Opacified secondary pulmonary lobules
in the lung periphery are suggestive of bland
pulmonary infarcts or septic or hemorrhagic Aspergillus
infarcts (if cavitated).
 Peribronchial distribution of CT
opacities is suggestive of fluid overload, viral or P.
carinii/jirovecii infection and, in the lung transplant recipient,
allograft rejection.
 Dense regional or lobar consolidation on
CT is usually seen in bacterial pneumonia or invasive fungal
infection.
 Lymphadenopathy is not a common finding in
immunosuppressed patients other than in those with
lymphoma or PTLD associated with Epstein-Barr virus (EBV).
 Lymphadenopathy may be observed with acute viral
infections (CMV, EBV), sarcoidosis, and infections due to
mycobacteria, Cryptococcus, and with drug reactions (eg,
TMP-SMX).
CT scans frequently will detect multiple
simultaneous patterns, in contrast to
conventional radiographs, which can raise
the possibility of :
. dual infection
. sequential infection of the lungs
Common Viral Infections in Immunocompetent and
Immunocompromised Adults
In patients who have AIDS, the pattern and
progression of abnormality should be correlated
with the
clinical scenario, including the CD4 count;
in patients who have undergon transplants, the
amount of time that has elapsed since
institution of chemotherapy or transplant is
important.
 CD4+ greater than 200 × 106 cells/L:
bacterial pneumonia, TB (reinfection)
 CD4+ 50 to 200 × 106 cells/L:
bacterial pneumonia, primary TB, PCP,
fungal infections
 CD4+ less than 50 × 106 cells/L:
bacterial pneumonia, atypical appearances
of TB, PCP, fungal infections, MAC, CMV
Pneumocystis jiroveci,
previously known as P carinii, was initially classified as a
protozoan but is now believed to be a fungus.
 The prevalence of PCP has been decreasing with antibiotic
prophylaxis.
 The diagnosis is suggested strongly by typical history, low
CD4 count, and hypoxia.
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Induced sputum can establish the diagnosis, or
alternatively, bronchoscopy with bronchoalveolar lavage
can be used in patients who are at risk but who have a negative
sputum induction result.
 The CXR can be normal;
 typical radiographic findings include bilateral perihilar air
space disease or reticular markings
 On CT, acute infection classically results in perihilar ground
glass opacification, often in a geographic distribution with
areas of affected lung interspersed by normal lung
parenchyma.
 linear or reticular pattern is demonstrated frequently with
thickening of the interlobular septa causing a ‘‘crazy paving’’
pattern
 Some patients develop thin-walled cystic areas
(pneumatoceles) that have an upper lobe distribution.
 Characteristically, pleural effusions are absent
 Atypical manifestations of PCP include focal
consolidation, mass lesions, cavitation, and
adenopathy
10% of HIV-positive patients who had PCP and a
normal CXR had an abnormal HRCT.
Ground glass areas were found in all of the
patients.
A normal HRCT is said to rule out PCP
pneumonia
A study of 200 non-HIV immunocompromised
patients demonstrated that a delay of greater
than 5 days in identifying the etiology of
infectious ‘‘infiltrates’’ was associated with a more
than threefold risk of death
The mortality in immunosuppressed
patients who require mechanical
ventilation exceeded 80%
Pulmonary complications can be classified
chronologically as occurring in the
neutropenic or pre-engraftment period (0–30
days after BMT),
early postengraftment period (31–100 days
after BMT),
late post-engraftment period (>100 days after
BMT).
CMV and Aspergillus were the most
commo n pathogens overall in one study
 During the neutropenic phase, patients are
particularly susceptible to bacterial and candidal
infections and invasive aspergillosis
 Bacterial infections during this time period are
related to severe granulopenia and often are caused
by gram negative bacteria.
Usually the appearance is similar to that
in an immunocompetent patient, with
focal or multifocal consolidation.
Aspergillus pneumonia
 risk groups for invasive aspergillosis are patients who have
severe, prolonged granulocytopenia secondary to hematologic
malignancy; hematopoietic stem cell/solid organ transplant
recipients; and patients who are taking high-dose
corticosteroids
 Angioinvasive aspergillosis results when Aspergillus invades
the pulmonary vasculature and causes thrombosis, pulmonary
hemorrhage, and infarction.
 CXRs often are abnormal, but nonspecific, and reveal patchy
segmental or lobar consolidation or multiple, ill-defined
nodular opacities.
 Characteristic CT findings consist of nodules that are
surrounded by a halo of ground glass attenuation (‘‘halo
sign’’) or pleural-based, wedgeshaped areas of consolidation.
 As the patient’s immune system recovers, about 2 weeks after the
onset of infection, CXR or CT may demonstrate an ‘‘air crescent
sign,’’ corresponding to necrotic lung around retracted infarcted
lung
 it is highly characteristic in the proper clinical setting, especially
when the initial lesion is consolidation or a mass
Predominant airway involvement by Aspergillus organisms,
termed ‘‘airway-invasive aspergillosis,’’ occurs most commonly in
immunocompromisedneutropenic patients and in patients who have
AIDS
Air crescent formation was shown to be
associated with improved survival
Early-phase complications after
bone marrow transplant
 The predominant infectious risk is viral, most commonly from CMV.
 Respiratory syncytial virus and parainfluenza commonly cause
upper respiratory symptoms during this time as well and progress to
clinically significant pneumonia in 30% to 40% of cases
 CMV pneumonia occurs in approximately 15%–30% of patients who
receive allogeneic BMT, usually between 6 and 12 weeks after
transplantation
 Infection most commonly occurs from reactivation of latent
endogenous virus
It is uniformly fatal if not treated
Late-phase complications after bone
marrow transplant
 Late-phase complications occur 100 days or more
after BMT, and the patient’s immune system is
near normal by 1 year.
 The most common infections in this phase are
bacterial, although mycobacterial infections
also should be considered.
Solid organ transplant infections
 Solid organ transplant recipients are susceptible to infections
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similar to those following BMT.
In organ transplant patients there are three important periods.
In the first month, infections are secondary to nosocomial
bacteria.
At 1 to 6 months after transplantation, viruses, such as CMV,
Epstein-Barr virus, and herpes simplex, become more important
potential causes of lung infection.
these viruses can impair immunity, they can predispose the host
to opportunistic pneumonia by PCP or Aspergillus fumigatus.
Beyond 6 months after transplantation, patients with adequate
graft function develop infection only occasionally, and the
infecting organisms tend to be those of the nontransplant
population
New/emerging infections
 Anthrax and severe respiratory syndrome (SARS) cause acute
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respiratory distress are emerging conditions
Anthrax is caused by the bacterium Bacillus anthracis.
It is a gram-positive aerobic spore-forming microorganism.
Infection occurs by three different portals of entry: the skin, the
gastrointestinal tract, and the lungs.
The inhalational form has the highest mortality.
abnormal findings on CXR. Manifestations include mediastinal
widening due to bulky lymphadenopathy and pleural effusions.
Hilar adenopathyalso may be present. Consolidation can be present
often secondary to pulmonary hemorrhage
CT findings include high attenuation mediastinal and hilar
adenopathy, pleural effusions that can be hemorrhagic, and
mediastinal widening. Ring-like nodal enhancement also is
described
Pathophysiology
Malignancy
 Neutrophil defects, immunoglobulin defects,
and T-cell defects are all seen in patients with
cancer.
 Cancer chemotherapy: Many treatment
protocols exist. Common adverse reactions
are leukopenia and lymphopenia.
 Immune dysfunction: Underlying malignancy
itself is a risk factor for subsequent infections
HIVT-cell dysfunction in the setting of HIV leads to a
number of infectious complications
 TB: HIV is considered to be the greatest risk factor for TB. Early diagnosis is
more difficult because of the lack of specific clinical findings, such as an
abnormal chest radiograph or a positive purified protein derivative (PPD) skin test
result.
 Bacterial pneumonia: HIV causes dysfunction of cell-mediated as
well as humoral immunity. CD4 T cells principally help other cells achieve their
effector function. As such, at low CD4 levels, a disruption of B-cell differentiation
occurs. Impaired B-cell functions, particularly of memory cells, are postulated to
account for increased risk of infection.1 Even after the initiation of HAART
therapy, patients with HIV have reduced marginal zone B-cell percentages.
 PCP: Transmission and infection from P jiroveci is incompletely understood.
Traditionally, infection in a patient with HIV has been thought to represent
reactivation latent colonization. Now, however, some evidence exists that the
epidemiology of this infection is defined on a more local geographical level.1 As
molecular analysis of P jiroveci improves, so will the understanding of the
transmission and epidemiology of this opportunistic infection
 Histoplasmosis: Spores of the mold phase are inhaled and
cause a localized or patchy bronchopneumonia. CD4 lymphocytes
normally activate macrophages to control the infection. In patients
with HIV and low CD4 counts, the likelihood of developing both
pulmonary and disseminated histoplasmosis is increased.
 Coccidioidomycosis: Spores are inhaled and then ingested
by pulmonary macrophages. Impaired cell-mediated immunity in
the HIV patient accounts for their increased risk of infection
 Cryptococcus: Most cases are the result of reactivation from a
latent infection. Recognition and treatment are important because
pulmonary cryptococcus is thought to herald the onset of
disseminated disease.
 HSV and VZV: The pathophysiology of these infections in the
setting of HIV is not well understood.
 MAC: This infection is thought to represent a recent acquisition
of organisms rather than a reactivation of latent infections
Primary immunodeficiencies
 Humoral deficiencies: Patients with defects of humoral
immunity are unable to create functional antibodies. Their
complications are characterized by severe, recurrent upper and
lower respiratory tract infections.
 Cellular deficiencies: Cellular deficiencies are rare
conditions that affect T-cell development and function. Dysfunction
of T cells invariably has an impact on B-cell activity; therefore, most
of these conditions manifest as combined deficiencies.
 Combined deficiencies: In combined deficiencies, both
T-cell and B-cell function is disturbed. These patients present not
only with recurrent episodes of respiratory syncytial virus (RSV),
herpes simplex virus (HSV), VZV, influenza, and other viral
respiratory infections but also chronic diarrhea and chronic
mucocutaneous candidiasis
Pregnancy
 Pregnancy results in immunologic changes that predispose
to infections.
 There is a decrease in helper-T-cell numbers, reduced
activity of natural killer cells, and decreased cell-mediated
immune function.
 Cardiopulmonary changes that occur as a part of normal
pregnancy may result in a diminished capacity to compensate
for the effects of respiratory disease.
 The elevated serum concentrations of progesterone and
17beta-estradiol observed in the latter half of pregnancy can
stimulate the growth and maturation of Coccidioides immitis
Alcohol consumption
 Alcohol consumption affects both systemic and pulmonary
immune function.
 Current alcohol use is an independent risk factor for severe
community-acquired pneumonia.
 Additionally, patients who are alcoholics are frequently also
smokers.
 The negative effect of these risk factors for pulmonary
infections are additive.
 Chronic alcohol drinkers also have decreased saliva
production, an important component of mucosal defense
Autoimmune diseases
Systemic lupus erythematosus:
 Distinguishing infection from an autoimmune flare is important.
 Treatment with steroids in the setting of infection could be deleterious.
 Susceptibility to infections derives from therapeutic and disease-related
factors.
 Complement deficiencies and elevated Fc gamma III and granulocytemacrophage colony-stimulating factor (GM-CSF) levels may contribute to
increased susceptibility to infection
 Deficiencies of functional mannose-binding lectin do not appear to be the
reason for increased infection burden.
 Low complement, use of more than 20 mg prednisone daily, and use
of cyclophosphamide were important risk factors in multivariate
analyses
 In one series of patients with SLE over the course
of 3 years, pneumonia was the third most
common infection, behind urinary tract
infection and skin/soft tissue infection.
 Risk factors for infection were low CH 50 levels
and taking more than 20 mg prednisone daily.
 Severe manifestations of disease are treated with
immunosuppressive therapies
Connective tissue diseases:
 Both the primary condition and the use of
immunosuppressive medications place patients at increased
risk.
 Of 5,411 cases reviewed, 29% of patients developed a serious
infection; 24% died from this infection—most reported as
bacteremia or pneumonia
Functionally immunocompromised
Neuromuscular disease:
 Pneumonia is a leading cause of death. Impairment of cough and
swallowing mechanisms contributes to increased risk of pneumonia.
 Gastroesophageal reflux is more common, persistent, and severe in
patients with cerebral palsy. Kyphoscoliosis secondary to unequal muscle
tone leads to restrictive lung function and predisposes to atelectasis.
 Cognitive dysfunction: Drooling, feeding problems, and aspiration place
these patients at higher risk of pulmonary infections. Asynchrony between
swallowing and breathing results in increased risk of aspiration.
 Spinal cord injury: Muscular weakness may contribute to dysfunctional
cough reflex.
Extremes of age
 Older patients may complain of fewer symptoms than
younger patients, making the diagnosis more challenging.
 Children and infants at risk of RSV infection include those
younger than 24 months with chronic lung disease who have
required medical therapy within 6 months of RSV season
onset, preterm infants born prior to 32 weeks’ gestation,
preterm infants born at 32-35 weeks’ gestation with at least 2
additional risk factors, and those with hemodynamically
significant heart disease.
Chronic steroids
 Both the dose and duration of use are
predictive of increased risk of pneumonia.
 Low-dose and short-term use carry minimal
additional risk of pneumonia;
 dosages more than 10 mg/d or cumulatively
700 mg of prednisone increased patients'
risk of pulmonary infection
Asplenic patients
 In asplenic patients, the overall incidence of
invasive pneumococcal disease is 500 cases
per 100,000 per year
Burn
 Complications arise from both direct lung injury
and indirect pulmonary effects (eg, decreased lung
expansion secondary to circumferential burns).
 Bacterial clearance is impaired in patients with
inhalational injury.
 Mechanisms for impaired clearance include
impaired cough, impaired mucociliary action, airway
plugging, and impaired alveolar macrophage function.
Procedures
 Diagnostic yield of bronchoalveolar lavage (BAL) is high in
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immunocompromised patients with respiratory complaints.2
BAL is rarely performed in the emergency department, CT scanning
can facilitate more efficient in-patient evaluation.
The frequent need for invasive diagnostic testing in
immunocompromised patients should support early pulmonary
consultation on these patients from the emergency department
(particularly in transplant recipients)
CMV immunostaining of BAL specimens is useful for the
diagnosis of CMV pneumonitis in immunocompromised patients.
Diffusing capacity of lung for carbon monoxide (DLCO): Some
authors have supported obtaining a DLCO measurement in HIVinfected patients who have normal findings on chest radiograph as
an algorithm for evaluation of PCP.
MEDICATION
The 2 goals of pharmacologic therapy are eradication of
infections and prophylaxis against common pathogens in
high-risk patients
• Inpatient, non-ICU treatment
• Respiratory fluoroquinolone
• Beta-lactam plus a macrolide
• Inpatient, ICU treatment
• Beta-lactam plus either azithromycin or fluoroquinolone
• For Pseudomonas infection, use an antipneumococcal,
antipseudomonal beta-lactam plus either ciprofloxacin or levofloxacin
(750-mg dose) or beta-lactam plus an aminoglycoside and
azithromycin or a beta-lactam plus an aminoglycoside and an
antipneumococcal fluoroquinolone.
• For community-acquired methicillin-resistant Staphylococcus aureus
infection, add vancomycin or linezolid
Special considerations
 HIV: Medication choices should be based on CD4 count and should be
made in consultation with an infectious disease specialist.
 TB treatment: Initiation of medications for TB rarely occurs in the
ED. Infectious disease consultation should be obtained prior to initiating
pharmacotherapy for TB in the immunocompromised patient.
 Elderly patients: Moxifloxacin is associated with faster clinical
recovery than levofloxacin
 Vitamin C: Some evidence suggests that in vitamin C–deficient
persons supplementation can lower the risk of pneumonia. Further study
is needed; however, it is promising, as it has a low cost and low risk.
 Cystic fibrosis: Addition of tobramycin to an antipseudomonal
semisynthetic penicillin (eg, carbenicillin, ticarcillin, mezlocillin,
piperacillin, azlocillin).
Burn
 Selective oral decontamination in burn patients has been
advocated in some burn centers. Reduced oral carriage of
organisms responsible for pulmonary infections is speculated to
account for a lower frequency of pneumonias in these patients.
 Drug pharmacokinetics in burn patients are complex and
incompletely understood.
 Broadly, treatment can be conceptualized into 2 groups:


First 48-hour acute phase: Protein-rich fluid is lost from intravascular
space. This leads to hypovolemia and a drop in cardiac output, which
results in tissue hypoperfusion and a fall in renal blood flow.
Beyond 48 hours: Complex changes frequently occur in drug
metabolism at the level of the liver, and renal function can be variable in
these patients
Deterrence/Prevention
 General influenza vaccination recommendations for
immunocompromised persons
 All persons 50 years old or older
 Women who will be pregnant during influenza season
 Adults and children who have any condition that can compromise
respiratory function or handling of secretions
 Residents of nursing homes or other long-term care facilities
 Adults and children who have immunosuppression from
medications or from HIV
 All children aged 6 months to 4 years
HIV
 MAC - Weekly azithromycin or daily clarithromycin for patients
with CD4 count less than 50
 Histoplasmosis - Persons at high risk because of occupational
exposure or those who live in a community with a hyperendemic
rate are recommended to consider prophylaxis with itraconazole
for CD4 counts less than 100.
 PCP - Prophylaxis recommendations are different for children
younger than 1 year who have HIV; these recommendations are
not based on CD4 count. In HIV-infected patients on HAART,
PCP prophylaxis can be safely discontinued after the CD4 count
has increased to more than 200 for more than 3 months
Cystic fibrosis
Chronic therapy with azithromycin for those who were
clinically infected with Pseudomonas
Autoimmune diseases
 SLE Pneumococcal and influenza vaccines are
recommended.
 Rheumatoid arthritis - Pneumococcal vaccine
is recommended for patients with rheumatoid
arthritis. The vaccine does not appear to trigger
exacerbations of rheumatoid arthritis, and it
induces adequate humoral response to
pneumococcus. Influenza vaccination is
recommended for patients with rheumatoid
arthritis
Chemotherapy
 American Society of Clinical Oncology has guidelines on the
use of hematopoietic colony-stimulating factors.
 These chemotherapy regimens have decreased the
incidence of febrile neutropenia by more than 40%;
however, the guidelines are still controversial.
 The use of colony-stimulating factors should be made in
collaboration with the patient’s treating oncologist and will
rarely be indicated in the emergency department.
 The Infectious Disease Society of America has guidelines on
use of antimicrobial medications in neutropenic patients with
cancer
Common pathogens in AIDS
Pathogens
Protozoa
P. carinii
T. gondii
Cryptosporidium
Isospora belli
Fungi
Candida spp.
C. neoformans
H. capsulatum
Viruses
Cytomegalovirus
Herpes simplex
VZV
Papovavirus
Clinical presentation
Pneumonia
Brain mass lesion or encephalitis, chorioretinitis
Chronic diarrhea
Recurrent diarrhoea
Oral thrush or esophagitis
Dissemination
Dissemination
Dissemination, chorioretinitis, pneumonia, colitis
Mucocutaneous ulcers or stomatitis
Dissemination
Progressive multifocal leukoencephalopathy
Common pathogens in AIDS
Pathogen
Clinical presentation
Bacteria
M. avium-intracelllare Dissemination
M. tuberculosis
Dissemination
Salmonella spp.
Gastroenteritis
any other unusual bacteria
FUO
(Fever of unknown origin)
Symptoms:
fever, shivering, night sweating, weight loss, nausea,
malaise for more than one week
In adults: infection (30-40%)
tumor
colitis ulcerosa
autoimmune diseases
In children:
>40% due to infection
Usual cause of FUO :
tuberculosis, abscess, osteomyelitis,
endocarditis, gall-bladder or urinary
tract infection
FUO : four categories
 Classic FUO
 Nosocomial FUO
 FUO in neutropenic patients
 HIV-associated
Case 4
A 37-year-old man was hospitalized with an increased white
blood cell count and a peripheral smear consistent with acute
leukemia. A bone-marrow biopsy found 70 to 80% blast forms
diagnostic of acute myelomonocytic leukemia. The patient
underwent induction chemotherapy.
Following the chemotherapy, a repeat bone-marrow biopsy again
demonstrated blast forms After the second round of induction
chemotherapy, he became neutropenic (<100 neutrophils/ul) and
developed fever without a clear source.
Broad-spectrum antibiotic therapy was begun, but the fever
persisted. Empirical i.v. amphotericin-B therapy was begun.
The chest radiograph revealed a new bilateral fluffy
pulmonary infiltration. Bronchoscopy with biopsy was performed:
the specimen demonstrated septate hyphae with acute-angle
branching and culture was carried out.
Aspergillus flavus
Often the diagnosis can be achieved only post mortem by cytology
Case 4 (cont.)
What pathogens may cause pulmonary infiltrate
in a leukemic patient?
Gram-negative rods
S. aureus
Fungi (Aspergillus, zygomycetes, P. carinii, C. neoformans, Candida
spp.)
Viruses (CMV)
Non-infectious cause: bleeding into the lung, leukemic infiltrates
Case 4 (cont.)
Would blood cultures have been useful in helping
to make a diagnosis?
What kind of other microbiological methods
could be used for the early diagnosis?
Where is this fungus found in nature ?
What predisposed this patient to this infection?
Aspergilloma. Tomogram of lung
cavity containing fungus ball
outlined by air space
Invasive aspergillosis. Histological section
showing masses of branching fungal hyphae
invading the lung parenchyma and blood
vessels
Risk assessment of infections in transplant
patients
 Organ - cell transplantation
 Autograft - allograft - heterograft
 Aggressivity of the immunsuppression
 The organ which will be transplanted
(infection mortality is increasing: kidney
heart
liver
 Depends on the length of transplantation
heart/lung)
Infections after transplantation
The frequency and character of the infections differ in different periods
 Early period (0-30 days)
 nosocomial infections:
i.v.-catheter sepsis
pneumonia
urinary tract infection
wound infection
superinfection of the pleural fluid
(sinusitis, prostatitis, disseminated fungal
infection)
 reactivation of earlier infections: CMV
toxoplamosis
tuberculosis
 infections transmitted by the allograft: CMV, HSV, HIV
toxoplasma
Infections after transplantation (cont.)
 Immunosuppressive period (1-6 months) (unusual fashion,
exotic pathogens)
 pulmonary infections (Legionella, Pneumocystis, Nocardia)
 dermal infections (herpes, VZV, Staphylococcus, Streptococcus




cellulitis)
central nervous system infections
urinary tract infections
gastrointestinal infections
FUO (fever of unknown origin)
 The late period (> 6 months) (well-known community-
acquired infections)