Pneumonia in Compromised hosts

Dr. M. ShahparianpourDr. M. Shahparianpour

Compromised hostsPatients with damaged defense mechanisms, which leads

to severe, life-threatening infections. These conditions are:acute leukemia (granulocytopenia, changed normal flora, damaged barriers)

lymphomatransplantationAIDScarcinoma, 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 problemsAny microorganism can cause infectionMicroorganisms 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 equiRhodococcus 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

Awareness of the epidemiology of infection 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 20 to 50 percent of febrile cancer patients

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 anti-tumor 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 

InfectiousConventional bacteria 37 percent Fungi 14 percent Viruses 15 percent Pneumocystis carinii/jirovecii 8 percent Nocardia asteroides 7 percent Mycobacterium tuberculosis 1 percent Mixed infections 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 SarcoidosisAcute 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 infectionAggressive tumors (eg, new leukemia or lymphoma or

with 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:

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 cluesTravel and employment: Exposures to mycobacteria, endemic fungi

(eg, H. 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.

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 markingsOn 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 transplantThe 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 infectionsSolid organ transplant recipients are susceptible to

infections 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 infectionsAnthrax and severe respiratory syndrome (SARS) cause

acute respiratory distress are emerging conditionsAnthrax 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

MalignancyNeutrophil 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 complicationsTB: 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

PregnancyPregnancy 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

granulocyte-macrophage 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 immunocompromisedNeuromuscular 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 ageOlder 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

BurnComplications 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.

ProceduresDiagnostic yield of bronchoalveolar lavage (BAL) is high in

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 HIV-infected 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 considerationsHIV: 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/PreventionGeneral influenza vaccination recommendations for

immunocompromised persons

All persons 50 years old or olderWomen who will be pregnant during influenza seasonAdults and children who have any condition that can

compromise respiratory function or handling of secretionsResidents of nursing homes or other long-term care

facilitiesAdults and children who have immunosuppression from

medications or from HIVAll children aged 6 months to 4 years

HIV MAC - Weekly azithromycin or daily clarithromycin for

patients with CD4 count less than 50Histoplasmosis - 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 AIDSPathogens Clinical presentationProtozoa

P. carinii PneumoniaT. gondii Brain mass lesion or encephalitis, chorioretinitisCryptosporidium Chronic diarrheaIsospora belli Recurrent diarrhoea

FungiCandida spp. Oral thrush or esophagitisC. neoformans DisseminationH. capsulatum Dissemination

VirusesCytomegalovirus Dissemination, chorioretinitis, pneumonia, colitisHerpes simplex Mucocutaneous ulcers or stomatitisVZV DisseminationPapovavirus Progressive multifocal leukoencephalopathy

Common pathogens in AIDS

Pathogen Clinical presentation

BacteriaM. avium-intracelllare DisseminationM. tuberculosis DisseminationSalmonella spp. Gastroenteritisany 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%)tumorcolitis ulcerosaautoimmune diseases

In children: >40% due to infectionUsual 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 4A 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?

Where is this fungus found in nature ?

What predisposed this patient to this infection?

What kind of other microbiological methods could be used for the early diagnosis?

Invasive aspergillosis. Histological section showing masses of branching fungal hyphae invading the lung parenchyma and blood vessels

Aspergilloma. Tomogram of lung cavity containing fungus ball outlined by air space

Risk assessment of infections in transplant patients

Organ - cell transplantationAutograft - allograft - heterograftAggressivity of the immunsuppressionThe organ which will be transplanted

(infection mortality is increasing: kidney heart liver heart/lung)

Depends on the length of transplantation

Infections after transplantationThe frequency and character of the infections differ in different periods

Early period (0-30 days)nosocomial infections: i.v.-catheter sepsis

pneumoniaurinary tract infectionwound infectionsuperinfection of the pleural fluid(sinusitis, prostatitis, disseminated fungal infection)

reactivation of earlier infections: CMVtoxoplamosistuberculosis

infections transmitted by the allograft: CMV, HSV, HIVtoxoplasma

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 infectionsurinary tract infectionsgastrointestinal infectionsFUO (fever of unknown origin)

The late period (> 6 months) (well-known community-acquired infections)