1. INFECTIONS IN THE IMMUNE-COMPROMISED HOSTS
Pocket ICU Management
M. Bassel Ericsoussi, MD
Resident, Internal Medicine
University of Illinois at Chicago
Advocate Christ Medical Center
Joehar Hamdan, MD
Resident, Internal Medicine
University of Illinois at Chicago
Advocate Christ Medical Center
Sherif Afifi, MD, FCCM, FCCP
Associate Professor
Anesthesiology and Surgery
Northwestern University Feinberg School of Medicine
Chicago, IL
Contact Information:
Sherif Afifi, MD
251 East Huron St.,
Feinberg 8 – 336A
Chicago, IL 60611-2908
Tel: 312-926-2537
Fax:312-926-4949
s-afifi@northwestern.edu

2. INFECTIONS IN THE IMMUNE-COMPROMISED HOSTS
DEFINITION
• A state in which the response of the host to a foreign antigen is sub-normal.
GENERAL PRINCIPLES
Potential etiologies:
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Common, community-acquired bacterial and viral diseases.
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Uncommon opportunistic infections.
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Multiple simultaneous processes are common.
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Early imaging (CT scan) and tissue-based diagnosis (histopathology and cultures) are critical to
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survival of the immunocompromised patient with pneumonia.
Microbicidal therapy must be started as soon as possible.
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Inflammatory responses are impaired by immunosuppressive therapy, which results in diminished
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symptoms and muted clinical and radiologic findings.
Infections are often advanced (ie, disseminated) at the time of clinical presentation.
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The choice of antimicrobial regimens is often more complex.
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Antimicrobial resistance is increased.
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Surgical intervention is often necessary.
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INITIAL EVALUATION
Rapid assessment of vital signs including oxygen saturation.
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Complete blood count with differential.
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Electrolytes, blood urea nitrogen and creatinine.
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Blood cultures (minimum of two with at least one peripheral and one from any indwelling catheter).
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Urine sediment examination and culture.
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Sputum for Gram's stain, fungal smears, and cultures.
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Imaging of the lungs (chest radiography or whenever possible, chest computed tomographic [CT]
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scanning) and imaging of any symptomatic site (eg, abdomen)
Perineal exam to exclude perirectal infection.
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DIAGNOSTIC APPROACHES
Serologic testing is not generally useful since seroconversion is often delayed.
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Antigen-based tests (ELISA, PCR) are needed in this population.
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3. Diagnosis often requires imaging studies (CT, MRI) due to the altered anatomy following transplant
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surgery.
Expectorated sputum should be sent for Gram stain examination, acid-fast bacilli smear, and
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bacterial and mycobacterial culture.
If transbronchial biopsy is contraindicated, BAL alone continues to have a good overall diagnostic
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yield.
Fiberoptic bronchoscopy (FOB) remains the procedure of choice for diagnosing many pulmonary
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diseases.
Tissue biopsies are often needed.
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INFECTIONS IN THE IMMUNO-COMPROMISED HOSTS
Infections in the hematopoietic bone transplant recipient.
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Infections in the solid organ transplant recipient.
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Infections in the HIV/AIDS patient.
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Infections in the chemotherapy-induced neutropenic fever.
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Infections in patient receiving immunesuppressive therapy.
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INFECTIONS IN THE HEMATOPOIETIC BONE TRANSPLANT RECIPIENT
Two types of allogeneic vs. autologous:
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• Allogeneic HCT: at increased risk for a variety of infections based upon their degree of
immunosuppression and exposures.
• Autologous HCT: only vulnerable to infection during the pre and immediate
postengraftment periods.
The types of infections can be roughly divide based upon the time elapsed since transplantation.
•
• Pre-engraftment (less than 3 weeks): The major risk factors are:
• Neutropenia.
• Organ dysfunction.
• Mucositis and cutaneous damage.
• Immediate postengraftment (3 weeks to 3 months): The major risk factors are:
• Mucositis and cutaneous damage.
• Cellular immune dysfunction.
• Immunomodulating viruses.
• Hyposplenism.
• Decrease in opsonization.
• Diminished reticuloendothelial function.
• Acute graft versus host disease (GVHD) and its therapy in allogeneic HCT
recipients.
• Late post-engraftment (after 3 months): The major risk factor is chronic GVHD and its
therapy

4. INFECTIONS IN THE SOLID ORGAN TRANSPLANT RECIPIENT
The types of infections can be roughly divide based upon the time elapsed since transplantation.
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Less than 1 month:
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• Infection with antimicrobial resistant species: MRSA, VRE, Candida Species (non-
albicans)
• Aspiration
• Catheter Infection
• Wound Infection
• Anastomotic leaks and ischemia
• Clostridium difficile colitis
• Donor Derived Infection: HSV, LCMV, rhabdovirus, West Nile Virus, HIV, Trypansoma
Cruzi
• Recipient Derived Infection (colonization): Aspergillus, Pseudomonas
1 to 6 months post transplant:
•
• With PCP and antiviral (CMV and HBV) prophylaxis: Polyomavirus BK infection,
Clostridium difficile colitis, HSV, Adenovirus, Cryptococcus Neoformans, Mycobacterium
Tuberculosis.
• Anastomotic Complications
• Without prophylaxis: Pneumocystis, HSV, VZV, EBV, CMV, HBV, Listeria, Norcardia,
Toxoplasma, Strongyloides, Leishmania, T. Cruzi,
More than 6 months:
•
• Community acquired pneumonia, urinary tract infections, Aspergillus atypical molds, mucor
species, Norcardia, Rhodococcus species.
Late Viral infections: CMV colitis and retinitis, HBV, HCV, HSV encephalitis, West Nile Virus,
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SARS, JC polyomavirus infection.
INFECTIONS IN THE HIV/AIDS PATIENT
The occurrence of specific infections is closely correlated with the degree of impairment of host
•
defenses
• The CD4 count (or the quot;stagequot; of HIV) can provide information about the type of infection to
which the patient is susceptible:
• Early (CD4 >500 cells/mm3): Bacterial pneumonia, TB and HHV-8 related Kaposi's
sarcoma.
• Intermediate (CD4 200 to 500 cells/mm3).
• Advanced (CD4 100 to 200 cells/mm3): PCP, disseminated fungal disease.
• Late stage disease (CD4 <100 cells/mm3): PCP, disseminated fungal disease
Sinusitis and bronchitis can occur at any CD4 count.
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Human herpesvirus-8 (HHV-8)-related Kaposi's sarcoma occurs almost exclusively in HIV-infected
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men who have sex with men (MSM).
The recommended prophylaxis according to CD4 count:
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• CD4 count <200/mm3 thrush; unexplained fever for more than two weeks; history of PCP:
Pneumocystis carinii pneumonia.
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• CD4 count <100/mm3 and Toxoplasma sero- positive toxoplasmosis:
• CD4 count <50/mm3 myocabacterium avium complex:

5. CD4 count <150/mm3 and lives in an endemic area histoplasmosis:
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INFECTIONS IN CHEMOTHERAPY-INDUCED NEUTROPENIC FEVER
Defined as a single temperature of >38.3ºC (101.3ºF), or a sustained temperature >38ºC (100.4ºF)
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for more than one hour.
Absolute neutrophil count (ANC) <500 cells/microL.
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Pathogenesis:
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• Chemotherapy-induced mucositis.
• Deficits related to the underlying malignancy.
Bacterial infections:
•
• More Common: Staphylococcus aureus, staphylococcus epidermidis, streptococci, and
tuberculosis reactivation.
• Less common: Corynebacterium jeikeium, bacillus, propionibacterium acne.
Fungal infections: Candida albicans, aspergillus, fusarium sp., reactivation of endemic fungi
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(histoplasmosis, blastomycosis, coccidioidomycosis).
Viral infections: HSV-1 and 2 (encephalitis, meningitis, myelitis, esophagitis, pneumonia, hepatitis,
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erythema multiforme, and ocular disease), herpes zoster, cytomegalovirus, epstein Barr virus,
HHV-6.
INFECTIONS IN PATIENT RECEIVING IMMUNESUPPRESSIVE THERAPY
The spectrum of infections may include common pathogens, opportunistic infections, and
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sometimes normal flora.
The degree of immune deficiency is dependent upon the condition being treated, the doses of
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single agents, and drug combinations that are frequently synergistic.
Laboratory studies of immune function are often used to monitor therapy.
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Mechanisms:
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• Alteration in macrophage function.
• The induction of suppressor T cells.
• Depression of cell-mediated.
• Production of immunosuppressive factors.
Microbial infections:
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• Measles: pneumonia, gastroenteritis, otitis media, gingivostomatitis, and
laryngotracheobronchitis.
• Herpesviruses:
• Bacterial infections
• Micobacterial infections
• Parasite infestation: Malaria infection
GENERAL MANAGEMENT PRINCIPLES
The central focus must be on disease prevention by drug therapy and vaccination.
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Microbicidal therapy must be started as soon as possible.
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Empiric therapy should be based upon available data. Overly broad antimicrobial therapy can then
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be modified based upon new microbiologic data.

6. The choice of antimicrobial regimens is often more complex than in other patients.
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Antimicrobial resistance is increased.
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Surgical intervention is often necessary to cure localized infections (debridement); antimicrobial
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agents alone are frequently inadequate.
Reduction of the overall level of immune suppression may be as important as antimicrobial therapy
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in the ultimate success of treatment.
PREVENTION AND PROPHYLAXIS IN TRANSPLANT PATIENT
1) Antibacterial prophylaxis
Suppress intestinal flora to prevent gram-negative bacterial infections during neutropenia.
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Levofloxacin (prophylactic agents of choice) reduce the frequency of gram-negative
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infection and provide excellent coverage against gram-positive infections.
The duration of prophylaxis depends upon the degree of immunosuppression and
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institutional protocols.
Patients with severe GVHD requiring immunosuppressive drugs remain on both
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antibacterial and antifungal prophylaxis until the immunosuppressive drugs are no longer
necessary.
Prophylaxis against the pneumococcus (penicillin, trimethoprim-sulfamethoxazole, and
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newer fluoroquinolones) in all allogeneic transplant recipients
Autologous recipients do not require routine prophylaxis directed at the pneumococcus
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following engraftment unless they are at additional risk for severe pneumococcal infection
or are receiving ongoing immunosuppresive therapy.
2) Antiviral prophylaxis: Both prophylaxis and preemptive strategies are employed for a variety of
viral infections.
• Herpes simplex virus
• When tolerated, oral acyclovir is equally effective and costs less.
• Continue acyclovir as long as the patient is severely immunosuppressed (CD4
count <200/mm3).
• Acyclovir (use for> 1 year) was associated with optimal suppression of disease
compared to shorter durations of prophylaxis.
• Cytomegalovirus
• Intravenous ganciclovir to prevent reactivation of endogenous CMV in CMV
seropositive recipients or in patients receiving organs from a seropositive.
• High-dose acyclovir may also be effective.
• Many centers favor a preemptive approach (screening for CMV following
transplantation and treating only those shedding antigen) rather than prophylaxis
to minimize toxicity.
Varicella zoster virus
•
• Varicella zoster virus (VZV) can cause severe disease in transplant patients.
• VZV prophylaxis with acyclovir for one year following transplantation and longer
prophylaxis to patients requiring ongoing immunosuppression.
Epstein-Barr virus
•

7. • Epstein-Barr virus (EBV) reactivation may progress to life-threatening EBV-related
posttransplantation lymphoproliferative disorder (PTLD): uncontrolled proliferation
of B cells.
• PCR is an important tool for monitoring EBV reactivation.
• CD20 monoclonal antibodies (rituximab) is effective in rapidly reducing levels of
proliferating B cells.
• Acyclovir and ganciclovir are unable to limit B cell proliferation in PTLD
3) Antifungal prophylaxis
• Fungal infections are a frequent cause of transplant-related mortality (Candida and
Aspergillus species).
• Fluconazole, itraconazole, posaconazole, and micafungin prevent invasive fungal
infections in transplant recipients without causing significant toxicity.
• Fluconazole prophylaxis is associated with significant reductions in fungal colonization,
systemic fungal infection and mortality.
• Itraconazole is poorly tolerated (hepatotoxicity and gastrointestinal irritation).
• The benefit of prophylactic amphotericin B remains uncertain.
• Prophylaxis for candidiasis
• Colonization with fluconazole-susceptible candida spp: Oral fluconazole starting
the first day of neutropenia and continuing until immunosuppression has resolved.
• Patients colonized with fluconazole-resistant Candida spp (C. glabrata or C.
krusei), an echinocandin, such as caspofungin, micafungin, or anidulafungin,
should be considered.
• Preemptive therapy for aspergillosis
• Screen high-risk patients for markers of colonization and/or infection.
• Nasal culture.
• Aspergillus polymerase chain reaction (PCR).
• Serum Aspergillus galactomannan.
• Serum beta-D-glucan.
• If markers are positive, high-resolution CT scan of chest and a CT scan of sinuses
and/or other potential sites of infection.
• If you suspect invasive aspergillosis, start voricinazole.
• If voriconazole cannot be given, amphotericin B is the preferred alternative.
• Posaconazole and voriconazole can be used for prophylaxis.
4) Antiparasitic prophylaxis
• Pneumocystis jiroveci
• Start after engraftment and continued for as long as immunosuppressive therapy
is given and the CD4 cell count is <200 cells/microL.
• TMP-SMX (the drug of choice)
• TMP-SMX offers protection against various potential pathogens in this
patient population including Streptococcus pneumoniae, Haemophilus
influenzae, enteric bacterial pathogens, and toxoplasmosis.
• Atovaquone, aerosolized pentamidine, and dapsone (if the patient is allergic to
TMP-SMX or there is concern about bone marrow toxicity)
• Toxoplasma gondii

8. • It is often fatal opportunistic infection.
• Since the disease mostly reflects reactivation of latent infection, it is advisable to
determine the toxoplasma serologic status of all patients undergoing
transplantation.
• Chemoprophylaxis for toxoplasmosis (pyrimethamine sulfadoxine, TMP-SMX)
after engraftment may be helpful in seropositive patients in highly endemic areas.
Anti-mycobacterial prophylaxis
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• Reserved for patients identified as high-risk during the pretransplant evaluation.
• Isoniazid prophylaxis, starting before transplantation and continuing during the
transplant period has been suggested.
PREVENTION AND PROPHYLAXIS IN HIV
Pneumocystis (CD4 count < 200 cells/microL).
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TMP-SMX as first-line (also in pregnancy 2nd, 3rd trimester).
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Dapsone (pt who cannot tolerate TMP-SMX).
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Atovaquone (who cannot tolerate TMP-SMX or dapsone).
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Aerosolized pentamidine (pregnancy, 1st trimester).
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Toxoplasma (CD4 count <100 cells/microL and are toxoplasma seropositive).
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TMP-SMX as first-line (also in pregnancy 2nd, 3rd trimester).
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Dapsone plus pyrimethamine plus leucovorin (pt who is allergic to TMP-SMX).
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atovaquone (pt who is intolerant or allergic to the above two regimens).
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Pyrimethamine is teratogenic and should not be used during pregnancy.
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Patients who are seronegative for toxoplasma should be counseled to avoid eating
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undercooked meats and to use gloves when cleaning cat litter boxes.
MAC (CD4 count less than 50 cells/microL).
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• Blood cultures for MAC isolation should be drawn if there is any suspicion of clinical
disease before starting any prophylactic treatment
• Macrolides (weekly azithromycin rather than daily clarithromycin).
• If azithromycin is not tolerated, clarithromycin should be initiated.
• Rifabutin(If neither macrolide is tolerated), a chest x-ray should be obtained to rule out
active tuberculosis.
• Azithromycin may be used during pregnancy. Clarithromycin is a teratogen in animals and
should not be used during pregnancy.
Histoplasmosis (CD4 count <100 cells/microL and lives in an endemic area)
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• Itraconazole
Candida
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• Primary prophylaxis is not recommended

9. Azoles are teratogenic and should not be used during pregnancy.
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Cryptococcus
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• Primary prophylaxis is not recommended
• Azoles are teratogenic and should not be used during pregnancy.
Coccidioidomycosis
•
• Primary prophylaxis is not recommended
Cytomegalovirus
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• Seropositive with CD4 counts <50 cells: Three to six month ophthalmologic examinations
for surveillance of CMV disease AND patient education about the symptoms of CMV
retinitis, including floaters and blurry vision.
• Seronegative, advice should be given about potential routes of transmission; additionally
they should receive CMV antibody negative blood transfusions or leukocyte-reduced
cellular blood products, when needed.
Cryptosporidium
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• Prophylaxis is not recommended