Immunocompromised Host

Published on 07/03/2015 by admin

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Chapter 40 Immunocompromised Host

Kristen K. Pierce, MD

1 What is the initial approach to the immunocompromised host in the intensive care unit (ICU)?

The approach in the ICU setting relies on several factors:

image High index of clinical suspicion: Immune-compromised hosts often have atypical presentations of infection. For example, patients with severe immunocompromise may lack fever or abscess formation.

image Understanding of the host’s immune defect: Recognizing the deficient pathway (cell mediated vs. humoral) enables the physician to expand the differential diagnosis and has implications for empiric therapy.

image Aggressive diagnostics: Blood work and cultures, imaging, bronchoscopy, and tissue biopsy, if indicated, are all essential in the initial work-up of a suspected infection.

image Early appropriate antimicrobial therapy: This is key when dealing with infections in the immunocompromised patient.

2 What is the “net state of immunosuppression,” and why is it important?

The concept of a net state of immunosuppression describes the infection potential in immunocompromised hosts. For example, a patient who underwent splenectomy 10 years ago after traumatic injury has a very different infection risk than does a patient with HIV/AIDS. This is important in understanding a patient’s susceptibility to, and risk for, infection. The net state of immunosuppression is determined by the following characteristics:

image Immunosuppressive medications. The degree of immunosuppression conferred by these medications will be influenced by their type, dose, and duration of therapy.

image Presence of leukopenia. Long-standing neutropenia carries a different risk of infection as compared with acute-onset neutropenia. For example, acute neutropenia conveys an increased risk of infections with gram-negative and enteric organisms. As the duration of neutropenia continues, these patients are at increasing risk for invasive fungal infections.

image Metabolic factors. Poor nutrition, hyperglycemia, and uremia all confer an increased risk for infection.

image Concurrent infection with immunomodulating viruses such as cytomegalovirus (CMV), Epstein-Barr virus (EBV), hepatitis B and C, human herpes virus 6 (HHV-6), and HIV. These infections can weaken the host’s defenses either by a low level of viral replication or by reducing the function of infected white blood cells. This leads to an increased risk for bacterial or fungal infection.

image Anatomic factors. The presence of obstructing tumors, stents, central venous catheters, and endotracheal tubes can affect a host’s risk for infection.

3 How is immunosuppression measured?

Assessment can be based on the following:

image Duration and level of neutropenia in those undergoing cytotoxic chemotherapy are used to determine the risk of infection and need for empiric antibiotic therapy. For example, patients with a longer duration of absolute neutropenia have a greater risk for invasive fungal infection compared with patients with acute neutropenia.

image CD4 cell count in patients with HIV is an accurate measure of their immune function. A patient with HIV who has an absolute CD4 count of 700/mm3 has a very different infection risk compared with someone whose CD4 counts are under 100/mm3.

image Treatment, type, and duration of therapy in patients receiving immunosuppression after solid organ, stem cell, or bone marrow transplantation (BMT). Also, the type of transplant (matched or unmatched donor) may be important. Patients who undergo stem cell transplantation or BMT from an allogeneic human leukocyte antigen–identical sibling or matched unrelated donor are at greatest risk for infection because they may require more immunosuppression.

4 Do certain immunosuppressive therapies carry a specific risk of infection?

See Table 40-1.

Table 40-1 Common Immunosuppressive Medications

Agent Mechanism of action Associated risk of infection
Corticosteroids Down-regulates lymphocyte and macrophage function
Interferes with inflammatory response		 Long-term use—PCP, hepatitis B, bacterial, molds, mycobacterial disease
Bolus use—CMV, BK virus nephropathy
Calcineurin inhibitors

image Cyclosporine

image Tacrolimus

Blocks T-cell activation targeting calcineurin Viral infections: BK, CMV, VZV
Bacterial and fungal infections Mycophenolate mofetil Blocks T- and B-cell proliferation Viral: CMV, BK virus Sirolimus Arrests cell replication
Decreases IL-2 PCP, CMV, BK virus T-lymphocyte depletion*

image Antithymocyte globulin

image OKT3

Depletes lymphocytes CMV, HSV reactivation late fungal and viral infections B-lymphocyte depletion

image Plasmapheresis

image Rituximab

Depletes B cells Encapsulated bacterial infections Anti-TNF (TNF-α agents) Neutralizes the biologic activity of TNF-α Mycobacterial infections
Hepatitis B reactivation
Lymphoma

IL, Interleukin; TNF, tumor necrosis factor; VZV, varicella-zoster virus.

* Immunosuppression is greater when used as a bolus for antirejection rather than when used as initial induction therapy.

Modified from Fishman JA, Issa NC: Infections in organ transplantation: risk factors and evolving patterns of infection. Infect Dis Clin North Am 24:273-283, 2010, and Danovitch G: Immunosuppressive medications and protocols for kidney transplantation. In Danovitch G (ed): Handbook of Kidney Transplantation. Philadelphia, Lippincott Williams & Wilkins, 2004, pp 72-134.

5 How does the timing of solid organ transplantation affect a patient’s risk for infection?

See Table 40-2.

Table 40-2 Risk of Infection and Time from Transplantation

Months after transplantation Type of infection
0-1 Hospital Derived

Surgical site infection

MRSA, VRE

Catheter infections

MRSA, VRE
Candidal infections

Ventilator-associated

Aspiration

C. difficile colitis

Donor-Derived Infections

Reactivated HSV

West Nile virus

HIV

1-6* Opportunistic Infections

CMV

PCP

Cryptococcus

L. monocytogenes

EBV

Adenovirus

HHV-6

Reactivation of Latent Recipient Infections

Coccidioides immitis

Mycobacterium tuberculosis

Histoplasmosis

Blastomycosis

Reactivation of Latent Donor Derived

HIV

Hepatitis B or C

≥ 6 Community Acquired

Pneumonia

Urinary tract infections

Fungal Infections

Atypical molds

Aspergillus

Atypical Bacterial

Nocardia

Listeria

Cryptococcus

Late Viral Infections

Polyomavirus infection

Reactivated VZV

CMV

EBV

VZV, Varicella-zoster virus.

* Generally thought to be the time of greatest immunosuppression.

Modified from Fishman J: Infection in solid organ transplant recipients. N Engl J Med 357:2601-2614, 2007, and Syndman DR: Epidemiology of infections after solid-organ transplantation. Clin Infect Dis 33(Suppl 1):S5, 2001.

6 Describe the timing of infection in hematopoietic stem cell transplant recipients

Preengraftment: generally accepted as the first 2 to 4 weeks after transplantation and lasting until the engraftment of the transplant. During this period patients often have profound neutropenia and may have neutropenic fever and the ensuing complications. Patients are at risk for bacterial infections from their own endogenous bowel flora (Escherichia coli, Klebsiella, and Pseudomonas) and from skin flora such as Staphylococcus and Streptococcus because of invasive intravenous (IV) lines or skin breakdown. The longer the duration of neutropenia, the greater is the risk of invasive fungal infection with opportunistic fungi, such as aspergillus. Reactivation of latent viruses, such as CMV and herpes simplex virus (HSV), can occur during this period as well, leading to systemic infection.

Early postengraftment: the period from the time of neutrophil engraftment until day 100. With the exception of those patients who still have indwelling catheters, bacterial infection is less common during this time period. Patients who have difficulties with engraftment or those in whom graft-versus-host disease (GVHD) may develop, requiring increased doses of steroids, are at risk for invasive fungal infections as well as viral infections (CMV and HSV).

Late postengraftment: ranging from around day 100 until immunity is restored. Patients are generally at risk for encapsulated bacterial infections (Haemophilus influenzae, Streptococcus pneumoniae, Neisseria meningitidis), fungal infections (Candida spp. and Aspergillus spp.), and late CMV infection.

7 What is the initial recommended work-up of suspected infection in the immunocompromised host?

History and physical. Clinical clues regarding unusual exposures can assist in creating a broad differential for suspected infection. Certain physical examination findings can be indicative of certain types of infection, and through physical examination, including visualization of the oropharynx, skin, and perirectal areas, looking for occult abscess is important.

However, it is important to recognize that digital rectal examinations should not be performed in patients with neutropenia, nor should they be allowed to have rectal instillation of contrast for abdominal computed tomography (CT) scans, because of the risk of hematogenous dissemination of the patients’ endogenous bowel flora.

Questions that may provide clinical clues to source of infection:

image Type and duration of immunosuppressive medication

image Duration of time since transplantation

image Sick exposures: family members, co-workers

image Recent travel, both in and outside of the country

image Pets or animal exposures

image Eating habits: raw fish, game meat

image Hobbies: hunting, fishing, gardening

image History of tuberculosis exposure

image Use of antimicrobial prophylaxis for viral or bacterial infection

image Insect exposures

image Food-borne illnesses

image Recent home renovations

image Recent unprotected sexual intercourse

Blood cultures. Two sets should be obtained. If a patient has an indwelling central venous catheter a set should be collected from each lumen; at least one peripheral set should be obtained as well.

Complete blood cell count with differential; serum creatinine, blood urea nitrogen, electrolytes, and liver function tests.

Cultures

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