By :- Pharm D4 Group 3 Pneumonia in Immunocompromised Host:- Samar mohammed El-Rewaney Pharm D4 Group 3

Pneumonia in Immunocompromised Host:- Pneumonia in an immunocompromised host describes a lung infection that occurs in a person whose ability to fight infection is greatly reduced. Causes People who are immunocompromised have a defective immune response. Because of this, they are susceptible to infections by germs that typically do not cause disease in healthy people. They are also more vulnerable to the usual causes of pneumonia, which can affect anyone.

immunosuppression can be caused by: Bone marrow transplantation Certain medications (including steroids and those used to treat cancer ) HIV infection Leukemia Organ transplant

Other symptoms that may occur: Symptoms of pneumonia Cough (may be dry or produce mucus-like, greenish, or pus-like sputum) Chills with shaking Easy fatigue Fever General discomfort, uneasiness, or ill feeling (malaise ) Headache Loss of appetite Nausea and vomiting Sharp or stabbing chest pain that gets worse with deep breathing or coughing Shortness of breath Other symptoms that may occur: Excessive sweating or night sweats Joint stiffness (rare) Muscle stiffness (rare) Swollen gland

PNEUMONIA IN IMMUNOCOMPROMISED PATIENTS Host Defect Disorders or Therapy Associated With Defect Likely Pathogens Defective PMNs Neutropenia Acute leukemia, aplastic anemia, cancer chemotherapy Gram-negative bacteria, Staphylococcus aureus, Aspergillus sp, Candida sp Defective chemotaxis Diabetes mellitus S. aureus, gram-negative aerobes Defective intracellular killing Chronic granulomatous disease S. aureus Defective alternative pathway Sickle cell disease Streptococcus pneumoniae, Haemophilus influenzae C5 deficiency Congenital disorder S. pneumoniae, S. aureus, gram-negative bacteria

Disorders or Therapy Associated With Defect Host Defect Likely Pathogens Disorders or Therapy Associated With Defect Host Defect Mycobacteria, viruses (herpes simplex virus, cytomegalovirus), Strongyloides sp, opportunistic fungi (Aspergillus, Mucor, Cryptococcus spp), Nocardia sp, Toxoplasma sp Hodgkin lymphoma, cancer chemotherapy, corticosteroid therapy Cell-mediated immuno deficiency (T-cell deficiency or dysfunction) Pneumocystis jiroveci, Toxoplasma sp, cytomegalovirus, herpes simplex virus, opportunistic Cryptococcus spp), mycobacteria AIDS

Disorders or Therapy Associated With Defect Host Defect Likely Pathogens Disorders or Therapy Associated With Defect Host Defect S. pneumoniae, H. influenzae, Neisseria meningitidis S. pneumoniae, H. influenzae P. jiroveci, cytomegalovirus, Multiple myeloma, agammaglobulinemia Selective deficiency: IgA, IgG, IgM Hypogammaglobulinemia Humoral immunodeficiency (B-cell deficiency or dysfunction)

Treatment :- Oxygen saturation and cardiac monitoring Oxygen administration Oxygen saturation and cardiac monitoring Empiric antimicrobial therapy Chest physiotherapy

Management of pneumonia in the immunocompromised patient Antibiotic rationale :-   Treatment must be initiated rapidly as disease progression can be swift.  Empirical treatment must take into account: Local pathogens and their resistance patterns The possibility of pseudomonal infections The broad-range of potential pathogens including atypical pathogens In the HIV-positive patient, infections such as Pneumocystis carinii should be considered.

Medication:- The 2 goals of pharmacologic therapy are eradication of infections and prophylaxis against common pathogens in high-risk patients. Consult the 2007 Infectious Diseases Society of America (IDSA)/Chest guidelines for optimal care. 1- Inpatient, non-ICU treatment * Respiratory fluoroquinolone * Beta-lactam plus a macrolide 2- Inpatient, ICU treatment * Beta-lactam plus either azithromycin or fluoroquinolone *For community-acquired methicillin-resistant Staphylococcus aureus infection, add vancomycin or linezolid * 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.

Special considerations HIV: Medication choices should be based on CD4 count and should be made in consultation with an infectious disease specialist. 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.

Pneumocystis jiroveci Pneumonia (PCP) -Trimethoprim-sulfamethoxazole (TMP-SMX) is the treatment of choice (AI). The dose must be adjusted for abnormal renal function. Adding leucovorin to prevent myelosuppression during acute treatment is not recommended because of questionable efficacy and some evidence for a higher failure rate (DII). Oral outpatient therapy of TMP-SMX is highly effective among patients with mild-to-moderate disease (AI). Mutations associated with resistance to sulfa drugs have been documented, but their effect on clinical outcome is uncertain. Patients who have PCP despite TMP-SMX prophylaxis are usually effectively treated with standard doses of TMP-SMX (BIII).

- Patients with documented PCP and moderate-to-severe disease, as defined by room air pO2 <70 mm/Hg or arterial-alveolar O2 gradient >35 mm/Hg, should receive corticosteroids as early as possible, and certainly within 72 hours after starting specific PCP therapy (AI). If steroids are started at a later time, their benefits are unclear, although the majority of clinicians would use them in such circumstances for patients with severe disease (BIII). The preferred corticosteroid dose and regimen is prednisone 40 mg by mouth twice a day for days 1 to 5, 40 mg daily for days 6 to 10, and 20 mg daily for days 11 to 21 (AI). Methylprednisolone at 75% of the respective prednisone dose can be used if parenteral administration is necessary.

Alternative therapeutic regimens include 1- dapsone and TMP for mild-to-moderate disease (BI) (this regimen may have similar efficacy and fewer side effects than TMP-SMX but is less convenient because of the number of pills) 2- primaquine plus clindamycin (BI) (this regimen is also effective in mild-to-moderate disease, and the clindamycin component can be administered intravenously for more severe cases; however, primaquine is only available orally) . 3- intravenous pentamidine (AI) (generally the drug of second choice for severe disease) 4- atovaquone suspension (BI) (this is less effective than TMP-SMX for mild-to-moderate disease but has fewer side effects); and (DI).

5- trimetrexate with leucovorin (BI) (this is less effective than TMP-SMX but can be used if the latter is not tolerated and an intravenous regimen is needed). Leucovorin must be continued 3 days after the last trimetrexate dose. The addition of dapsone, sulfamethoxazole, or sulfadiazine to trimetrexate might improve efficacy on the basis of the sequential enzyme blockade of folate metabolism, although no study data exist to confirm this (CIII). Aerosolized pentamidine should not be used for the treatment of PCP because of limited efficacy and more frequent relapse

Core Pathogens Core Antibiotics Pseudomonas Aeruginosa Ciprofloxacin or amikacin PLUS either An anti-pseudomonal beta-lactam/beta-lactamase inhibitor (piperacillin/tazobactam), or Ceftazidime or carbepenems (imipenem, meropenem) Resistant Acinetobacter species Anti-pseudomonal cephalosporin (ceftazidime), or imipenem/meropenem, or amikacin MRSA* Add vancomycin

Enteric Gram-negative bacilli Klebsiella species and Escherichia coli Core Antibiotics Core Pathogens 3rd-generation cephalosporin e.g. intravenous ceftriaxone, or beta-lactam / beta-lactamase inhibitor e.g. intravenous ampicillin-sulbactam or amoxicillin-clavulanic acid, or quinolone e.g. ciproflaxin. Enteric Gram-negative bacilli Klebsiella species and Escherichia coli Consider adding cloxacillin or clindamycin. Consider adding azithromycin or clarithromycin Alternative to above: newer quinolone as monotherapy. Also, Staphylococcus aureus Hemophilus influenzae and Streptococcus pneumoniae Consider adding vancomycin. If MRSA* isolated >50% in ICU

Pathogen Risk Factor Antibiotic Anaerobic Observed aspiration Abdominal surgery Putrid discharge Clindamycin, metronidazole, or Beta-lactam/beta-lactamase inhibitor Staphylococcus aureus Coma Head injury Diabetes Renal failure Vancomycin MRSA* Outbreaks Legionella species Corticosteroid use Outbreaks Erythromycin

Antibiotic Risk Factor Pathogen As in severe hospital acquired pneumonia (see Table: "Antibiotics for patients with no risk factors" above) Prolonged ICU stay Antibiotic exposure Chronic lung disease AIDS Pseudomonas aeruginosa

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