Opportunistic Infection

Question 1

PCP - cause

Answer 1

PneumoCystis Pneumonia
Pneumoncystis Jirovecii
classified as fungus, however, not grow on fungal culture
and have cholesterol in their cell wall instead of ergosterol
treat with antibiotic and anti parasitis agents

Question 2

Opportunistic infection

Answer 2

HIV Pt with low CD 4 count

Question 3

PCP risk

Answer 3

HIV CD4 <200, oral thrush, recurrent bacterial pneumonia, unintentional weight loss, higher plasma HIV RNA levels
Hematopoietic stem cell and sold organ transplant
Cancer
Immunosuppressive medication, glucocorticoids, chemotherapy

Question 4

PCP clinical presentation

Answer 4

gradual onset
fever, nonproductive cough, dyspnea progressing over days to weeks
fatigue with usual activities, chill, weight loss or chest pain
most common adventitial sounds are crackles and rhonchi
Oral thrush is a common co-infection

Question 5

PCP lab & Imaging

Answer 5

CD4 <14%
Hypoxia: wide alveolar- arterial O2 gradient, O2 Desaturation with exercise
Elevated LDH
Elevated plasma 1-3-beta-D-glucan

CXR: Diffuse, bilateral, interstital, or alveolar infiltrates
Lobar or segmental infiltrate, cysts, nodules, and pleural effusions less common
CT: High sensitive
Gallium-67 citrate scanning

Question 6

PCP - diagnosis

Answer 6

 Advanced immunosuppression (CD4 < 200)
 Cough, fever, dyspnea, hypoxemia (especially with exercise)
 CXR (interstitial, or alveolar infiltrates) or CT (patchy or nodular ground-glass attenuation) findings consistent with PCP
 Elevated 1-3-beta-D-glucan level (> 80 pg/mL)

Of note, the occurrence of PCP in patients who are compliant with TMP-SMX PCP prophylaxis is highly unusual.

Breakthrough PCP in patients previously on dapsone, atovaquone, or aerosolized pentamidine prophylaxis is relatively more common.

Question 7

PCP treatment

Answer 7

DOC: bactrim IV/PO
DOT: 21 days in HIV; 14-21 days in non-HIV Pt
Pt should start show improvement at 5th day of therapy
Start ART within 2 week of PCP treatment if not on

Drugs:
Trimethoprim-sulfamethoxazole (TMP-SMX): IV or PO
o Dosing: 15-20 mg/kg of TMP component in divided doses q6-8 hours, needs renal adjustment for CrCl < 30 ml/min
o Note dosing is based on TMP componen
o ADRs: rash, fever, GI intolerance, hyperkalemia, hepatotoxicity, neutropenia
o Preferred in pregnancy

 TMP-dapsone: PO
o ADRs: GI upset, rash, hemolytic anemia, methemoglobinemia
o Test for G6PD deficiency when starting dapsone
o Ok in pregnancy

 Clindamycin-primaquine: PO, clindamycin component may be IV
o ADR: rash, hemolytic anemia, neutropenia, methemoglobinemia, diarrhea, C.diff colitis
o Test for G6PD deficiency when starting primaquine

 Atovaquone: PO
o ADRs: GI distress, rash

 Pentamidine: IV
o Greater toxicity than other regimens  reserved for severe infections / intolerant to other options
o ADRs: nausea, taste disturbance, cardiac arrhythmias, hyper/hypokalemia, nephrotoxicity (cumulative), pancreatitis, hypocalcemia, hyper/hypoglycemia, hypotension (life-threatening)
o Give while patient is supine, adequately hydrated, over at least 60 minutes (usually in hospital setting)

 Corticosteroids: adjunctive for more severe illness
o Decreases mortality and respiratory failure associated with severe PCP

Question 8

MAC - cause

Answer 8

Mycobacterium avium complex
M. avium, M. intracellulare
a recent acquisition
no latent phase

Question 9

MAC prophylaxis

Answer 9

CD4 count < 50
clarithromycin 500mg PO daily
azithromycin 1200 mg PO weekly
D/C three months after attaining CD 4 >100

Question 10

MAC risk

Answer 10

CD4 <50

Question 11

MAC persentation

Answer 11

disseminated or localized
fever, night sweats, abdominal pain, diarrhea, weight loss

leukocytosis, focal inflammation in a lymph node

Question 12

MAC diagnosis

Answer 12

Blood culture, Aspiration of local lymph node

anemia, elevated alkaline phosphatase and lactate dehydrogenase

Question 13

MAC treatment

Answer 13

combination therapy (at least 2 drugs) is necessary 
Preferred first line regimen includes clarithromycin + ethambutol + rifabutin if patient is not on a protease inhibitor.

DOT: at least 12 month, life long w/o immune reconstitution 
1st DRUG –
 Clarithromycin  (preferred 1st agent)
o ADR: increased LFTs
 Azithromycin (instead of clarithromycin if clarithromycin is not tolerated or concerns for DDIs)
o ADR: increased LFTs
2nd DRUG –
 Ethambutol 
o ADR: optic neuritis
3rd DRUG (optional) – for patients with high mycobacterial loads or absence of ART
 Rifabutin 
 Fluoroquinolones
 Amikacin

Symptom should be improve 2-4 weeks after treatment

Question 14

CMV (Cytomegalovirus)

risk

Answer 14

 Solid organ transplant: seropositive donor to seronegative recipient
 Hematopoetic stem cell transplant: seronegative donor stem cells to seropositive recipient
 Immunosupression: T lymphocyte depleting therapies used in transplant
 Advanced HIV infection (CD4 < 12) and severe immunodeficiency
o CMV as a sole cause of pneumonia is not common until the late stages of HIV disease

Question 15

CMV prophylaxis

Answer 15

Ganciclovir IV
Valganciclovir PO

alternative: High dose acyclovir and valacyclovir

Question 16

CMV Clinical presentation

Answer 16

rarely detected before 2nd week after transplant
fever, malaise, weakness, myalgias, and arthalgias
leukopenia, thrombocytopenia that occur in the setting of viremia
Pneumonitis (low-grade fever, shortness of breath, nonproductive cough, and changes in measured pulmonary function)
CMV has also been associated with acute rejection of transplant.

CMV pneumonitis is associated with radiographic evidence of bilateral, symmetrical, peribronchovascular, and alveolar process predominantly affecting the lower lobes.

Question 17

CMV- INFECTION VS. DISEASE

Answer 17

CMV infection is defined as evidence of CMV replication regardless of symptoms or signs. CMV disease is defined as evidence of CMV infection with attributable symptoms or signs. CMV disease may manifest as a viral syndrome (fever, malaise, leukopenia, thrombocytopenia) or as tissue invasive disease.

Question 18

CMV diagnosis

Answer 18

If CMV is suspected, test the blood for CMV replication. The test will vary by transplant center but a common option is viral load testing using quantitative polymerase chain reaction (PCR).
Serology should NOT be used to diagnose active CMV infection or disease in transplant recipients.

Question 19

CMV treatment decision

Answer 19

Treatment of CMV is recommended in the presence of symptomatic pulmonary disease, evidence of CMV in the lung, and the absence of other treatable pulmonary infections
 Treatment if CMV is considered for lung transplant recipients with asymptomatic CMV viremia to prevent development of invasive disease and to prevent potential indirect effects of CMV viremia (rejection)
 Treatment of asymptomatic patient with evidence of pulmonary CMV is not recommended
 Treatment of CMV when concomitant pathogens are present is not recommended

Question 20

CMV treatment

Answer 20

Ganciclovir - DOC for children and adults with severe disease, and CMV pneumonitis (regardless of severity)
o ADR: hematologic suppression (neutropenia, thrombocytopenia)
o Requires renal adjustments

Valganciclovir
o Highly bioavailable prodrug of ganciclovir
o Oral option for non-severe CMV disease
o ADR: hematologic suppression (neutropenia, thrombocytopenia)
o Requires renal adjustments

Cytomegalovirus immune globulin (CytoGam)
o In addition to antiviral therapy in patients with severe disease

Foscarnet
o Alternative if suspected or confirmed ganciclovir-resistant CMV
ADR: nephrotoxicity (especially when given with cyclosporine or tacrolimus), electrolyte disturbances
o Requires renal adjustments

DOT: minimal of 2 weeks

Question 21

Nocardiosis cause

Answer 21

Norcardia spp (gram + bacterial )
2 distinguishing characteristics: 1) Nocardiosis is able to disseminate to virtually any organ, especially the CNS, and 2) has a tendency to relapse or progress despite appropriate therapy, making it difficult to treat.

Question 22

Nocardiosis Risk

Answer 22

Immunocompermise:
 Solid organ or hematopoietic stem cell transplant
 Glucocorticoid therapy
 HIV infection (especially if CD4 < 100)
 Malignancy (especially after recent chemo or glucocorticoid therapy)
 Diabetes

Question 23

Norcardiosis presentation

Answer 23

 Lungs: Primary site of nocardial infection in > 2/3 of cases. Fever, night sweats, fatigue, anorexia, weight loss, dyspnea, cough, hemoptysis, and pleuritic chest pain. ~50% of pulmonary cases disseminate to sites outside the lungs, most commonly to the brain
 CNS: Parenchymal abscess that can occur in any region of the brain. Fever, headache, meningismus, seizures, and/or focal neurologic deficits.
 Cutaneous: Usually from direct inoculation of organisms into the skin during gardening, farming, trauma, surgery, or animal scratch/bite. Ulcerations, pyoderma, cellulitis, nodules, and subcutaneous abscesses.

Question 24

Norcardiosis diagnosis

Answer 24

Blood culture hold for 4 weeks (acid fast)
sputum culture - indicative
susceptibility test
CT/MRI for Pt with evidence of CNS disease to assess for abscess

Question 25

Norcardiosis treatment

Answer 25

Since Nocardia spp are variably resistant to antibiotics, patient with severe infection should be empirically covered with 2 or 3 agents.

For severe infection not involving the CNS, treat with TMP/SMX + amikacin or imipenem + amikacin. For CNS disease, TMP-SMX + imipenem

 Cutaneous disease: 3-6 months in immunocompetent, minimum of 1 year for immunocompromised
 Serious infection: 6-12+ months
 CNS involvement: at least 1 year
 Immunocompromised patients: at least 1 year, with possible indefinite PO suppressive therapy

Question 26

Norcardiosis drugs

Answer 26

Trimethoprim-sulfamethoxazole
o 1st line drug of choice
o ADR: rash, fever, GI intolerance, hyperkalemia, hepatotoxicity, neutropenia
o Adjust for renal function

Imipenem
o ADR: increased risk for seizures
o Adjust for weight / renal function

3rd generation cephalosporins (ceftriaxone)
Amikacin
o Aminoglycoside reserved for severe infections, organisms with increased resistance
o ADR: nephrotoxicity, ototoxicity
o Adjust for renal function

PO options when eligible to change to oral therapy
o SMX-TMP
o Minocycline
o Amoxicillin-clavulanate