opportunistic infections Flashcards
why all HIV patients eventually develop severe immunodeficiency
Virtually all individuals infected with HIV eventually develop severe immunodeficiency as a result of CD4 cell depletion** making the patient prone to infection** by intracellular pathogens, fungi and viruses with decreased protection against cancer** and decreased antibody formation**.
A normal CD4 count in adults is between 500 and 1200 cells/mm3. During HIV infection, a progressive depletion in CD4 cells is observed, with an average decline of 50 to 100 CD4 cells per year without antiretroviral therapy (ART).
CD4 cell counts associated with opportunistic infections
CD4 cell counts below 500 cells/mm3, and especially below 200 cells/mm3, are associated with the development of opportunistic infections (OI).**
Opportunistic infections continue to cause significant morbidity and mortality in patients with HIV infection because:
-13% of HIV-infected patients in the US are unaware of their HIV infection and may present with an OI as initial indicator of their disease.
-Some individuals are aware of their HIV infection but do not take ART due to psychosocial or economic factors.
-Some patients are receiving HIV care and have been prescribed ART but do not have a sustained virologic response due to poor adherence, the presence or acquisition of drug resistance, drug interactions, etc.
At CD4 counts under 500 cells/mm3, patients may develop bacterial pneumonia, vaginal candidiasis, thrush, shingles, and oral leukoplakia.
At CD4 counts between 0 and 200 cells/mm3, patients may develop Pneumocystis jirovecii/carinii pneumonia (PCP), Kaposi’s sarcoma, disseminated cytomegalovirus (CMV), Toxoplasmosis encephalitis, disseminated Mycobacterium avium complex (MAC), lymphoma, Cryptococcal meningitis, Cryptosporidium diarrhea, etc.
primary vs secondary prophylaxis
Primary prophylaxis is the administration of an anti-infective agent to prevent the first** episode of a particular OI in an HIV-infected patient when they are at risk for developing that OI based on their CD4 cell count. Secondary prophylaxis (AKA chronic maintenance therapy or chronic suppressive therapy) is the administration of anti-infective therapy to prevent further recurrences** of a particular OI in an HIV-infected patient after they have been successfully treated for that OI.
initiation of ART in the setting of an acute OI
One of the main goals of ART is to restore immune function.
Initiation of ART during an acute OI is very useful in the management of OIs for which effective therapy is not available, such as progressive multifocal leuko-encephalopathy (PML), cryptosporidiosis, and Kaposi’s sarcoma. The improvement in immune function from ART contributes to resolution of these OIs.
For other OIs, there are several disadvantages of immediately starting ART in the setting of an acute OI, which include:
-The potential development of the “immune reconstitution inflammatory syndrome” (IRIS) characterized by fever and worsening clinical manifestations of the OI.**
—IRIS can be seen during the acute treatment of infections due to Mycobacterium avium complex (MAC); Mycobacterium tuberculosis (TB); Pneumocystis jirovecii (PCP); Toxoplasma gondii; hepatitis B and C virus; Cytomegalovirus; Cryptococcus neoformans; Histoplasma capsulatum; and Varicella-zoster virus.
—IRIS typically develops within the first 4 to 8 weeks of initiation of ART, if it is going to occur.
—Most clinicians wait for a clinical response to OI therapy, usually 2 weeks, before initiating ART (except for TB → initiate ART within 4 weeks of starting the continuation phase of TB therapy).
-Overlapping or additive drug toxicities.
-Drug interactions between ART and OI-specific therapy.
candida infections
Oropharyngeal candidiasis (thrush) and esophageal candidiasis are among the most common OIs observed in patients with HIV infection, and are both considered indicators of immune suppression. Infections with Candida spp. may occur at all stages of HIV infection, but are most often observed when the CD4 cell count is under 200 cells.
candida pathogenesis and epidemiology
Candida spp. are normal inhabitants of the mucocutaneous surfaces of humans found in the GI tract, oropharynx, and female genital tract.
Alterations in the host immune system, such as defects in cell-mediated immunity, can alter the commensal status of Candida spp. so that invasion of host tissue and infection occurs.
Majority of infections are caused by Candida albicans, which is usually susceptible to azole antifungals such as fluconazole. Infections due to non-albicans Candida spp. and/or fluconazole-resistant organisms may develop in patients who have received repeated** or long-term exposure** to fluconazole.
clinical manifestations and management of oropharyngeal candidiasis
“thrush”
Diagnosis is usually based on clinical exam → thrush is characterized by painless, creamy white, plaque-like lesions on the buccal mucosa, hard or soft palate, oropharyngeal mucosa or tongue surface. Patients may also experience dry mouth and taste alterations.
Lesions can be easily scraped off with a tongue depressor, and submitted to the lab for staining and culture, if necessary.
Treatment
-Topical therapy – useful for initial, mild to moderate episodes only; however, effectiveness is hampered by their unpleasant taste, gastrointestinal adverse effects, and the need for multiple daily dosing for some agents.
-Systemic therapy – SUPERIOR to topical therapy, especially in patients with multiple episodes; is more convenient and better tolerated; MUST be used in patients suspected of having concomitant Candida esophagitis**. Regimen of choice = fluconazole 100mg PO QD for 7 to 14 days
topical agents used for oropharyngeal candidiasis
nystatin susp 5 ml swish and swallow QID x 10-14 - should be throughly rinsed in mouth and retained for as long as possible
clotrimazole troches 10 mg 5x/day x 10-14 - should be dissolved slowly over 15-30 min
miconazole mucoadhesive buccal tab 50 mg applied QD x 14 - $900; applied to upper gum just above in incisor and gradually dissolved
esophageal candidiasis
Usually occurs in association with oropharyngeal candidiasis.
Diagnosis often made empirically based on symptoms including fever, retrosternal burning pain or discomfort, dysphagia, and odynophagia.*
Endoscopic examination reveals whitish plaques (similar to thrush) with superficial ulceration of the esophageal mucosa with white surface exudates, which can be sent for histopathologic examination.
Treatment - use systemic agents because topical therapy is NOT effective.*
-Regimen of Choice = Fluconazole 100 mg (up to 400 mg) IV or PO QD for 14 to 21 days***
vulvovaginitis
Women with HIV/AIDS appear to be very susceptible to the development of recurrent vaginal infections with C. albicans - May occur earlier in the course of HIV disease than thrush, before any significant drop in CD4 count occurs.
Diagnosis is based on clinical presentation → symptoms include thick adherent white vaginal discharge, vaginal itching, vaginal burning, and vulvar erythema; episodes may be more severe or more frequent with advanced immunosuppression. Vaginal secretions are occasionally examined microscopically.
Treatment – can use topical azoles (clotrimazole, butoconazole, miconazole, tioconazole, terconazole), topical nystatin, single dose oral fluconazole (150 mg), or itraconazole oral solution.
Severe or recurrent episodes should be treated with oral fluconazole or topical antifungal therapy for ≥ 7 days.
prophylaxis for candidiasis
Routine primary prophylaxis and chronic suppressive therapy to prevent recurrent infections (secondary prophylaxis) is NOT recommended** because of the effectiveness of therapy for acute infection, the low attributable mortality associated with mucosal candidiasis, the potential for resistant Candida spp. to emerge, potential drug interactions, and cost.
Daily prophylaxis should only be considered for patients with frequent or severe recurrences of esophagitis or vaginitis.
infections due to cryptococcus neoformans
The incidence of infection due to Cryptococcus neoformans has decreased with the introduction of potent combination ART.
Before the availability of ART (or in patients not receiving ART), 5 to 8% of patients with HIV/AIDS developed infection due to Cryptococcus neoformans.
The majority of infections due to Cryptococcus neoformans are observed among AIDS patients with CD4 cell counts under 100 cells/mm3.***
clinical manifestations and diagnosis - cryptococcal meningitis
the most frequent form in AIDS patients
Usually presents as subacute (chronic) meningitis with symptoms present for weeks to months.
Symptoms may be mild and nonspecific and include fever, malaise, headache*, neck stiffness, photophobia, nausea, dizziness, lethargy, irritability, impaired memory, and behavioral changes.
Diagnosis - CSF analysis** typically demonstrates mild abnormalities in AIDS patients. Up to 75% of patients have an elevated opening pressure (> 25 cm H20, signifying increased intracranial pressure) when obtaining CSF.
-Mildly elevated protein, slightly low glucose
-Few white blood cells with lymphocytic predominance
-Elevated cryptococcal antigen titer in CSF (> 1:16)
-India Ink stain demonstrates encapsulated yeast forms
-CSF culture positive for Cryptococcus neoformans
Patients also have a positive serum cryptococcal antigen titer**
clinical manifestations and diagnosis - cryptococcal pneumonia
under 15% of AIDS patients with disseminated Cryptococcal infections develop pneumonia.
May develop when a large inoculum is inhaled.
Symptoms are nonspecific and include cough, chest pain, sputum production, weight loss, fever, hemoptysis, dyspnea, night sweats, and malaise; skin lesions may be present.
Diagnosis of pneumonia includes lobar or nodular infiltrates on CXR, positive serum cryptococcal antigen titers; positive blood, skin, or respiratory tract cultures for Cryptococcus neoformans
Concomitant meningitis MUST be excluded in AIDS patients.***
treatment overview of cryptococcal infections
Meningitis is an absolute indication for systemic antifungal therapy because untreated Cryptococcal meningitis is fatal. Even with treatment, the mortality rate is under 10%.
Treatment consists of 3 phases → induction, consolidation, and maintenance*
The preferred regimen for induction and consolidation treatment of the acute infection = intravenous liposomal amphotericin B + oral flucytosine for ≥ 2 weeks (induction) followed by oral fluconazole for 8 weeks (consolidation).**
Therapy for acute infection should be continued for at least 10 to 12 weeks.**
Patients with increased intracranial pressure may require repeated lumbar puncture as adjunctive therapy.
If the patient is not on ART, the initiation of ART should be delayed until induction (first 2 weeks) and possibly the total induction/consolidation phase (10 weeks) has been completed to avoid IRIS
prophylaxis for cryptococcal infections
Primary Prophylaxis: NOT routinely recommended** because of the relative infrequency of Cryptococcal infection in the US, lack of survival benefit, possibility of drug interactions, potential for the development of antifungal drug resistance, and cost.
Secondary Prophylaxis:
-After initial treatment, 35 to 65% of AIDS patients may suffer a relapse with Cryptococcal infection so that chronic maintenance or suppressive therapy with oral fluconazole for at least one year is necessary***
-May be discontinued if patient has completed one year of maintenance therapy, is asymptomatic, and has sustained immune reconstitution with ART defined as a CD4 count ≥ 100 cells for > 3 months with a suppressed viral load. A repeat LP may be considered before secondary prophylaxis is discontinued to ensure the organism has been eradicated from the CSF.
-Secondary prophylaxis should be restarted if the patient’s CD4 count decreases to under 100 cells.
epidemiology of penumocystis jirovecii (carinii) pneumonia (PCP)
For many patients with AIDS, PCP is the index diagnosis.
Before the widespread use of primary prophylaxis and ART, PCP occurred in 70 to 80% of patients with AIDS.
pathogenesis of PCP
Pneumocystis jirovecii is a ubiquitous organism that is classified as a fungus but shares biologic characteristics with protozoa. Pneumocystis jirovecii is spread by the airborne route → infection from new acquisition or reactivation; primarily causes infection in severely immune-compromised patients (impaired cell-mediated immunity) such as premature, malnourished infants; children with primary immunodeficiencies; patients receiving immunosuppressive drugs (esp corticosteroids); patients with AIDS. Most cases (90%) develop in HIV-infected patients with CD4 counts of under 200 cells/mm3****. Other factors associated with the development of PCP include CD4 percentage under 14%, previous episodes of PCP, oral thrush, recurrent bacterial pneumonia, and unintentional weight loss. The majority of cases occur in patients unaware of their HIV infection, are not receiving care for their HIV infection, or are noncompliant.
