JAWAHARLAL NEHRU TECHNOLOGICAL UNIVERSITY HYDERABAD Pharm. D III Year PHARMACOTHERAPEUTICS - II Previous Question Paper (January/February - 2021 - R08)

Infective endocarditis (IE) is a microbial infection of the endocardial surface of the heart, typically involving the heart valves. It is a serious condition requiring prompt diagnosis and prolonged antimicrobial therapy.

Etiology: The most common causative pathogens are Gram-positive cocci. Staphylococcus aureus is the most frequent cause, especially in healthcare-associated cases and intravenous drug users. Viridans group streptococci (e.g., S. sanguinis, S. mutans) are common in community-acquired cases involving damaged valves. Other organisms include Enterococcus species, coagulase-negative staphylococci (often in prosthetic valves), and the HACEK group (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella).

Diagnosis: Diagnosis is primarily established using the modified Duke Criteria, which rely on clinical, microbiological, and echocardiographic findings. Major criteria include positive blood cultures for typical organisms and evidence of endocardial involvement on echocardiography (vegetations, abscesses, or new valvular regurgitation). Minor criteria include predisposing heart conditions or intravenous drug use, fever, vascular phenomena (e.g., Janeway lesions, emboli), and immunological phenomena (e.g., Osler's nodes, Roth spots, glomerulonephritis).

Therapy: Treatment involves high-dose, bactericidal, intravenous antibiotics administered for 4 to 6 weeks to eradicate organisms within the vegetation. Initial empirical therapy must cover staphylococci, streptococci, and enterococci (e.g., vancomycin plus gentamicin). Once the pathogen is identified, therapy is narrowed based on susceptibility testing (e.g., penicillin G or ceftriaxone for susceptible streptococci). Surgical intervention (valve repair or replacement) is indicated for patients with heart failure, persistent infection despite appropriate antibiotic therapy, large mobile vegetations with high embolic risk, or fungal endocarditis.

HIV infection is caused by the Human Immunodeficiency Virus, a retrovirus that primarily targets CD4+ T-lymphocytes, macrophages, and dendritic cells. The pathogenesis involves several critical stages: viral entry via binding of the viral gp120 protein to the CD4 receptor and CCR5 or CXCR4 co-receptors, fusion, reverse transcription of viral RNA into DNA, integration into the host genome via the enzyme integrase, and subsequent viral replication, assembly, and budding. This leads to the progressive depletion of CD4+ T-cells, resulting in profound immunosuppression and susceptibility to opportunistic infections and malignancies.

Treatment guidelines for HIV, known as Antiretroviral Therapy (ART), aim to suppress viral load to undetectable levels, restore immune function, reduce morbidity and mortality, and prevent transmission. Current guidelines recommend initiating ART in all individuals living with HIV, regardless of CD4 count.

The standard initial regimen typically consists of a combination of three antiretroviral drugs, usually comprising two Nucleoside Reverse Transcriptase Inhibitors (NRTIs) combined with an Integrase Strand Transfer Inhibitor (INSTI). Preferred first-line regimens often include:

• Dolutegravir plus Emtricitabine and Tenofovir disoproxil fumarate or alafenamide.
• Bictegravir/Emtricitabine/Tenofovir alafenamide.

Monitoring involves regular assessment of CD4+ T-cell counts and plasma HIV-1 RNA viral load. Adherence to therapy is critical to prevent the development of drug resistance. In cases of treatment failure, resistance testing is performed to guide the selection of a new, effective regimen. Additionally, patients are screened for opportunistic infections and provided with appropriate prophylaxis (e.g., trimethoprim-sulfamethoxazole for Pneumocystis jirovecii pneumonia) when CD4 counts fall below specific thresholds.