NCLEX Immune and Infection Review: HIV, Sepsis, and TB

Quick answer: For NCLEX infection and immune questions, know four things: match each pathogen to its precaution (airborne for TB, measles, varicella; droplet for influenza and pertussis; contact for MRSA and C. diff), sequence the sepsis Hour-1 bundle (lactate, blood cultures before broad-spectrum antibiotics, 30 mL/kg crystalloid for hypotension or lactate of 4 or higher, and norepinephrine if needed to keep MAP at 65 or higher), link HIV opportunistic infections to CD4 counts, and know the RIPE drugs for active TB.

Infection control and immune response questions show up on every NCLEX because they test whether you can protect your patient, your coworkers, and yourself. HIV management, sepsis bundles, isolation precautions, tuberculosis, C. difficile, and MRSA are all high-yield content. Get these down and you will pick up points on infection questions throughout the exam.

Key takeaways

• Match the pathogen to the precaution category: airborne (TB, measles, varicella, disseminated zoster) needs an AIIR plus N95; droplet (influenza, pertussis, meningococcus) needs a surgical mask within 6 feet; contact (MRSA, VRE, C. diff) needs gown and gloves.
• C. difficile is the classic exception: use soap and water for hand hygiene (alcohol does not kill spores) and a bleach-based cleaner for surfaces.
• Sepsis runs on a clock: the Hour-1 bundle is measure lactate, obtain blood cultures before antibiotics, give broad-spectrum antibiotics, start 30 mL/kg crystalloid for hypotension or lactate ≥4, and add norepinephrine to keep MAP ≥65.
• HIV is an adherence and CD4 story: ART is recommended for everyone regardless of CD4, opportunistic infections track to specific CD4 thresholds (PCP at <200, MAC and CMV at <50), and sustained undetectable viral load means untransmittable (U=U).
• Active TB requires the RIPE regimen (rifampin, isoniazid, pyrazinamide, ethambutol) and airborne isolation continued until the patient is on effective therapy, is clinically improving, and has three consecutive negative AFB smears.
• Hand hygiene is the single most important measure, and PPE has a strict order on and off to prevent self-contamination.

HIV: pathophysiology and nursing priorities

HIV destroys CD4 T-helper cells, crippling cell-mediated immunity. Without treatment, the CD4 count falls and opportunistic infections emerge.

Stages and diagnostics

• Acute HIV (2-4 weeks after exposure): flu-like illness – fever, lymphadenopathy, rash, sore throat, myalgia. Highly infectious period.
• Chronic HIV: asymptomatic or mild symptoms for years while CD4 declines.
• AIDS (CD4 less than 200 or AIDS-defining illness): immune system cannot control opportunistic infections.

Diagnostic testing: Fourth-generation antigen/antibody combination assay is the screening test of choice (detects earlier than antibody-only tests). Confirmatory testing includes HIV-1/2 antibody differentiation assay and, if discordant, HIV RNA viral load. Window period for a lab-based 4th-generation antigen/antibody assay on venous blood is 18-45 days after exposure (per CDC); point-of-care fingerstick antigen/antibody tests run longer (18-90 days) and nucleic acid testing detects HIV earliest (10-33 days). After a known exposure, repeat testing on the follow-up schedule below rather than relying on a single early negative.

AIDS-defining opportunistic infections

Know what appears at which CD4 threshold.

• CD4 less than 200: Pneumocystis jirovecii pneumonia (PCP) – dyspnea, dry cough, hypoxia out of proportion to chest exam. Treated with high-dose TMP-SMX (Bactrim); prophylaxis with TMP-SMX when CD4 drops below 200.
• CD4 less than 100: toxoplasmosis encephalitis (prophylaxis with TMP-SMX), esophageal candidiasis.
• CD4 less than 50: Mycobacterium avium complex (MAC) – disseminated infection causing fevers, night sweats, weight loss (azithromycin is the prophylaxis drug to know, though current guidelines omit primary MAC prophylaxis when the patient is starting or already on effective ART). CMV retinitis – vision loss is rapid and permanent without treatment.
• Kaposi sarcoma (purple skin lesions – HHV-8 related) and non-Hodgkin lymphoma at lower CD4 counts.

Antiretroviral therapy (ART)

Current CDC and DHHS guidelines recommend ART for every patient with HIV regardless of CD4 count, and recommend starting therapy as soon as possible after diagnosis.

• Common regimens combine agents from different classes (integrase inhibitors, NRTIs, NNRTIs, protease inhibitors). Integrase strand transfer inhibitor (INSTI) based regimens such as bictegravir or dolutegravir are commonly preferred as first-line.
• Adherence is everything. Missed doses drive viral resistance. Patients on oral ART must take it at the same time every day, indefinitely (long-acting injectables are an option for some patients).
• Monitor viral load and CD4 count at baseline and periodically. Goal is viral load below the limit of detection.
• Undetectable = Untransmittable (U=U): per CDC, patients with sustained undetectable viral load do not sexually transmit HIV.
• Side effects to monitor: lactic acidosis (NRTIs), hepatotoxicity, renal toxicity (tenofovir), rash and hypersensitivity (abacavir – HLA-B*5701 testing before starting), lipodystrophy, metabolic abnormalities.
• Pre-exposure prophylaxis (PrEP) with tenofovir-emtricitabine (or newer agents) prevents HIV acquisition in high-risk HIV-negative patients.
• Post-exposure prophylaxis (PEP) after occupational or sexual exposure: start within 72 hours (sooner is better), 28-day course of 3-drug ART.

Needlestick and occupational exposure

• Wash the site with soap and water immediately (flush mucous membranes with water)
• Report to employee health or emergency department immediately
• Source patient testing if consent obtained
• Baseline HIV, HBV, HCV testing for the exposed worker
• PEP started within hours if indicated
• Follow-up testing at 6 weeks, 3 months, and 6 months (2025 USPHS guidance shortens this, concluding follow-up at 12 weeks with an antigen/antibody immunoassay plus HIV nucleic acid test)

Sepsis: the Hour-1 bundle

Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. Septic shock is sepsis with persistent hypotension requiring vasopressors plus lactate greater than 2 despite adequate fluid resuscitation. Mortality rises every hour treatment is delayed. The Surviving Sepsis Campaign Hour-1 bundle is a core NCLEX concept.

The Hour-1 bundle

Complete these within the first hour of sepsis recognition.

1. Measure lactate. Remeasure if initial lactate is greater than 2 mmol/L to guide resuscitation. Lactate is a marker of tissue hypoperfusion.
2. Obtain blood cultures before antibiotics. Two sets from separate sites. Only if this does not delay antibiotic administration significantly.
3. Administer broad-spectrum antibiotics. Cover likely pathogens for the suspected source. Every hour of delay in septic shock increases mortality.
4. Begin rapid crystalloid infusion at 30 mL/kg for hypotension or lactate greater than or equal to 4 mmol/L, initiated within the first hour. Note: 2021 SSC downgraded this to a conditional (weak) recommendation — titrate to response rather than treating 30 mL/kg as mandatory.
5. Start vasopressors if hypotensive during or after fluid resuscitation to maintain MAP greater than or equal to 65 mmHg. Norepinephrine is first-line.

Remember the order of bundle tasks, and especially remember that blood cultures come before antibiotics. Antibiotics before cultures can produce falsely negative cultures and miss the pathogen.

Recognizing sepsis early

The qSOFA (quick SOFA) score is a bedside risk stratifier. Note: 2021 SSC recommends against qSOFA as a sole sepsis screening tool — NEWS, MEWS, or SIRS are the preferred screens. qSOFA retains utility for risk stratification once infection is already suspected. Any two of the following suggests higher risk:

• Respiratory rate greater than or equal to 22/min
• Altered mentation (GCS less than 15)
• Systolic BP less than or equal to 100 mmHg

Other red flags: temperature greater than 38°C (100.4°F) or less than 36°C (96.8°F), heart rate greater than 90, WBC greater than 12,000 or less than 4,000 or greater than 10% bands, new hypoxia, mottled skin, decreased urine output, new confusion.

Post-resuscitation care

• Titrate vasopressors to maintain MAP 65 or greater
• Monitor urine output greater than 0.5 mL/kg/hr as a perfusion marker
• Trend lactate – clearance indicates response to therapy
• Identify and treat the source (abscess drainage, line removal, surgical source control)
• Glucose control (target less than 180 mg/dL)
• Stress ulcer and VTE prophylaxis
• Low tidal volume ventilation if intubated (6 mL/kg ideal body weight)

Isolation precautions

Standard precautions apply to all patients. Transmission-based precautions are added based on the pathogen. For a deeper drill on PPE, room setup, and pathogen-to-category matching, see our full isolation precautions guide.

Standard precautions (for every patient, every time)

• Hand hygiene before and after every patient contact
• Gloves for contact with blood, body fluids, secretions, non-intact skin, or mucous membranes
• Gown, mask, and eye protection when splashes or sprays are anticipated
• Safe injection practices and sharps disposal
• Respiratory hygiene – cover cough, offer masks to symptomatic patients at triage

Contact precautions

For pathogens spread by direct or indirect contact.

• PPE: gown and gloves for all room entry
• Room: private room preferred; cohorting acceptable for same organism
• Equipment: dedicated (stethoscope, BP cuff, thermometer) when possible; disinfect before leaving the room
• Common pathogens: MRSA, VRE, C. difficile, multidrug-resistant gram-negatives (ESBL, CRE), RSV, norovirus (enteric precautions), scabies, lice, herpes zoster (disseminated or in immunocompromised)
• C. difficile-specific: soap and water for hand hygiene (alcohol-based sanitizer does not kill C. diff spores); bleach-based cleaner for room surfaces; private room; contact precautions continue until symptoms resolve per facility policy.

Droplet precautions

For pathogens spread by large respiratory droplets (travel less than approximately 6 feet and drop quickly).

• PPE: surgical mask within 6 feet of the patient
• Room: private room if possible; otherwise maintain 3-6 feet between patients; door may remain open
• Patient transport: surgical mask on the patient during transport
• Common pathogens: influenza, pertussis, Neisseria meningitidis, mumps, rubella, group A Streptococcus (pharyngitis/pneumonia), Haemophilus influenzae type b, diphtheria

Airborne precautions

For pathogens carried on small particles that remain suspended and travel long distances.

• PPE: fit-tested N95 respirator (or PAPR) for all room entry
• Room: airborne infection isolation room (AIIR) with negative pressure, 6-12 air changes per hour, exhaust to outside or through HEPA filtration; door must remain closed
• Patient transport: limited; if required, patient wears a surgical mask
• Common pathogens: tuberculosis, measles (rubeola), varicella (chickenpox), disseminated herpes zoster, SARS-CoV-2 in certain settings (institution-specific)
• Memory trick – “My Chicken Has TB”: Measles, Chickenpox, Herpes zoster (disseminated), TB – airborne precautions.

Protective environment (reverse isolation)

For severely immunocompromised patients (allogeneic stem cell transplant recipients, severe neutropenia). The goal is to keep pathogens out.

• Positive-pressure room with HEPA filtration (over 12 air changes per hour)
• No fresh flowers or plants
• No raw fruits/vegetables per protocol
• Screening of visitors for illness
• Often combined with contact or other precautions if the patient has a second infection

Tuberculosis (TB)

TB is caused by Mycobacterium tuberculosis, an acid-fast bacillus.

Latent vs active TB

• Latent TB infection (LTBI): positive TST (PPD) or IGRA (QuantiFERON or T-SPOT), normal chest X-ray, no symptoms, not contagious. Treat to prevent reactivation. CDC-preferred regimens are now short-course: 3HP (weekly isoniazid + rifapentine for 12 weeks), 4 months of daily rifampin (4R), or 3 months of daily isoniazid plus rifampin (3HR). Isoniazid for 6-9 months remains an acceptable alternative where short-course is not feasible.
• Active TB: positive sputum AFB smear or culture, abnormal chest X-ray (cavitary upper lobe lesions classic), symptoms (chronic cough, hemoptysis, weight loss, night sweats, fever), contagious.

Treatment: RIPE regimen

Standard initial treatment for active TB is four drugs for two months (intensive phase), then two drugs for four months (continuation phase).

• Rifampin – red-orange body fluids (tears, urine, sweat, contact lenses will stain), hepatotoxicity, reduces effectiveness of oral contraceptives and many other drugs (CYP450 inducer)
• Isoniazid (INH) – peripheral neuropathy (give pyridoxine/vitamin B6 to prevent), hepatotoxicity, drug-induced lupus
• Pyrazinamide – hepatotoxicity, hyperuricemia and gout
• Ethambutol – optic neuritis (red-green color blindness, decreased visual acuity); baseline eye exam and monthly vision checks during therapy

Monitoring: baseline LFTs, repeat monthly or if symptomatic. Stop hepatotoxic drugs if AST/ALT rises more than 3 times upper limit with symptoms or more than 5 times without. Monthly sputum cultures to document conversion. Patient remains on airborne precautions until all three criteria are met: on standard multidrug anti-TB therapy, showing clinical improvement, and three consecutive negative AFB sputum smears collected 8-24 hours apart, at least one an early-morning specimen.

Directly observed therapy (DOT): a health department worker watches the patient take each dose. DOT improves adherence and is recommended for all patients with active TB when feasible. Non-adherence creates multidrug-resistant TB.

C. difficile

C. difficile is a spore-forming gram-positive anaerobe that causes antibiotic-associated diarrhea and colitis. Risk factors: recent broad-spectrum antibiotics (clindamycin, fluoroquinolones, cephalosporins are notorious), healthcare exposure, advanced age, PPI use.

Clinical and diagnostic

• Watery diarrhea (three or more loose stools in 24 hours), abdominal cramping, fever, leukocytosis
• Severe disease: pseudomembranous colitis, toxic megacolon, perforation
• Diagnosis: stool PCR for toxin B genes, GDH antigen plus toxin EIA, or two-step algorithm per facility

Treatment

• Fidaxomicin is preferred first-line for initial episodes per IDSA/SHEA 2021; oral vancomycin is an acceptable alternative. Metronidazole is no longer preferred except when neither of the above is available.
• Fulminant disease (hypotension, shock, ileus, or megacolon): high-dose oral vancomycin plus IV metronidazole; surgical consultation if toxic megacolon or perforation
• Recurrent disease: fidaxomicin, tapered/pulsed oral vancomycin, or fecal microbiota transplantation
• Stop unnecessary antibiotics if possible – ongoing antibiotics perpetuate C. diff

Infection control for C. diff (NCLEX high-yield)

• Contact precautions – gown and gloves for all room entry
• Hand hygiene with soap and water. Alcohol-based hand sanitizer does not kill C. diff spores. Wash with soap and water to physically remove spores.
• Environmental cleaning with a bleach-based agent (sodium hypochlorite) – standard quaternary ammonium cleaners do not kill spores
• Private room or cohort with same organism
• Dedicated equipment
• Continue precautions until symptoms resolve per facility policy (typically 48 hours symptom-free)

MRSA

Methicillin-resistant Staphylococcus aureus causes skin and soft tissue infections, pneumonia, bacteremia, and endocarditis. Two epidemiologic types: healthcare-associated MRSA (HA-MRSA) and community-associated MRSA (CA-MRSA).

• Isolation: contact precautions for any active MRSA infection
• Treatment: vancomycin IV for serious infection (monitor trough levels, renal function; watch for red man syndrome with rapid infusion); oral options include TMP-SMX, doxycycline, clindamycin, linezolid depending on site and susceptibility
• Nasal colonization: mupirocin ointment and chlorhexidine bathing are used for decolonization in high-risk patients
• Active surveillance cultures (nasal swabs on admission) in high-risk units

Core infection control principles

Beyond the specific pathogens, NCLEX infection questions reward the basics.

• Hand hygiene is the single most important measure. Alcohol-based sanitizer for most organisms; soap and water for C. diff, norovirus, and visibly soiled hands.
• PPE order on: gown, mask/respirator, goggles, gloves.
• PPE order off (to avoid self-contamination): gloves, goggles, gown, mask/respirator. Perform hand hygiene immediately after removing all PPE, and between steps whenever your hands become contaminated.
• Do not recap needles – use safety-engineered devices and dispose directly into sharps containers.
• Know your N95 fit test – annually and whenever facial features change.
• Immunocompromised patients need protective environment, not just standard precautions.

Putting infection control together

Infection questions reward knowing the category. Airborne goes in an AIIR with an N95. Droplet needs a surgical mask and some space. Contact needs gown and gloves – soap and water for C. diff. HIV is an ART adherence problem with opportunistic infection risk at specific CD4 thresholds. Sepsis runs on a clock – bundle tasks in the first hour, antibiotics after cultures, fluids for hypoperfusion. If you can match the pathogen to the right precautions, the bundle to the right timeline, and the opportunistic infection to the CD4 count, infection questions will become some of your fastest points on the NCLEX.

For the antibiotics, antivirals, and antifungals that run through this content – vancomycin, RIPE drugs, Bactrim, antiretrovirals – see our pharmacology review. For the labs that flag infection and sepsis (WBC differential, lactate, cultures, CD4), see the lab values guide. For NGN case studies that build infection scenarios across multiple tabs, see the NGN question types guide.

To see how septic shock compares with hypovolemic, cardiogenic, anaphylactic and neurogenic shock, use our types of shock guide.

Frequently Asked Questions

Why do you wash with soap and water for C. difficile instead of using hand sanitizer?

Alcohol-based hand sanitizer does not kill C. difficile spores. You need soap and water to physically scrub and remove the spores from your hands. The same logic drives environmental cleaning: use a bleach-based (sodium hypochlorite) cleaner for surfaces, because standard quaternary ammonium cleaners do not kill spores either. C. diff also requires contact precautions with gown and gloves for all room entry.

Which infections require airborne precautions?

Airborne precautions apply to pathogens carried on small particles that stay suspended and travel long distances: tuberculosis, measles (rubeola), varicella (chickenpox), and disseminated herpes zoster, plus SARS-CoV-2 in certain institution-specific settings. The memory trick is “My Chicken Has TB” – Measles, Chickenpox, Herpes zoster, TB. These patients go in a negative-pressure airborne infection isolation room (AIIR) with the door closed, and staff wear a fit-tested N95 respirator for room entry.

What is the order of the sepsis Hour-1 bundle?

Within the first hour of recognizing sepsis you measure lactate, obtain blood cultures before antibiotics, administer broad-spectrum antibiotics, begin 30 mL/kg crystalloid for hypotension or lactate of 4 mmol/L or greater, and start vasopressors (norepinephrine first-line) if hypotension persists to maintain a MAP of 65 mmHg or greater. The critical sequencing point for the NCLEX is that blood cultures come before antibiotics, because antibiotics given first can produce falsely negative cultures and miss the pathogen.

At what CD4 count do opportunistic infections appear in HIV?

Opportunistic infections track to CD4 thresholds. Below 200, watch for Pneumocystis jirovecii pneumonia (PCP), which is also when PCP prophylaxis with TMP-SMX starts. Below 100, toxoplasmosis encephalitis and esophageal candidiasis appear. Below 50, Mycobacterium avium complex (MAC) and CMV retinitis become risks. ART is recommended for every patient with HIV regardless of CD4 count, started as soon as possible after diagnosis.

What are the four drugs in the RIPE regimen for active TB, and what are their key side effects?

RIPE is rifampin, isoniazid, pyrazinamide, and ethambutol, given as four drugs for two months then two drugs for four months. Rifampin causes red-orange body fluids and is a CYP450 inducer that reduces effectiveness of oral contraceptives. Isoniazid causes peripheral neuropathy, so give pyridoxine (vitamin B6) to prevent it. Pyrazinamide causes hyperuricemia and gout. Ethambutol causes optic neuritis with red-green color changes, so baseline and monthly vision checks are required. Isoniazid, rifampin, and pyrazinamide can all cause hepatotoxicity, so monitor LFTs.