Infectious Disease Survival Guide
Evaluation of Fever
Fever is a regulated increase in body temperature, distinct from unregulated hyperthermia. Understanding the underlying etiology is essential for appropriate management.
Fever Pathophysiology Categories
Environmental/Thermoregulatory Failure: - Heat stroke - Excessive environmental heat overwhelming dissipation mechanisms - Malignant hyperthermia - Genetic predisposition triggered by certain anesthetics - Neuroleptic malignant syndrome (NMS) - Dopamine antagonist-induced rigidity and hyperthermia - Serotonin syndrome - Excessive serotonergic activity from drug interactions
Inflammation-Mediated Fever: - Infection (bacterial, viral, fungal) - Thromboembolic phenomena (myocardial infarction, pulmonary embolism) - Autoimmune conditions (rheumatoid arthritis, systemic lupus erythematosus) - Malignancy (lymphoma, renal cell carcinoma) - Medication reactions
Diagnostic Approach
Clinical Assessment
Begin by characterizing the fever pattern. A detailed history of exposures, travel, sick contacts, and medication changes guides the differential diagnosis.
Key History Elements: - Duration of fever and temperature pattern (constant vs intermittent) - Associated systemic symptoms (chills, night sweats, weight loss) - Recent travel and endemic exposures - Sick contacts and epidemiologic risk factors - Medication history (especially antibiotics, anticonvulsants) - Recent procedures or interventions
Physical Examination: - Obtain full vital signs including accurate temperature - Comprehensive physical exam for localizing signs - Look for rashes, lymphadenopathy, hepatosplenomegaly - Cardiac exam for murmurs (endocarditis)
Fever of Unknown Origin (FUO)
FUO is classically defined as fever documented on multiple occasions during ≥3 weeks of illness without an established diagnosis after at least one week of investigation.
Classic FUO Etiologies (in order of frequency):
| Category | Common Diagnoses | Frequency |
|---|---|---|
| Infection | Tuberculosis, endocarditis, abscess, osteomyelitis | ~30% |
| Malignancy | Lymphoma, leukemia, renal cell carcinoma | ~20% |
| Rheumatologic | Systemic lupus erythematosus, vasculitis, adult Still's disease | ~15% |
| Other | Granulomatous colitis, drug fever, pulmonary embolism | ~20% |
| Unknown | No diagnosis despite thorough evaluation | ~15% |
Investigation Strategy:
Avoid Unnecessary Antibiotics
Do not empirically treat FUO with antibiotics. Comprehensive workup must precede treatment to avoid masking diagnosis and selecting resistant organisms.
- Laboratory: CBC with differential, comprehensive metabolic panel, liver function tests, inflammatory markers (ESR, CRP), blood cultures (multiple sets before antibiotics)
- Imaging: Chest X-ray, abdominal ultrasound or CT, consider PET scan if diagnosis remains elusive
- Specific testing: TB testing (PPD, IGRA), serologies (EBV, CMV, toxoplasma, brucella depending on exposure), ECG and echocardiography if endocarditis suspected
- Medication review: Discontinue unnecessary medications; "drug fever" resolves within 48-72 hours of cessation
Neutropenic Fever
Neutropenic fever is a medical emergency defined as a single temperature ≥38.3°C or ≥38°C sustained for ≥1 hour with absolute neutrophil count <500.
Risk Stratification: - High-risk: Prolonged neutropenia (>7 days expected), unstable vital signs, signs of organ dysfunction - Low-risk: Brief neutropenia, stable, no comorbidities
Empiric Antibiotic Algorithm:
Key Principles: - Obtain cultures before any antibiotics - Avoid delays - empiric broad-spectrum coverage within 1 hour - Reassess at 48-72 hours; de-escalate if cultures identify organism - Continue until ANC recovery, not just clinical improvement
Fever in Returned Traveler
Fever developing in a traveler or in the weeks after travel requires consideration of endemic pathogens. Geographic region is paramount.
| Geographic Region | Most Common Etiologies | Less Common But Important |
|---|---|---|
| Sub-Saharan Africa | Malaria, typhoid, dengue | Sleeping sickness, typhus, Q fever |
| Southeast Asia | Dengue, malaria, typhoid | Chikungunya, typhus, leptospirosis |
| Central America | Dengue, malaria | Enteric fever, chagas disease |
| South America | Dengue, malaria, enteric fever | Yellow fever, chagas disease, bartonellosis |
| Caribbean | Dengue, chikungunya | Malaria (limited areas) |
| South Asia | Typhoid, dengue, malaria | Enteric fever, chikungunya |
| Middle East | Enteric fever, brucellosis | Q fever, leishmaniasis |
Diagnostic Approach
Always ask specifically about the geographic region and time since return. Malaria can present up to a year after exposure. Blood smear or rapid antigen testing should be obtained early given the potentially fatal consequences of delayed diagnosis.
Sepsis and Septic Shock
Sepsis represents the body's dysregulated response to infection, characterized by systemic inflammation and organ dysfunction.
Definition and Diagnostic Criteria
SIRS Criteria (≥2 required; retained by CMS): - Temperature >38°C or <36°C - Heart rate >90 bpm - Respiratory rate >20/min or PaCO₂ <32 mmHg - WBC count >12,000 or <4,000 cells/mm³
Sepsis = SIRS criteria + documented or presumed infection
Septic Shock = Sepsis + hypotension unresponsive to 30 mL/kg crystalloid OR need for vasopressors to maintain MAP ≥65 mmHg
SOFA Score for Risk Stratification
The SOFA (Sequential Organ Failure Assessment) score quantifies organ dysfunction and predicts mortality.
| System | Score 0 | Score 1 | Score 2 | Score 3 | Score 4 |
|---|---|---|---|---|---|
| Respiratory | PaO₂/FiO₂ ≥400 | PaO₂/FiO₂ <400 | PaO₂/FiO₂ <300 | PaO₂/FiO₂ <200 (on MV) | PaO₂/FiO₂ <100 (on MV) |
| Coagulation | Platelets ≥150 | 100-149 | 50-99 | 20-49 | <20 |
| Liver | Bili <1.2 | 1.2-1.9 | 2-5.9 | 6-11.9 | >11.9 |
| Cardiovascular | MAP ≥70 | MAP <70 | Dopamine <5 or dobutamine | Dopamine 5-15 or epi <0.1 | Dopamine >15 or epi >0.1 |
| Renal | Cr <1.2 | Cr 1.2-1.9 | Cr 2-3.5 | Cr 3.6-5 | Cr >5 |
| Neuro | GCS 15 | 13-14 | 10-12 | 6-9 | <6 |
Mortality Risk
Each point increase in SOFA score correlates with increasing mortality risk. SOFA ≥2 in the setting of infection has mortality approaching 10%; SOFA ≥3 approaches 50% mortality.
qSOFA Score
The quick SOFA (qSOFA) identifies high-risk patients at bedside using three variables:
| Variable | Criterion |
|---|---|
| Respiratory rate | ≥22 breaths/min |
| Altered mental status | Any confusion or decreased consciousness |
| Systolic blood pressure | ≤100 mmHg |
Interpretation: ≥2 qSOFA points indicates high risk for adverse outcome and warrants aggressive intervention.
Initial Diagnostic Workup
Time-Sensitive Interventions
Every hour of delay in appropriate antibiotics increases mortality. Obtain cultures before antibiotics but do not delay treatment for cultures.
Laboratory Studies: - Complete blood count with differential - Comprehensive metabolic panel (assess organ function) - Prothrombin time (PT/INR) - Lactate level (marker of tissue hypoperfusion) - Blood cultures - minimum 2 sets before antibiotics - Arterial or venous blood gas - Procalcitonin (markers of bacterial infection; not diagnostic alone)
Source Identification: - Chest X-ray (pneumonia, acute respiratory distress) - Urinalysis and urine culture - Wound cultures if open wound - Consider abdominal imaging if intra-abdominal source suspected
Lactic Acidosis in Sepsis
Lactate accumulates from tissue hypoperfusion and impaired hepatic metabolism:
| Type | Mechanism | Clinical Context | Prognosis |
|---|---|---|---|
| Type A (Hypoxic) | Tissue hypoxia and anaerobic metabolism | Septic shock, cardiogenic shock, hypovolemic shock | Worse; indicates severe tissue hypoperfusion |
| Type B (Non-hypoxic) | Toxin-mediated, impaired clearance, or metabolism | Liver disease, malignancy, medications (nucleoside reverse transcriptase inhibitors) | Variable; depends on underlying cause |
Early Goal-Directed Therapy (EGDT)
Aggressive early intervention in the first 3 hours improves sepsis outcomes:
Key Interventions: - Fluid: Balanced crystalloid (normal saline, Lactated Ringer's) 30 mL/kg for hypotension or lactate ≥4 - Vasopressors (if MAP remains <65 mmHg after fluids): Norepinephrine 0.01-2 μg/kg/min + vasopressin 0.04 units/min (not titrated) as first-line - Source control: Drainage of abscess, removal of infected device, operative debridement as needed - Reassess lactate: 2-3 hours after initial resuscitation; persistent elevation indicates ongoing hypoperfusion
Empiric Antibiotic Selection by Source
| Infection Source | First-Line Regimen | Alternative | Duration |
|---|---|---|---|
| Critical illness/urosepsis | Ceftriaxone 1-2g q12h + azithromycin 500mg daily OR respiratory fluoroquinolone (levofloxacin 750mg daily) | Vancomycin if penicillin allergy | 5-7 days |
| Healthcare-associated pneumonia | Antipseudomonal: piperacillin-tazobactam 4.5g q6h or meropenem 1g q8h + MRSA coverage if risk factors | Add fluoroquinolone for coverage expansion | 7-10 days |
| Community-acquired pneumonia | Ceftriaxone 1g q12h + azithromycin 500mg daily OR respiratory fluoroquinolone | Amoxicillin-clavulanate if outpatient | 5-7 days |
| Uncomplicated UTI | Ceftriaxone 1-2g q12h | Fluoroquinolone, TMP-SMX | 7 days |
| Skin/soft tissue | Vancomycin 15-20mg/kg q12h + piperacillin-tazobactam 4.5g q6h + clindamycin 600mg q8h | Beta-lactam/beta-lactamase inhibitor monotherapy if not severe | 7-14 days |
| Intra-abdominal (peritonitis, cholecystitis) | Piperacillin-tazobactam 4.5g q6h OR meropenem 1g q8h | Add fluoroquinolone for additional coverage | 7-10 days |
De-escalation: - At 48-72 hours, review culture results and adjust to narrowest appropriate spectrum - Transition to oral antibiotics when clinical improvement and GI tolerance established - Discontinue vasopressors when hemodynamically stable
Pneumonia
Pneumonia classification and empiric antibiotic selection depend on patient risk factors and epidemiologic context.
Pneumonia Classification and Microbiology
| Classification | Risk Factors | Common Organisms | Mortality |
|---|---|---|---|
| CAP | Healthy outpatient | Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma, Legionella, viruses | 1-5% |
| HAP | Hospitalization >48 hrs, no mechanical ventilation | Gram-negatives (Pseudomonas, Klebsiella), MRSA, anaerobes | 20-30% |
| VAP | Mechanical ventilation >48 hrs | Pseudomonas, MRSA, Acinetobacter, Enterobacteriaceae | 25-50% |
| Aspiration PNA | Loss of airway protection (swallow dysfunction, decreased LOC) | Anaerobes, microaerophilic streptococci, gram-negatives | Variable |
CURB-65 and Pneumonia Severity Index
CURB-65 Score (≥2 predicts severe disease): - Confusion (acute mental status change) - Urea >7 mmol/L - Respiratory rate ≥30 - Blood pressure (SBP ≤100 or DBP ≤60) - 65+ years old
Pneumonia Severity Index (PSI) Classes for Disposition:
| Class | CURB-65 | Clinical Features | Disposition | Mortality |
|---|---|---|---|---|
| I | 0 | Age <50, no comorbidities | Outpatient | <1% |
| II | 1 | Mild-moderate CAP | Brief hospitalization | 1-2% |
| III | — | Moderate CAP | Hospital admission | 2-3% |
| IV | — | Severe features | Hospital admission | 8-15% |
| V | — | Very severe features | ICU admission | >30% |
Severe Community-Acquired Pneumonia Criteria
Severe CAP requires ICU admission and intensive management:
Major Criteria (one sufficient): - Septic shock requiring vasopressors - Respiratory failure requiring mechanical ventilation
Minor Criteria (≥3 needed for "severe"): - Respiratory rate ≥30 breaths/min - Partial pressure of oxygen <60 mmHg - Multilobar opacities on imaging - Core body temperature <36°C - Encephalopathy - Uremia (BUN >7 mmol/L or Cr ≥1.5 mg/dL) - WBC <4 × 10³/L - Platelets <100 × 10³/L
Pneumonia Treatment Guidelines
| Pneumonia Type | Empiric Regimen | Duration | Notes |
|---|---|---|---|
| CAP (outpatient) | Amoxicillin-clavulanate OR macrolide OR respiratory fluoroquinolone | 5-7 days | Macrolide alone insufficient for most patients |
| CAP (hospitalized) | Ceftriaxone 1g q12h + azithromycin 500mg daily OR respiratory fluoroquinolone | 5-7 days | Add vancomycin if risk for MRSA |
| Severe CAP | Add vancomycin to ceftriaxone + azithromycin regimen | 7-10 days | Consider pseudomonal coverage if risk factors |
| HAP/VAP | Piperacillin-tazobactam OR carbapenem (meropenem, imipenem) + consider MRSA coverage | 7-10 days | Avoid aminoglycosides as monotherapy |
| Aspiration PNA | Piperacillin-tazobactam OR ampicillin-sulbactam | 7-10 days | Anaerobic coverage essential if abscess/empyema |
| PCP (HIV+, CD4 <200) | TMP-SMX (high-dose) IV or PO | 21 days | Add corticosteroids if PaO₂ <70 or A-a gradient >35 |
De-escalation Strategy
Do not continue broad-spectrum empiric regimens once cultures identify organism and antibiotic sensitivities are known. Narrow spectrum to reduce resistance selection and adverse effects.
Urinary Tract Infections
UTIs range from asymptomatic bacteriuria to life-threatening urosepsis. Treatment decisions depend on complexity and symptoms.
Uncomplicated vs Complicated UTI
Uncomplicated UTI: - Non-pregnant women with acute cystitis or pyelonephritis - No structural or neurologic urinary tract abnormalities - Normal renal function
Complicated UTI: - Pregnant women (risk of hematogenous spread) - Men (longer urethra, risk of prostatitis) - Urinary catheters or stents - Structural abnormalities (obstruction, reflux, neurogenic bladder) - Renal impairment - Immunosuppression
Common Uropathogens
| Organism | Uncomplicated Cystitis | Pyelonephritis | Catheterized Patients | Nosocomial UTI |
|---|---|---|---|---|
| E. coli | ++ | ++ | + | + |
| K. pneumoniae | + | + | ++ | ++ |
| P. aeruginosa | — | — | ++ | ++ |
| Enterococcus | — | — | ++ | + |
| S. saprophyticus | ++ | — | — | — |
UTI Treatment by Type
| Diagnosis | Empiric Therapy | Duration | Alternative |
|---|---|---|---|
| Asymptomatic bacteriuria | No treatment (except pregnant women) | — | Pregnant: cephalexin or nitrofurantoin 7 days |
| Acute cystitis (uncomplicated) | Nitrofurantoin 100mg BID OR TMP-SMX DS BID OR fosfomycin 3g single dose | 3-5 days | Avoid fluoroquinolones for uncomplicated disease |
| Acute pyelonephritis (outpatient) | Fluoroquinolone (levofloxacin 750mg daily) OR TMP-SMX DS BID | 7-14 days | Ceftriaxone if unable to tolerate PO |
| Acute pyelonephritis (inpatient) | Ceftriaxone 1-2g q12h OR fluoroquinolone IV OR piperacillin-tazobactam | 10-14 days | Transition to PO after defervescence |
| Urethritis (NGU/chlamydia) | Ceftriaxone 250mg IM single dose + doxycycline 100mg BID | 7 days (doxy) | Azithromycin 1g × 1 if doxycycline contraindicated |
| Prostatitis (acute) | Fluoroquinolone (ciprofloxacin, levofloxacin) | 10-14 days | TMP-SMX DS BID as alternative |
| Prostatitis (chronic) | Fluoroquinolone OR TMP-SMX | 6-12 weeks | Requires prolonged therapy for tissue penetration |
| Renal abscess | IV antibiotics (cephalosporin, fluoroquinolone, or carbapenem) + percutaneous drainage | 4-6 weeks | Nephrectomy if drainage unsuccessful |
Avoid Catheter-Induced Delays
Do not treat asymptomatic catheter-associated bacteriuria unless symptomatic or patient is pregnant. Catheter replacement without antimicrobials is preferred management.
Skin and Soft Tissue Infections
Bacterial skin infections range from minor impetigo to life-threatening necrotizing fasciitis. Rapid recognition and appropriate therapy are essential.
Definitions and Epidemiology
| Entity | Definition | Typical Organism | Key Features |
|---|---|---|---|
| Impetigo | Superficial skin infection in stratum corneum | Group A Streptococcus, S. aureus | Honey-crusted lesions, highly contagious |
| Erysipelas | Infection of superficial dermis with lymphatic involvement | Group A Streptococcus | Sharply demarcated, raised, often facial |
| Cellulitis | Non-suppurative deeper dermal and subcutaneous infection | Streptococci (GAS, GBS), S. aureus | Spreading erythema, warmth, edema |
| Necrotizing fasciitis (NF) | Rapidly spreading deep tissue infection with high mortality | Polymicrobial (Type I) or monomicrobial (Type II) | Systemic toxicity out of proportion to exam |
| Gas gangrene | Myonecrosis from gas-producing organisms | Clostridium perfringens | Severe pain, crepitus, shock |
| Osteomyelitis | Bone infection, hematogenous or contiguous | S. aureus most common | Localized pain, swelling, fever (may be absent) |
Special Exposures and Organisms
| Exposure/Bite | Key Organisms | Notable Agents |
|---|---|---|
| Cat bite | Pasteurella multocida (50-80%) | Aggressive infection risk |
| Dog bite | Pasteurella, Staphylococcus, Streptococcus | Lower infection rate than cat bites |
| Human bite | Eikenella, Staphylococcus, Streptococcus | High polymicrobial infection risk |
| Seawater exposure | Vibrio vulnificus, Vibrio parahaemolyticus | Aggressive, often with bacteremia |
| Fresh water | Aeromonas, Vibrio | Risk with open wounds |
Necrotizing Fasciitis: A Clinical Emergency
NF requires immediate recognition and surgical intervention. Mortality approaches 30% even with treatment.
Clinical Red Flags
Systemic toxicity (shock, delirium) out of proportion to cutaneous findings is the hallmark of NF. Severe pain beyond the area of visible erythema is another warning sign. These patients require immediate surgical consultation.
Type I (Polymicrobial ~70% of cases): - Typically follows abdominal surgery or perforation - Mixed gram-positive, gram-negative, and anaerobic organisms - Often includes anaerobes
Type II (Monomicrobial ~25% of cases): - Group A Streptococcus ± Staphylococcus aureus - Often follows minor trauma or surgery - Rapid progression
Type III (Monomicrobial ~5% of cases): - Gram-negative organisms - IV drug use-related - Marine-associated (Vibrio)
Surgical Urgency: Do not delay for imaging. Clinical suspicion warrants immediate surgical exploration.
Osteomyelitis Classification and Management
| Type | Pathogenesis | Common Organisms | Imaging | Treatment |
|---|---|---|---|---|
| Hematogenous | Bacteremia seeding bone | S. aureus, Streptococci | MRI most sensitive | 4-6 weeks IV ABx |
| Contiguous | Direct inoculation (trauma, surgery) | S. aureus, gram-negatives, anaerobes | X-ray, CT | 4-6 weeks IV ABx + surgical debridement |
| Vascular insufficiency | Compromised blood flow (diabetes) | Gram-negatives, anaerobes, polymicrobial | Plain films, vascular assessment | Extended oral ABx + wound care |
Special Population - Sickle Cell Disease: - Organisms: Salmonella (atypical for non-sickle patients) - Mechanism: Splenic infarction impairs opsonization and complement activation
Cellulitis Treatment Approach
Non-Purulent Cellulitis (no collection present): - Ceftriaxone 1-2g q12h IV OR cefazolin 1-2g q8h IV - Or cephalexin 500mg QID PO for mild cases
Purulent Cellulitis (collection present - drain first, then antibiotics): - TMP-SMX DS BID × 7 days OR - Doxycycline 100mg BID × 7 days OR - Vancomycin for severe disease
Necrotizing Fasciitis: - Surgical debridement FIRST (may require multiple operations) - Vancomycin 15-20mg/kg q12h + - Piperacillin-tazobactam 4.5g q6h OR - Penicillin G 4 million units q4h + clindamycin 600mg q8h (for streptococcal anaerobic coverage)
Meningitis
Bacterial meningitis is a medical emergency with mortality approaching 20% even with treatment. Recognition and empiric therapy within the first hour dramatically improve outcomes.
Clinical Presentation
Classic meningitis triad occurs in only 50% of patients: - Fever - Headache (severe) - Neck stiffness (meningismus)
Additional findings: - Photophobia - Altered mental status or confusion - Kernig's sign (pain with knee extension when hip flexed) - Brudzinski's sign (neck flexion causes hip/knee flexion) - Petechial or purpuric rash (characteristic of meningococcemia)
Etiologies by Age and Risk
| Age Group | Primary Organisms | Secondary Organisms |
|---|---|---|
| Neonates (0-3mo) | Group B Streptococcus, E. coli (K1), Listeria monocytogenes | Gram-negatives |
| Children (3mo-18yr) | Neisseria meningitidis, Streptococcus pneumoniae | H. influenzae (if unvaccinated) |
| Adults (18-50yr) | N. meningitidis, S. pneumoniae | Gram-negatives |
| Elderly (>50yr) | S. pneumoniae, Listeria monocytogenes, Gram-negatives | N. meningitidis |
| Immunocompromised | Listeria, Cryptococcus, Gram-negatives | Mycobacteria |
Meningococcemia
Neisseria meningitidis bacteremia often presents with petechial or purpuric rash. Watch for fulminant sepsis (meningococcal septic shock). Young patients with rash + fever warrant empiric meningitis coverage immediately.
Diagnostic Approach and CSF Findings
Before Lumbar Puncture (LP): - Obtain blood cultures immediately (before antibiotics) - CT head if: focal neurologic deficit, papilledema, immunosuppression, age >60, signs of increased ICP - Do NOT delay antibiotics for imaging or LP
Cerebrospinal Fluid (CSF) Analysis:
| Parameter | Normal | Bacterial | Tuberculous | Fungal | Viral |
|---|---|---|---|---|---|
| Appearance | Clear | Turbid/purulent | Clear/turbid | Clear/turbid | Clear |
| Opening Pressure | 10-20 cm H₂O | 20-100+ | 20-100+ | 20-100 | 15-40 |
| WBC count | <5 | 100-26,000 | 10-500 | 10-500 | 10-1,000 |
| WBC predominant | — | PMN | Lymphocytes | Lymphocytes | Lymphocytes |
| Glucose | 40-70 | <40 (CSF:blood <0.4) | <40 | <40 | >40 (CSF:blood >0.5) |
| Protein | <45 | 100-500 | 100-500 | 100-500 | 50-100 |
| Gram stain | Negative | 60-90% sensitive | Negative | Negative | Negative |
| Culture | Negative | 70-80% (pre-ABx) | 10-80% | 10-50% | Negative |
Empiric Treatment
Do Not Delay Treatment
If meningitis is suspected clinically, initiate antibiotics immediately, even before lumbar puncture or imaging. Delay in antibiotics increases mortality.
Empiric Antibiotic Regimens:
| Patient Population | Regimen | Notes |
|---|---|---|
| Age 18-50 (meningitis coverage) | Ceftriaxone 2g IV q12h + Vancomycin 15-20mg/kg IV q12h | Add ampicillin if age >50 or immunocompromised |
| Age >50 OR immunocompromised | Ceftriaxone 2g IV q12h + Vancomycin 15-20mg/kg IV q12h + Ampicillin 2g IV q4h | Ampicillin covers Listeria |
| Severe penicillin allergy | Fluoroquinolone (moxifloxacin) + Vancomycin | Chloramphenicol if not available |
Additional Therapies: - Dexamethasone: 10mg IV q6h × 4 days (initiated with first antibiotic dose reduces mortality) - Adjunctive agents: Vancomycin levels should be 15-20 μg/mL; ensure adequate penetration into CSF
Viral Meningitis (HSV Suspected): - Acyclovir 10mg/kg IV q8h × 7-14 days - Continue until HSV and VZV excluded by PCR
Fungal Meningitis (Cryptococcal in immunocompromised): - Amphotericin B 0.7-1 mg/kg/day IV + Fluconazole 400-800mg daily × 8-10 weeks
HIV and Opportunistic Infections
Opportunistic infections (OIs) are the primary driver of morbidity and mortality in advanced HIV. Prophylaxis and treatment regimens depend on CD4 count and immune reconstitution.
Opportunistic Infection Prophylaxis by CD4 Count
| CD4 Count | Primary Prophylaxis | Additional | Duration |
|---|---|---|---|
| <200 | TMP-SMX DS daily (also covers Toxo + PCP) | — | Until CD4 >200 × 3 months on ART |
| <100 | Continue TMP-SMX | Add azithromycin 1200mg weekly (MAC prophylaxis) | Until CD4 >100 × 3 months |
| <50 | Continue above | Add itraconazole 200mg daily (fungal prophylaxis) | Until CD4 >50 × 3 months |
| >200 | Discontinue PCP prophylaxis | Consider discontinuing others if CD4 sustained | Monitor for immune reconstitution |
Opportunistic Infection Treatment
Tuberculosis (TB-HIV co-infection): - Standard TB regimen: INH + rifampin + pyrazinamide + ethambutol - Dosing adjusted in HIV due to drug interactions - ART initiation timing depends on CD4 (earlier if CD4 <50)
Pneumocystis Pneumonia (PCP): - First-line: TMP-SMX (15-20mg/kg/day TMP component) × 21 days - Alternative: Dapsone + trimethoprim or atovaquone - Add corticosteroids if PaO₂ <70 or A-a gradient >35
Toxoplasma Encephalitis: - Pyrimethamine 200mg load then 50-100mg daily + - Sulfadiazine 1-1.5g q6h × - Folinic acid (leucovorin) 10-20mg daily for bone marrow protection - Duration: minimum 6 weeks, often until immune reconstitution
Cryptococcal Meningitis: - Induction: Amphotericin B 0.7-1 mg/kg/day IV + fluconazole 400-800mg daily - Consolidation: Fluconazole 400mg daily × 8 weeks - Maintenance: Fluconazole 200mg daily (long-term suppression)
Cytomegalovirus (CMV): - CMV retinitis: Ganciclovir IV 5mg/kg q12h or foscarnet - CMV esophagitis/colitis: Ganciclovir or foscarnet
Candidiasis: - Oropharyngeal: Fluconazole 200-400mg daily × 7-14 days - Esophageal: Fluconazole 400-800mg daily × 14-21 days - Disseminated: Fluconazole or amphotericin B
Immune Reconstitution Inflammatory Syndrome (IRIS)
Rapid CD4 recovery on ART may cause paradoxical worsening of OI symptoms as immune system reactivates against pathogens. Monitor closely in first weeks of ART initiation, especially with CD4 <50.