Approach to the Patient with an Infectious Disease¶
Part 5: Infectious Diseases | Part 5 – Infectious Diseases: Bacterial · Part 5 – Infectious Diseases: Bacterial · Chapter 124
Key Clinical Points¶
- Infectious diseases remain the second leading cause of death globally, with 9.6 million deaths in 2019.
- Fever is defined as a core temperature ≥38.3°C (≥101°F) for diagnosis of fever of unknown origin (FUO).
- An extremely elevated ESR (>100 mm/h) has a 90% predictive value for a serious underlying disease.
- Palpable epitrochlear nodes are always pathologic.
- Empirical antibiotic regimens should be narrowed once a specific diagnosis is made.
- Infectious disease consultation is associated with a 56% reduction in 28-day mortality for S. aureus bacteremia.
- CSF Gram's stain typically requires >10^5 bacteria/mL for reliable positivity.
- Travel history and exposure history are critical for broadening the differential diagnosis in returning travelers.
- Microbiota provides benefits including metabolism, immune system shaping, and colonization resistance.
- Relative bradycardia (Faget's sign) is associated with specific intracellular organisms and viruses.
1. DEFINITION & OVERVIEW¶
• Global Impact: Infectious diseases remain the second leading cause of death globally. • Mortality Data: 9.6 million deaths in 2019; disproportionately affects children <1 year, adults >70 years, and low- to middle-income countries. • Historical Evolution: Transition from miasma theory (mid-16th century) to germ theory (Pasteur/Koch, late 19th century). • 20th Century Milestones: Smallpox eradication, development of antibiotics, and vaccines.
1.1 Global Considerations¶
• Regional Disparities: ~69% of global deaths from communicable diseases occur in sub-Saharan Africa. • Antimicrobial Resistance: Drug-resistant tuberculosis is rampant in former Soviet-bloc countries, India, China, and South Africa. • Migration & Transmission: Human migration links to epidemics (Yersinia pestis, smallpox, SARS-CoV-2). Travelers can transmit infections (SARS-CoV-2, HIV) or introduce vector-borne pathogens (chikungunya, Zika).
1.2 Historic Perspective¶
• Theory Shift: Miasma theory → Germ theory via Pasteur/Koch. • Key Milestones: Smallpox eradication, antibiotics, vaccines. • Historical Context: Burnet (1962) noted 'virtual elimination' of infectious disease; Petersdorf (1978) highlighted the need for infectious disease training.
1.3 Understanding the Microbiota¶
• Scale: Humans host ~40 trillion microbes (bacteria, viruses, fungi, archaea); microorganisms outnumber human cells by ~10:1. • Locations: Primary reservoirs are the gastrointestinal tract, skin, and mucosal surfaces. • Benefits: Metabolism support, immune system shaping, and colonization resistance. • Clinical Relevance: 80% of infections involve commensal organisms (S. aureus, S. pneumoniae). • Preservation: Rational antibiotic use is necessary to prevent dysbiosis.
2. EPIDEMIOLOGY¶
• Trends: Absolute number of infectious disease deaths has decreased since 1990. • Vulnerable Populations: Highest rates in children <5 years and adults >70 years. • Risk Factors: ◦ Modifiable: Travel, diet, animal exposure, social behaviors. ◦ Non-modifiable: Age, sex, geography, immune status.
2.1 Global Mortality Trends¶
• Regional Burden: ~69% of global deaths from communicable diseases in sub-Saharan Africa.
2.2 Risk Factors¶
• Transmission Drivers: Global travel accelerates spread (pandemic influenza, mpox). • Historical Context: Migration linked to 1918 flu and Y. pestis.
3. ETIOLOGY & PATHOPHYSIOLOGY¶
• Malignancy Link: 16% of all malignancies are linked to infectious agents (H. pylori, HPV, HBV/HCV). • Emerging Threats: Antimicrobial resistance (CRE, C. auris) and bioterrorism risks. • Microbiota Role: Influences host susceptibility and vaccine response.
3.1 Microbiota and Host Susceptibility¶
• Antibiotic Selection: Site-specific microbiota guides empirical choices. • Dysbiosis Risk: Increases infection risk (e.g., C. difficile after broad-spectrum antibiotics). • Immune Modulation: Microbiota shapes immune responses to vaccines.
3.2 Immune Defects and Opportunistic Infections¶
• Opportunistic Pathogens: Immunocompromised patients at risk for Pneumocystis, Aspergillus, JC virus. • Causes of Immunodeficiency: Malignancy, HIV, immunosuppressive drugs, splenectomy. • Prevention: Review vaccination history to identify gaps.
4. CLINICAL FEATURES¶
• Presentation Range: Varies from acute sepsis to latent TB.
4.1 History Taking¶
• Exposure History: Focus on drug-resistant microbes, travel, and animal contact. ◦ Specific risks: Gardening (Sporothrix), funeral work (TB). • Social/Dietary Risks: ◦ IV drug use. ◦ Raw meat (E. coli, T. gondii). ◦ Unpasteurized milk (L. monocytogenes). • Travel Details: Geographic regions, activities, and prophylaxis adherence.
4.2 Physical Examination¶
• Vital Signs: Fever ≥38.3°C (≥101°F) is diagnostic for F/UO. • Lymphadenopathy: Palpable epitrochlear nodes are always pathologic. • Skin Findings: Rashes, splinter hemorrhages (endocarditis), Janeway lesions. • Foreign Bodies: IV lines and drains increase infection risk.
5. DIFFERENTIAL DIAGNOSIS¶
• Core Distinction: Differentiating infectious from noninfectious causes (drug fever, autoimmune disease, malignancy).
5.1 Infectious vs. Noninfectious Etiologies¶
• Infectious Range: Acute sepsis to asymptomatic TB. • Noninfectious Mimics: Drug fever, autoimmune disease, malignancy.
5.2 Specific Syndromic DDx¶
• Meningitis: Bacterial (S. pneumoniae), viral (enterovirus), fungal (Cryptococcus). • Sepsis: Common pathogens include S. aureus, E. coli. • Endocarditis: Look for splinter hemorrhages, Osler's nodes. • Eosinophilia: Refer to Table 124-2 for infectious causes.
6. INVESTIGATIONS & DIAGNOSIS¶
- Initial Laboratory Screening: • WBC count: Bacterial infections → neutrophilia; viral → lymphodoris. • ESR: Value >100 mm/h → 90% predictive value for serious disease.
- CSF Analysis (for Meningitis/Encephalitis): • Gram stain: Requires >10^5 bacteria/mL for reliable positivity. • Protein levels and WBC counts to differentiate etiology (Table 124-4).
- Molecular Diagnostics: • PCR used for rapid diagnosis of N. meningitidis or HSV encephalitis.
6.1 Laboratory Testing¶
• ESR Threshold: >100 mm/h → high suspicion of serious disease. • CSF Gram Stain: Reliability depends on bacterial load (>10^5 bacteria/mL).
7. MANAGEMENT & TREATMENT¶
- Empirical Antibiotic Therapy: • Start with broad-spectrum regimens. • Narrow based on culture and sensitivity results. • Consider MRSA/VRE in high-risk patients.
- Infection Control: • Implement isolation for contagious pathogens (TB, MRSA). • Maintain hand hygiene and environmental decontamination.
- Specialized Consultation: • Infectious disease consultation → 56% reduction in 28-day mortality for S. aureus bacteremia.
7.1 Empirical Antibiotic Therapy¶
• Septic Shock: Vancomycin (15 mg/kg q12h) + antipseudomonal β-lactam (Piperacillin-tazobactam 4.5 g q6h, Imipenem 1 g q8h, Meropenem 1 g q8h, or Cefepime 1–2 g q8–12h). • CNS Abscess: Vancomycin (15 mg/kg q12h) + Ceftriaxone (2 g q12h) + Metronidazole (500 mg q8h); OR Vancomycin + Cefepime (2 g q8h). • Pneumonia (CAP, no comorbidities): Azithromycin (500 mg PO x1, then 250 mg qd x4 days) or Levofloxacin (750 mg PO qd). • Pneumonia (Inpatient, non-ICU): Respiratory fluoroquinolone (Moxifloxacin 400 mg, Gemifloxacin 320 mg, or Levofloxacin 750 mg) OR β-lactam (Cefotaxime, Ceftriaxone, or Ampicillin-sulbactam) + Azithromycin. • Pneumonia (HAP): Antipseudomonal β-lactam (Cefepime 2 g q8h, Ceftazidime 2 g q8h, Imipenem 500 mg q6h, Meropenem 1 g q8h, or Piperacillin-tazobactam 4.5 g q6h) + Antipseudomonal fluoroquinolone (Levofloxacin 700 mg qd, Ciprofloxacin 400 mg q8h) OR Aminoglycoside (Amikacin 15–20 mg/kg q24h, Gentamicin 5–7 mg/kg q24h, or Tobramycin 5–7 mg/kg q24h).
7.2 Infection Control¶
• Isolation: Required for TB, MRSA. → Critical: Hand hygiene and decontamination.
8. PROGNOSIS & COMPLICATIONS¶
• Prognosis Factors: Dependent on timely diagnosis and treatment. • Global Burden: Infectious diseases account for ≈17% of global deaths; highest burden in Sub-Saharan Africa.
9. SPECIAL CONSIDERATIONS¶
• Travel History: ◦ Fever in returning travelers requires broad differential (malaria, dengue, leptospirosis). ◦ Immunization status is critical for risk assessment.
9.1 Travel History¶
• Broad Differential: Required for fever in returning travelers. → Include malaria, dengue, leptospirosis.
10. KEY PEARLS & HIGH-YIELD POINTS¶
• Faget's Sign: Relative bradycardia suggests intracellular pathogens or specific viruses (Table 124-1). • Epitrochlear Nodes: Palpable nodes are always pathologic. • ESR Utility: Use >100 mm/h as a high-sensitivity marker for serious disease (Table 124-3).
10.1 Diagnostic Clues¶
• Relative Bradycardia: Associated with intracellular organisms and viruses. • Epitrochlear Nodes: Always pathologic.
TABLES & FIGURES¶
Table 124-1: Causes of Relative Bradycardia (Faget's sign). → Intracellular organisms: Salmonella typhi, Francisella tularensis, Brucella spp., Coxiella burnetii (Q fever), Leptospira interrogans, Legionella pneumophila, Mycoplasma pneumoniae. → Tick-borne: Rickettsia spp., Orientia tsutsugamushi (scrub typhus), Babesia spp. → Other: Corynebacterium diphtheriae, Plasmodium spp. (malaria). → Viruses/viral infections: Yellow fever virus, Dengue virus, Viral hemorrhagic fevers, Viral myocarditis.
Table 124-2: Major Infectious Causes of Eosinophilia. → CNS: Angiostrongylus (Asia, Mild), Gnathostoma (Asia, Moderate to extreme), Loa loa (Africa), Onchocerca (Africa). → Lung: Chlamydia trachomatis (Worldwide, Mild), Strongyloides (Tropical, Mod/Mild), Toxocara (Worldwide, Mod-Ext), Paragonimus (Asia, Mod/Mild), Coccidioides immitis (SW US, Mild/Extreme), Brugia malayi (Asia, Mild-Mod), Pneumocystis jirovecii (Worldwide, Mild), Schistosoma spp., Fasciola (Worldwide), Clonorchis (Asia), Opisthorchis (Asia). → Intestines: Ascaris (Worldwide, Mild-Ext), Hookworm (Worldwide, Mild-Mod), Trichuris (Tropical, Mild), Cystoisospora belli (Worldwide, Mild), Dientamoeba fragilis (Worldwide, Mild), Capillaria (Asia, Extreme), Heterophyes (Asia/MidEast, Mild), Anisakis (Worldwide, Mild), Baylisascaris procyonise (N. America, Mod-Ext), Hymenolepis nana (Worldwide, Mild), Schistosoma haematobium (Africa/MidEast). → Muscle: Trichinella (Worldwide, Mod-Ext), Wuchereria bancrofti (Tropical), Bartonella henselae (Worldwide). → Other: Recovery from infection (Mild), HIV (Worldwide, Mild), Cryptococcus neoformans (Worldwide, Mod-Ext).
Table 124-3: Causes of Extremely Elevated ESR (>100 mm/h). → Infectious diseases (35–40%): Subacute bacterial endocarditis, Abscesses, Osteomyelitis, Tuberculosis, Urinary tract infection. → Malignancies (15–20%): Multiple myeloma, Leukemias, Lymphomas, Carcinomas.
Table 124-4: Typical CSF Profiles for Meningitis and Encephalitis. → Bacterial: WBC >1000 (≥80% PMNs), Protein >100, Gram stain positive in >60%. → Viral: WBC 25–500 (predominantly lymphocytes), Protein 20–80. → Fungal: WBC 40–600, Protein 150–300. → Parasitic: WBC 150–2000, Eosinophils ≥50%. → Tuberculous: WBC 25–100, Protein 50–200. → Encephalitis: WBC 50–500, Protein 100–200.
Table 124-5: Initial Empirical Antibiotic Therapy. → Septic Shock: Vancomycin (15 mg/kg q12h) + antipseudomonal β-lactam (Piperacillin-tazobactam 4.5 g q6h, Imipenem 1 g q8h, Meropenem 1 g q8h, or Cefepime 1–2 g q8–12h). → CNS Abscess: Vancomycin (15 mg/kg q12h) + Ceftriaxone (2 g q12h) + Metronidazole (500 mg q8h); OR Vancomycin + Cefepime (2 g q8h). → Pneumonia (CAP, no comorbidities): Azithromycin (500 mg PO x1, then 250 mg qd x4 days) or Levofloxacin (750 mg PO qd). → Pneumonia (Inpatient, non-ICU): Respiratory fluoroquinolone (Moxifloxacin 400 mg, Gemifloxacin 320 mg, or Levofloxacin 750 mg) OR β-lactam (Cefotaxime, Ceftriaxone, or Ampicillin-sulbactam) + Azithromycin. → Pneumonia (HAP): Antipseudomonal β-lactam (Cefepime 2 g q8h, Ceftazidime 2 g q8h, Imipenem 500 mg q6h, Meropenem 1 g q8h, or Piperacillin-tazobactam 4.5 g q6h) + Antipseudomonal fluoroquinolone (Levofloxacin 700 mg qd, Ciprofloxacin 400 mg q8h) OR Aminoglycoside (Amikacin 15–20 mg/kg q24h, Gentamicin 5–7 mg/kg q24h, or Tobramycin 5–7 mg/kg q24h).
Reference Tables¶
TABLE 124-1 Causes of Relative Bradycardia Infectious Causes Intracellular organisms¶
Harrison's 22e, p.960
| Infectious Causes | |
|---|---|
| Intracellular organisms | |
| Gram-negative bacteria | Salmonella typhi Francisella tularensis Brucella spp. Coxiella burnetii (Q fever) Leptospira interrogans Legionella pneumophila Mycoplasma pneumoniae |
| Tick-borne organisms | Rickettsia spp. Orientia tsutsugamushi (scrub typhus) Babesia spp. |
| Other | Corynebacterium diphtheriae Plasmodium spp. (malaria) |
| Viruses/viral infections | Yellow fever virus Dengue virus Viral hemorrhagic feversa Viral myocarditis |
| Noninfectious Causes |
TABLE 124-2 Major Infectious Causes of Eosinophilia a¶
Harrison's 22e, p.961
| ORGAN INVOLVED | ORGANISM | EXPOSURE | GEOGRAPHIC DISTRIBUTION | DEGREE OF EOSINOPHILIAb |
|---|---|---|---|---|
| Central nervous system | Angiostrongylus | Raw seafood | Asia | Mild |
| Gnathostoma | Raw poultry and seafood | Asia | Moderate to extreme | |
| Loa loa | Insect bite | Africa | ||
| Onchocerca | Insect bite | Africa | ||
| Lung | Chlamydia trachomatis | Sexual transmission | Worldwide | Mild |
| Strongyloides | Soil | Tropical | Moderate (acute), mild (chronic) | |
| Toxocara canis/Toxocara catic | Dogs, soil | Worldwide | Moderate to extreme | |
| Paragonimus | Crabs and crayfish | Asia | Moderate (acute), mild (chronic) | |
| Coccidioides immitis | Soil | Southwestern United States | Mild (acute), extreme (disseminated) | |
| Brugia malayi | Insect bite | Asia | Mild to moderate | |
| Pneumocystis jirovecii | Air | Worldwide | Mild | |
| Schistosoma japonicum | Freshwater swimming | Asia | ||
| Schistosoma mansoni | Freshwater swimming | Africa, Middle East, Latin America |
||
| Fasciola | Watercress | Worldwide | ||
| Clonorchis | Raw seafood | Asia | ||
| Opisthorchis | Raw seafood | Asia | ||
| Intestines | Ascarisd | Raw fruits and vegetables, contaminated water |
Worldwide | Mild to extreme |
| Hookworm | Soil | Worldwide | Mild to moderate | |
| Trichuris | Raw fruits and vegetables, contaminated water |
Tropical | Mild | |
| Cystoisospora belli | Contaminated water and food | Worldwide | Mild | |
| Dientamoeba fragilis | Unclear; spread via fecal–oral route |
Worldwide | Mild | |
| Capillaria | Raw seafood | Asia | Extreme | |
| Heterophyes | Raw seafood | Asia, Middle East | Mild | |
| Anisakis | Raw seafood | Worldwide | Mild | |
| Baylisascaris procyonise | Soil | North America | Moderate to extreme | |
| Hymenolepis nana | Contaminated water, soil | Worldwide | Mild | |
| Schistosoma haematobium | Freshwater swimming | Africa, Middle East | ||
| Muscle | Trichinella | Pork | Worldwide | Moderate to extreme |
| Wuchereria bancroftid | Insect bite | Tropical | ||
| Bartonella henselae | Cats | Worldwide | ||
| Other | Recovery from bacterial or viral infections |
— | — | Mild |
| HIV | Contaminated bodily fluid | Worldwide | Mild | |
| Cryptococcus neoformans | Soil | Worldwide | Moderate to extreme (disseminated) |
TABLE 124-3 Causes of an Extremely Elevated Erythrocyte Sedimentation Rate (>100 mm/h)¶
Harrison's 22e, p.962
| ETIOLOGIC CATEGORY (% OF CASES) | SPECIFIC CAUSES |
|---|---|
| Infectious diseases (35–40) | Subacute bacterial endocarditis Abscesses Osteomyelitis Tuberculosis Urinary tract infection |
| Malignancies (15–20) | Multiple myeloma Leukemias Lymphomas Carcinomas |
TABLE 124-4 Typical Cerebrospinal Fluid Profiles for Meningitis and Encephalitis a WBC count (per μL) Differential of…¶
Harrison's 22e, p.962
| NORMAL | BACTERIAL MENINGITIS |
VIRAL MENINGITIS |
FUNGAL MENINGITISb |
PARASITIC MENINGITIS |
TUBERCULOUS MENINGITIS |
ENCEPHALITIS | |
|---|---|---|---|---|---|---|---|
| WBC count (per μL) | <5 | >1000 | 25–500 | 40–600 | 150–2000 | 25–100 | 50–500 |
| 60–70% lymphocytes, ≤30% monocytes/ macrophages |
↑↑PMNs (≥80%) | Predominantly lymphocytesc |
Lymphocytes or PMNs, depending on specific organism |
↑↑ Eosinophils (≥50%)d |
Predominantly lymphocytesc |
||
| Gram’s stain | Negative | Positive (in >60% of cases) |
Negative | Rarely positive | Negative | Occasionally positivee |
Negative |
| 40–85 | <40 | Normal | ↓ to normal | Normal | <50 in 75% of cases |
||
| Protein (mg/dL) | 15–45 | >100 | 20–80 | 150–300 | 50–200 | 100–200 | 50–100 |
| 50–180 | >300 | 100–350 | 160–340 | Normal | 150–280 | ||
| Common causes | — | Streptococcus pneumoniae, Neisseria meningitidis |
Enteroviruses | Candida, Cryptococcus, and Aspergillus spp. |
Angiostrongylus cantonensis, Gnathostoma spinigerum, Baylisascaris procyonis |
Mycobacterium tuberculosis |
Herpesviruses, enteroviruses, influenza virus, rabies virus |
TABLE 124-5 Initial Empirical Antibiotic Therapy for Common Infectious Disease Presentations a¶
Harrison's 22e, p.963
| CLINICAL SYNDROME | COMMON ETIOLOGIES | ANTIBIOTIC(S) | COMMENTS | SEE CHAPTER(S) |
|---|---|---|---|---|
| Septic shock | Staphylococcus aureus, Streptococcus pneumoniae, enteric gram-negative bacilli |
Vancomycin, 15 mg/kg q12hb plus A broad-spectrum antipseudomonal β-lactam (piperacillin-tazobactam, 4.5 g q6h; imipenem, 1 g q8h; meropenem, 1 g q8h; or cefepime, 1–2 g q8–12h) |
If a pseudomonal species is likely, a second antipseudomonal agent should be added. |
315 |
| S. pneumoniae, Neisseria meningitidis |
Vancomycin, 15 mg/kg q12hb plus Ceftriaxone, 2 g q12h |
Dexamethasone (0.15 mg/kg IV q6h for 2–4 d) should be added for patients with suspected or proven pneumococcal meningitis, with the first dose administered 10–20 min before the first dose of antibiotics. |
||
| CNS abscess | Streptococcus spp., Staphylococcus spp., anaerobes, gram-negative bacilli |
Vancomycin, 15 mg/kg q12hb plus Ceftriaxone, 2 g q12h plus Metronidazole, 500 mg q8h |
— | 143 |
| S. aureus, Streptococcus spp., coagulase-negative staphylococci |
Vancomycin, 15 mg/kg q12hb plus Cefepime, 2 g q8h |
— | ||
| Pneumonia Community- acquired, outpatient |
S. pneumoniae, Mycoplasma pneumoniae, Haemophilus influenzae, Chlamydia pneumoniae |
No comorbiditiesh: Azithromycin, 500 mg PO? 1, then 250 mg PO qd 4 days With comorbiditiesh: Levofloxacin, 750 mg PO qd |
If MRSA is a consideration, add vancomycin (15 mg/kg q8–12hb) or linezolid (600 mg q12h); daptomycin should not be used in patients with pneumonia. |
131 and pathogen- specific chapters |
| Inpatient, non-ICU | Above plus Legionella spp. | A respiratory fluoroquinolone (moxifloxacin, 400 mg IV/PO qd; gemifloxacin, 320 mg PO qd; or levofloxacin, 750 mg IV/PO qd) or A β-lactam (cefotaxime, ceftriaxone, or ampicillin-sulbactam) plus azithromycin |
||
| Inpatient, ICU | Above plus S. aureus | A β-lactam plus Azithromycin or a respiratory fluoroquinolone |
||
| Hospital-acquired pneumoniad |
S. pneumoniae, H. influenzae, S. aureus, gram-negative bacilli (e.g., Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter spp.) |
An antipseudomonal β-lactam (cefepime, 2 g q8h; ceftazidime, 2 g q8h; imipenem, 500 mg q6h; meropenem, 1 g q8h; or piperacillin-tazobactam, 4.5 g q6h) plus An antipseudomonal fluoroquinolone (levofloxacin, 700 mg qd, or ciprofloxacin, 400 mg q8h) or an aminoglycoside (amikacin, 15–20 mg/kg q24hc; gentamicin, 5–7 mg/kg q24he; or tobramycin, 5–7 mg/kg q24he) |
If MRSA is a consideration, add vancomycin (15 mg/kg q8–12hb) or linezolid (600 mg q12h); daptomycin should not be used in patients with pneumonia. |
|
| Anaerobes (Bacteroides spp., Clostridium spp.), gram-negative bacilli (Escherichia coli), Streptococcus spp. Same as above |
Cefoxitin, 2 g q6h or A combination of metronidazole (500 mg q8–12h) plus one of the following: cefazolin (1–2 g q8h), cefuroxime (1.5 g q8h), ceftriaxone (1–2 g q12–24h), cefotaxime (1–2 g q6–8h), ciprofloxacin (400 mg q12h), levofloxacin (750 mg qd) A carbapenem (imipenem, 500 mg q6h; meropenem, 1 g q8h; doripenem, 500 mg q8h) or Piperacillin-tazobactam, 3.375 g q6hf or A combination of metronidazole (500 mg q8h) plus an antipseudomonal cephalosporin (cefepime, 2 g q8h; ceftazidime, 2 g q8h) |
If MRSA is a consideration, add vancomycin (15 mg/kg q12hb) |