Approach to the Acutely Ill Infected Febrile Patient¶

Chapter 127 | Harrison's 22e · Part 5 – Infectious Diseases: Bacterial · Chapter 127

Key Clinical Points¶

Immediate assessment of general appearance is critical for early sepsis detection.
Petechial rash indicates meningococcemia or RMSF; erythroderma suggests TSS.
Three sets of blood cultures are required for suspected endocarditis.
Neurologic evaluation must include mental status and nuchal rigidity assessment.
Blood smears are essential for diagnosing malaria, babesiosis, ehrlichiosis, and anaplasmosis.
Hypothermia in critically ill patients correlates with high risk of organ failure and mortality.
CSF analysis should be performed before starting antibiotics in suspected meningitis.
Dexamerthasone (10 mg q6h for 4 days) improves outcomes in adult meningitis, especially pneumococcal.
Artesunate is the preferred treatment for Plasmodium falciparum; avoid glucocorticoids.

1. CLINICAL ASSESSMENT & GENERAL APPEARANCE¶

Initial evaluation should focus on the patient's general appearance:

• Appearance: A toxic or septic appearance may manifest as agitation, lethargy, or apathy. • Atypical Presentation: Elderly patients and immunocompromised hosts may present with atypical signs (e.g., afebrile state despite severe infection). • Hypothermia: In critically ill patients, hypothermia correlates with a high risk of organ failure and mortality. • Hemodynamics: Vital sign monitoring (BP, HR, RR, SpO2) is essential for assessing hemodynamic compromise.

2. PHYSICAL EXAMINATION¶

Comprehensive examination should include:

• Skin Assessment: Look for petechial rashes (meningococcemia/RMSF), erythroderma (TSS), or signs of necrotizing fasciitis (erythema, duskiness, tenderness). • Soft Tissue Evaluation: Identify edema, erythema, or focal tenderness suggesting myositis/myonecrosis. • Neurologic Examination: Assess mental status for encephalopathy and check for nuchal rigidity/focal deficits.

3. HISTORY TAKING¶

Key historical elements include:

• Host Factors: Age extremes, splenectomy (risk of encapsulated bacterial infection), immunocompression (HIV, chemotherapy), and comorbidities (diabetes, malignancy). • Exposure History: Recent infections (influenza, varicella), trauma, surgical procedures, or tick/mosquito exposure. • Travel/Social History: Natural disasters, animal contact, occupational risks, and vaccination status. • Pregnancy Considerations: Increased risk of severe illness from influenza/Covid-19 and fetal complications with Listeria/Zika.

4. DIAGNOSTIC APPROACH¶

Blood Cultures: Obtain three sets for suspected endocarditis.
Laboratory Work: CBC with differential, electrolytes, BUN, creatinine, glucose, LFTs, lactate, and d-dimer.
Blood Smears: Essential for identifying parasites (malaria, babesiosis, ehrlichiosis, anaplasmosis).
CSF Analysis: Perform before starting antibiotics in suspected meningitis; contraindicated if focal neurologic signs or papilledema are present.
Imaging: CT/MRI for focal processes requiring surgical intervention.

5. MANAGEMENT & TREATMENT¶

General Management Principles:

• Antibiotics: Initiate IV antibiotics without delay for suspected bacterial infection. • Supportive Care: Concurrent fluid resuscitation and vasopressor support as needed. • Splenectomy Status: Note that median 4-6 year interval to sepsis occurs; S. pneumoniae accounts for 40-70% of infections. • Diagnostics: Use molecular diagnostics (16S rRNA PCR) for rapid identification of bacterial meningitis pathogens.

Empirical Treatment by Clinical Syndrome (Table 127-1):

Sepsis without a Clear Focus / Septic Shock: ◦ Vancomycin (15 mg/kg q12h) plus either Piperacillin/tazobactam (4.5 g q8h via EI) or cefepime (2 g q8h via EI). ◦ Note: Tailor to local resistance; consider Carbapenem or aminoglycoside if multidrug-resistant gram-negative organisms are likely. Adjust treatment when culture data become available.
Overwhelming Post-Splenectomy Sepsis: ◦ Ceftriaxone (2 g q12h) plus vancomycin (15 mg/kg q12h). ◦ Note: If a β-lactam–sensitive strain is identified, vancomycin can be discontinued and a narrower-spectrum agent, such as penicillin, considered based on susceptibility testing.
Babesiosis: ◦ Atovaquone (750 mg q12h) plus azithromycin (500 mg q24h). ◦ Severe disease not responding to atovaquone and azithromycin: Clindamycin (600 mg q8h) plus quinine (650 mg q8h). ◦ Potential co-infection (Borrelia burgdorferi or Anaplasma spp.): Doxycycline (100 mg bid).
Sepsis with Skin Findings: ◦ N. meningitidis: Ceftriaxone (2 g q12h) or penicillin (4 mU q4h). Note: Ceftriaxone eradicates nasopharyngeal carriage; prophylaxis for contacts with rifampin (600 mg q12h for 2 days) or ciprofloxacin (500 mg single dose). ◦ Rickettsia rickettsii: Doxycycline (100 mg bid). If both meningococcemia and RMSF are considered, use ceftriaxone (2 g q12h) plus doxycycline (100 mg bid); if RMSF is diagnosed, ceftriaxone can be discontinued. ◦ S. pneumoniae, H. influenzae, N. meningitidis: Ceftriaxone (2 g q12h) plus vancomycin (15 mg/kg q12h). ◦ Group A Streptococcus, Staphylococcus aureus: Vancomycin (15 mg/kg q12h) plus clindamycin (600 mg q8h). If a β-lactam–sensitive strain is identified, use penicillin (2 mU q4h) or oxacillin (2 g IV q4h). Action: Debride site of toxigenic bacteria; IV immunoglobulin for severe cases. ◦ Necrotizing Fasciitis: Vancomycin (15 mg/kg q12h) plus piperacillin/tazobactam (4.5 g q8h via EI) plus clindamycin (600 mg q8h). Note: Urgent surgical evaluation is critical; for mixed aerobic/anaerobic infections, clindamycin can be discontinued. ◦ Clostridial Myonecrosis: Penicillin (2 mU q4h) plus clindamycin (600 mg q8h). Action: Urgent surgical evaluation is critical.
Neurologic Infections: ◦ S. pneumoniae, N. meningitidis: Ceftriaxone (2 g q12h) plus vancomycin (15 mg/kg q12h). Add Dexamethasone (10 mg q6h for 4 days) started before or at the time of first dose of antibiotic. ◦ Staphylococcus spp., gram-negative bacilli, anaerobes: Vancomycin (15 mg/kg q12h) plus metronidazole (500 mg q8h) plus ceftriaxone (2 g q12h). If a β-lactam–sensitive strain is identified, use penicillin (4 mU q4h) or oxacillin (2 g q4h). ◦ Plasmodium falciparum: Artesunate (2.4 mg/kg IV at 0, 12, and 24 h; then once daily). Note: Avoid glucocorticoids. ◦ Staphylococcus spp., gram-negative bacilli (surgical): Vancomycin (15 mg/kg q12h) plus either Piperacillin/tazobactam (4.5 g q8h via EI) or cefepime (2 g q8h via EI). Action: Surgical evaluation is essential; if β-lactam–sensitive strain identified, oxacillin (2 g q4h) or cefazolin (2 gm IV q8h) is superior.
Focal Infections: ◦ Acute Bacterial Endocarditis: Ceftriaxone (2 g q12h) or cefepime (2 g q8h via EI) plus vancomycin (15 mg/kg q12h). Action: Evaluation by cardiology and cardiothoracic surgery is essential.

Reference Tables¶

TABLE 127-1 Empirical Treatment for Common Infectious Disease Emergencies a¶

Harrison's 22e, p.991

CLINICAL SYNDROME	POSSIBLE ETIOLOGIES	TREATMENT	COMMENTS	SEE CHAP(S)
Sepsis without a Clear Focus
Septic shock	Pseudomonas spp., gram- negative enteric bacilli, Staphylococcus spp., Streptococcus spp.	Vancomycin (15 mg/kg q12h)b plus either Piperacillin/tazobactam (4.5 g) q8h via extended infusion (EI)c or cefepime (2 g) q8h via EI	Empirical therapy should be tailored to local resistance patterns. Carbapenem or aminoglycoside antibiotics should be considered for empirical therapy when rates of multidrug- resistant gram-negative organisms are high or for patients with risk factors for resistant organisms. Adjust treatment when culture data become available.	152, 153, 166, 170, 315
Overwhelming post- splenectomy sepsis	Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis	Ceftriaxone (2 g q12h) plus vancomycin (15 mg/kg q12h)b	If a β-lactam–sensitive strain is identified, vancomycin can be discontinued and a narrower-spectrum agent, such as penicillin, considered based on susceptibility testing.	315
Babesiosis	Babesia microti (U.S.), B. divergens (Europe)	Atovaquone (750 mg q12h) plus azithromycin (500 mg q24h)	Clindamycin (600 mg q8h) plus quinine (650 mg q8h) can be used in severe disease not responding to atovaquone and azithromycin. Treatment with doxycycline (100 mg bid) for potential co-infection with Borrelia burgdorferi or Anaplasma spp. may be prudent.	229, 232
Sepsis with Skin Findings
N. meningitidis	Ceftriaxone (2 g q12h) or penicillin (4 mU q4h)	Ceftriaxone eradicates nasopharyngeal carriage of the organism. Close contacts require chemoprophylaxis with rifampin (600 mg q12h for 2 days) or ciprofloxacin (a single dose, 500 mg).
Rickettsia rickettsii	Doxycycline (100 mg bid)	If both meningococcemia and RMSF are being considered, use ceftriaxone (2 g q12h) plus doxycycline (100 mg bid). If RMSF is diagnosed, ceftriaxone can be discontinued.
S. pneumoniae, H. influenzae, N. meningitidis	Ceftriaxone (2 g q12h) plus vancomycin (15 mg/kg q12h)b	If a β-lactam-sensitive strain is identified, vancomycin can be discontinued.
Group A Streptococcus, Staphylococcus aureus	Vancomycin (15 mg/kg q12h)b plus clindamycin (600 mg q8h)	If a penicillin- or oxacillin-sensitive strain is isolated, these agents are superior to vancomycin (penicillin, 2 mU q4h; or oxacillin, 2 g IV q4h). The site of toxigenic bacteria should be debrided; IV immunoglobulin can be used in severe cases.d
Sepsis with Soft Tissue Findings
Necrotizing fasciitis	Group A Streptococcus, mixed aerobic/anaerobic flora	Vancomycin (15 mg/kg q12h)b plus piperacillin/tazobactam (4.5 q q8h via EI)c plus clindamycin (600 mg q8h)	Urgent surgical evaluation is critical. Empirical therapy should be tailored to local resistance patterns. For mixed aerobic/ anaerobic infections, clindamycin can be discontinued. Adjust treatment when culture data become available.	134, 152, 153
Clostridial myonecrosis	Clostridium perfringens	Penicillin (2 mU q4h) plus clindamycin (600 mg q8h)	Urgent surgical evaluation is critical.	159
Neurologic Infections
S. pneumoniae, N. meningitidis	Ceftriaxone (2 g q12h) plus vancomycin (15 mg/kg q12h)b	If a β-lactam–sensitive strain is identified, vancomycin can be discontinued. If the patient is >50 years old or has comorbid disease, add ampicillin (2 g q4h) for Listeria coverage. Dexamethasone (10 mg q6h for 4 days) started before, or at the time of, the first dose of antibiotic improves outcome in adults with meningitis (especially pneumococcal).
Streptococcus spp., Staphylococcus spp., anaerobes, gram-negative bacilli	Vancomycin (15 mg/kg q12h)b plus metronidazole (500 mg q8h) plus ceftriaxone (2 g q12h)	Urgent surgical evaluation is critical. If a penicillin- or oxacillin-sensitive strain is isolated, these agents are superior to vancomycin (penicillin, 4 mU q4h; or oxacillin, 2 g q4h).
Plasmodium falciparum	Artesunate (2.4 mg/kg IV at 0, 12, and 24 h; then once daily)	Avoid glucocorticoids. Until IV artesunate is available, treatment can be initiated with oral artemether-lumefantrine. Atovaquone-proguanil, quinine, and mefloquine are other options.
Staphylococcus spp., gram-negative bacilli	Vancomycin (15 mg/kg q12h)b plus either Piperacillin/tazobactam (4.5 g q8h via EI) or cefepime (2 g q8h via EI)c	Surgical evaluation is essential. If a β-lactam–sensitive strain is isolated, oxacillin, 2 g q4h or cefazolin 2 gm IV q8h is superior to vancomycin.
Focal Infections
Acute bacterial endocarditis	S. aureus, β-hemolytic streptococci, HACEK group,e Neisseria spp., S. pneumoniae	Ceftriaxone (2 g q12h) or cefepime (2 g q8h via EI)c plus vancomycin (15 mg/kg q12h)b	Adjust treatment when culture data become available. Evaluation by cardiology and cardiothoracic surgery is essential.	133