What is the appropriate treatment and management for suspected infections?

Management of Suspected Infections: Treatment and Pathophysiology

For suspected serious infections, appropriate antibiotic therapy should be administered at the earliest sign or symptom, with empirical treatment initiated immediately in high-risk patients or those with septic shock, even before culture results are available. 1

Initial Recognition and Risk Stratification

Clinical Assessment

• Monitor for key signs and symptoms daily: fever, headache, backache, erythema, tenderness at insertion sites, neurologic changes, hypotension, and new-onset abdominal pain 1
• Assess severity using clinical factors: temperature >37.8°C, heart rate >100/min, respiratory rate >24/min, systolic blood pressure <90 mmHg, oxygen saturation <90% 2
• High-risk patients include those with anticipated prolonged neutropenia (>7 days, ANC <100 cells/mm³), significant medical comorbidities, hypotension, pneumonia, or immunosuppression 1

Immediate Diagnostic Workup

• Obtain at least 2 sets of blood cultures before initiating antibiotics: one from peripheral vein and one from each lumen of any central venous catheter if present 1
• Order baseline laboratory tests: complete blood count with differential, creatinine, electrolytes, hepatic enzymes, C-reactive protein, and leukocyte count 1
• Obtain cultures from other suspected infection sites as clinically indicated (urine, sputum, wound, cerebrospinal fluid) 1
• Chest radiograph is indicated for patients with any respiratory signs or symptoms 1

Empirical Antibiotic Selection by Clinical Scenario

High-Risk Patients Requiring Hospitalization

Initiate IV monotherapy with an anti-pseudomonal β-lactam agent 1:

• Preferred agents: cefepime, meropenem, imipenem-cilastatin, or piperacillin-tazobactam 1
• Add vancomycin if suspected catheter-related infection, skin/soft-tissue infection, pneumonia, hemodynamic instability, or MRSA risk 1
• Add aminoglycoside or fluoroquinolone for complications such as hypotension or suspected antimicrobial resistance 1

Specific Infection Types

Neuraxial/CNS Infections

• Remove indwelling catheter immediately if infection suspected 1
• Obtain imaging studies (MRI or CT) if abscess suspected or neurologic deficit present 1
• For bacterial meningitis: ceftazidime or meropenem plus ampicillin (to cover Listeria monocytogenes) 1
• For viral encephalitis: high-dose acyclovir (500 mg/m² every 8 hours for ages 3 months-12 years; 10 mg/kg every 8 hours for >12 years) within 6 hours of admission 1

Febrile Neutropenia

• Start empirical therapy immediately upon fever recognition in neutropenic patients 1
• Add empirical antifungal therapy if fever persists after 4-7 days of antibiotics and neutropenia expected to last >7 days 3
• Switch to different antifungal class (liposomal amphotericin B 3 mg/kg/day or echinocandin) if patient was receiving azole prophylaxis 3

Intra-Abdominal Infections

• Ciprofloxacin plus metronidazole for polymicrobial coverage 4
• Source control procedure should be performed as soon as possible, even if physiologic stabilization measures need to continue during the procedure 1

Catheter-Related Infections

• Most infections can be treated without catheter removal 1
• Remove catheter for tunnel infections, persistent bacteremia despite treatment, atypical mycobacterial infection, or candidemia 1
• Add vancomycin when line infection suspected, administered through the catheter when possible 1

Bite Wounds (Animal/Human)

• Ampicillin-sulbactam IV or amoxicillin-clavulanate oral to cover Pasteurella species (dog/cat bites) and Eikenella corrodens (human bites) 5

Low-Risk Patients

• Oral empirical therapy acceptable: ciprofloxacin plus amoxicillin-clavulanate 1, 4, 6
• Initial doses should be given in clinic/hospital setting before transitioning to outpatient management 1
• Do not use oral quinolones if patient was taking quinolone prophylaxis 1

Timing Considerations

Critical Time Windows

• Septic shock: administer antibiotics as soon as possible, ideally within the first hour 1
• Without septic shock: start antimicrobials in the emergency department once infection suspected 1
• Viral encephalitis: initiate acyclovir within 6 hours of admission if CSF/imaging suggests viral etiology or while awaiting results 1
• Intra-abdominal infection with peritonitis: emergency surgical intervention as soon as possible 1

Maintaining Drug Levels

• Ensure satisfactory antimicrobial levels during source control procedures, which may require additional dosing immediately before the intervention 1

Assessment of Response and Modification

48-Hour Reassessment

If afebrile and ANC ≥0.5 × 10⁹/L 1:

• Low-risk with no identified pathogen: consider switching to oral antibiotics 1
• High-risk with no identified pathogen: discontinue aminoglycoside if on dual therapy 1
• Pathogen identified: continue appropriate specific therapy 1

If still febrile at 48 hours 1:

• Clinically stable: continue initial antibacterial therapy 1
• Clinically unstable: rotate antibacterial therapy or broaden coverage; seek infectious disease consultation immediately 1
• Consider adding antifungal therapy if fever persists 4-6 days 1, 3

Daily Monitoring Requirements

• Assess fever trends, bone marrow function, and renal function daily until patient is afebrile and ANC ≥0.5 × 10⁹/L 1
• Frequency of clinical assessment determined by severity: every 2-4 hours for patients requiring resuscitation 1
• Repeated imaging may be required in patients with persistent fever, particularly high-resolution chest CT if invasive aspergillosis suspected 1, 3

Duration of Therapy

General Principles

• Continue antibiotics until neutropenia resolves in neutropenic patients 1
• Minimum 14 days for demonstrated fungal infections 1
• Once-daily aminoglycosides are effective and reduce toxicity risk 7
• 24 hours of adjunctive therapy is as efficacious as longer duration for traumatic injuries with high infection probability 5

Catheter Management

• Remove all indwelling IV catheters promptly at completion of antimicrobial therapy 1
• Do not obtain routine blood cultures after completing therapy in asymptomatic patients 1

Pathophysiology and Source Control

Infection Spread Mechanisms

• Polymicrobial infections are the rule: 50% involve mixed aerobic and anaerobic bacteria 5
• Nosocomial infections most commonly affect lower respiratory tract, followed by bloodstream and urinary tract 5
• Respiratory infections account for 49% of all antibiotic use in ICU settings, predominantly in intubated patients 8

Source Control Principles

• Antibiotics do not sterilize wounds or body cavities; they limit bacterial proliferation to supplement immune control 5
• Appropriate source control procedure required to drain infected foci, control ongoing contamination, and restore anatomic/physiologic function 1
• Percutaneous drainage may be effective for abscess resolution in selected cases 1

Common Pitfalls to Avoid

Diagnostic Errors

• Do not delay imaging if abscess suspected or neurologic deficit present—perform MRI/CT the same day 1
• Do not rely on CT alone for CNS infections in children; it may be normal even in severe bacterial meningitis or encephalitis 1
• Immunocompromised patients may not manifest typical signs of infection 1

Treatment Errors

• Do not initiate empirical antibiotics for undefined febrile illness without obtaining blood cultures first—this is a major cause of culture-negative endocarditis 1
• Do not use vancomycin routinely as part of initial fever and neutropenia regimen; reserve for specific clinical indications 1
• Do not continue the same antifungal class when breakthrough fungal infection occurs during prophylaxis 3
• Do not use ciprofloxacin as first-line for presumed or confirmed Streptococcus pneumoniae pneumonia 4

Monitoring Failures

• Do not remove catheters without culturing the tip when infection suspected 1
• Do not continue antibiotics longer than clinically necessary—catheters should not remain in situ beyond clinical need 1
• For patients on long-term aminoglycosides: consider serial audiograms, particularly with underlying renal or otic disorders 1

Antimicrobial Resistance Considerations

High-Risk Scenarios Requiring Modified Coverage

Modify empirical therapy for patients at risk of resistant organisms 1:

• MRSA: previous infection/colonization or high hospital endemicity—add vancomycin 1
• VRE: similar risk factors—consider linezolid or daptomycin 1
• ESBL-producing gram-negatives: use carbapenem 1
• Carbapenemase-producing organisms (KPC): consider polymyxin-colistin or tigecycline early 1

Allergy Management

• Penicillin-allergic patients generally tolerate cephalosporins 1
• Immediate-type hypersensitivity (hives, bronchospasm): use ciprofloxacin plus clindamycin, or aztreonam plus vancomycin 1

Follow-Up and Prevention

Short-Term Monitoring

• Monitor for IE relapse and heart failure in endocarditis patients 1
• Educate patients about infection signs and urge immediate medical attention if fever, chills, or systemic toxicity develops 1
• Thorough dental evaluation is reasonable, especially for patients likely requiring valve replacement 1

Long-Term Considerations

• Emphasize daily dental hygiene and serial dental evaluations 1
• Poor oral hygiene and periodontal disease are associated with community-acquired endocarditis, not dental procedures 1
• Referral to drug cessation programs for injection drug users 1