What are the recommended antibiotics for treating pneumonia in the Philippines, considering patient factors such as impaired renal function and history of penicillin allergy?

Philippine Guidelines for Pneumonia Antibiotic Treatment

Outpatient Treatment for Community-Acquired Pneumonia

For previously healthy adults without comorbidities, amoxicillin 1 gram orally three times daily for 5-7 days is the first-line treatment, targeting Streptococcus pneumoniae which accounts for 48% of identified cases. 1, 2

Standard Outpatient Regimens

• Healthy adults without comorbidities: Amoxicillin 1 g orally every 8 hours for 5-7 days provides optimal coverage against common respiratory pathogens including penicillin-resistant strains 1, 2
• Alternative for penicillin allergy: Doxycycline 100 mg orally twice daily for 5-7 days is the preferred alternative 1, 2
• Macrolide consideration: Azithromycin 500 mg on day 1, then 250 mg daily for 4 days should ONLY be used if local pneumococcal macrolide resistance is documented <25% 1, 2

Outpatient Treatment with Comorbidities

For patients with COPD, diabetes, chronic heart/liver/renal disease, or recent antibiotic use within 3 months, combination therapy is mandatory. 1

• Preferred combination: Amoxicillin-clavulanate 875 mg/125 mg orally twice daily PLUS azithromycin 500 mg day 1, then 250 mg daily for days 2-5 1
• Alternative combination: Cefpodoxime or cefuroxime PLUS macrolide or doxycycline 1
• Fluoroquinolone monotherapy option: Levofloxacin 750 mg daily OR moxifloxacin 400 mg daily for 5-7 days 1, 3

Hospitalized Non-ICU Patients

The standard regimen for hospitalized patients is ceftriaxone 1-2 grams IV daily PLUS azithromycin 500 mg IV or oral daily, providing coverage for both typical bacterial pathogens and atypical organisms. 1, 2

Standard Inpatient Regimens

• Preferred combination: Ceftriaxone 1-2 g IV daily PLUS azithromycin 500 mg IV/PO daily 1, 2
• Alternative β-lactams: Cefotaxime 1-2 g IV every 8 hours OR ampicillin-sulbactam 3 g IV every 6 hours, always combined with azithromycin 1
• Fluoroquinolone monotherapy: Levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily as equally effective alternative 1, 3

Transition to Oral Therapy

• Switch criteria: Hemodynamically stable, clinically improving, afebrile for 48-72 hours, able to take oral medications, normal GI function—typically by day 2-3 1, 2
• Oral step-down options: Amoxicillin 1 g orally three times daily PLUS azithromycin 500 mg orally daily 1

Severe CAP Requiring ICU Admission

Combination therapy is mandatory for all ICU patients: ceftriaxone 2 grams IV daily PLUS either azithromycin 500 mg IV daily OR levofloxacin 750 mg IV daily. 1, 2

ICU Treatment Regimens

• Standard ICU regimen: Ceftriaxone 2 g IV daily PLUS azithromycin 500 mg IV daily 1, 2
• Alternative ICU regimen: Ceftriaxone 2 g IV daily PLUS levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily 1, 3
• Duration: 10-14 days for severe pneumonia, extended to 14-21 days for Legionella, Staphylococcus aureus, or Gram-negative enteric bacilli 1, 2

Special Considerations for Renal Impairment

For patients with impaired renal function, dose adjustments are critical to prevent nephrotoxicity while maintaining efficacy. 4, 5

Antibiotic Adjustments in Renal Impairment

• Ceftriaxone: No dose adjustment needed—primarily biliary excretion 4
• Levofloxacin: Reduce to 750 mg loading dose, then 500 mg every 48 hours if CrCl 20-49 mL/min; 500 mg loading dose, then 250 mg every 48 hours if CrCl 10-19 mL/min 4
• Moxifloxacin: No dose adjustment needed 3
• Azithromycin: No dose adjustment needed 4
• Amoxicillin: Reduce to 500 mg every 12 hours if CrCl 10-30 mL/min 4
• Avoid piperacillin-tazobactam 4.5 g doses: Use 2.25 g three times daily maximum in renal impairment, as higher doses (4.5 g twice or three times daily) cause AKI in 25-38.5% of patients 5

Preferred Regimens for Renal Impairment

• Hospitalized non-ICU with renal impairment: Ceftriaxone 1-2 g IV daily (no adjustment) PLUS azithromycin 500 mg daily (no adjustment) 4
• Alternative for renal impairment: Moxifloxacin 400 mg IV daily monotherapy (no adjustment needed) 3

Penicillin Allergy Management

For patients with documented penicillin allergy, respiratory fluoroquinolone monotherapy is the preferred alternative for both outpatient and inpatient treatment. 1

Penicillin Allergy Regimens

• Outpatient with penicillin allergy: Levofloxacin 750 mg daily OR moxifloxacin 400 mg daily for 5-7 days 1, 3
• Hospitalized non-ICU with penicillin allergy: Levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily 1, 3
• ICU with penicillin allergy: Aztreonam 2 g IV every 8 hours PLUS levofloxacin 750 mg IV daily 1
• Alternative for mild allergy: Doxycycline 100 mg twice daily can be used for outpatients 1

Coverage for Drug-Resistant Pathogens

Pseudomonas aeruginosa Risk Factors

Add antipseudomonal coverage only when specific risk factors are present: structural lung disease (bronchiectasis, cystic fibrosis), recent hospitalization with IV antibiotics within 90 days, frequent antibiotic use (>4 courses/year), severe COPD (FEV1 <30%), or oral steroid use (>10 mg prednisolone daily for 2 weeks). 4, 1

• Antipseudomonal regimen: Piperacillin-tazobactam 4.5 g IV every 6 hours OR cefepime 2 g IV every 8 hours PLUS ciprofloxacin 400 mg IV every 12 hours OR levofloxacin 750 mg IV daily 1
• Dual antipseudomonal therapy: Add aminoglycoside (gentamicin 5-7 mg/kg IV daily) for septic shock or high mortality risk 4

MRSA Risk Factors

Add MRSA coverage when risk factors present: prior MRSA infection/colonization, recent hospitalization with IV antibiotics, post-influenza pneumonia, or cavitary infiltrates on imaging. 1

• MRSA regimen: Add vancomycin 15 mg/kg IV every 8-12 hours (target trough 15-20 mg/mL) OR linezolid 600 mg IV every 12 hours to base regimen 4

Treatment Duration and Monitoring

Treat for a minimum of 5 days and until afebrile for 48-72 hours with no more than one sign of clinical instability; typical duration for uncomplicated CAP is 5-7 days. 1, 2

Clinical Stability Criteria

• Afebrile for >48 hours 1
• Heart rate <100 bpm 1
• Respiratory rate <24 breaths/min 1
• Systolic blood pressure >90 mmHg 1
• Oxygen saturation >90% on room air 1

Failure to Improve by Day 2-3

• Obtain repeat chest radiograph, CRP, white cell count, additional microbiological specimens 2
• Consider chest CT to reveal pleural effusions, lung abscess, or central airway obstruction 2
• For non-severe pneumonia on amoxicillin monotherapy: add or substitute macrolide 2
• For severe pneumonia not responding: consider adding rifampicin 2

Critical Pitfalls to Avoid

• Never use macrolide monotherapy in hospitalized patients—provides inadequate coverage for typical bacterial pathogens like S. pneumoniae 1
• Never delay antibiotic administration beyond 8 hours in hospitalized patients—increases 30-day mortality by 20-30% 1
• Never use macrolides in areas where pneumococcal resistance exceeds 25%—leads to treatment failure 1, 2
• Avoid indiscriminate fluoroquinolone use in uncomplicated outpatient CAP due to resistance concerns and serious adverse events including tendinitis, tendon rupture, peripheral neuropathy, and CNS effects 1, 3
• Avoid piperacillin-tazobactam 4.5 g doses in renal impairment—causes AKI in 25-38.5% of patients 5

Diagnostic Testing for Hospitalized Patients

• Obtain blood cultures and sputum Gram stain/culture before initiating antibiotics in all hospitalized patients 1, 2
• Urinary antigen testing for Legionella pneumophila serogroup 1 in severe CAP or ICU patients 1
• Administer first antibiotic dose in emergency department immediately upon diagnosis 1