What are the newest approved antibiotics?

Newest Approved Antibiotics

The most recently FDA-approved antibiotics include cefiderocol (2019), lefamulin (2019), imipenem-cilastatin-relebactam (2019), omadacycline (2018), eravacycline (2018), plazomicin (2018), and sarecycline (2018), with cefiderocol and lefamulin representing the newest options for multidrug-resistant Gram-negative infections and community-acquired bacterial pneumonia respectively. 1, 2, 3

2019 FDA Approvals

Cefiderocol (Fetroja)

• Novel siderophore cephalosporin approved for complicated urinary tract infections (cUTI) including pyelonephritis, and hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP) 1, 3
• Dosing: 2 grams IV every 8 hours over 3-hour infusion in patients with creatinine clearance 60-119 mL/min 1
• Critical caveat: Increased all-cause mortality was observed in cefiderocol-treated patients compared to best available therapy in carbapenem-resistant Gram-negative infections, requiring close monitoring of clinical response 1
• Activity against carbapenem-resistant Acinetobacter baumannii, carbapenem-resistant Pseudomonas aeruginosa, and carbapenem-resistant Enterobacterales 4, 5

Lefamulin (Xenleta)

• First-in-class pleuromutilin antibiotic approved for community-acquired bacterial pneumonia (CABP) 6, 3
• In Phase 3 LEAP 2 trial, 5 days of oral lefamulin was non-inferior to 7-day moxifloxacin for CABP patients (PORT risk class II-IV) 6
• Covers typical, atypical, and resistant CAP pathogens including drug-resistant Streptococcus pneumoniae and MRSA 6

Imipenem-Cilastatin-Relebactam

• Carbapenem-β-lactamase inhibitor combination approved for complicated urinary tract infections and complicated intra-abdominal infections 3, 7
• Relebactam protects imipenem from various β-lactamases including extended-spectrum β-lactamases 8

2018 FDA Approvals

Omadacycline (Nuzyra)

• Aminomethycycline tetracycline derivative approved for acute bacterial skin and skin structure infections (ABSSSI) and CABP 2, 3
• CABP dosing: Loading dose of 200 mg IV over 60 minutes OR 300 mg PO twice on Day 1, then 100 mg IV daily OR 300 mg PO daily 2
• In randomized trial, showed similar early clinical response to moxifloxacin in CAP patients (PORT risk class II-IV) 6
• Important warning: Mortality imbalance observed in CABP trial (2% vs 1% with moxifloxacin), requiring close monitoring 2
• Contraindicated in tooth development (pregnancy second half, infancy, childhood to age 8) due to permanent tooth discoloration and enamel hypoplasia 2

Eravacycline

• Fully synthetic fluorocycline approved for complicated intra-abdominal infections 3, 7
• Tetracycline-class agent with activity against resistant Gram-negative organisms 5

Plazomicin

• Aminoglycoside antibiotic targeting Enterobacteriaceae infections, primarily for complicated urinary tract infections 3, 7
• Maintains activity against aminoglycoside-resistant strains 5

Sarecycline

• Tetracycline-derived antibiotic approved specifically for non-nodular moderate to severe acne 3

Recently Approved β-Lactam/β-Lactamase Inhibitor Combinations (Pre-2018)

Fifth-Generation Cephalosporins

• Ceftaroline: Superior to ceftriaxone for severe CAP (OR 1.66; 95% CI 1.34-2.06), with activity against MRSA and drug-resistant S. pneumoniae 6
• Ceftobiprole: Non-inferior to ceftriaxone for CAP, with extended spectrum against MSSA, penicillin-resistant S. pneumoniae, and P. aeruginosa (not FDA-approved in US for pneumonia) 6

Combination Agents for MDR Gram-Negatives

• Ceftolozane-tazobactam: Approved for complicated intra-abdominal infections (with metronidazole), valuable for ESBL-producing Enterobacterales and MDR P. aeruginosa to preserve carbapenems 6, 7
• Ceftazidime-avibactam: Active against carbapenem-resistant Gram-negative bacteria, included in WHO Essential Medicines List under "reserve" category 6
• Meropenem-vaborbactam: Carbapenem-β-lactamase inhibitor combination for resistant Gram-negative infections 7, 5

Novel Fluoroquinolones

Delafloxacin

• Novel fluoroquinolone with 16-fold greater activity than moxifloxacin against Gram-positive and fastidious Gram-negative pathogens 6
• Retained activity against resistant phenotypes: penicillin/macrolide/multidrug-resistant S. pneumoniae, β-lactamase-producing Haemophilus species, and MRSA 6

Nemonoxacin

• Non-fluorinated quinolone showing comparable clinical and microbiological cure rates to levofloxacin in Phase 3 CAP study 6

Clinical Algorithm for Selection

For carbapenem-resistant Gram-negative infections:

• First-line: Consider ceftazidime-avibactam, meropenem-vaborbactam, or imipenem-cilastatin-relebactam based on susceptibility 6
• For metallo-β-lactamase producers: Aztreonam plus ceftazidime-avibactam combination 9
• Last resort: Cefiderocol (with mortality monitoring) or polymyxins 9, 1

For ESBL-producing Enterobacterales:

• Carbapenem-sparing options: Ceftolozane-tazobactam (with metronidazole for intra-abdominal infections) 6
• Alternative: Aminoglycosides for short-duration therapy in non-septic shock patients 9

For community-acquired bacterial pneumonia:

• Novel options: Lefamulin, omadacycline (both with mortality monitoring requirements) 6, 2
• For resistant pathogens: Delafloxacin, ceftaroline 6

Critical stewardship principle: Reserve new antibiotics (particularly those on WHO Essential Medicines "reserve" list) for severe infections meeting sepsis-3 criteria and documented resistant pathogens to prevent further resistance development 6