Anti-Pseudomonas Classes of Drugs with Examples
The main classes of antibiotics with activity against Pseudomonas aeruginosa include antipseudomonal β-lactams (penicillins, cephalosporins, carbapenems, monobactams), fluoroquinolones, aminoglycosides, and polymyxins. Each class has specific agents that demonstrate reliable activity against this challenging pathogen.
Antipseudomonal β-lactams
Penicillins
- Piperacillin-tazobactam (4.5g IV q6h) is a preferred first-line antipseudomonal penicillin for susceptible P. aeruginosa infections 1
- Other antipseudomonal penicillins include ticarcillin (no longer widely available) and ureidopenicillins, which have better activity against Enterococcus, Klebsiella, and P. aeruginosa 2
- Piperacillin-tazobactam has shown comparable efficacy to ceftazidime and carbapenems in the treatment of P. aeruginosa bloodstream infections 3
Cephalosporins
- Ceftazidime (2g IV q8h) is an important antipseudomonal third-generation cephalosporin 1, 4
- Cefepime (2g IV q8-12h) is a fourth-generation cephalosporin with potent antipseudomonal activity 1
- Newer cephalosporin combinations include ceftolozane-tazobactam (1.5-3g IV q8h) and ceftazidime-avibactam (2.5g IV q8h), which are effective against many resistant P. aeruginosa strains 1, 5
Carbapenems
- Imipenem (500mg IV q6h), meropenem (1g IV q8h), and doripenem are carbapenems with activity against P. aeruginosa 6, 1
- Newer carbapenem combinations like imipenem-cilastatin-relebactam (1.25g IV q6h) provide activity against some resistant strains 1
- Ertapenem lacks reliable antipseudomonal activity 6
Monobactams
- Aztreonam (2g IV q8h) is the only available monobactam with antipseudomonal activity 6
- It can be used in patients with severe β-lactam allergies as it has a different structure 6
Fluoroquinolones
- Ciprofloxacin (400mg IV q8h) has excellent antipseudomonal activity 1, 6
- Levofloxacin (750mg IV/PO qd) also has activity against P. aeruginosa but is generally less potent than ciprofloxacin 6
Aminoglycosides
- Amikacin (15-20mg/kg IV q24h), gentamicin (5-7mg/kg IV q24h), and tobramycin (5-7mg/kg IV q24h) all have activity against P. aeruginosa 6
- Aminoglycosides are often used in combination with β-lactams for synergistic effect but are not recommended as monotherapy except for uncomplicated urinary tract infections 1
- Drug levels and dosage adjustments are required due to potential nephrotoxicity and ototoxicity 6
Polymyxins
- Colistin (polymyxin E) and polymyxin B are used for multidrug-resistant P. aeruginosa infections 6
- Colistin dosing: 5mg/kg IV loading dose, followed by 2.5mg maintenance dose based on renal function 6, 1
- These agents should be reserved for settings with high prevalence of multidrug resistance due to toxicity concerns 6
Treatment Considerations
Combination Therapy
- For severe P. aeruginosa infections, particularly in critically ill patients, combination therapy may be considered 1, 7
- Common combinations include an antipseudomonal β-lactam plus either a fluoroquinolone or an aminoglycoside 1
- Combination therapy may help prevent resistance development in difficult-to-treat infections 7
Resistance Patterns
- Local resistance patterns should guide empiric therapy choices 6
- P. aeruginosa can develop resistance through multiple mechanisms, including production of β-lactamases, efflux pumps, and altered membrane permeability 5
- Carbapenem use has been associated with higher rates of subsequent resistant P. aeruginosa compared to ceftazidime or piperacillin-tazobactam 3
Special Considerations
- For patients who have received recent antibiotic therapy (within 90 days), consider using an alternative class to prevent resistance development 1
- Treatment duration typically ranges from 7-10 days for most infections, but 10-14 days for P. aeruginosa pneumonia or bloodstream infections 1