What is the antibiotic of choice for a patient with suspected Pseudomonas infection, particularly after recent hip replacement surgery?

Antibiotic of Choice for Suspected Pseudomonas Infection After Hip Replacement

For suspected Pseudomonas infection following hip replacement surgery, initiate an antipseudomonal β-lactam—specifically piperacillin-tazobactam 4.5g IV every 6 hours, ceftazidime 2g IV every 8 hours, cefepime 2g IV every 8 hours, or meropenem 1g IV every 8 hours—and add a second antipseudomonal agent (aminoglycoside or ciprofloxacin) for severe infections or sepsis. 1, 2

First-Line Antipseudomonal β-Lactams

The WHO and major infectious disease societies universally recommend these agents as first-line therapy for Pseudomonas aeruginosa infections 1:

• Piperacillin-tazobactam: 4.5g IV every 6 hours (preferred for broad coverage including anaerobes in surgical site infections) 1, 2
• Ceftazidime: 2g IV every 8 hours 1, 2
• Cefepime: 2g IV every 8 hours 1, 2
• Meropenem: 1g IV every 8 hours (superior outcomes in severe infections) 1, 2

For post-surgical orthopedic infections, piperacillin-tazobactam is often preferred because it provides both antipseudomonal coverage and activity against staphylococci (including MSSA) commonly encountered in prosthetic joint infections. 1, 2

When to Add Combination Therapy

Add a second antipseudomonal agent from a different class in these situations 1, 2:

• Critically ill patients or septic shock
• Prior IV antibiotic use within 90 days
• Documented Pseudomonas on Gram stain
• High local prevalence of multidrug-resistant Pseudomonas (>10-20% resistance)
• Structural bone/joint involvement with hardware

Second agent options 2:

• Tobramycin: 5-7 mg/kg IV daily (preferred aminoglycoside; requires therapeutic drug monitoring)
• Amikacin: 15-20 mg/kg IV daily (alternative aminoglycoside)
• Ciprofloxacin: 400mg IV every 8 hours (or 750mg PO twice daily for less severe infections)

Critical Pitfalls to Avoid

Never use these antibiotics for Pseudomonas coverage 1, 2:

• Ceftriaxone (no antipseudomonal activity)
• Cefazolin (no antipseudomonal activity)
• Ampicillin-sulbactam (no antipseudomonal activity)
• Ertapenem (explicitly lacks antipseudomonal coverage despite being a carbapenem)
• Levofloxacin monotherapy (inferior to ciprofloxacin for Pseudomonas; requires combination therapy) 3

Avoid monotherapy in severe infections: Monotherapy leads to resistance emergence in 30-50% of patients with serious Pseudomonas infections. 2, 4

Ensure adequate dosing: Underdosing is a common cause of treatment failure. Use maximum recommended doses, especially for severe infections. 2

Surgical Site Infection Context

For incisional surgical site infections after orthopedic surgery (trunk/extremity), the WHO recommends coverage primarily targeting staphylococci (oxacillin, nafcillin, cefazolin, or vancomycin if MRSA risk). 1 However, if Pseudomonas is specifically suspected (e.g., prolonged hospitalization, prior antibiotics, immunosuppression), escalate immediately to antipseudomonal coverage as outlined above.

For healthcare-associated infections with resistant flora risk, the IDSA emphasizes that local nosocomial resistance patterns should dictate empirical treatment, and adequate empirical therapy is critical for reducing mortality. 1

Treatment Duration and De-escalation

• Standard duration: 7-14 days depending on infection severity and source control 2
• De-escalate to monotherapy once susceptibility results confirm the organism is susceptible and the patient is clinically improving 2, 4
• Longer courses may be needed for osteomyelitis (4-6 weeks) or if bacteremia persists >72 hours after source control 1

Monitoring Requirements

• Aminoglycoside levels: Target tobramycin peak 25-35 mg/mL with once-daily dosing 2
• Renal function and auditory function: Monitor for nephrotoxicity and ototoxicity 2
• Clinical response: Obtain repeat cultures if no improvement by 48-72 hours 1

Special Considerations for Prosthetic Joint Infections

Hardware removal is often necessary for cure, particularly if infection persists despite >72 hours of appropriate antibiotics, or if suppurative thrombophlebitis or endocarditis develops. 1 Antibiotic therapy alone rarely eradicates Pseudomonas from prosthetic material due to biofilm formation. 5