Doripenem and Ventilator-Associated Pneumonia (VAP)
Doripenem does not cause ventilator-associated pneumonia (VAP); rather, it is an antibiotic used to treat VAP and other serious bacterial infections. Doripenem is a carbapenem antibiotic with broad-spectrum activity against gram-negative and gram-positive bacteria.
Doripenem's Role in VAP Treatment
Efficacy in VAP Treatment
- Doripenem has been studied specifically for VAP treatment in clinical trials
- In a multicenter, randomized study, doripenem (500 mg every 8 hours via 4-hour IV infusion) was found to be noninferior to imipenem in treating VAP 1
- Clinical cure rates were 68.3% for doripenem and 64.2% for imipenem in clinically evaluable patients 1
Concerns with Shortened Treatment Duration
- A significant concern emerged in a 2012 study that compared a 7-day course of doripenem to a 10-day course of imipenem-cilastatin for VAP 2
- This study was stopped prematurely because:
- Clinical cure rates were numerically lower in the doripenem arm (45.6% vs 56.8%)
- 28-day mortality was higher in the doripenem arm (21.5% vs 14.8%)
- For P. aeruginosa VAP specifically, mortality was significantly higher with doripenem (35.3% vs 0%) 2
- This suggests that shortened treatment courses (7 days) with doripenem may be inadequate for VAP treatment
Doripenem's Place in Treatment Guidelines
According to the 2016 IDSA/ATS guidelines for managing hospital-acquired and ventilator-associated pneumonia:
- Doripenem is considered part of the antipseudomonal carbapenem class (Group 2 carbapenems) along with imipenem and meropenem 3, 4
- For patients with suspected VAP, coverage for S. aureus, Pseudomonas aeruginosa, and other gram-negative bacilli should be included in all empiric regimens 3
- When empiric treatment for multidrug-resistant organisms is indicated, an antipseudomonal carbapenem like doripenem may be used as part of the regimen 3
Comparative Efficacy with Other Carbapenems
- A 2019 study comparing doripenem to meropenem for HAP and VAP found no significant difference in 30-day mortality between the two treatments 5
- However, patients with hematological diseases showed poorer outcomes with doripenem compared to meropenem 5
- Against Pseudomonas aeruginosa specifically, doripenem showed better microbiological cure rates (65.0%) compared to imipenem (37.5%) in one study 1
- Doripenem demonstrated a lower propensity for developing resistance in P. aeruginosa compared to imipenem 1, 6
Clinical Considerations for Doripenem Use
Dosing and Administration
- Standard dosing: 500 mg every 8 hours via intravenous infusion
- Extended infusion (4-hour) is recommended for VAP to optimize pharmacodynamics 1
- Treatment duration should be at least 7-14 days for VAP, with evidence suggesting that shorter courses may lead to worse outcomes 2
Antimicrobial Stewardship Considerations
- According to the ESCMID guidelines, when treating severe infections caused by carbapenem-resistant Pseudomonas aeruginosa, combination therapy may be considered 3
- For non-severe infections, monotherapy with an in vitro active drug may be appropriate 3
Important Caveats
- Doripenem should not be used in shortened treatment courses (7 days) for VAP as this has been associated with worse outcomes 2
- For patients with hematological malignancies, alternative treatments may be preferable 5
- Local resistance patterns should always guide empiric therapy choices
In conclusion, doripenem is an effective treatment option for VAP but does not cause VAP. When using doripenem for VAP treatment, adequate duration (>7 days) should be ensured, and patient-specific factors like the presence of hematological disease should be considered.