treat pseudomonas HAP with 14 days antibiotics

This patient has developed ventilator-associated pneumonia (VAP) with P aeruginosa, a nonfermenting gram-negative bacillus. Of the available choices, continuing piperacillin-tazobactam for a 14-day course.

Nonfermenting gram-negative bacilli, such as P aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia, are important nosocomial pathogens contributing significantly to morbidity and mortality. They often are also multidrug resistant and require special attention to antibiotic treatment choice and duration, often including consultation with the hospital’s specific antibiogram.

Piperacillin-tazobactam is a combination medication containing the antibiotic piperacillin and the β-lactamase inhibitor tazobactam with activity against many gram-positive and gram-negative bacteria, including P aeruginosa. Two studies have now demonstrated worse clinical outcomes, including increased microbiological recurrence of pseudomonal infection and VAP, and potentially higher mortality rates in patients treated with 7 days of antipseudomonal antibiotics compared with 14 days. In the iDIAPASON study, 7 days of antipseudomonal antibiotics failed to demonstrate noninferiority to 14-day treatment courses. In this patient who has developed VAP from P aeruginosa, treatment with appropriate antibiotics should continue for 14 days, and a 7-day course would be inadequate.

Gram-negative bacteria acquiring resistance to broad-spectrum penicillins and cephalosporins through extended-spectrum β-lactamases should always be a concern. However, this patient appears to be improving with treatment, with resolved fevers and shock. Furthermore, although the carbapenem class of antibiotics is the treatment for VAP caused by extended-spectrum β-lactamase-producing gram-negative rods, ertapenem does not have adequate coverage of P aeruginosa and would be an inappropriate antibiotic choice in this patient with documented Pseudomonas VAP.

Past observational studies raised concern that piperacillin-tazobactam was associated with the development and progression of acute kidney injury, especially when used in combination with vancomycin. However, the published randomized ACORN trial (ACORN trial showed zosyn does not cause AKI) demonstrated that piperacillin-tazobactam does not cause or propagate acute kidney injury any more than does cefepime, even when combined with vancomycin treatment.1234567

Footnotes

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  2. Bouglé A, Tuffet S, Federici L, et al; iDIAPASON Trial Investigators. Comparison of 8 versus 15 days of antibiotic therapy for Pseudomonas aeruginosa ventilator-associated pneumonia in adults: a randomized, controlled, open-label trial. Intensive Care Med. 2022;48(7):841-849. PubMed ↩

  3. Chastre J, Wolff M, Fagon JY, et al; PneumA Trial Group. Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. JAMA. 2003;290(19):2588-2598. PubMed ↩

  4. Kollef MH, Chastre J, Clavel M, et al. A randomized trial of 7-day doripenem versus 10-day imipenem-cilastatin for ventilator-associated pneumonia. Crit Care. 2012;16(6):R218. PubMed ↩

  5. Langsjoen J, Brady C, Obenauf E, et al. Nasal screening is useful in excluding methicillin-resistant Staphylococcus aureus in ventilator-associated pneumonia. Am J Infect Control. 2014;42(9):1014-1015. PubMed ↩

  6. Melling PA, Noto MJ, Rice TW, et al. Time to first culture positivity among critically ill adults with methicillin-resistant Staphylococcus aureus growth in respiratory or blood cultures. Ann Pharmacother. 2020;54(2):131-137. PubMed ↩

  7. Qian ET, Casey JD, Wright A, et al; Vanderbilt Center for Learning Healthcare and the Pragmatic Critical Care Research Group. Cefepime vs piperacillin-tazobactam in adults hospitalized with acute infection: the ACORN randomized clinical trial. JAMA. 2023;330(16):1557-1567. PubMed

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