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How long should antibiotics be given for VAP caused by non-fermenting gram-negative bacteria?

Updated: Apr 26, 2023


Duration of antibiotics in VAP

Ventilator-associated pneumonia (VAP) frequently impacts patients in the intensive care unit (ICU) and contributes to unfavorable outcomes. VAP occurs between 2 and 16 times per 1000 ventilator days. This is linked to increased mortality and morbidity rates, prolonged hospital stays, and greater use of healthcare resources [1].

Guidelines exist for the treatment of VAP. However, the optimal duration of antibiotic therapy for VAP caused by non-fermenting Gram-negative Bacilli (NF-GNB) is uncertain.


Definition of Ventilator-associated Pneumonia

Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are both forms of hospital-acquired respiratory infections. HAP refers to any pneumonia that develops 48 hours or more after admission to a hospital or any other healthcare facility, while VAP is a pneumonia that develops 48 hours or more after endotracheal intubation and mechanical ventilation.


What Are the Non-fermenting Gram-negative Bacilli?

NF-GNB are a group of bacteria that cause severe and sometimes fatal infections in humans. Among the main microorganisms that fall into this category are Pseudomonas aeruginosa, Acinetobacter baumannii, Burkholderia cepacia, Burkholderia pseudomallei, Stenotrophomonas, Alcaligenes, and Moraxella. Among these organisms, Pseudomonas, acinetobacter and stenotrophomonas are the most likely encountered organisms in the ICU.


Unlike Enterobacteriaceae, these bacteria are aerobic and non-sporulating, and they lack the ability to ferment sugars, instead using the oxidative pathway for energy generation.


Diagnosis of VAP

The diagnosis of ventilator-associated pneumonia (VAP) requires evidence of inflammation, pulmonary dysfunction, and radiographic evidence. Evidence of inflammation can be detected by leukocytosis, left-shift, neutrophil/lymphocyte ratio, fever, purulent secretions, hypothermia, or septic shock. A decline in oxygenation, as evidenced by the requirement for higher FiO2 and/or PEEP, is a sign of respiratory dysfunction.


Radiographic evidence can be obtained through a chest X-ray or CT scan, although the former is less specific, and the latter can be logistically challenging. The presence of infiltrates on a CT scan is highly sensitive for pneumonia, but the specificity varies depending on the particular findings.


Short Course of Antibiotic is Associated with Higher Recurrence of VAP caused by NF-GNB (2015)

A previous metanalysis that was published in 2015 included six randomized controlled trials and involved 1088 participants with VAP. A short course of antibiotics (seven to eight days) was compared to a longer course (10 to 15 days). This increased antibiotic-free days and reduced the recurrence of VAP due to multi-resistant organisms. It did not have any negative effect on mortality or other recurrence outcomes.

Recurrence of VAP due to NF-GNB was greater after short-course therapy. However, mortality outcomes were not significantly different. A major limitation was that only two randomized controlled trials (RCTs) were included in the meta-analysis. These trials studied patients with ventilator-associated pneumonia due to nonfermenting Gram-negative bacteria [2].


A Recent RCT on Duration of Antibiotics in Pseudomonas VAP (2022)

This study compared the effectiveness of two different antibiotic treatments for ventilator-associated pneumonia caused by Pseudomonas aeruginosa.


The treatments consisted of an 8-day regimen and a 15-day regimen. The trial was randomized, open-labeled, multicenter, and non-inferiority. It did not show that short-duration therapy was non-inferior. However, the 8-day group had a higher recurrence rate.


Both groups had similar median days of mechanical ventilation, ICU stay, and number of extra pulmonary infections. There was also a similar acquisition of multidrug-resistant pathogens during ICU stay. The study had limited interpretation due to its lack of power and slow inclusion rate. However, the increased rate of relapse did not affect clinical outcomes, such as ICU length of stay and mortality rates [3].


A More Recent Meta-analysis on Duration of Antibiotics in VAP caused by NF-GNB (2023)

This meta-analysis aimed to compare the effectiveness of different duration of antibiotic therapies for ventilator-associated pneumonia (VAP). Short-course therapy was ≤8 days, while long-course therapy was ≥10-15 days. Specifically, the study focused on VAP caused by non-fermenting Gram-negative bacilli (NF-GNB).

It included five relevant studies with a total of 1069 patients. The primary outcome was rates of VAP recurrence and relapse. Secondary outcomes included 28-day mortality, mechanical ventilation duration, number of extra-pulmonary infections, and length of ICU stay.


The analysis showed no significant difference in VAP recurrence and relapse rates between short- and long-course antibiotic therapy. This includes those caused by non-fermenting Gram-negative bacilli. There was also no significant difference in 28-day mortality, mechanical ventilation duration, number of extra-pulmonary infections, and length of ICU stay. However, short-course therapy resulted in a significant increase in the number of antibiotic-free days [4].

Relapse of VAP due to non-fermenting Gram-negative bacilli
Relapse of VAP due to non-fermenting Gram-negative bacilli

The study found that decreased antibiotic exposure did not cause an increase in recurrence or relapses of VAP. This was also true for VAP caused by NF-GNB and late onset VAP.

How long would you use antibiotics in pseudomonas VAP?

  • 7 days

  • 10-14 days

  • It depends on clinical improvement and procalcitonin.

  • I have no idea!


What Do I DO?

From the mentioned study, one could argue that a brief course of antibiotics may be suitable for all types of VAP, including those caused by NF-GNB. However, the approach I follow is based on a 2018 study, which demonstrated that for patients with VAP caused by NF-GNB, antibiotics can be discontinued if the clinical pulmonary infection score (CPIS) is ≤ 6 and spot serum PCT is < 0.5 ng/ml on day 8. The study indicated that utilizing CPIS and procalcitonin effectively and safely guides the cessation of antibiotic treatment without increasing the relapse rate [5].

REFERENCES:

  1. Torres, Antoni, et al. "International ERS/ESICM/ESCMID/ALAT guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia: guidelines for the management of hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) of the European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Asociación Latinoamericana del Tórax (ALAT)." European Respiratory Journal 50.3 (2017). Link

  2. Pugh R, Grant C, Cooke RP, Dempsey G. Short-course versus prolonged-course antibiotic therapy for hospital-acquired pneumonia in critically ill adults. Cochrane Database Syst Rev. 2015 Aug 24;2015(8):CD007577. doi: 10.1002/14651858.CD007577.pub3. PMID: 26301604; PMCID: PMC7025798. Link

  3. Bouglé A, 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 Jul;48(7):841-849. doi: 10.1007/s00134-022-06690-5. Epub 2022 May 13. Erratum in: Intensive Care Med. 2022 Jun 21;: PMID: 35552788. Link

  4. Daghmouri MA, Dudoignon E, Chaouch MA, Baekgaard J, Bougle A, Leone M, Deniau B, Depret F. Comparison of a short versus long-course antibiotic therapy for ventilator-associated pneumonia: a systematic review and meta-analysis of randomized controlled trials. EClinicalMedicine. 2023 Mar 1;58:101880. doi: 10.1016/j.eclinm.2023.101880. PMID: 36911269; PMCID: PMC9995933. Link

  5. Wongsurakiat P, Tulatamakit S. Clinical pulmonary infection score and a spot serum procalcitonin level to guide discontinuation of antibiotics in ventilator-associated pneumonia: a study in a single institution with high prevalence of nonfermentative gram-negative bacilli infection. Ther Adv Respir Dis. 2018 Jan-Dec;12:1753466618760134. doi: 10.1177/1753466618760134. PMID: 29506460; PMCID: PMC5941665. Link







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