Patients with  Ventilator-Associated  Pneumonia  with  Short-Course  Antimicrobial  Treatment

Attapon  Cheepsattayakorn^1,2,3,4*, Ruangrong  Cheepsattayakorn⁵, Porntep  Siriwanarangsun²

1. Faculty  of  Medicine  Vajira  Hospital, Navamindradhiraj  University, Bangkok, Thailand.

2. Faculty  of  Medicine, Western  University, Pathumtani  Province, Thailand.

3. 10th  Zonal  Tuberculosis  and  Chest  Disease  Center, Chiang  Mai, Thailand.

4. Department  of  Disease  Control, Ministry  of  Public  Health, Thailand.

5. Department  of  Pathology, Faculty  of  Medicine, Chiang  Mai  University, Chiang  Mai, Thailand.

                                             
Correspondence to: Attapon  Cheepsattayakorn, 10th  Zonal  Tuberculosis  and  Chest  Disease  Center, 143  Sridornchai  Road  Changklan  Muang  Chiang  Mai  50100  Thailand.

Copyright

© 2024 Attapon  Cheepsattayakorn. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Received: 30 Nov 2024

Published: 21 Dec 2024

Pneumonia, the  second most prevalent nosocomial infection among patients in critical care, affects almost 27% of all critically ill patients [1]. An estimated 86% of cases of nosocomial pneumonia are linked to mechanical ventilation and are referred to as ventilator-associated pneumonia (VAP) [1]. Due to instrumentation of the airway during mechanical ventilation, which lasts for >48 h, the architecture of the oropharynx and trachea may be affected. This may allow secretions and flora from the upper respiratory tract to infiltrate the lower respiratory system and affect the parenchyma of the lung which causes VAP [2]. Antimicrobial resistance is common in critically ill patients, hence prudent antibiotic use with appropriate coverage for the organisms targeted is vital [3]. VAP-related mortality has been estimated to be about 6% with excess risk estimates ranging between 0% and 50% [4-6].  Ventilator-associated pneumonia (VAP) is associated with increased mortality, prolonged hospitalization, excessive antimicrobial use and, consequently, increased antimicrobial resistance (Figure 1) [7].

The current literature on the optimal duration of antibiotic therapy for VAP is limited and restricted to the findings of a few clinical trials. Current guidelines for the length of management of VAP recommend a short-duration treatment of 7–8 days [8, 9] which was largely based on the evidence provided within the previous two meta-analyses [10, 11]. Meta-analysis conducted  by Pugh et al. was published in 2015 and reported that short duration was non-inferior to the long duration for mortality and recurrence [12, 13]. Nevertheless, within the subgroup of patients with VAP due to non-fermenting Gram-negative bacilli (NF-GNB), a higher rate of recurrence of pneumonia in the short-duration therapy arm  was  found. Augmenting this concern, the results from a recently published randomized controlled trial (RCT), named  “ iDIAPASON trial ”, conducted  by Bougle et al. failed to demonstrate the non-inferiority of short-duration antimicrobial therapy in patients with VAP due to Pseudomonas aeruginosa because of a higher risk of recurrence of pneumonia with the shorter regimen. Nevertheless, this trial did not have a sample size large enough to make a definitive conclusion.  A  recent  study  was  conducted  between May 25, 2018, and Dec 16, 2022, 461 patients were enrolled and randomly assigned to the short-course treatment group (n=232) or the usual care group (n=229) [7]. After excluding one withdrawal (231 in the short-course group, and 229 in the usual care group), median age was 64 years (IQR 51-74) and 181 (39%) participants were female. 460 were included in the intention-to-treat analysis  and  in  the  per-protocol  population; 435 participants received the allocated treatment and fulfilled eligibility criteria. Median antimicrobial treatment duration for the index episodes of VAP was 6 days (IQR : 5-7) in the short-course group and 14 days (10-21) in the usual care group. In  comparison with 100 (44%) of 229 in the usual care group (risk difference -3% [one-sided 95% CI -∞ to 5%]), compared  with  95 (41%) of 231 participants in the short-course group met the primary outcome. The  study  results were similar in the per-protocol population. In  analyses, although superiority compared with usual care was not established, non-inferiority of short-course antibiotic treatment was met [7].

  In  conclusion, in light of the previous uncertainty and the availability of newer data, there is a need to re-evaluate systematically the optimal duration of antibiotic therapy for VAP, especially due to NF-GNB. VAP is associated with excessive  antimicrobial  use, increased  antimicrobial  resistance, prolonged hospitalization, and  increased  mortality.  Individualized, short-course antimicrobial treatment for VAP could help to reduce the burden of side-effects and the risk of antibiotic resistance in high-resource and resource-limited settings (Figure  2) [13, 14].

Figure 1 : Demonstrating  percentage  of  patients  with  VAP  died  or  experienced  pneumonia  recurrence  at  day  60 [7].

Figure 2 :  Demonstrating  absolute  risk  difference (one-side  95 % CI)  of  short-course  antimicrobial  treatment  strategy  compared  with  usual  course  antimicrobial  treatment  strategy [13, 14].

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DOI : 10.1016/S2213-2600(23)00418-6

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