Thank you, everybody. So regard VAP, reducing antibiotic treatment duration for ventilator-associated pneumonia. I have nothing to disclose, and this involves six hospitals, one in Nepal, two in Singapore, and three in Thailand. And Oxford University is the study sponsor, as well as Moroo. And the funding is from Medical Research Council UK and National Medical Research Council Singapore. So a lot of good people are involved in this research. Moin is the research fellow and infectious disease specialist who put all these things together. So I'll try to cover a little bit about background research, methodology, results, discussion and conclusion, introduction. So VAP, ventilator-associated pneumonia, is very common in ICU. And it's one of the main drivers of antibiotic prescription. So quite often we start with clinical suspicions, and you see clinical diagnosis is overly sensitive, poorly specific, and costly. Sources are not identified initially, and quite often it's wrongly diagnosed. Microbiology is very important, but it's time-consuming. And quite often we cannot differentiate between colonizers versus pathogens. And so empiric antibiotics, broad-spectrum antibiotics we tend to use. Antibiotic stewardship is important, but usually it is not available in developing countries. And it is important in the sense of reducing inappropriate antibiotic choice use and inappropriate durations. So what do we know? This is the most recent study, systemic review and meta-analysis of randomized control trials in comparing short versus long-course antibiotic therapy in ventilator-associated pneumonia. This was done by Dangmuri et al. And published in eClinical Medicine in April 2023. They looked at five different studies after screening for more than 300 trial studies. And three of them are from France. One from the United States. And one from Tunisia. So in this meta-analysis, there is no significant differences between primary outcome and secondary outcome. Primary outcome in the sense recurrence and relapse of pneumonia. Secondary outcome, mortality, ICU stay, and ventilator days. So in these studies, actually, there's no mortality difference. You can see arbitrary durations not catered to clinical response. And there's a small trend towards increased recurrence in non-fermenting gram-negatives. And it is exclusively done in high-income settings. And there is no income as such inclusion of culture-negative path. And you can see here in this first plot, all these studies cross one at 95% confidence interval. Even in VAP, due to non-fermenting bacillus and gram-negatives, there's no difference. So our methodology regard VAP as a pragmatic, multicenter, non-inferior, individual randomized controlled trial. So it starts with screening. And we take consent mainly from the patient's relatives. And once the patient is fit for antibiotic stopping criteria, very simple criteria. No fever for 48 hours or more. And patient is hemodynamically stable without any use of inotropes or vasopressors. And we randomize the patient. And we stop antibiotic as early as three days if it's culture-negative. And in culture-positive cases, as early as five days in short course antibiotic therapy. But as in long course, we give at least eight days. So we try to give culturally-directed antibiotic choice and individualized duration in terms of short or long course. And primary outcome, 60-day mortality of pneumonia, 60-day mortality or pneumonia recurrence. Secondary outcome, length of hospital stay, ICU stay. Similarly, these carbapenem resistant cases. And this is spread on 39 ICUs in six hospitals. Two in Nepal, two ICUs. And eight in Singapore in two hospitals. And rest in Thailand in three hospitals. So enrollment started May 25, 2018 to December 16, 2022. So we screened about 11,000 patients. And about 10,000 patients are excluded. And most of them didn't meet the criteria. About 2,200, 22 made exclusion criteria. Out of that, about 1,000 had concurrent infections. Some of them had SOPA score more than 11. And 403 patients were immunocompromised. And 203 had already received antibiotics. So a lot of patients didn't meet the criteria. And out of that, 461 patients were randomly assigned in short-term, 232. And long-term, 229. So one patient was excluded from short-term. Altogether, 231 in short course. And 229 in usual care group. So baseline characteristics, you can see. Age is 64 years average. And 42% female. Not that much difference between the two groups. Most of the patients are referred from other hospitals. And most of the patients are from surgical ICU. And duration of intubation prior to VAP is about 15 days in short-term and 14 days in long-term. And SARS-CoV-2 score is also not that different between the two groups. And reason for intubation, mostly respiratory cause. And second most common is neurological cause. And infection severity on enrollment, like SOPA score, mean heart rate, and SbO2, FiO2 ratio is not that different. So isolated bacteria for index episodes of VAP. It's very interesting. 94% are gram-negative. And only 4% gram-positive and 2% others. Out of gram-negatives, 53% are non-fermenters. And 41% are intra-bacterials. And then you see there's 28% carapenem resistance. And this in non-fermenters. And about 4% in intra-bacterials. So altogether there are 51% resistant. 34% carapenem, and 17% cephalosporin. Duration of antibiotic received. You see in short-term, it's six days average. Into quarter range, five to seven days. In long-term, 14 days. And dotted line represents the average, this thing. Duration of antibiotic therapy. And primary outcome, 60-day mortality or recurrence. In both groups, comparing short course versus long course, there is no difference in this Kaplan-Meier curve. So primary outcome, if you see combined mortality recurrence in both intention to treat and for protocol analysis, it's similar. And there's a 3% difference, you can see. Minus 3% as I said, and minus 2% in both analysis. So it favors short course at absolute risk difference of 12%. You can see here. And this M2, or at 95% confidence ratio, this is less than 12% absolute risk difference, favoring short course. And it did not satisfy superiority because although point estimate is less than zero, but it causes the confidence interval of one. So secondary outcome is very interesting. You can see median duration of antibiotic is significantly different. Minus 5.2 days. Similarly, side effects is 30% difference. 8% in short arm and usually cure long arm is 38%. And both are statistically highly significant. And mean duration of mechanical ventilation during admission, mean duration of intensive care unit admission. Similarly, secondary outcomes, mean duration of hospital stay, readmission rate, pneumonia recurrence, and bloodstream infection as well as carotene resistance bacteria, not that different between the two. So among the secondary income, sorry, secondary outcome, AKI is the most common, most common side effect. You see, 35% usually cure long arm, long course group. So the antibiotic side effect in terms of liver injuries, diarrhea, allergies, not that different. But AKI is significantly different. And both are statistically significant. Discussion. So individualized short course antibiotic duration for ventilator-associated pneumonia based on simple clinical criteria is non-inferior to usual care. This can be used in developing country setting, low-income setting as well. So the strength of this study is first to, to our knowledge, is first to use clinical response to determine antibiotic duration in high-stake patient population. P dominantly in low, middle-income setting. And there is no increase recurrence of subgroup analysis of 218 episodes of non-fermenting gram-negatives. And it is generalizable given the diverse resource setting. And the limitation is usually care duration is longer than recommended guidelines. The CDC recommends only seven to eight days. But in practice, it's usually 14, 15 days or more. And majority of patients enrolled are 81% are from Thailand. So in conclusion, it's the first RCT conducted in hospital across low-middle-income countries. Carbapenem resistant gram-negative bacilli constitute 34%. And it's a major driver of antibiotics. And most commonly used antibiotics, polystyrene, polymyxin, beta-lactam, including carbapenem, aminoglycosides. And they are the cause of frequent AKI. It's non-inferior at less than 12% absolute risk. However, there is no difference in outcome. But short course has less side effects, less antibiotics used, definitely low cost. And the risk of antimicrobial resistance is also lower. So this is the article published just yesterday in Lancet Respiratory. Individualized short course antibiotic treatment versus usual long course treatment for ventilator-associated pneumonia. We got VAP, our trademark. So multi-center, individually randomized, open-level non-inferiority trial. So just yesterday, it came out in Lancet Respiratory Medicine. Thank you all. And thanks also goes to all the investigators from hospitals across Nepal, Thailand, and Singapore, especially to Ben Cooper from Oxford University. And thank you all from regard VAP family to all of you. Thank you.

ventilator-associated pneumonia

antibiotic treatment duration

antimicrobial resistance

personalized treatment

Lancet Respiratory Medicine