Shortened Antibiotic Therapy for Ventilator-Associated Pneumonia

(DATE Trial)

Overseen By Jonathan Meizoso, MD, MSPH

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Miami

Must not be taking: Immunosuppressives

Disqualifiers: Age < 18, Pregnancy, Septic shock, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4-7 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if shorter courses of antibiotics can effectively treat ventilator-associated pneumonia (VAP) without increasing patient risks. Researchers compare two groups: one receiving 7 days of antibiotics and another receiving just 4 days. The goal is to reduce antibiotic side effects while ensuring safety. This trial suits surgical patients who developed VAP within 2–7 days of being on a ventilator and have been in the hospital for under 10 days at diagnosis. As a Phase 4 trial, the treatment is already FDA-approved and proven effective, and this research helps understand how it benefits more patients.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive medications or have been on antibiotics for more than 5 of the last 10 days, you may not be eligible to participate.

What is the safety track record for this treatment?

Research has shown that a shorter course of antibiotics can effectively treat ventilator-associated pneumonia (VAP) as well as longer treatments. One study found that patients on a shorter antibiotic course did not experience more recurrences of VAP. This suggests that a short course could be effective for many patients.

Additionally, shorter antibiotic courses significantly reduced side effects. In one study, only 8% of patients on a short course experienced side effects, compared to 38% on longer treatments. Fewer side effects can make the treatment easier for patients to manage.

However, some research has indicated that a shorter course might slightly increase the risk of pneumonia returning. Therefore, discussing the benefits and risks with a doctor before deciding is important. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the potential of shortened antibiotic therapy for ventilator-associated pneumonia (VAP) because it could significantly reduce the duration of treatment without compromising effectiveness. Unlike the standard approach, which often involves longer courses of antibiotics, this trial investigates whether just 4 days of antibiotic treatment can be as effective as the typical 7-day regimen. This shorter treatment could help minimize antibiotic exposure, thereby reducing the risk of antibiotic resistance and side effects. If successful, this protocol could transform how we manage early VAP, making treatments faster and potentially safer for patients.

What evidence suggests that this trial's treatments could be effective for ventilator-associated pneumonia?

This trial will compare two durations of antibiotic therapy for treating ventilator-associated pneumonia (VAP). Participants in one arm will receive 7 days of antibiotic therapy, while those in the other arm will receive 4 days. Research has shown that shorter antibiotic treatments can be as effective as longer ones for VAP. One study found that fewer days of antibiotics did not increase the risk of death or recurrence of pneumonia. Another study confirmed that shorter treatment did not lead to more cases of VAP returning. Importantly, using antibiotics for a shorter time also reduced side effects, dropping from 38% to 8% in that study. These findings suggest that a shorter antibiotic course can safely and effectively manage VAP. ^{2 6 7 8 9}

Who Is on the Research Team?

Jonathan Meizoso, MD, MSPH

Principal Investigator

University of Miami

Are You a Good Fit for This Trial?

This trial is for surgical patients with early ventilator-associated pneumonia (VAP) that occurred within 2-7 days of intubation, who haven't been in the hospital for more than 10 days at VAP diagnosis. Participants must be able to consent or have a representative do so. Excluded are those with septic shock, recent immunosuppressant use, legal incarceration, prior VAP this admission, certain resistant infections, extensive recent antibiotics use, imminent death prognosis, transfer from another facility after 72 hours+, and pregnant or breastfeeding women.

Inclusion Criteria

I am scheduled for or have had surgery.

I developed a lung infection within 2-7 days after being put on a breathing machine.

I or my legal representative can give consent for my participation.

Exclusion Criteria

I was hospitalized for more than 72 hours before being transferred.

I've been on antibiotics for more than 5 days recently.

I have septic shock and need more than one medication to maintain my blood pressure.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either 4 or 7 days of antibiotic therapy for early ventilator-associated pneumonia (VAP)

4-7 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of VAP recurrence and clinical improvement

Up to 30 days

Long-term Follow-up

Participants are monitored for hospital length of stay and in-hospital mortality

Up to 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Standard of Care Antibiotic Therapy

Trial Overview The study tests if shorter antibiotic treatment (4 days) is as safe and effective as the standard duration (7 days) for early ventilator-associated pneumonia. The goal is to minimize antibiotic-related side effects without compromising patient safety.

How Is the Trial Designed?

Group I: 4 Days of Antibiotics Group Experimental Treatment 1 Intervention

Participants will receive 4 days of antibiotic therapy administered as per the standard of care for the treatment of early ventilator associated pneumonia (VAP).

Group II: 7 Days of Antibiotics Group Active Control 1 Intervention

Participants will receive 7 days of antibiotic therapy administered as per the standard of care for the treatment of early ventilator associated pneumonia (VAP).

Standard of Care Antibiotic Therapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Standard Antibiotic Therapy for:

• Ventilator-associated pneumonia (VAP)
• Bacterial infections
• Respiratory tract infections

Approved in United States as Standard Antibiotic Therapy for:

• Ventilator-associated pneumonia (VAP)
• Bacterial infections
• Respiratory tract infections

Approved in Canada as Standard Antibiotic Therapy for:

• Ventilator-associated pneumonia (VAP)
• Bacterial infections
• Respiratory tract infections

Approved in Japan as Standard Antibiotic Therapy for:

• Ventilator-associated pneumonia (VAP)
• Bacterial infections
• Respiratory tract infections

Approved in China as Standard Antibiotic Therapy for:

• Ventilator-associated pneumonia (VAP)
• Bacterial infections
• Respiratory tract infections

Approved in Switzerland as Standard Antibiotic Therapy for:

• Ventilator-associated pneumonia (VAP)
• Bacterial infections
• Respiratory tract infections

Who Is Running the Clinical Trial?

University of Miami

Lead Sponsor

Trials

976

Recruited

423,000+

Published Research Related to This Trial

A review of nine trials indicates that short courses of antimicrobial treatment (≤10 days) for ventilator-associated pneumonia are as effective as longer courses (14-21 days) without negatively impacting patient outcomes such as mortality or ICU stay.

The evidence supports using short-course therapy for patients with ventilator-acquired pneumonia, particularly when the infection is not caused by nonfermenting Gram-negative bacilli, potentially leading to reduced antibiotic exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal duration of the antimicrobial treatment of ventilator-acquired pneumonia. Grammatikos, AP., Siempos, II., Michalopoulos, A., et al.[2008]

The REGARD-VAP trial is investigating whether a shorter course of antibiotics can effectively treat ventilator-associated pneumonia (VAP) without increasing the risk of death or pneumonia recurrence, involving 460 patients across ICUs in Nepal, Thailand, and Singapore.

Participants in the short-course treatment group may stop antibiotics as early as day 3 if cultures are negative, compared to at least 8 days for standard care, aiming to reduce antibiotic exposure while maintaining safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reducing antibiotic treatment duration for ventilator-associated pneumonia (REGARD-VAP): a trial protocol for a randomised clinical trial. Mo, Y., West, TE., MacLaren, G., et al.[2021]

Shorter antibiotic regimens for treating ventilator-associated pneumonia (VAP) lead to significantly more antibiotic-free days without negatively affecting patient mortality, based on recent randomized controlled trials.

While shorter treatments reduce the emergence of multidrug-resistant pathogens, they may result in higher relapse rates for infections caused by nonfermenting Gram-negative bacilli, highlighting the need for a comprehensive treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duration of therapy of ventilator-associated pneumonia. Dimopoulos, G., Matthaiou, DK.[2016]

Ventilator-associated pneumonia is a major cause of infections in intensive care units, leading to significant antibiotic use; invasive diagnostic methods can help accurately identify bacterial pneumonia and optimize antibiotic treatment.

An 8-day antibiotic regimen is suggested as a standard treatment for ventilator-associated pneumonia, but exceptions exist for certain high-risk patients, emphasizing the need to avoid unnecessary prolonged antibiotic use to prevent the development of multidrug-resistant bacteria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of quantitative cultures and reduced duration of antibiotic regimens for patients with ventilator-associated pneumonia to decrease resistance in the intensive care unit. Chastre, J., Luyt, CE., Combes, A., et al.[2007]

In a study of 156 critically ill patients with suspected ventilator-associated pneumonia (VAP), those treated with antipseudomonal penicillins plus beta-lactamase inhibitors had significantly lower in-hospital mortality rates, suggesting these antibiotics are effective for initial empiric therapy.

The study found no significant difference in outcomes between monotherapy and combination therapy, indicating that the choice of antibiotic regimen may not impact length of hospital stay or days free of antibiotics, but appropriate initial treatment is crucial for improving survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Variability in antibiotic prescribing patterns and outcomes in patients with clinically suspected ventilator-associated pneumonia. Fowler, RA., Flavin, KE., Barr, J., et al.[2022]

In a study of 111 ICU patients with ventilator-associated pneumonia (VAP), appropriate initial antibiotic therapy significantly reduced the length of ICU stay for survivors, averaging 12 days compared to 20 days for those with inappropriate therapy.

While not statistically significant, there was a trend towards lower hospital mortality in patients receiving appropriate initial antibiotics (47.3% vs 60.7%), suggesting that timely and effective antibiotic treatment may improve outcomes in VAP cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of appropriateness of initial antibiotic therapy on the outcome of ventilator-associated pneumonia. Dupont, H., Mentec, H., Sollet, JP., et al.[2022]

This systematic review analyzed 12 studies with 3571 participants and found no significant difference in all-cause mortality or clinical cure rates between monotherapy and combination therapy for treating ventilator-associated pneumonia (VAP), suggesting that effective monotherapy can be safely used.

Carbapenem antibiotics showed a statistically significant increase in clinical cure rates compared to non-carbapenem therapies, indicating that carbapenems may be a more effective option for treating VAP, although the overall quality of evidence was moderate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibiotics for ventilator-associated pneumonia. Arthur, LE., Kizor, RS., Selim, AG., et al.[2023]

Ventilator-associated pneumonia is a serious condition that can lead to high rates of illness and death in critically ill patients, highlighting the need for effective treatment strategies.

Using an initial aggressive approach with broad-spectrum antibiotics tailored to local pathogen distribution and patient risk factors can improve outcomes by reducing the likelihood of inappropriate therapy and antibiotic resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapy for ventilator-associated pneumonia: what works, what doesn't. Hijazi, M., Al-Ansari, M.[2005]

Antibiotic treatment for ventilator-associated pneumonia (VAP) diagnosed using invasive methods (like bronchoscopic protected specimen brush) improves survival compared to withholding treatment, while treatment based on clinical criteria may actually lower survival rates.

The study suggests that using invasive or semi-invasive diagnostic techniques is crucial for accurately diagnosing VAP and guiding effective therapy, as the mortality rate for untreated VAP can be significantly high, approaching 70%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnosis and treatment of ventilator-associated pneumonia--impact on survival. A decision analysis. Sterling, TR., Ho, EJ., Brehm, WT., et al.[2019]

Recent studies suggest that a shorter duration of antibiotic therapy (7-8 days) is effective for treating ventilator-associated pneumonia without increasing mortality rates, challenging the traditional 2-week treatment standard.

There is a need for further research to definitively establish the minimum effective duration of antibiotic therapy for this condition, especially in the context of rising multi-drug-resistant infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ventilator-associated pneumonia: gearing towards shorter-course therapy. Chua, Tde J., File, TM.[2006]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11579304/

an economic analysis of the REGARD-VAP trial - PMC The REGARD-VAP trial showed that individualised shortened antibiotic therapy was non-inferior to usual care for mortality and pneumonia ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9995933/

Comparison of a short versus long-course antibiotic therapy ... Our meta-analysis showed that short-course antibiotic therapy did not result in increased number of recurence and relapses of VAP, suggesting ...

3. atsjournals.org atsjournals.org/doi/abs/10.1164/ajrccm.2025.211.Abstracts.A3719

Short-course Versus Long-course Antibiotic Treatment for ... Our meta-analysis suggests that while a short course of antibiotics increases the risk of pneumonia recurrence in NF-GNB VAP, it does not impact mortality ...

4. thelancet.com thelancet.com/journals/lanres/article/PIIS2213-2600(23)00418-6/fulltext

Individualised, short-course antibiotic treatment versus ... There was a substantial reduction in antibiotic side-effects, from 38% in the usual care group to 8% in the individualised short-course group.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0883944123000953

Short-course versus prolonged-course antibiotic regimens ... Low-quality evidence suggests that a short course of antibiotics is associated with a higher recurrence of pneumonia in NF-GNB VAP with no difference in ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38272050/

Individualised, short-course antibiotic treatment versus ... In this study of adults with VAP, individualised shortened antibiotic duration guided by clinical response was non-inferior to longer treatment durations.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03382548

Defining Antibiotic Treatment Duration for Ventilator Shortening antibiotic duration has the potential to improve individual patient outcomes and indirectly benefit other patients by reducing the selection pressure ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2589537023000573

Comparison of a short versus long-course antibiotic ... Our meta-analysis showed that short-course antibiotic therapy did not result in increased number of recurence and relapses of VAP, suggesting that short-course ...

9. journals.lww.com journals.lww.com/ccmjournal/fulltext/2023/01001/937__short_versus_prolonged_course_of_antibiotics.902.aspx

short versus prolonged course of antibiotics for ventilator- ... Administration of a short course of antibiotics increased the risk of recurrence of pneumonia (RR 1.34; 95% CI: 1.02-1.75); however, in sensitivity analyses, ...