Summary of Results

Clinical research studies cannot be performed without study participants who volunteer to be involved. The ARLG appreciates the time and commitment of these participants who play a significant role in advancing medical science. The ARLG is committed to providing lay summaries of results, which describe what researchers learned from the study in a language and format that is understandable and easy to read. In addition to the results, the summary includes information about why the research is needed, the purpose of the research, when the study was conducted, who was involved, what happened during the study, and how patients and researchers can use the results.

SUMMARIES

Clinical Outcomes and Bacterial Characteristics of Carbapenem-Resistant Acinetobacter baumannii Among Patients from Different Global Regions 

The Study Network of Acinetobacter baumannii as Carbapenem-Resistant Pathogen (SNAP) study is part of the Multi-Drug Resistant Organism (MDRO) Network of studies aimed at providing observational data to help design randomized clinical trials for MDRO infections, developing new diagnostic and treatment paradigms, and informing clinical practice.  

The SNAP study investigated differences in how Carbapenem-resistant A. baumannii affects patients around the world, enrolling cases from five different global regions. Learning which strains of A. baumannii are most prevalent in various parts of the world and why, as well as which strains pose the greatest risk for poor health outcomes, is essential in helping doctors better treat patients at risk. 

Read the SNAP Study results

Clinical Impact of Ceftriaxone Resistance in Escherichia coli Bloodstream Infections: A Multicenter Prospective Cohort Study

Escherichia coli infections are one of the most common types of bacterial infections found in the bloodstream, and ceftriaxone is commonly used to treat such infections. The number of E. coli bloodstream infections that are resistant to ceftriaxone in the United States rose between 2012 to 2017. The Study of Highly Resistant Escherichia Coli (SHREC) Study compared the clinical outcomes of patients with E. coli blood infections that were susceptible to the antibiotic ceftriaxone to those of patients with ceftriaxone-resistant E. coli infections.

Clinical outcomes of 300 adult and pediatric participants across the U.S. were described in the study using the Desirability of Outcome Ranking (DOOR) method, where outcomes ranged from alive with no events to death within 30 days after diagnosis. Results showed that participants with ceftriaxone-resistant E. coli infections had overall worse clinical outcomes than participants with ceftriaxone-susceptible infections. Participants with ceftriaxone-resistant E. coli infections tended to be less healthy at the onset of the study though, which is thought to be the primary reason for the worse outcomes. Study findings indicate that being infected with a ceftriaxone-resistant E. coli may impact quality of life more so than infection with ceftriaxone-susceptible E. coli.

Read the SHREC Study results

Global epidemiology and clinical outcomes of carbapenem-resistant Pseudomonas aeruginosa and associated carbapenemases (POP): a prospective cohort study

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a group of bacteria that resists treatment by a class of antibiotics called carbapenems. Infections due to CRPA are common and often lead to death. The World Health Organization lists CRPA as one of the top three drug-resistant pathogens and a threat to global public health.

Before the POP study, researchers had a limited understanding of CRPA. Earlier research studies of CRPA lacked clinical data or molecular characterization of the bacteria or they only included a single geographic region. The purpose of the POP study was to identify characteristics of the types of patients who have CRPA, characterize their treatment and outcomes, and determine how often these bacteria resist antibiotic treatment across different geographical regions.

Read the POP Study Results

Targeted Reduction of Antibiotics using Procalcitonin in a multi-center, randomized, blinded, placebo-controlled, non-inferiority study of azithromycin treatment in outpatient adults with suspect Lower Respiratory Tract Infections (LRTI) and a procalcitonin level of < 0.1 ng/mL (TRAP-LRTI)

 When a patient has a lower respiratory tract infection (LRTI) such as bronchitis or COPD, it can be difficult for the doctor to know whether a bacterium or a virus is the cause. This diagnosis is important because doctors typically treat a bacterial infection with an antibiotic, but antibiotics will not work on an infection caused by a virus.

One method that can sometimes help doctors find what caused an LRTI is to measure the concentration of a substance called procalcitonin in a patient’s blood sample. Often, higher levels of procalcitonin can mean that a bacterium caused the infection and that antibiotics may be helpful. However, this method cannot provide a definite answer on whether a doctor should withhold antibiotics for a patient with an LRTI and low procalcitonin level.

The purpose of the TRAP-LRTI Study was to help researchers learn more about whether a low procalcitonin measurement can be used to identify patients who will not benefit from antibiotic treatment.

Read the TRAP-LRTI Results

Ceftazidime-Avibactam in Combination with Aztreonam (COMBINE)
Combination regimen of Ceftazidime-Avibactam with Aztreonam Hollow Fiber Infection Model against NDM-1-producing Enterobacteriaceae (COMBINE HFIM)

Doctors have few options for treating infections caused by antibiotic-resistant Gram-negative bacteria. Like many antibiotics, ceftazidime-avibactam (CZA) and aztreonam (ATM) do not work against some types of bacteria when used alone, but they do work when combined together.

Researchers wondered if combining CZA and ATM could become a new treatment option that is more effective and resilient against the MBLs made by antibiotic-resistant Gram-negative bacteria. CZA and ATM can be prescribed on their own, but doctors do not know when it may be safe to combine the two antibiotics or which doses may work best. To find out, researchers conducted the COMBINE and COMBINE HFIM studies. Researchers performed the COMBINE Hollow-fiber Infection Model (HFIM) Study to see which doses of CZA plus ATM would kill the most bacteria and prevent antibiotic resistance. Using the effective doses from the HFIM study, researchers performed the COMBINE Study to see how safe these doses were compared to ATM alone and CZA alone.

Read the COMBINE and COMBINE HFIM Results

Short-course Therapy and the Antibiotic Resistome (STAR) Study

Community-acquired pneumonia (CAP) is one of the most common serious infections in children. It is often treated with 10 days of antibiotics, which can cause diarrhea, a common side effect. Researchers were interested in learning about the specific microorganisms in the gut associated with diarrhea in children receiving antibiotics for CAP. They also wanted to learn whether shorter treatment plans could be as effective which would help to decrease the problem of antibiotic resistance.

Two analyses from the Short-course Therapy and the Antibiotic Resistome (STAR) research study identified microorganisms related to antibiotic side effects (diarrhea) and showed that antibiotic use should be decreased whenever possible.

 

Read the STAR Study Summary of Results

Desirability of Outcome Ranking (DOOR)

ARLG’s Desirability of Outcome Ranking (DOOR) is an innovative method to help doctors and researchers design, analyze, and interpret clinical trials. They can use this information to compare the risks and benefits of different treatment options and create better strategies customized to fit their patients.

The infographic was created by Helen Boucher, MD, FACP, FIDSA, and Jessica Howard-Anderson, MD, MSc, to show how DOOR uses ordinal categories to classify clinical outcomes while taking the possible treatment harms and benefits into account. This method provides a more informative and pragmatic benefit-risk evaluation.

DOOR was developed by Scott Evans, PhD, with support from members of ARLG’s Statistical and Data Management Center (SDMC) Toshimitsu (Toshi) Hamasaki, Lauren Komarow, and Carol Hill. It is being used in several current studies as well as many completed studies including CRACKLE I, PROVIDE, and SCOUT-CAP.

 

Read the ARLG DOOR Infographic

 

Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE-2)

The CRACKLE-2 study investigated types of carbapenem-resistant Enterobacteriaceae (CRE). CRE is a family of bacteria that resists treatment by a class of antibiotics called carbapenems. The World Health Organization lists CRE as one of the top three drug-resistant pathogens and recognizes CRE as a threat to global public health.

The goal of the study was to learn about patients infected with CRE, understand and describe the different types of CRE, and learn how each type affected different patient populations.

Read the CRACKLE-2 Study Summary of Results

 

Short Course Outpatient Antibiotic Therapy for Community-Acquired Pneumonia in Children (SCOUT-CAP)

Community-acquired pneumonia (CAP) is a common and serious infection that leads to 1.5 million doctor visits in the United States each year. Doctors usually treat CAP with a seven to 10-day course of antibiotics, but that can have adverse effects for patients and contribute to the spread of antimicrobial resistance.

The purpose of the SCOUT-CAP study was to learn if a shorter five-day antibiotic treatment strategy would work better than the typical 10-day strategy to treat children under six years of age with community-acquired pneumonia (CAP).

Read the SCOUT-CAP Study Summary of Results

Pharmacokinetic and Pharmacodynamic Profiling of Minocycline for Injection following a Single Infusion in Critically Ill Adults in a Phase IV Open-Label Multicenter Study (ACUMIN)

Acinetobacter baumannii is a highly antibiotic resistant bacteria that causes infections in the blood, urinary tract, and lungs (pneumonia), or in wounds in other parts of the body. Because the rate of infections is rising worldwide, the Centers for Disease Control (CDC) has called this bacteria an urgent public health threat.

Although hospitals primarily use minocycline to treat patients with infections due to Acinetobacter baumannii, we don’t know very much about how this drug works in critically ill patients. Most of the research on the correct dose for minocycline was done with healthy people. The ACUMIN study will help doctors learn more about the best dose of minocycline for critically ill patients with serious infections.

Read the ACUMIN Study Summary of Results

Stewardship Interventions in Duke Infection Control Outreach Network (DICON) community hospitals Study

Community hospitals in the United States have high rates of antibiotic use. Overuse of antibiotics results in infections by drug-resistant bacteria, also called “superbugs,” which can lead to deaths and increased hospital costs. To prevent antibiotic overuse, the Infectious Diseases Society of America recommends that hospitals implement antibiotic review strategies.

Community hospitals usually do not have the resources or staff training to routinely review antibiotic therapies. This study was done to understand if community hospitals could put in place an antibiotic review strategy if the appropriate training is provided to the pharmacist staff.

Read the DICON Study Summary of Results.

 

RAPid IDentification and Susceptibility testing for Gram Negative bacteremia (RAPIDS-GN)

Gram-negative bacteria are a problem worldwide because they cause up to 33% of bloodstream infections. If these infections are not properly treated they can lead to death.

In order to treat bloodstream infections, doctors need to know what type of bacteria is causing the infection. This information helps doctors prescribe the right antibiotic to kill the bacteria. Time is important because the sooner the correct antibiotic is given, the faster the patient will get better and the infection will be cured.
Results from standard testing typically take two to four days. Results from rapid testing can be available in hours.

This study was conducted to learn if doctors could prescribe the correct antibiotic faster when a rapid-testing device was used instead of standard testing.

Read the RAPIDS-GN Study Summary of Results

 

Master Protocol - Gonorrhea and Chlamydia testing of Extragenital Specimens

The purpose of this study was to look at how well three different tests would work to diagnose gonorrhea and chlamydia in the throat and the rectum. These tests are currently approved to diagnose gonorrhea and chlamydia in the urinary and genital tracts.

The study tested samples from the throat and rectum on the three tests with the results being positive, negative, unclear, or no result. Researchers compared the results across tests to determine whether people were infected and the accuracy of the tests in detecting gonorrhea and chlamydia.

Read the MASTER-GC Study Summary of Results

 

Prospective Observational Evaluation of the Association between Initial Vancomycin Exposure and Failure Rates among Adult Hospitalized Patients with MRSA Bloodstream Infections (PROVIDE) Study

Vancomycin is the most commonly administered antibiotic in hospitalized patients. It is used to treat patients infected with methicillin-resistant Staphylococcus aureus (MRSA), but the optimal dosing remains uncertain. In this study, researchers evaluated the relationship between vancomycin administered over time (exposure) and outcomes in patients with MRSA bacteremia.

The purpose of this study was to determine the best dose of vancomycin to treat MRSA blood infections in hospitalized adults.

Read the PROVIDE Study Summary of Results

 

Rapid Diagnostics in Categorizing Acute Lung Infections (RADICAL) Study

Antibiotics are drugs that treat infections caused by bacteria, but they do not work on viruses, such as colds and the flu. Taking antibiotics when you do not need them can be harmful to you. It can also create drug-resistant bacteria, which is a serious public health issue that can lead to antibiotics that do not work and increased health care costs.

Doctors could better know when to prescribe an antibiotic if they had an easy and quick way to diagnose whether it was a virus or bacteria that caused a patient’s infection. Rather than trying to test for the presence of a virus or bacteria, the RADICAL study focuses on how patients respond to the infection.

Read the RADICAL Study Summary of Results

 

Phase I Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Two Dosing Regimens of Oral Fosfomycin Tromethamine in Healthy Adult Participants (PROOF)

Fosfomycin is approved for the treatment of urinary tract infections and cystitis, which is inflammation of the bladder.

The most recommended adult dose is three grams taken orally (by mouth) every other day, for a total of three doses. However, there are many different dosing regimens prescribed today that have not been studied or approved. In addition, based on activity observed in the lab, doctors are interested in prescribing this drug for its ability to treat infections caused by antibiotic-resistant bacteria (bacteria that are not controlled or killed by antibiotics). However, the drug has not been approved for this indication.

This study gathered information to help doctors identify alternative dosing regimens.

Read the PROOF Lay Summary of Results