Successful Trial of Cefiderocol For Resistant & Complicated Urinary Tract Infections

MedicalResearch.com Interview with:
https://www.shionogi.com/Simon Portsmouth, MD

Senior Medical Director
Shionogi Inc.

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Antibiotics for multidrug resistant  Gram-negative infections are desperately needed. Cefiderocol is the first siderophore antibiotic to reach patients.

Siderophore antibiotics bind to free iron and use the bacterial active iron transport channels to cross the outer membrane of Gram-negative bacteria. Laboratory studies have shown that cefiderocol is active against multi-drug resistant Gram-negative bacteria, often where no other antibiotics are active. It is able to overcome most types of antibiotic resistance due to its active transport into cells and stability against all carbapenemases.

The need for antibiotics for carbapenem resistant Gram-negative infections is described as a critical need by the WHO. This trial was the first in humans with serious infections and demonstrated excellent efficacy in a complicated patient population where almost ¼ were over 75 years of age. Additionally cefiderocol did not appear to have any safety problems, and was well tolerated.

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Real World Treatment of Serious Infections with Ceftolozane/Tazobactam

MedicalResearch.com Interview with:

Thomas P. Lodise Jr., PharmD, PhD Clinical Pharmacist at the Stratton VA Medical Center in Albany, NY Albany College of Pharmacy and Health Sciences Albany, NY

Dr. Lodise

Thomas P. Lodise Jr., PharmD, PhD
Clinical Pharmacist at the Stratton
VA Medical Center in Albany, NY
Albany College of Pharmacy and Health Sciences
Albany, NY

MedicalResearch.com: What is the background for this study? How does Ceftolozane/Tazobactam differ from other antibiotics for serious Gram-negative infections including Pseudomonas aeruginosa?

Response: Treatment of patients with Gram-negative infections is increasingly difficult due to rising resistance to commonly used agents. Ceftolozane/tazobactam (C/T) is a potent anti-pseudomonal agent with broad Gram-negative coverage that is indicated for complicated urinary tract infections (cUTI) and complicated intra-abdominal infections (cIAI) and is currently being studied for ventilated nosocomial pneumonia. C/T differs from other antibiotics in terms of its potency against multi-drug resistant Pseudomonas aeruginosa, one of the most concerning and difficult-to-treat Gram-negative pathogens. This study evaluates C/T in a large database of US hospitals to better understand treatment patterns and associated outcomes.

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Drinking More Water May Reduce Frequency of Urinary Tract Infections

MedicalResearch.com Interview with:
"Glass of Water" by Iwan Gabovitch is licensed under CC BY 2.0Professor Yair Lotan MD

Chief of Urologic Oncology
Holder of the Helen J. and Robert S. Strauss Professorship in Urology
UT Southwestern Medical Center at Dallas
Department of Urology
Dallas, Texas 75390-9110 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Urinary tract infections are extremely common in women and many women experience recurrent episodes which impact their quality of life.  There are also many women who do not drink as much water as is recommended.

This study found that in healthy women with recurrent UTIs who drink less than 1.5 liters per day, the additional intake of 1.5 liters of water daily reduced the risk of recurrent infections by nearly 50%.  Continue reading

SMARTPHONE, M.D. : A NEW APP TO DIAGNOSE URINARY TRACT INFECTIONS

MedicalResearch.com Interview with:
SMARTPHONE, M.D. A NEW APP TO DIAGNOSE URINARY TRACT INFECTIONS Michael J. Mahan PhD
Professor, Microbiology and Molecular Genetics
Dept of Molecular, Cellular, and Developmental Biology
University of California, Santa Barbara, CA

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Urinary tract infections (UTIs) cause nearly 10 million doctor visits each year in the United States. Women are much more likely to have a UTI than men, and are particularly harmful to pregnant women and can cause miscarriage. Thus, there is a medical need for rapid, low-cost, on-site testing — particularly in resource-limited settings.

We developed a new app that enables a smartphone to identify (ID) bacteria causing UTIs in just one hour — a fraction of the time and cost of clinical diagnostics.

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Ibuprofen Can Not Replace Antibiotics in Uncomplicated UTI

MedicalResearch.com Interview with:

Ingvild Vik MD Doctoral Research Fellow Department of General Practice Institute of Health and Society - UiO University of Oslo, Norway.

Dr. Vik

Ingvild Vik MD
Doctoral Research Fellow
Department of General Practice
Institute of Health and Society – UiO
University of Oslo, Norway

MedicalResearch.com: What is the background for this study?

Response: Uncomplicated urinary tract infection (UTI) is the most common bacterial infection in women. It is painful and troublesome, and even though it is often self-limiting most women who see a doctor will be prescribed an antibiotic, as antibiotics provide quick symptom relief.  Antibiotic resistance is a growing, serious public health problem. Antibiotic use is the main contributor to antibiotic resistance, and to stop the rapid development it is crucial that we reduce unnecessary use of antibiotics. Antibiotics can cause unpleasant and potentially severe side effects, so avoiding unnecessary use is also beneficial for the individual patient.

A small German trial published in 2010 by Bleidorn et al. suggested that ibuprofen was non-inferior to the antibiotic ciprofloxacin in achieving symptomatic cure in uncomplicated UTI. This inspired us to conduct a larger trial to compare the anti-inflammatory drug ibuprofen to antibiotics in the treatment of uncomplicated UTI.  Continue reading

Combination Meropenem-Vaborbactam (Vabomere) Successfully Treats Complicated Urinary Tract Infections

MedicalResearch.com Interview with:

Keith S. Kaye, MD, MPH Professor of Medicine, Division of Infectious Diseases University of Michigan Medical School Ann Arbor MI 

Dr. Kaye

Keith SKayeMD, MPH
Professor of Medicine, Division of Infectious Diseases
University of Michigan Medical School
Ann Arbor MI 

MedicalResearch.com: What is the background for this study?

Response: Complicated complicated urinary tract infections (cUTI), including acute pyelonephritis, are a major cause of hospital admissions, and are associated with significant morbidity and mortality and can be difficult to treat. While the most common pathogen is Escherichia coli, the more problematic pathogens are multidrug-resistant (MDR) gram-negative organisms including other Enterobacteriaceae species. The prevalence of cUTI due to MDR gram-negative bacteria has risen. In some instances, MDR gram-negative bacteria isolated from the urinary tract can cause bacteremia.

Vabomere was approved by the U.S. Food and Drug Administration (FDA) in August 2017 for the treatment of adult patients with cUTI, including pyelonephritis, caused by designated susceptible Enterobacteriaceae: Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae species complex.   Vabomere is a fixed-dose (2g/2g) combination product of a carbapenem and a β-lactamase inhibitor with potent in vitro activity against Klebsiella pneumoniae carbapenemase (KPC)-producing carbapenem-resistant Enterobacteriaceae (CRE), an important MDR organism associated with serious infections.

The Targeting Antibiotic Non-susceptible Gram-negative Organisms (TANGO I) trial was the pivotal Phase 3 study that compared the efficacy and safety of Vabomere to piperacillin-tazobactam in the treatment of patients with cUTI and acute pyelonephritis.

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Cranberry Juice Capsules Ineffective in Reducing UTIs in Older Women

MedicalResearch.com Interview with:

Manisha Juthani-Mehta, MD, FACP, FIDSA, FSHE</strong>A Associate Professor, Section of Infectious Diseases Infectious Diseases Fellowship Program Director Yale University School of Medicine

Dr. Manisha Juthani-Mehta

Manisha Juthani-Mehta, MD, FACP, FIDSA, FSHEA
Associate Professor, Section of Infectious Diseases
Infectious Diseases Fellowship Program Director
Yale University School of Medicine

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: One of the first studies that showed that cranberry juice was effective in older women living in nursing homes and assisted living facilities was published in 1994. Since that time, there have been multiple conflicting studies as to the effect of cranberry juice or capsules. We started our study in 2012. Shortly thereafter, a Cochrane review suggested that the vast body of evidence did not suggest that cranberry products work for UTI prevention, but questions still existed as to whether the appropriate dose of cranberry was being tested. Since cranberry juice is hard for older women to drink (taste, sugar load, volume), capsules at a high dose of the active ingredient (72mg type A proanthocyanidin [PAC}) was worthwhile to test.

This study was a clinical trial of two cranberry capsules with a total of 72mg of proanthocyanidin (pac) vs two placebo capsules to prevent bacteria in the urine of older women who live in nursing homes.

Unfortunately, it didn’t work. It also didn’t reduce the number of hospitalizations, deaths, antibiotics used, or antibiotic resistant bugs in the urine.

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Phase 2 Study of New Combination Antibiotics Successfully Treats Complicated UTIs

MedicalResearch.com Interview with:

Amanda Paschke, MD Director, Infectious Disease Clinical Research Merck Research Laboratories

Dr. Amanda Paschke

Amanda Paschke, MD
Director, Infectious Disease Clinical Research
Merck Research Laboratories

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Relebactam is an investigational beta-lactamase inhibitor being developed as a fixed-dose combination with imipenem/cilastatin, which is a broad-spectrum antibiotic in the carbapenem class. In preclinical studies, this combination demonstrated antibacterial activity against a broad range of multidrug-resistant Gram-negative pathogens, including those producing extended-spectrum beta-lactamases such as Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae and AmpC-producing Pseudomonas aeruginosa. Many of the most concerning infections caused by “superbugs” are caused by Gram-negative bacteria. These bacteria have evolved to be resistant to commonly used antibacterials, and even to antibacterials used as “last resort” treatment, which is why finding ways to treat them has become urgent. The addition of relebactam to imipenem is designed to restore activity of imipenem against certain imipenem-resistant strains of Gram-negative bacteria known to cause serious infections among people who often have other underlying medical conditions, which complicates treatment.

This was a Phase 2, multicenter, randomized, double-blind, non-inferiority study. The study looked at the use of relebactam plus imipenem versus imipenem alone for the treatment of adult patients with complicated urinary tract infections. The primary endpoint for the trial was microbiological response at the completion of IV study therapy. The study met its primary endpoint, demonstrating that the combination of relebactam with imipenem was as at least as effective as imipenem alone for the treatment of complicated urinary tract infections. The trial also demonstrated that the combination of relebactam plus imipenem is well-tolerated, with a safety profile similar to that of imipenem alone in this patient.

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National Program Reduces Urinary Tract Infections in Hospitalized Patients

Sanjay Saint, MD, MPH Chief of Medicine, VA Ann Arbor Healthcare System George Dock Professor of Internal Medicine & Senior Associate Chair - Department of Internal Medicine University of Michigan Medical School

Dr. Sanjay Saint

MedicalResearch.com Interview with:
Sanjay Saint, MD, MPH
Chief of Medicine
VA Ann Arbor Healthcare System
George Dock Professor of Internal Medicine & Senior Associate Chair –
Department of Internal Medicine
University of Michigan Medical School

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Saint: Catheter-associated urinary tract infection (CAUTI) is a common, costly, and morbid complication of hospitalization. Urinary tract infection (UTI) is one of the most common device-related infections in the United States. CAUTI rates rose nationally between 2009 and 2013.

We put in place a national program to reduce CAUTI. Specifically, we enrolled 926 intensive care unit (ICU) and non-ICU hospital units in 603 hospitals spread over 32 states, the District of Columbia and Puerto Rico between March 2011 and November 2013.

By the end of the 18-month program, UTI rates among hospital patients in general wards had dropped by a third. Specifically:
• The rate of CAUTIs dropped from 2.40 per 1000 days of catheter use to 2.05 (a ~14 percent overall drop).
• Nearly all of the decrease in CAUTI rates was due to changes in infection rates in non-ICUs, which went from 2.28 to 1.54 infections per 1,000 catheter-days – a drop of 32 percent. In non-ICUs, the overall use of catheters decreased by 7%.
• ICUs didn’t see a substantial change in either CAUTI or catheter use, likely because the nature of patients treated in ICUs means more frequent urine output monitoring and culturing of urine, so UTIs are more likely to be spotted.

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Dogs Strong Sense of Smell Can Detect Urinary Tract Infections

MedicalResearch.com Interview with:
Maureen Maurer, MS 
American Institute for Research
Makawao, HI  

MedicalResearch.com: What is the background for this study?

Response: Complications from UTIs are a serious medical problem for many people with neurological impairment such as spinal cord injuries. Detection is often difficult in these patients, resulting in delayed diagnosis and more serious infections such as pyelonephritis and sepsis.  UTIs are also the most common hospital acquired infection for all patients. Given the prevalence of UTIs, their complications, and increasing drug therapy resistance, improved early detection methods are needed.

The olfactory acuity of dogs is over 100,000 times stronger than humans. Dogs’ superior olfactory capabilities have been employed to assist humans by detecting bombs, drugs, and more recently, cancer. Trained dogs may present a novel method for early UTI detection. Our objective was to determine whether canines could be trained to discriminate culture-positive from culture-negative urine samples.  Continue reading

Study Examines NSAIDs vs Antibiotics For Uncomplicated Urinary Tract Infection

Ildikó Gágyor MD Senior researcher in primary care Department of General Practice University Medical Center Göttingen Göttingen, Germany

Dr. Gágyor

MedicalResearch.com Interview with:
Ildikó Gágyor MD
Senior researcher in primary care
Department of General Practice
University Medical Center Göttingen
Göttingen, Germany

Medical Research: What is the background for this study? What are the main findings?

Dr. Gágyor: Uncomplicated urinary tract infection is a common problem for women. Affected patients are usually treated with antibiotics to combat both unpleasant symptoms and to combat infection. However, prescription of antibiotics for a self-limiting condition, contributes to increased resistance rates posing a serious long-term threat to public health. In a double blind randomised controlled trial we examined whether symptomatic treatment of uncomplicated urinary tract infection with ibuprofen reduces the rate of antibiotic prescriptions without a significant increase in symptoms, recurrences, or complications. In all, 494 women were randomly assigned to receive: either ibuprofen for three days and antibiotics only if symptoms are persistent; or antibiotic treatment with fosfomycin. Results showed that antibiotic use could be reduced significantly: of the 248 women in the ibuprofen group two thirds recovered without antibiotics and one third received antibiotics subsequently. Women in the ibuprofen group had a higher symptom burden but in both groups, symptoms decreased within the first week (Figure 1). Six cases of pyelonephritis occurred, one in the fosfomycin group, five in the ibuprofen group.

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Complex Bacterial Biofilms Can Rapidly Obstruct Catheters

Dr Sandra A. Wilks PhD Senior Research Fellow IfLS Knowledge Mobilisation Fellow in Healthcare Technologies Faculty of Natural and Environmental Science & Faculty of Health Sciences Centre for Biological Sciences, University of Southampton, Southampton, UK

Dr. Sandra Wilks

MedicalResearch.com Interview with:
Dr Sandra A. Wilks PhD

Senior Research Fellow
IfLS Knowledge Mobilisation Fellow in Healthcare Technologies
Faculty of Natural and Environmental Science & Faculty of Health Sciences
Centre for Biological Sciences,
University of Southampton,
Southampton, UK 

Medical Research: What is the background for this study? What are the main findings?
Dr. Wilks: The use of indwelling Foley urinary catheters for extended periods of time results in high risks of urinary tract infections (UTI) and catheter blockages. Blockages are often caused by the presence of Proteus mirabilis, a urease-producing bacterium which results in an increase of the urine pH and the development of crystalline biofilms. Biofilms develop when bacteria attach to a surface, forming a community structure, held together by extracellular polymeric substances (EPS). Once in a biofilm, bacteria exhibit high resistance to the action of antibiotics and are protected by other stress factors. The crystalline biofilms resulting from the presence of Proteus are highly complex environments and cause complete blockage of the catheter within days. Such blockages cause pain and trauma for patients, and result in high demands on healthcare resources.

In this study, we have used an advanced microscopy technique (episcopic differential interference contrast, EDIC microscopy developed by Best Scientific) to track the development of these crystalline encrustations on two commonly used catheter materials; silicone and hydrogel latex. We have identified four distinct stages to crystalline biofilm formation;

  • (1) an initial foundation layer (conditioning film) formed by individual ‘colonising’ P. mirabilis cells, which occurred in less than 1 hour;
  • (2) this was rapidly followed by a sheet-like microcrystalline material (after 24 hours) that covers this conditioning film;
  • (3) after 4 days exposure, large amounts of crystalline material was seen to extend out from the surface with;
  • (4) defined struvite crystals embedded within the structure and P. mirabilis visible throughout. This pattern was the same on both materials.

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Standardized Model Empowers Nurses To Decrease Urinary Catheter Use

Jerome A. Leis, MD MSc FRCPC Staff physician, General Internal Medicine and Infectious Diseases Physician Lead, Antimicrobial Stewardship Team Staff member, Centre for Quality Improvement and Patient Safety Sunnybrook Health Sciences Centre Assistant Professor, Department of Medicine, University of Toronto

Dr. Jerome Leis

MedicalResearch.com Interview with:
Jerome A. Leis, MD MSc FRCPC

Staff physician, General Internal Medicine and Infectious Diseases
Physician Lead, Antimicrobial Stewardship Team
Staff member, Centre for Quality Improvement and Patient Safety
Sunnybrook Health Sciences Centre
Assistant Professor, Department of Medicine, University of Toronto

Medical Research: What is the background for this study? What are the main findings?

Dr. Leis: Overuse of urinary catheters leads to significant morbidity among hospitalized patients.  In most hospitals, discontinuation of urinary catheters relies on individual providers remembering to re-assess whether patients have an ongoing reason for a urinary catheter.  We engaged all of the attending physicians to agree on the appropriate reasons for leaving a urinary catheter in place and developed a medical directive for nurses to remove all urinary catheters lacking these indications.  This nurse-led intervention resulted in a significant reduction in urinary catheter use and catheter-associated urinary tract infections, compared with wards that continued to rely on usual practice.

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Acidification May Be Counterproductive For Some Patients With Urinary Tract Infections

MedicalResearch.com Interview with:
Jeffrey P. Henderson, M.D., Ph.D.
Assistant Professor of Medicine and Molecular Microbiology
Center for Women’s Infectious Diseases Research
Division of Infectious Diseases

and Robin Shields-Cutler, Ph.D
Ph.D. Student, Molecular Microbiology and Microbial Pathogenesis
Washington University School of Medicine
St. Louis, Missouri

Medical Research: What is the background for this study?

Response: Increasing antibiotic resistance, together with an appreciation that many patients are particularly susceptible to recurrent Urinary Tract Infections UTIs following antibiotic therapy, motivated interest in the events that occur during early stages of UTI pathogenesis.

Abundant evidence suggests that uropathogenic E.coli must obtain iron from human hosts in order to cause a clinical infection. Early in infection, human cells secrete a protein called siderocalin that is known to limit bacterial growth by sequestering iron. This protein is detectable in the urine of Urinary Tract Infections patients.

Medical Research: What are the main findings?

Response: We obtained urine from a diverse panel of healthy volunteers, inoculated them individually with a uropathogenic E.coli strain, and monitored growth in the presence and absence of a fixed amount of siderocalin. Siderocalin exhibited a remarkably wide range of activity between individuals.

We traced this variation back to differences in urinary pH and to phenolic urinary metabolites. We could significantly facilitate siderocalin’s antibacterial activity in urine by alkalinizing it above 6.5 and adding phenolic metabolites. The metabolites that potentiate siderocalin’s antibacterial effect have been linked to dietary sources such as coffee, tea, and berries. Some of these compounds may further derive from the actions of gut microbes on dietary phenols. The functional basis for these compounds’ properties seems to arise from siderocalin’s ability to use them as molecular grips that chelate iron ions in a form that is difficult for bacteria to access.

From the pathogen perspective, we found that enterobactin, a molecule secreted by E.coli, acts as a microbial countermeasure to urinary siderocalin. Adding a drug-like inhibitor to urine that blocks enterobactin biosynthesis greatly increased siderocalin’s antibacterial effect.

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No Knee-Jerk Antibiotics Campaign Aims To Reduce Antibiotic Overusage

Barbara W. Trautner, MD, PhD Houston Veterans Affairs Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center Section of Infectious Diseases, Department of Medicine Baylor College of Medicine, Houston, TexasMedicalResearch.com Interview with:
Barbara W. Trautner, MD, PhD
Houston Veterans Affairs Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center
Section of Infectious Diseases
Department of Medicine
Baylor College of Medicine, Houston, Texas

Medical Research: What is the background for this study? What are the main findings?

Dr. Trautner: Reducing antimicrobial overuse, or antimicrobial stewardship, is a national imperative. If we fail to optimize and limit use of these precious resources, we may lose effective antimicrobial therapy in the future. CDC estimates that more than $1 billion is spent on unnecessary antibiotics annually, and that drug-resistant pathogens cause 2 million illnesses and 23,000 deaths in the U.S. each year. The use of antibiotics to treat asymptomatic bacteriuria (ASB) is a significant contributor to antibiotic overuse in hospitalized and nursing home patients, especially among patients with urinary catheters. In catheterized patients, ASB is very often misdiagnosed and treated as catheter-associated urinary tract infection (CAUTI). Therefore, we designed the “Kicking CAUTI: The No Knee-Jerk Antibiotics Campaign intervention” to reduce overtreatment of ASB and to reduce the confusion about distinguishing CAUTI from asymptomatic bacteriuria.

This study evaluated the effectiveness of the Kicking CAUTI intervention in two VAMCs between July 2010 and June 2013. The primary outcomes were urine cultures ordered per 1,000 bed-days (inappropriate screening for ASB) and cases of ASB receiving antibiotics (overtreatment). The study included 289,754 total bed days, with 170,345 at the intervention site and 119,409 at the comparison site. Through this campaign, researchers were able to dramatically decrease the number of urine cultures ordered. At the intervention site, the total number of urine cultures ordered decreased by 71 percent over the course of the intervention. Antibiotic treatment of asymptomatic bacteriuria decreased by more than 75 percent during the study. No significant changes occurred at the comparison site over the same time period. Failure to treat catheter-associated urinary tract infection when indicated did not increase at either site. Continue reading

Electronic Health Record Alerts Reduced Urinary Tract Infections

Craig A Umscheid, MD, MSCE, FACP Assistant Professor of Medicine and Epidemiology Director, Center for Evidence-based Practice Medical Director, Clinical Decision Support Chair, Department of Medicine Quality Committee Senior Associate Director, ECRI-Penn AHRQ Evidence-based Practice Center University of Pennsylvania, Philadelphia, PA 19104MedicalResearch.com Interview with:
Craig A Umscheid, MD, MSCE, FACP
Assistant Professor of Medicine and Epidemiology
Director, Center for Evidence-based Practice
Medical Director, Clinical Decision Support
Chair, Department of Medicine Quality Committee

Senior Associate Director, ECRI-Penn AHRQ Evidence-based Practice Center
University of Pennsylvania, Philadelphia, PA 19104

Medical Research: What are the main findings of the study?

Dr. Umscheid: We found that targeted automated alerts in electronic health records significantly reduce urinary tract infections in hospital patients with urinary catheters. In addition, when the design of the alert was simplified, the rate of improvement dramatically increased.

Approximately 75 percent of urinary tract infections acquired in the hospital are associated with a urinary catheter, which is a tube inserted into the bladder through the urethra to drain urine.  According to the Centers for Disease Control and Prevention, 15 to 25 percent of hospitalized patients receive urinary catheters during their hospital stay. As many as 70 percent of urinary tract infections in these patients may be preventable using infection control measures such as removing no longer needed catheters resulting in up to 380,000 fewer infections and 9,000 fewer deaths each year.

Our study has two crucial, applicable findings.  First, electronic alerts do result in fewer catheter-associated urinary tract infections. Second, the design of the alerts is very important. By making the alert quicker and easier to use, we saw a dramatic increase in the number of catheters removed in patients who no longer needed them. Fewer catheters means fewer infections, fewer days in the hospital, and even, fewer deaths. Not to mention the dollars saved by the health system in general.

In the first phase of the study, two percent of urinary catheters were removed after an initial “off-the-shelf” electronic alert was triggered (the stock alert was part of the standard software package for the electronic health record). Hoping to improve on this result in a second phase of the study, we developed and used a simplified alert based on national guidelines for removing urinary catheters that we previously published with the CDC. Following introduction of the simplified alert, the proportion of catheter removals increased more than seven-fold to 15 percent.

The study also found that catheter associated urinary tract infections decreased from an initial rate of .84 per 1,000 patient days to .70 per 1,000 patient-days following implementation of the first alert and .50 per 1,000 patient days following implementation of the simplified alert. Among other improvements, the simplified alert required two mouse clicks to submit a remove-urinary-catheter order compared to seven mouse clicks required by the original alert.

The study was conducted among 222,475 inpatient admissions in the three hospitals of the University of Pennsylvania Health System between March 2009 and May 2012. In patients’ electronic health records, physicians were prompted to specify the reason (among ten options) for inserting a urinary catheter. On the basis of the reason selected, they were subsequently alerted to reassess the need for the catheter if it had not been removed within the recommended time period based on the reason chosen.
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Skin Irritants Increase Risk of Urinary Tract Infections

Steve J. Hodges MD Associate Professor, Department of Urology Wake Forest University School of Medicine Medical Center Blvd, Winston-Salem, NCMedicalResearch.com Interview with:
Steve J. Hodges MD
Associate Professor, Department of Urology
Wake Forest University School of Medicine
Medical Center Blvd, Winston-Salem, NC

Medical Research: What are the main findings of this study?

Dr. Hodges: The main findings of this study were that skin irritants (typically urine) may cause vulvitis in prepubertal girls, which leads to an alteration of their perineal microbiome, with increased colonization by uropathogenic bacteria, increasing the risk of UTI.
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Urinary Tract Infections Reporting Change Reduced Antibiotic Use

Dr. Jerome A. Leis, MD, MSc Sunnybrook Health Sciences Centre Toronto, ON, M4N 3M5, CanadaMedicalResearch.com Interview with:
Dr. Jerome A. Leis, MD, MSc
Sunnybrook Health Sciences Centre
Toronto, ON, M4N 3M5, Canada
MedicalResearch.com: What are the main findings of the study?

Dr. Leis: We know that positive urine cultures from patients who lack signs and symptoms of urinary tract infection are a trigger FOR unnecessary antibiotic prescriptions in hospitals. This problem has not improved despite many educational initiatives.  We identified a subset of patients in our hospital where only 2% of all urine specimens sent to the laboratory were associated with symptomatic infection and decided to no longer routinely report positive results from these specimens on the electronic medical record, unless a special telephone request was made.  We found that with this simple change, unnecessary antibiotic prescriptions declined markedly and this did not require any education of care providers. Most importantly, based on our safety audits, patients who had a urinary tract infection all received appropriate treatment.

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Acute Cystitis in Premenopausal Women: How Valuable is Midstream Urine Culture?

Thomas M. Hooton M.D. Associate Chief of Staff, Medical Service, Miami VA Healthcare System Professor of Clinical Medicine and Vice Chair for VA Affairs, Department of Medicine, UMSOM Clinical Director, Division of Infectious Diseases, UMSOMMedicalResearch.com Interview with:
Thomas M. Hooton M.D.
Professor of Medicine and Vice Chair for VA Affairs,
University of Miami Miller School of Medicine
Associate Chief of Staff, Medical Service, Miami VA Healthcare System
Clinical Director, Division of Infectious Diseases

MedicalResearch.com: What are the main findings of the study?

Dr. Hooten: The main findings from this study are:

·        Voided urine colony counts of E. coli as low as 101 to 102 cfu/mL are highly sensitive and specific for their presence in bladder urine in symptomatic women (growth of bacteria in bladder urine is the gold standard for the etiology of UTI). Moreover, even when E. coli is found along with other mixed flora in voided urine, it should not be considered a contaminant since it likely represents true bladder infection.

·        On the other hand, enterococci and Group B streptococci, which are frequently isolated from voided urine, are rarely isolated from paired catheter specimens, suggesting that these organisms only rarely cause acute uncomplicated cystitis. In our study, E. coli frequently grew from the urines of these women and is the likely cause for UTI symptoms in such episodes.

·        Organisms usually considered contaminants, such as lactobacilli, occasionally grow from catheter urines, but they are rarely found alone with pyuria, suggesting that these bacteria rarely cause acute uncomplicated cystitis.

·        The etiology of a quarter of acute uncomplicated cystitis episodes is unknown.  It is possible that some of these women have E. coli urethritis, which has been documented in some women with UTI symptoms, but we did not do further studies to evaluate this. It is possible also that enterococci and Group B streptococci may also cause urethritis, but there is no published evidence of this in young women with UTI symptoms.

·        Although voided urine cultures growing mixed flora are common in women with acute cystitis, true polymicrobic cystitis, as determined by sampling bladder urine, appears to be rare in this population.
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Urinary Catheter Infections: Clinical Assessment vs National Safety Network Definition

MedicalResearch.com Interview with:
Mohamad Fakih, MD, MPH
Medical Director, Infection Prevention and Control
St John Hospital and Medical Center

MedicalResearch.com: What are the main findings of the study?

Dr. Fakih: Urinary catheters are commonly used in the hospital.  Although they help in the management of the sickest patients, they also present a risk for infection and other harms to the patient. The Centers for Medicaid and Medicare Services (CMS) have made catheter associated urinary tract infections (CAUTI) publicly reportable, and no longer reimburse hospitals for these infections if they occur in hospital setting. The definition of CAUTI is based on the surveillance definition of the National Healthcare Safety Network (NHSN) by the Centers for Disease Control and Prevention (CDC). We looked at clinician practice, including the Infectious Diseases specialist’s impression and compared them to the NHSN definition. We found a significant difference between what clinicians think is a urinary catheter infection and give antibiotics for it compared to the NHSN definition. The NHSN definition predicted clinical infection by the Infectious Diseases specialist in only about a third of the cases. We also found that Infectious Disease specialists considered patients to have true CAUTI in only half of what clinicians treated as CAUTI.
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Antibiotic appears more effective than cranberry capsules for preventing urinary tract infections

In premenopausal women who have repeated urinary tract infections (UTIs), the antibiotic trimethoprim-sulfamethoxazole (TMP-SMX) appeared more effective than cranberry capsules for preventing recurrent infections, at the risk of contributing to antibiotic resistance, according to a report in the July 25 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

Urinary tract infections are common in women, affecting nearly half at some point in their lives, according to background information in the article. The authors note that up to 30 percent of women develop recurrent UTIs (rUTIs), a condition for which a low-dose antibiotic is frequently used as a preventive measure. “However, this may lead to drug resistance not only of the causative microorganisms but also of the indigenous flora,” write the authors. Studies of cranberries and cranberry products have shown some effectiveness in preventing rUTIs, but these trials have not compared those interventions directly with TMP-SMX, the standard antibiotic used in these cases.

Mariëlle A.J. Beerepoot, M.D., from the Academic Medical Center, Amsterdam, and colleagues conducted a double-blind noninferiority trial of cranberry capsules and TMP-SMX. The 221 participants were premenopausal adult women who had reported at least three symptomatic UTIs in the previous year. They were randomized to take either TMP-SMX (480 mg at night, plus one placebo capsule twice daily) or cranberry capsules (500 mg twice daily, plus one placebo tablet at night) for 12 months. Researchers assessed participants’ clinical status once a month (and for three months after stopping the study medication) via urine and feces samples and a questionnaire; participants also submitted urine samples when they experienced UTI-like symptoms.

At 12 months, the average number of clinical recurrences was 1.8 in the TMP-SMX group and 4.0 in the cranberry capsules group. Recurrence occurred, on average, after eight months in the drug group and after four months in the cranberry capsules group. Antibiotic resistance rates tripled in the pathogens found in patients in the TMP-SMX group, although three months after the drug was discontinued, resistance rates returned to the levels they had been at when the study began.

The antibiotic used in this study appeared to be more effective at preventing rUTIs than cranberry capsules, but the researchers noted that achieving this result also seemed to increase the rate of antibiotic resistance. “From clinical practice and during the recruitment phase of this study, we learned that many women are afraid of contracting drug-resistant bacteria using long-term antibiotic prophylaxis and preferred either no or nonantibiotic prophylaxis,” they report. “In those women, cranberry prophylaxis may be a useful alternative despite its lower effectiveness.”

(Arch Intern Med. 2011;171[14]:1270-1278. Available pre-embargo to the media at www.jamamedia.org.)

Editor’s Note: This study was supported by a grant from the Netherlands Organization for Health Research and Development. The authors received the cranberry and placebo capsules from Springfield Nutraceuticals BV, Oud Beijerland, the Netherlands. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Commentary: Cranberries as Antibiotics?

An accompanying commentary by Bill J. Gurley, Ph.D., from the University of Arkansas for Medical Sciences, Little Rock, evaluates the results obtained by Beerepoot and colleagues in the context of nonpharmacologic remedies. Botanical dietary supplements are not intended to be used to treat, cure or prevent disease, he writes, but “most U.S. consumers, however, have expectations of health benefits from the dietary supplements they consume.” Nevertheless, supplements such as cranberry capsules may not demonstrate optimal efficacy due to issues with poor water solubility and the type of metabolism that occurs.

Dr. Gurley notes that the report by Beerepoot and colleagues has two important features. Given that one month into the study, antibiotic resistance for Escherichia coli was higher than 85 percent in the TMP-SMX group but less than 30 percent in the cranberry capsule group, “such a marked reduction in antibiotic resistance certainly favors the therapeutic potential of cranberry as a natural UTI preventative.” Further, Gurley points out that TMP-SMX showed superior efficacy to cranberry capsules, but that the low rate of bioavailability of bacteria-fighting chemicals in the dosage used of the latter may have affected the study’s results. “Because optimal doses have not been established for many botanicals, clinical efficacy trials have often yielded negative or inconclusive results,” Gurley points out. He mentions an ongoing dose-ranging study for cranberry that may provide more information on this supplement’s effectiveness.