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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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

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

Bladder Urine Is Not Sterile

Alan J. Wolfe PhD, Professor Department of Microbiology and Immunology Stritch School of Medicine, Loyola University Chicago Maywood, ILMedicalResearch.com Interview with:
Alan J. Wolfe PhD, Professor
Department of Microbiology and Immunology
Stritch School of Medicine, Loyola University Chicago
Maywood, IL

Medical Research: What is the background for this study?

Dr. Wolfe: Several years ago, Dr. Brubaker and I began a conversation. As a urogynecologist, she was concerned about the general lack of improvement in diagnosis and treatment in her urogynecological practice and thus in clinical outcome. As a microbiologist, I was extremely skeptical of the dogma that urine in the bladder was sterile in the absence of a clinical infection. This skepticism was based upon my former work in bacterial motility and biofilm formation and on the knowledge that most bacteria are not cultured by the standard clinical microbiology urine culture method. With the goal of ultimately improving urogynecological practice, and with the help of our colleagues in the Loyola Urinary Education and Research Collaborative (LUEREC), we decided to test the sterile bladder hypothesis by seeking evidence of bacteria in urine taken directly from the bladder to avoid vulva-vaginal contamination. To detect bacterial DNA, we used high-throughput DNA sequencing technology. To detect live bacteria, we developed an Expanded Quantitative Urine Culture (EQUC) protocol. We applied these complementary approaches to women with and without urgency urinary incontinence (UUI) whose standard clinical urine culture was negative.

Medical Research: What are the main findings?

Dr. Wolfe: First and foremost, the bladder is not sterile. We can detect bacteria and/or bacterial DNA in most women whether they have urgency urinary incontinence (UUI) or not. Thus, the female bladder contains a resident bacterial community, which we call the female urinary microbiome (FUM). We found that bacterial members of the FUM are distinct from the bacteria that typically cause urinary tract infections (UTI). Thus, the bacteria that make up the FUM are not the bacteria that cause typical UTIs. Indeed, detection of the female urinary microbiome was associated with reduced risk of UTIs that often occur after instrumentation or surgery. We therefore hypothesize that the FUM or some members of the FUM could protect against UTI. We also saw that the FUM in women with UUI differs from the FUM in women without UUI and that certain bacterial species were considerably more common in women with urgency urinary incontinence than in women without urgency urinary incontinence . We hypothesize that some of these bacteria could be causative or contributory to UUI or they could be a consequence of urgency urinary incontinence.

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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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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.