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Image result for Klebsiella pneumoniae bacteria A few days ago the CDC (Centers for Disease Control and Prevention) released a report about a Nevada woman who died in August 2016 of a bacterial infection that was resistant to all 26 antibiotics available in the US, including the antibiotic of last resort - colistin. Apparently she had picked up the bacterial infection in India, where she been staying for an extended visit and where she had been hospitalized (a fractured leg, which led to a hip infection). Because of the antibiotic resistance, the infection spread, and she went into septic shock and died.

India has soaring rates of antibiotic resistance due to misuse of antibiotics (or antimicrobials). But this is not just a problem with infections acquired in India, but throughout the world. Antibiotic resistance is increasing everywhere (post with video of how superbugs evolve). This is because bacteria are constantly evolving against the antibiotics they're exposed to. We may reach a point where simple cuts or infections could lead to death because no antibiotics will work. The World Health Organization said in a 2014 report that: "The problem is so serious that it threatens the achievements of modern medicine. A post-antibiotic era—in which common infections and minor injuries can kill—far from being an apocalyptic fantasy, is instead a very real possibility for the twenty-first century."

New antibiotic development is not keeping pace with the emergence of new antibiotic resistant bacteria. According to the CDC: "Each year in the United States, at least 2 million people become infected with bacteria that are resistant to antibiotics and at least 23,000 people die each year as a direct result of these infections." On top of that, too few antibiotics are under development, and those antibiotics tend to be developed by small companies, not the big pharmaceutical companies. Farmers are still giving antibiotics (antimicrobials) to farm animals unnecessarily, typically as "growth promoters" or to try to prevent disease. The sale of antibiotics routinely fed to animals has been increasing in recent years, and currently about 80% of all antibiotics used in the US are given to livestock animals (of which nearly 70 percent of those used are considered “medically important” for humans).

Excerpts from The Atlantic: A Woman Was Killed by a Superbug Resistant to All 26 American Antibiotics

Yesterday morning, I published a story about the silent spread of resistance against the antibiotic of last resort, colistin—a major step toward the emergence of a superbug resistant to all antibiotics. While reporting this story, I interviewed Alex Kallen, an epidemiologist at the CDC, and I asked if anyone had found such a superbug yet. “Funny you should ask,” he said.

Funny—by which we all mean scary—because yesterday afternoon, the CDC also released a report about a Nevada woman who died after an infection resistant to 26 antibiotics, which is to say all available antibiotics in the U.S. The woman, who was in her 70s, had been previously hospitalized in India after fracturing her leg, eventually which led to an infection in her hip. There was nothing to treat her infection—not colistin, not other last-line antibiotics. Scientists later tested the bacteria that killed her, and found it was somewhat susceptible to fosfomycin, but that antibiotic is not approved in the U.S. to treat her type of infection.

The woman was isolated so that her superbug would not infect other patients in the hospital. And subsequent samples from other patients near her in the hospital have not turned it up. If this superbug is somehow gone from the hospital and gone from the U.S., that would be great news. But even if so, other pan-resistant superbugs are likely to emerge.

Here’s why: The most worrisome kind of colistin resistance is caused by a single gene called mcr-1....What makes mcr-1 special is that sits on a loop of free-floating DNA called a plasmid, which bacteria of different species can pass back and forth. And there are many plasmids out there with genes that confer resistance to this or that class of antibiotics. Where might bacteria go to hang out and swap plasmids? Well your gut is a big bag of bacteria. One day, you might pick up some bacteria with a plasmid carrying resistance to colistin. Years later, you might pick up some bacteria with a plasmid carrying resistance to carbapenems. And so. They start swapping plasmids. All this time you are healthy, and these bacteria just lurk in your gut, not causing much trouble. Then you get sick, your immune system is down, and you take antibiotics for an infection. The antibiotics kill everything but the resistant bacteria, which have by now collected all the resistance genes and no competition. That’s how you get a pan-resistant infection.

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How does the medical profession currently view probiotics in the prevention and treatment of urinary tract infections (UTIs), especially recurrent infections? Answer: Only a few studies have been done, but what little is known is promising, which is good because traditional antibiotic treatment has problems (especially antibiotic resistance). The following article excerpts are from Medscape. Medscape is a popular web resource for physicians and health professionals. It features peer-reviewed original medical journal articles, CME (Continuing Medical Education), daily medical news, drug information, etc. To read the entire article without registering with Medscape (registration is free for everyone), just Google the title and then click on it. From Medscape:

Probiotics in Preventing Recurrent Urinary Tract Infections in Women: A Literature Review

Increasing antibiotic resistance and increasing resistance to commonly used antibiotics makes treatment and prevention of urinary tract infections difficult. Although more research is needed, probiotics should be considered a useful and safe alternative to antibiotics. Urinary tract infections (UTIs) are one of the most common bacterial infections in women, accounting for over 6 million primary care visits annually (Zak, 2014). Approximately 50% to 60% of women will develop a UTI in their lifetime...

Treatment is often complicated by the high rates of reoccurrence. Approximately 20% to 30% of women with a UTI will have a reoccurrence (Beerepoot, Geerlings, van Haarst, van Charante, & ter Riet, 2013)... Ikaheimo et al. (1996) found that in the primary care setting, 53% of women over 55 years of age and 36% of younger women will have a reoccurrence within a year. Women are diagnosed with recurrent UTIs if they have three UTIs with three positive urine cultures within a 12-month period or two infections in the previous six months (Al-Badr & Al-Shaikh, 2013).

Symptoms of UTIs include dysuria, frequency, urgency, nocturia, suprapubic pain, and hematuria, all of which significantly affect the quality of life. Contributing factors to UTIs include inadequate hydration, voiding patterns, diaphragm and spermicide use, tight undergarments, wiping technique, immuno-suppression, postmenopausal women, diabetes mellitus, and frequent sexual intercourse (Al-Badr & Al-Shaikh, 2013). Escheria coli (E. coli) causes the majority of UTIs in women, accounting for 75% to 95% of infections (Al-Badyr & Al-Shaikh, 2013; Nosseir, Lind, & Winkler, 2012). Recurrent UTIs are most often (~80% of time) caused by reinfection with the same pathogen (Al-Badyr & Al-Shaikh, 2013; Nosseir et al., 2012).

Continuous antibiotics are currently used as treatment and prophylaxis for recurrent UTIs. The literature recommends treating anywhere from 6 to 12 months to 2 to 5 years (Zak, 2014). However, the long-term effects of antibiotics are unknown. We are currently in an age of increasing antibiotic resistance, and increasing resistance to commonly used antibiotics, such as trimethoprim-sulfamethoxazole (Gupta, Hooton, & Stamm, 2001), makes treatment and prevention of infections difficult. Therefore, finding safe and effective alternatives to preventing recurrent UTIs in women is imperative. 

The literature provides low-to-moderate evidence that probiotics are effective in preventing UTIs in women. Abdulwahab, Abdulazim, Nada, and Radi (2013) examined the effect of vaginal Lactobacillus from 100 healthy women on the growth of uropathogenic E. coli isolates from 100 women with recurrent UTIs. They found that the majority of Lactobacilli in healthy women without UTIs were L. acidophilus, L. fermentum, and L. delburekii. In addition, they found that all vaginal Lactobacilli strains (from asymptomatic women) could inhibit the growth of E. coli on the agar plate. The weakness of this study, however, is that it was done in a laboratory. 

Two studies went one step further by examining human prophylaxis with Lactobacilli, either orally or vaginally, as means to prevent recurrent UTIs. Beerepoot et al. (2012) compared the effects of oral L. rhamnosus and L. reuteri (109 CFU twice daily) with trimethoprim-sulfamethoxazole (TMP-SMX, 480 mg daily) on preventing recurrent UTIs in 252 postmenopausal women. In their randomized control trial, they found that after 12 months of prophylaxis, the mean number of symptomatic UTIs decreased form 7.0 (from the previous year) to 2.9 in the TMP-SMX group and from 6.8 to 3.3 in the Lactobacilli group.

Antibiotic resistance from E. coli (causing UTI and in urine and feces of asymptomatic women) to sulfamethoxazole, trimethoprim and amoxicillin increased...after 12 months of TMP-SMX prophylaxis, 100% of urinary E. coli was found resistant to trimethoprim and sulfamethoxazole. No antibiotic resistance occurred in the Lactobacilli group.

Stapleton et al. (2011) considered the effect of an intravaginal probiotic, L. crispatus, for prevention of recurrent UTIs in 100 premenopausal women. In their randomized, placebo-controlled phase 2 trial, they found that L. crispatus was associated with reduced symptomatic UTIs. Fifteen percent of women taking L. crispatus and 27% of women taking placebo experienced recurrent UTIs. 

Each of the three studies above examined different species of Lactobacilli. Abdulwahab et al. (2013) investigated the effects of L. acidophilus, L. fermentum, and L. delburekii. Beerepoot et al. (2012) studied L. rhamnosus and L. reuteri and Stapleton et al. (2011) investigated L. crispatus....However, all three studies provide evidence that even with different strains of Lactobacilli and different routes of receiving the probiotic, Lactobacilli can reduce recurrent UTIs in women.

The literature review reveals that Lactobacillus probiotics, taken either orally or vaginally, are likely effective in reducing recurrent UTIs in women. Lactobacilli may be especially useful for women with a history of recurrent, complicated UTIs or prolonged antibiotic use. Although Lactobacilli are found slightly less effective to antibiotics in reducing recurrent UTIs (at least in the dose and frequency studied), probiotics do not cause antibiotic resistance and may offer other health benefits due to vaginal re-colonization with Lactobacilli. In addition, long-term health effects of continual antibiotic use are still lacking. 

Future studies should examine optimum frequency, duration, species, and route of Lactobacilli... In an age of increasing antimicrobial resistance, other non-antibiotic methods of preventing recurrent UTIs, such as cranberry tablets, herbs, and acupuncture, should also be further studied, especially in comparative effectiveness research with Lactobacilli. 

EscherichiaColi NIAID.jpgE. coli bacteria.  Photo:Wikipedia, Rocky Mountain Laboratories