Urinary Tract Infections Not Prevented By Antibiotics, Future Infections May Become Antibiotic Resistant

After a first childhood urinary tract infection (UTI), daily antibiotics may not prevent another such infection, and may actually increase the risk that the next urinary tract infection is caused by resistant bacteria, according to a new study in the July 11 issue of the Journal of the American Medical Association. In the first large study of children diagnosed with UTI in a primary care pediatric setting, researchers from The Children's Hospital of Philadelphia reviewed the electronic health records of 74,974 children with at least two clinic visits in The Children's Hospital of Philadelphia's pediatric healthcare network between July 2001 and May 2006. The researchers found that 611 children had a first urinary tract infection and 83 had a recurrent UTI. Children between ages three and five, Caucasians, and those with severe vesicoureteral reflux had the highest risk of recurrent UTI. Receiving a daily dose of preventive antibiotics was not associated with a lower risk of recurrent UTI. "The majority of children with first UTI were female, Caucasian and two through six years old. Most did not have an imaging study performed and did not receive daily antibiotics to prevent infections," said Patrick Conway, M.D. M.Sc., primary investigator of the study. "We found that daily antibiotic treatment was not associated with a decreased risk of recurrent UTIs, but was associated with an increased risk of resistant infections." Currently at Cincinnati Children's Hospital Medical Center, Dr. Conway conducted the research while at The Children's Hospital of Philadelphia and a Robert Wood Johnson Clinical Scholar at the University of Pennsylvania. "More definitive studies, such as clinical trials, are needed to look at this issue." said Ron Keren, M.D., M.P.H., a general pediatrician at The Children's Hospital of Philadelphia and senior author on this study. "But given these findings, it is appropriate for pediatricians to discuss with families the risks and unclear benefits of daily preventive antibiotic treatment after a child has had a first UTI." UTIs are common in children. In fact, of all the children born in one year, 70,000 to 180,000 will have a UTI by age six. The American Academy of Pediatrics (AAP) practice guideline for management of children after a first UTI recommends an imaging study to evaluate the presence and degree of vesicoureteral reflux (VUR), a condition found in approximately 30 to 40 percent of children who have had a UTI. If the child has VUR, daily antibiotic treatment is recommended in an attempt to prevent recurrent UTIs. Vesicoureteral reflux (VUR) occurs when urine in the bladder flows back into the ureters or kidneys during urination. It is thought that a child who has VUR is at risk for developing recurrent kidney infections, which, over time, can cause damage to the kidneys. However, Dr. Conway summarized, "The majority of children have lower grade VUR and this lower grade VUR was not associated with an increased risk of recurrent UTI in our study."

IBS, targeted antibiotics lead to long-lasting improvement in symptoms, study

Researchers at Cedars-Sinai Medical Center have found that a nonabsorbable antibiotic - one that stays in the gut - may be an effective long-term treatment for irritable bowel syndrome (IBS), a disease affecting more than an estimated 20 percent of Americans. The findings, which showed that participants benefited from the antibiotic use even after the course of treatment ended, support previously published research identifying small intestine bacterial overgrowth (SIBO) as a possible cause of the disease. The research was presented at the recent American College of Gastroenterology's annual meeting in Honolulu, HI. "This study is important as it is the first to show that the use of targeted antibiotics results in a more significant and long-lasting improvement in IBS symptoms," said Mark Pimentel, M.D., first author on the study and director of the GI Motility Program at Cedars-Sinai. "These results clearly show that antibiotics offer a new treatment approach - and a new hope - for people with IBS." The randomized, double blind study involved 87 patients. Those on the rifaximin experienced a 37 percent overall improvement of their IBS symptoms as compared to 23 percent on the placebo. Among study subjects whose primary symptom was diarrhea, those on the antibiotic showed more than twice the improvement of those on the placebo (49 percent vs. 23 percent). Patients received the drug (or placebo) for 10 days and were then followed for a total of 10 weeks. Participants kept a stool diary, took a questionnaire and were given methane breath tests. The positive effects of the drug were shown to continue throughout most of the 10-week study, not just during the actual antibiotic course. Because the cause of IBS has been elusive, treatments for the disease have historically focused on reducing its symptoms - diarrhea and constipation - by giving medications that either slow or speed up the digestive process. In 2000, Pimentel linked bloating, the most common symptom of IBS, to bacterial fermentation, showing that small intestine bacteria overgrowth (SIBO) may be the causative factor in IBS (The American Journal of Gastroenterology, Dec. 2000). To show evidence of small intestine bacterial overgrowth, participants in both studies were given a lactulose breath test, which monitors the level of hydrogen and methane (the gases emitted by fermented bacteria) on the breath. In the first study, an abnormal breath methane profile was shown to be 100 percent predictive of constipation-predominant IBS. In the current study, the correlation between the amount of methane and the amount of constipation was confirmed, another key finding. "We were pleased - but not surprised - with the results of this study," said Pimentel. "The next step is to start larger, multi-centered studies to confirm the positive results of this study, which suggest that people can benefit from targeted antibiotic treatment for their IBS." Irritable Bowel Syndrome is an intestinal disorder that causes abdominal pain or discomfort, cramping or bloating and diarrhea and constipation. It is a long-term condition that usually begins in adolescence or in early adult life. Episodes may be mild or severe and may be exacerbated by stress. It is one of the top ten most frequently diagnosed conditions among U.S. physicians and affects women more often than men. Other authors from Cedars-Sinai include Sandy Park, B.A., Yuthana Kong M.P.H. and Robert Wade. Sunanda V. Kane from the University of Chicago also participated in the study. Rifaximin is made by Salix Pharmaceuticals, Inc. Funding for the study was provided by Salix Pharmaceuticals, Inc.

Antibiotics May Not Prevent Urinary Tract Infections From Recurring In Children And May Cause Resistance

Prescribing antibiotics to prevent urinary tract infection from recurring in children under age 6 appears to have no effect and may increase the risk of drug resistance, according to a new study supported by HHS' Agency for Healthcare Research and Quality and published in the July 11, 2007 issue of JAMA. Urinary tract infections are a common problem in children; it is estimated that 70,000 to 180,000 children born in a given year will have this type of infection by the age of 6. Urinary tract infections may cause obvious symptoms in older children, such as frequent or painful urination, but these symptoms are harder to detect in infants and younger children. The American Academy of Pediatrics currently recommends daily preventive antibiotics if a child has vesicoureteral reflux, a condition in which urine flows backward from the bladder towards the kidneys to varying degrees, ranging from 1 (mild) to 5 (severe). It has been postulated that this reflux increases the risk of repeated urinary tract infections and infection-related scarring of the kidneys. However, the investigation by the AHRQ-funded University of Pennsylvania Center for Education and Research on Therapeutics found that the majority of the children in the study had milder grades of vesicoureteral reflux and these were not associated with increased risk of recurrent urinary tract infection. The researchers, who were led by Patrick Conway, M.D., also found no association between giving antibiotics to prevent an infection from recurring and the risk of recurrent urinary tract infection. But they did find significant increased risk of resistant infection in those children who were exposed to preventive antibiotics. The patients in the study were from a Children's Hospital of Philadelphia-supported network of 27 primary care pediatric practices spanning three states. Of the approximately 75,000 children ranging from infancy through the age of 6 who were in the network from July 2001 to May 2006, 611 had a first urinary tract infection and 83 had a recurrent infection. Sixty-one percent of the cases of recurrent urinary tract infection were caused by a pathogen with antibiotic resistance, including Escherichia coli and Enterococcus. The researchers also found that a child's age and race may play a role in the risk of urinary tract infection recurring and being resistant to antibiotics. Children between 2 and 6 years of age had a higher risk of recurrent urinary tract infection in comparison to children less than 2 years of age. Furthermore, although the non-white children in the study were less likely than white children to have recurrent urinary tract infection, they had a greater risk of having an antibiotic-resistant recurrent infection. According to Dr. Conway, it would be prudent for physicians to discuss the potential risks and unclear benefits of giving children antibiotics tp prevent recurrent infections with parents, who can then decide whether to start daily preventive antibiotics or closely monitor their child with their physician's guidance. Dr. Conway and his team say that this is the first study to estimate the effectiveness of preventive antibiotics in a large primary care pediatric population and the first to determine risk factors for the disease in such a large group.

Too Many Antibiotics Prescribed For Sinus Infections

US scientists researching treatments for sinus infections suggest that antibiotics are overprescribed to treat the condition. And they are concerned this could be increasing the drug resistance and virulence of infectious bacteria.The study is published in the March issue of Archives of Otolaryngology-Head & Neck Surgery.According to the study, by Hadley J. Sharp and colleagues at the University of Nebraska Medical Center, Omaha, US, antibiotics were prescribed for 82 per cent of acute sinus infections and nearly 70 per cent of chronic sinus infections.This is surprising because most sinus infections are caused by viruses, and antibiotics only kill bacteria. The scientists used national data from 1999 and 2002 to find out which drugs were being prescribed for sinus infections by general practitioners, outpatient and emergency departments. The data was representative of the US population and came from two national surveys collected by the National Center for Health Statistics.Rhinosinusitis, commonly known as sinus infection or sinusitis, is an inflammation of the sinus cavities that connect with the nasal passage. According to the study, it is a common and expensive medical condition in the US.Acute sinusitis occurs for up to 4 weeks and is thought to be caused mostly by infectious agents. Chronic sinusitis is thought to be affected mostly by allergies, hormone changes and facial anatomy and symptoms persist for 12 or more weeks.In 2002, of all the antibiotic prescriptions that year in the US, 21 per cent were for adults with sinus infections and 9 per cent was for children.According to the survey data, over 14 million visits are paid to health care facilities in the US every year are for chronic sinusitis, while over 3 million are for acute sinusitis. As a proportion of all ambulatory care in the US per year, chronic sinusitis represents 1.39 per cent of visits and acute sinusitis 0.30 per cent.In 69.95 percent of visits for chronic sinusitis at least one antibiotic was prescribed. For acute sinusitis this figure was 82.74 per cent.Sharp and colleagues assessed that "The most frequently recommended medications for treatment of both acute and chronic rhinosinusitis are antibiotic agents, followed by antihistamines; nasal decongestants; corticosteroids; and antitussive, expectorant and mucolytic agents, respectively".The most commonly used antibiotics for both chronic and acute bacterial infections were penicillins (mainly amoxicillin and amoxicillin-clavulanate potassium, brand name Augmentin). These were prescribed appropriately, they said, with 30.35 per cent of chronic and 27.18 per cent of acute infection visits mentioning penicillin prescriptions.However, the researchers questioned the use of the stronger antibiotics such as erythromycins, lincosamides, and macrolides, amongst others. These were mentioned in 24.32 per cent of acute sinusitis visits, which, in order, makes them more frequently prescribed than cephalosporins, sulfonamides and trimethprim, and tetracyclines.The authors assessed the relative proportions of the causes of sinusitis from other studies. Comparing these proportions with the relative proportions of what is actually being prescribed to treat sinusitis they found major discrepancies.They concluded that "Prescription antibiotic drugs are being used far more than bacterial causes studies would indicate." Sharp and colleagues also assessed that "Nasal and inhaled corticosteroids are prescribed more frequently to treat acute rhinosinusitis than published studies imply is necessary". However, they estimated that where antihistamines were prescribed, this was roughly in proportion with estimated prevalence of allergic sinusitis.In trying to fathom why the use of antibiotics is so high, the authors suggest that some doctors could be trying to treat secondary infections. On the other hand, it could be because doctors think antibiotics are working because patients get better while taking them, whereas they could be getting better anyway.They express concern about the problems that overuse of antibiotics bring, including drug resistance and increased virulence of bacteria.They conclude, "When two-thirds of patients with sinus symptoms expect or receive an antibiotic and as many as one-fifth of antibiotic prescriptions for adults are written for a drug to treat rhinosinusitis, these disorders hold special pertinence on the topic."

Antibiotics. How do antibiotics work? What are they for? Side effects

Antibiotics, sometimes known as antibacterials, are drugs used to treat infections caused by bacteria. These are tiny organisms, too small to see with the naked eye, that sometimes cause illness in humans. Well-known illnesses caused by bacteria include tuberculosis, salmonella, syphilis and some forms of meningitis. However many types of bacteria do not cause illness and live harmlessly on, and in, the human body. Our immune systems, with their antibodies and special white blood cells, can usually kill harmful bacteria before they multiply enough to cause symptoms. And even when symptoms do occur, the body can often fight off the infection. But sometimes the body is overwhelmed by a bacterial infection and needs help to get rid of it. This is where antibiotics come in. The very first antibiotic was penicillin and along with a family of related antibiotics (such as ampicillin, amoxicllin and benzylpenicillin) it is still widely used to treat many common infections. Now there are several other different kinds of antibiotics. All of them are only available on prescription. HOW DO ANTIBIOTICS WORK? Some antibiotics, such as the penicillins, are 'bactericidal', meaning that they work by killing bacteria. They do this by interfering with the formation of the cell walls or cell contents of the bacteria. Other antibiotics are 'bacteriostatic', meaning that they work by stopping bacteria multiplying. WHAT ARE ANTIBIOTICS FOR? Antibiotics are usually used to treat infections caused by bacteria. They do not work against other organisms such as viruses or fungi. It's important to bear this in mind if you think you have some sort of infection, because many common illnesses, particularly of the upper respiratory tract such as the common cold and sore throats, are usually caused by viruses. Overuse of antibiotics can lead to bacteria becoming resistant to them so it's important to only take them when necessary. Some antibiotics can be used to treat a wide range of infections and are known as 'broad-spectrum' antibiotics. Others are only effective against a few types of bacteria and are called 'narrow-spectrum' antibiotics. Some antibiotics work against aerobic bacteria, that is organisms that need oxygen to live, while others work against anaerobic bacteria, organisms that don't need oxygen. Sometimes antibiotics are given to prevent an infection occurring, for example, before certain operations. This is known as prophylactic use of antibiotics and is common before orthopaedic and bowel surgery. SIDE EFFECTS OF ANTIBIOTICSThe most common side effects with antibiotic drugs are diarrhoea, feeling sick and being sick. Fungal infections of the mouth, digestive tract and vagina can also occur with antibiotics because they destroy the protective 'good' bacteria in the body (which help prevent overgrowth of any one organism), as well as the 'bad' ones, responsible for the infection being treated. Rare, but more serious side effects, include the formation of kidney stones with the sulphonamides, abnormal blood clotting with some of the cephalosporins, increased sensitivity to the sun with the tetracyclines, blood disorders with trimethoprim, and deafness with erythromycin and the aminoglycosides. Sometimes, particularly in older people, antibiotic treatment can cause a type of colitis (inflamed bowel) leading to severe diarrhoea. Penicillins, cephalosporins and erythromycin can all cause this problem but it is most common with clindamycin, an antibiotic usually reserved for serious infections. If you develop diarrhoea while taking an antibiotic, immediately contact your doctor. Some people are allergic to antibiotics, particularly penicillins, and can develop Side effects such as a rash, swelling of the face and tongue, and difficulty breathing when they take them. Always tell your doctor or pharmacist if you have had an allergic reaction to an antibiotic; sometimes the reaction can be serious or even fatal. This is called an anaphylactic reaction. USE ANTIBIOTICS WITH CARE IF ... You should use an antibiotic with care if you have reduced liver or kidney function. You should avoid using any antibiotic to which you have previously had an allergic reaction. TELL YOUR DOCTOR OR PHARMACIST IF YOU ARE PREGNANT OR BREASTFEEDING BEFORE TAKING ANY ANTIBIOTIC. INTERACTIONS WITH OTHER MEDICINESDo not take any other medicines or herbal remedies with an antibiotic, including those you have bought without a prescription, before talking to your doctor or pharmacist. -- Certain antibiotics (e.g. penicillins, cephalosporins) can reduce the effectiveness of oral contraceptives. If you have diarrhoea or vomiting while taking an antibiotic, the absorption of the pill can be disrupted. In either case, you should take additional contraceptive precautions while you are taking the antibiotic. -- There are a number of important interactions between antibiotics and other medicines so it's important to tell which your doctor or pharmacist about any other medicines you are taking. HOW TO USE AN ANTIBIOTICAntibiotics are usually taken orally but can also be given by injection, or applied to the affected part of the body such as the skin, eyes or ears. The drugs begin to tackle most infections within a few hours. It is vital to take the whole course of treatment to prevent recurrence of the infection. Sometimes bacteria become 'resistant' to an antibiotic you have been taking, meaning that the drug will no longer work. Resistance tends to occur when the bacterial infection responsible for the symptoms is not completely cured, even if the symptoms have cleared up. Some of the residual bacteria, having been exposed to, but not killed by, the antibiotic are more likely to grow into an infection that can survive that particular antibiotic. This explains why finishing the course of antibiotics, even if you feel better, is important. Certain antibiotics should not be taken with certain foods and drinks. Some antibiotics are best taken when there is no food in your stomach, usually an hour before meals or two hours after - make sure you follow the instructions on the dispensing label. Do not drink alcohol if you are taking metronidazole. Do not take tetracyclines with dairy products, as these can reduce the absorption of this type of antibiotic.

Non-Stick Technology Utilised To Produce Better Antibiotics

By creating "Teflon" versions of natural antibiotics found in frog skin, a research team led by biological chemist E. Neil Marsh has made the potential drugs better at thwarting bacterial defenses, an improvement that could enhance their effectiveness. Marsh discussed the work at the 234th national meeting of the American Chemical Society in Boston. Marsh and collaborators work with compounds called antimicrobial peptides (AMPs), which are produced by virtually all animals, from insects to frogs to humans. AMPs are the immune system's early line of defense, battling microbes at the first places they try to penetrate: skin, mucous membranes and other surfaces. They're copiously produced in injured or infected frog skin, for instance, and the linings of the human respiratory and gastrointestinal tracts also crank out the short proteins in response to invading pathogens. In addition to fighting bacteria, AMPs attack viruses, fungi and even cancer cells, so drugs designed to mimic them could have widespread medical applications. Scientists have been interested in exploiting these natural antibiotics since their discovery in the 1980s, but they haven't been able to overcome some limitations. In particular, AMPs are easily broken down by protein-degrading enzymes (proteases) that are secreted by bacteria and are also naturally present in the body. Increasing the concentration of AMPs in an effort to get around that problem can cause toxic side effects, such as the destruction of red blood cells---those critical carriers of oxygen in the bloodstream. That seems to happen because sticky parts of the AMP molecule interact with the cell membrane in a harmful way. Marsh had the idea of replacing sticky portions of the peptides with nonstick analogs. His inspiration came from the kitchen as much as the chemistry lab: nonstick cookware is coated with fluorinated polymers, plastic-like compounds composed of chains of carbon atoms completely surrounded by fluorine atoms. The fluorine not only makes Teflon slippery, it also makes the coating inert to almost every known chemical. When Marsh and co-workers swapped sticky parts of their AMP molecule with nonstick, fluorinated versions, the molecules became much more resistant to proteases. "The difference was quite striking," said Marsh, a U-M professor of chemistry. "When we treated them with purified proteases, the nonfluorinated AMPs were all degraded within 30 minutes. Under the same conditions, the fluorinated AMP was completely intact after 10 hours. We think that should make them more effective, as they'll stay around longer in the body. "We also showed that they seem to be at least as good at killing bacteria as their nonfluorinated counterparts, and for some bacteria they're actually significantly better." Next, the researchers plan experiments to learn whether Teflon AMPs are also less toxic than their stickier equivalents. If they are, and if further studies continue to point to their promise, eventually producing large enough quantities of fluorinated AMPs for clinical trials should be quite feasible, Marsh said. Though the research now has obvious practical applications, it started as an exploration in basic science. "We were just interested in translating useful properties of man-made materials into biological molecules," Marsh said. "But fairly immediately we saw the potential for applying our fundamental science to a very important clinical problem, which is the way that more and more bacteria are becoming resistant to more and more conventional antibiotics."

Potential For More Effective Antibiotics Against 'Superbugs'

Biomedical researchers at Boston University's College of Engineering may have discovered the path toward developing better drugs capable of defeating so-called "superbugs," bacteria that have developed resistance to common antibiotics. The researchers have discovered a previously unknown chain of events occurring in bacteria that opens to door to new avenues of research. Currently, three classes of bactericidal antibiotics are used to target different bacterial functions: inhibiting DNA replication; blocking protein-building; or halting construction of cell walls. Research from the laboratory of Professor James Collins found the three classes more alike than anyone realized, and the commonalities may be the bugs' downfall. Collins and colleagues' article, "A Common Mechanism of Cellular Death Induced by Bactericidal Antibiotics," appears in Cell. The researchers discovered a common process, or pathway, that was triggered by all three types of antibiotics. "There's an underlying pathway beyond the drug interacting with the target," said graduate student and lead author Michael Kohanski, "and the endpoint of this pathway is excessive free radical production." Free radicals -- such as hydroxyl or superoxide radicals -- are molecules that carry a free, or unpaired, electron like a weapon. "They'll damage DNA, proteins, lipids in the membrane, pretty much anything. They're equal opportunity damagers," said Kohanski. This hidden pathway and resultant free radical overload appears to help current antibiotics do their job, but is not always enough to kill all bacteria by itself. Collins' group theorizes that if this effect can be amplified, or if the cell's genetic defense against it can be weakened, no bacteria could withstand its effect and the emergence of antibiotic-resistant bacteria could be limited. "Importantly, we showed that if you can inhibit or block the bacterial defense mechanisms to hydroxyl radical damage, you can potentiate or enhance the lethality of bactericidal antibiotics. This highlights the value of taking a network biology approach to antibiotics and provides a framework for creating new classes of drugs," said Collins. "What we think is happening is the cell is getting a signal that says, 'There's something wrong with our energy production system and we need to make more energy.' But, there's really nothing wrong. The cell becomes confused, turns on too many processes at once and it's overwhelmed," said Kohanski. Previous work by Kohanski and co-lead author Dan Dwyer, a postdoctoral researcher in Collins' lab, revealed the first hints that this underlying pathway exists. In studying bacterial response to a quinolone, an antibiotic that inhibits DNA replication, they noted a surprising change in genes responsible for energy production and iron uptake. In the current study, the researchers used DNA microarray studies to see if all three classes of bactericidal antibiotics triggered this process. Across the board, they noted increased gene activity along the intracellular assembly lines that make energy for the bacterial cell, just as in the earlier study. They began to deduce the details of the new pathway. Cells produce free superoxide radicals naturally in oxygen-rich environments, but when they unnecessarily ramp up energy production to a frantic pace -- such as when triggered by antibiotics -- more radicals get churned out than the cell's safety measures can mop up. The superoxide radicals then pull iron from other components of the cell, and this iron rapidly stimulates production of toxic levels of hydroxyl radicals. "It's really amazing that despite the diversity of targets, you have everything funneling into this common pathway, where there's a global meltdown occurring," said Dwyer. "There's almost no way for the cell to recover from this. It shows you how potent these molecules are to damaging and killing the cell." In addition to potentially making bacteria more vulnerable to current drugs, this finding may revitalize development of antibiotic drugs sidelined because of narrow differences between therapeutic and toxic doses. Such drugs might re-enter the pipeline, if this free-radical producing pathway is exploited to lower the therapeutic dose, making formerly dangerous drugs safer.

Study: Antibiotics linked to breast cancer

Antibiotics linked to breast cancer
Feb. 17: NBC's Robert Bazell reports on a new study indicating that women who take antibiotics for a prolonged period are at a greater risk of developing breast cancer.

Bug mutates into medical mystery

WASHINGTON - First came stomach cramps, which left Christina Shultz doubled over and weeping in pain. Then came nausea and fatigue -- so overwhelming she couldn't get out of bed for days. Just when she thought things couldn't get worse, the nastiest diarrhea of her life hit -- repeatedly forcing her into the hospital.
Doctors finally discovered that the 35-year-old Hilliard, Ohio, woman had an intestinal bug that used to be found almost exclusively among older, sicker patients in hospitals and was usually easily cured with a dose of antibiotics. But after months of treatment, Shultz is still incapacitated.
"It's been a nightmare," said Shultz, a mother of two young children. "I just want my life back."
Shultz is one of a growing number of young, otherwise healthy Americans who are being stricken by the bacterial infection known as Clostridium difficile -- or C. diff -- which appears to be spreading rapidly around the country and causing unusually severe, sometimes fatal illness.
That is raising alarm among health officials, who are concerned that many cases may be misdiagnosed and are puzzled as to what is causing the microbe to become so much more common and dangerous.
"It's a new phenomenon. It's just emerging," said L. Clifford McDonald of the federal Centers for Disease Control and Prevention in Atlanta. "We're very concerned. We know it's happening, but we're really not sure why it's happening or where this is going."
Antibiotics to blame?
It may, however, be the latest example of a common, relatively benign bug that has mutated because of the overuse of antibiotics.
"This may well be another consequence of our use of antibiotics," said John G. Bartlett, an infectious-disease expert at Johns Hopkins University in Baltimore. "It's another example of an organism that all of a sudden has gotten a lot meaner and nastier."
In addition, new evidence released last week suggests that the enormous popularity of powerful new heartburn drugs may also be playing a role.
The antibiotics Flagyl (metronidazole) and vancomycin still cure many patients, but others develop stubborn infections like Shultz's that take over their lives. Some resort to having their colon removed to end the debilitating diarrhea. A small but disturbingly high number have died, including an otherwise healthy pregnant woman who succumbed earlier this year in Pennsylvania after miscarrying twins.
The infection usually hits people who are taking antibiotics for other reasons, but a handful of cases have been reported among people who were taking nothing, another unexpected and troubling turn in the germ's behavior.
The infection has long been common in hospital patients taking antibiotics. As the drugs kill off other bacteria in the digestive system, the C. diff microbe can proliferate. It spreads easily through contact with contaminated people, clothing or surfaces.
Infections doubleThere are no national statistics, but the number of infections in hospitals appears to have doubled from 2000 to 2003 and there may be as many as 500,000 cases each year, McDonald said. Other estimates put the number in the millions.
The emerging problem first gained attention when unusually large and serious outbreaks began turning up in other countries. In Canada, for example, Quebec health officials reported last year that perhaps 200 patients died in an outbreak involving at least 10 hospitals. Similar outbreaks were reported in England and the Netherlands.
After the CDC began receiving reports of severe cases among hospital patients in the United States -- and in people who had never, or just briefly, been hospitalized -- it launched an investigation.
In the Dec. 8 issue of the New England Journal of Medicine, the CDC reported that an analysis of 187 C. diff samples found that the unusually dangerous strain that caused the Quebec cases was also involved in outbreaks at eight health care facilities in Georgia, Illinois, Maine, New Jersey, Oregon and Pennsylvania.
"This strain has somehow been able to get into hospitals widely distributed across the United States," said Dale N. Gerding of Loyola University in Chicago, who helped conduct the analysis. "We're not sure how."
But scientists do have a few clues. The dangerous strain has mutated to become resistant to a class of frequently used antibiotics known as fluoroquinolones. That means anyone taking those antibiotics for other reasons would be particularly prone to contract C. diff .
"Because this strain is resistant, it can take advantage of that situation and establish itself in the gut," Gerding said.
Experts said the resistant germ's proliferation offers the latest reason why people should use antibiotics only when necessary, to reduce both their risk for C. diff and the chances that other microbes will mutate into more dangerous forms.
"That's one theory for what's happening here," said J. Thomas Lamont of Harvard Medical School. "If we reduce the number and amount of antibiotics given for trivial infections like colds and stuffy noses, we'd all be a lot better off."
Overuse of antibiotics can make germs more dangerous by killing off susceptible strains, leaving behind those that by chance have mutated to become less vulnerable to the drugs. The resistant strains then become dominant.
High toxin levelsIn addition to being resistant, the dangerous C. diff strain also produces far higher levels of two toxins than do other strains, as well as a third, previously unknown toxin. That would explain why it makes people so much sicker and is more likely to kill. In Quebec, C. diff killed 6.9 percent of patients -- which is much higher than the disease's usual mortality rate -- and was a factor in more than 400 deaths.
Adding to the alarm is evidence that the infection is occurring outside of hospitals. When the CDC began looking for such cases earlier this year, investigators quickly identified 33 cases in New Hampshire, New Jersey, Ohio and Pennsylvania, including 23 people who had never been in the hospital and 10 women who had been hospitalized only briefly to deliver a baby, the agency reported this month. Eight of the patients had never taken antibiotics.
"This is the first time we've started to see this not only in people who have never been in the hospital but also in those who are otherwise perfectly healthy and have not even taken antibiotics," McDonald said.
"It's probably going on everywhere," he said.
It remains unclear whether the cases occurring outside the hospital are being caused by the same dangerous strain.
"We don't really know what's going on here," McDonald said. "We know it's changing in some ways; we know it's changing the kinds of patients it's attacking, and we know it's causing more severe disease. But we don't know exactly why."
Canadian researchers, however, have found one possible culprit: popular new heartburn drugs. Patients taking proton pump inhibitors, such as Prilosec and Prevacid, are almost three times as likely to be diagnosed with C-diff , the McGill University researchers reported in the Dec. 21 issue of the Journal of the American Medical Association. And those taking another type called H2-receptor antagonists, such as Pepcid and Zantac, are twice as likely. By suppressing stomach acid, the drugs may inadvertently help the bug, the researchers said.
Whatever the cause, the infection often resists standard treatment. That is what happened to Shultz, who had been taking antibiotics to help clear up her acne when C. diff hit in June. Because the bacterium can hibernate in protective spores, patients can be prone to recurrences. It can take multiple rounds of antibiotics -- or sometimes infusions of antibodies or ingesting competing organisms such as yeast or the bacteria found in yogurt -- to finally cure them.
"I'm trying to stay positive," Shultz said. "People tell me it does go away and I will get rid of it someday. I'm looking forward to getting my life back, but I'm not convinced I'll ever be normal again."

Travelers possibly exposed to drug-proof TB

ATLANTA - A man with a rare and dangerous form of tuberculosis ignored doctors’ advice and took two trans-Atlantic flights, leading to the first U.S. government-ordered quarantine since 1963, health officials said Tuesday.
The man, who officials did not identify, is at Atlanta’s Grady Memorial Hospital in respiratory isolation.
He was potentially infectious at the time of the flights, so officials at the Centers for Disease Control and Prevention recommended medical exams for cabin crew members on those flights, as well as passengers sitting in the same rows or within two rows.
CDC officials did not release row numbers but said the airlines were working with health officials to contact those passengers. Passengers who should be tested will be contacted by health officials from their home countries.
The infected man flew from Atlanta to Paris on May 12 aboard Air France Flight 385. He returned to North America on May 24 aboard Czech Air Flight 0104 from Prague to Montreal. The man then drove into the United States at the Champlain, N.Y., border crossing.
The man told health officials he was not coughing during the flights. Tests indicated the amount of TB bacteria in him was low, so passengers are not considered to be at high risk of infection, said Dr. Martin Cetron, director of the CDC’s division of global migration and quarantine.
The man had been told by health officials in early May that he had a form of TB that was resistant to first-line antibiotics and was advised not to travel to Europe. “He was told traveling is against medical advice,” said Dr. Steven Katkowsky, director of the Fulton County Department of Health & Wellness.
Health officials said they don’t know how the Georgia man was infected.
Man told not to flyThe government issued the quarantine after a CDC official reached the man by phone in Rome and told him not to take commercial flights, but he flew back to North America anyway. “He was told in no uncertain terms not to take a flight back,” Cetron said.
Cetron reached the man once he was back in the United States. At that point, he voluntarily went to a New York hospital, then was flown by the CDC to the Atlanta hospital. He is not facing prosecution, health officials said.
The quarantine order was the first since 1963, when the government quarantined a patient with smallpox, according to the CDC.
The man, who went on the trip with his wife, also traveled within Europe, but CDC officials said they did not have information to release about whether the trips were by plane, train or other public transportation.
His wife tested negative for TB before the trip and is not considered a public health risk, health officials said.
CDC officials said they are concentrating on investigating the trans-Atlantic flights, when possibility of spread of the disease was greatest because he was in a confined space with other people for many hours.
TB at an all-time lowTuberculosis is a disease caused by germs that are spread from person to person through the air. It usually affects the lungs and can lead to symptoms such as chest pain and coughing up blood. It kills nearly 2 million people each year worldwide.
Because of antibiotics and other measures, the TB rate in the United States has been falling for years. Last year, it hit an all-time low of 13,767 cases, or about 4.6 cases per 100,000 Americans.
Health officials worry about “multidrug-resistant” TB, which can withstand the mainline antibiotics isoniazid and rifampin. The man was infected with something even worse — “extensively drug-resistant” TB, also called XDR-TB, which resists many drugs used to treat the infection.
There have been 17 U.S. XDR-TB cases since 2000, according to CDC statistics.
Three-quarters were people from foreign countries. One case was a Russian man who arrived in Phoenix last year. He was jailed after he stopped taking medications and went unmasked to a restaurant and other businesses, threatening the health of others.
The CDC’s statement that the patient is at the low end of communicability “provides some reassurance,” said Dr. William Schaffner, chairman of the department of preventive medicine at Vanderbilt University.
The highly dangerous form is “expanding around the world,” particularly in South Africa, eastern Europe and the former states of the Soviet Union, he said.

TB patient has less severe strain of disease

ATLANTA - The globe-trotting American lawyer who caused an international health scare by traveling while infected with tuberculosis has a less severe form of the disease than previously diagnosed, a Denver hospital official said Tuesday.
Andrew Speaker was diagnosed in May with extensively drug resistant TB, based on an analysis of a sample taken in March by the U.S. Centers for Disease Control and Prevention. The XDR-TB, as it is called, is considered dangerously difficult to treat.
But three later tests have all shown Speaker’s TB to be a milder form of the disease, multidrug-resistant TB, a federal health official said on condition of anonymity before a news conference in Denver.
Multidrug-resistant TB can be treated with some antibiotics that the more severe form resists.
“Laboratory tests conducted at National Jewish Medical and Research Center indicate that patient Andrew Speaker’s tuberculosis is susceptible to some of the medication previously thought ineffective against his disease,” the hospital said in a written statement.
An about-face on the XDR diagnosis would be a major embarrassment for the CDC. The diagnosis was a key factor in issuing a quarantine order on Speaker, who had traveled to Greece to be married in May despite warnings from health officials that he shouldn’t travel.
On Tuesday, the CDC did not immediately clarify whether they were wrong in the earlier diagnosis or whether there are two conflicting results.
In Denver, hospital spokesman William Allstetter said doctors would announce changes in Speaker’s treatment at a news conference.
An international storySpeaker’s case was an international public health story and even raised questions about U.S. border security. Congress held a hearing on the CDC’s handling of the case and Speaker’s father-in-law, a TB researcher who works for the CDC, also came under scrutiny.
Speaker’s family appeared on TV news talk shows to argue that health officials in Georgia had given confusing advice about whether he could travel.
The young lawyer was originally diagnosed with multidrug-resistant tuberculosis — which can withstand mainline antibiotics used to treat TB — before he left for a wedding and honeymoon in Europe. While there, he was told he had the more dangerous form.
The XDR-TB diagnosis stemmed from a sample taken in March through a bronchoscopy, in which samples are removed through a tube is pushed down a patient’s throat. Other tests analyze sputum that a patient simply coughs up.
There are different lab techniques used to test samples, and it’s not clear how the analysis at National Jewish hospital differs from the CDC’s methods. However, a CDC official said the agency analyzed one of the three sputum samples and came up with the same result as the hospital — that Speaker had the more treatable form of the disease.
Federal health officials said Speaker ignored their warnings to seek help in Europe. Instead, Speaker and his wife crossed the border into the United States after taking a commercial flight to Canada and he was briefly placed under federal quarantine.
The incident prompted a hunt for passengers on the cross-Atlantic flights taken by Speaker so they could be tested for the disease.
Doctors at National Jewish had previously announced Speaker would undergo surgery in July to remove infected lung tissue, a practice sometimes used when drugs can’t completely kill a TB infection. Allstetter wouldn’t say if the surgery was still planned.