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Fewer drugs, more bugs: Antibiotic resistance tops concerns at infectious diseases conference

From the November ACP Hospitalist, copyright © 2007 by the American College of Physicians

By Jessica Berthold

How to best treat patients in an era of increasingly drug-resistant infections and lagging antibiotic development was a core issue at the 25th annual Infectious Diseases Society of America conference in San Diego in early October.

"Not only do we have more and more resistance, but we have fewer and fewer drugs," said IDSA president Henry Masur, FACP, chief of the critical care medicine department at the National Institutes of Health Clinical Center. "We think it's extremely important for the public to understand that we need to do something to both reduce resistance and increase our armamentarium."

One way to cut back on resistance is through careful use of antibiotics, said Louis Rice, FACP, of Louis Stokes Cleveland VA Medical Center, who gave the Maxwell Finland lecture at the conference. While a common treatment strategy is to rotate the type of antibiotic a patient uses so that resistance to any one drug doesn't have enough time to develop, Dr. Rice expressed skepticism about the approach.

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One way to cut back on resistance is through careful use of antibiotics.

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"It's like telling an alcoholic patient with liver disease to alternate drinking beer, whiskey and gin every three months," Dr. Rice said. "It doesn't work because it's the alcohol, not the flavor, that matters."

The best plan to prevent resistance, then, is to "stop irritating [the bacteria]," Dr. Rice said. That means withholding antibiotics from those who don't truly need them—which can be risky for liability reasons, and because patients may feel dissatisfied if they expected a prescription, he said. Physicians also shouldn't give multiple antibiotics when one type will suffice—which also can be difficult since the nature of the pathogen is often unknown at the onset of therapy and "we want to cover our [rear ends]," Dr. Rice said.

Of course, antibiotics shouldn't be given any longer than necessary, but that's easier said than done, Dr. Rice noted. The correct treatment length is fairly certain only for some conditions, like outpatient urinary tract infections, sexually transmitted diseases, tuberculosis, endocarditis and streptococcal pharyngitis, he said. For others, the data are limited, conflicting or both.

"The duration of therapy is a 'known unknown'—we know we don't know enough about it," Dr. Rice said. "We need to make it clear to our colleagues that there is no magic to the current established durations of therapy."

The IDSA has proposed three trials to the National Institute of Allergy and Infectious Diseases (NIAID) that would look at the question of antibiotic treatment length—and the NIAID has given an encouraging response, Dr. Rice said. Recent studies showing that infection rates can be improved through means like hand-washing protocols, as well as quality improvement programs focusing on reducing infections, may also help nip infections in the bud before antibiotics are necessary, he added.

The recent introduction of the Strategies to Address Antimicrobial Resistance (STAAR) Act in the U.S. House (H.R. 3697) is also an encouraging sign, as it will help strengthen federal antimicrobial resistance surveillance, prevention and control by establishing networks of consulting experts, several speakers noted during the conference, including Drs. Rice and Masur.

"There is hope," Dr. Rice said. "But we need to continue to push for legislation and studies on this issue, and be consistent in our message [to prescribe responsibly]."

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The difficult dilemma of C. difficile

Treatment of Clostridium difficile was a particular topic of concern at the conference, and with good reason: 253,000 hospitalized patients were affected by C. difficile-associated disease (CDAD) in 2005—more than double the number in 2000, according to the CDC.

"C-diff rates are going up, and there aren't any good new drugs out yet. We need to see the peak of this epidemic, and soon," said Dale Gerding, FACP, of ACOS Research and Development at Hines VA Hospital in Chicago.

In one session, experts debated whether to use oral metronidazole or vancomycin as the first course of treatment for C. difficile. John G. Bartlett, MACP, professor and chief of Johns Hopkins University School of Medicine's division of infectious diseases, noted that several recent studies have found vancomycin performed best in treating severe cases of C. difficile infection and had better hospital outcomes than metronidazole, though the drug results for mild and moderate cases weren't significantly different. Vancomycin's only true disadvantage is that it's more expensive than metronidazole—which shouldn't be an issue when morbidity and mortality are at stake, according to Dr. Bartlett.

"In summary, you give vancomycin to your mother and metronidazole to your mother-in-law," he said.

But Jacques Pepin, MD, of the University of Sherbrooke in Quebec, questioned the validity of the studies cited by Dr. Bartlett, saying they used outcomes—such as not having diarrhea by day six of treatment—that weren't the most relevant. When audience members were asked to vote on which drug they'd prescribe in different scenarios involving C. difficile, a majority seemed to prefer metronidazole.

A separate session discussed how to prevent recurrences of C. difficile infection. Research indicates that the risks for recurrence include ongoing or new exposure to an antibiotic, age older than 65, prolonged hospitalization, serum albumin level of less than 2.5 g/dL, and reduced serum IgG antibodies to toxin A, according to Johan S. Bakken, FACP, of St. Luke's Infectious Disease Associates in Duluth, Minn. Dr. Bakken's presentation was given in absentia by a colleague while Dr. Bakken stayed home to care for a very ill patient.

There is no proven treatment in the U.S. to prevent C. difficile recurrence after an initial course of therapy, but fecal bacteriotherapy has become the first-line treatment for recurrences in Scandinavia, according to Dr. Bakken. The nontraditional method restores colon homeostasis by reintroducing missing bacterial flora from a stool collected by a healthy donor. Instillation procedures include gastroscopy, X-ray tip verification, nasogastric tube, colonoscopy and enema.

Eleven published reports, involving a total of 80 cases of treatment with fecal bacteriotherapy—usually through fecal enema—exhibit a cure rate that is "enviable," said Dr. Bakken's proxy presenter Thomas Moore, FACP, of Wichita, Kan. In nine of the studies, the cure rate was 100%; in the other two, it was 94% and 81%, he noted.

"Never underestimate the healing power of stool," said Dr. Moore, who himself has performed at least 65 fecal enemas and seen a 97% success rate. Sick elephants in the wild are fed stool from their mothers, he noted, so the treatment idea is "nothing new."

The treatment's other benefits include the fact that it is inexpensive, has no known side effects and reduces the risk of antibiotic-associated bacterial resistance. It also breaks the cycle of antibiotic usage, and may save costs when compared to repeat courses of antibiotic therapy. Normal bowel function is usually restored within 24 hours of the treatment, Dr. Moore said. Pretreatment with oral vancomycin and omeprazole is "probably a good idea," he added.

"Fecal transplant is 'dirt cheap,'" Dr. Moore quipped. "It is a low-tech therapy that can be administered in most hospitals…and re-treatment usually isn't necessary."

A fecal donor is usually a patient's spouse or loved one because "you don't just want anyone's stool in your colon," said Dr. Moore. Indeed, one of the biggest problems with the treatment is the "ick" factor, Dr. Bartlett said at an earlier session.

Other potential obstacles to the treatment include the possibility that new pathogens could be introduced with the donor sample; a potential for physical complications from the instillation procedure, such as perforation of the intestine; and perceived medico-legal implications, according to Dr. Bakken. Medicare doesn't cover donor stool screening and instillation procedures either, he noted.

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New research

New research on HIV/AIDS, Lyme disease and Rocky Mountain spotted fever was presented at the meeting as well. Highlights included a study that found Rocky Mountain spotted fever cases nearly tripled between 2001 and 2005 in the U.S., from 695 to 1,936 cases. The illness was most common in men 50 to 59 years old and in the South Atlantic states, but there was a substantial increase in adults over age 50, women and suburban dwellers, the study found.

"This is the highest level of [Rocky Mountain spotted fever] in the history of its surveillance." —John Openshaw, MS

"This is the highest level of the disease in the history of its surveillance," said John Openshaw, MS, study co-author and an applied epidemiology fellow at the CDC. "It likely reflects a combination of factors, including greater physician awareness, more people spending time outdoors and a habitat modification."

Meanwhile, the first study to evaluate molecular evidence of recurrent Lyme disease found that people who experience a second episode of erythema migrans were probably bitten by another tick rather than experiencing a relapse of the first infection.

"Our findings underscore the importance of preventing exposure to ticks," said Robert Nadelman, MD, the study's lead author and professor of medicine at New York Medical College, Valhalla. "It appears that even when people have already had Lyme disease, they are not taking sufficient steps to avoid being bitten again."

Two HIV/AIDS studies challenged perceptions about the disease. While "wasting," or excessive weight loss, was once a key characteristic of HIV/AIDS, a new study found that 63% of HIV-positive patients are overweight or obese, about the same percentage as the general population. Use of highly active antiretroviral therapy (HAART) wasn't related to weight gain, it found.

"Doctors have been caught up in saving people's lives and keeping opportunistic infections at bay, but those rates are low and people are living longer," said Nancy Crum-Cianflone, MD, MPH, lead author of the study and an HIV research physician with TriService AIDS Clinical Consortium in San Diego. "Now we need to start focusing on regular health issues like cancer prevention, blood pressure control and excess weight gain."

A separate study found that HIV-positive people over age 50 on HAART were no more likely to have heart disease, diabetes, osteoporosis or cognitive deficits than the general population. They were more likely to have high blood pressure (51%) compared to a control group (31%), however.

"Earlier studies have shown that patients on HAART had a higher risk of heart attack, but we didn't see that," said Nur Onen, MD, lead author of the study and an infectious diseases fellow at Washington University School of Medicine in St. Louis. "But those studies looked at younger people, and those in our study were over 50, and were on therapy for an average of seven years."

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ACP Hospitalist provides news and information for internists about the practice of medicine and reports on the policies, products and activities of ACP. All published material, which is covered by copyright, represents the views of the contributor and does not reflect the opinion of the American College of Physicians or any other institution unless clearly stated