Links of interest: Antibiotic resistance

Rising Plague (Brad Spellberg)

Before getting to the numerous recent news items on antibiotic resistance and urinary tract infections, let me quote from Dr. Brad Spellberg’s Rising Plague: The Global Threat from Deadly Bacteria and Our Dwindling Arsenal to Fight Them. (In the following, “community-acquired” means an infection that begins outside a hospital, and fluoroquinolones are commonly used broad-spectrum antibiotics. Emphasis added.)

[R]esistance of E. coli to fluoroquinolone antibiotics (such as ciprofloxacin) is making it increasingly difficult to treat urinary tract infections with oral antibiotics. Unfortunately E. coli are by far the most common cause of urinary tract infections, accounting for 80 percent or more of them. As the resistance to fluoroquinolones begins to approach 50 percent in community strains of E. coli, it is possible that tens of thousands of women per year will have to be hospitalized to receive intravenous antibiotics just to treat urinary tract infections! How close are we to this nightmare scenario? A recent international study has reported that up to 30 percent of E. coli isolates [separated pure strains of bacteria] from urinary tract infections are now resistant to fluoroquinolones. That compares to less than 5 percent only a decade earlier. Although the resistance rates are lower for community-acquired infections as compared to hospital-acquired infections, the resistance rate among community-acquired E. coli infections has still risen fiftyfold in just the last decade. It is expected that a continued increase is going to occur in the coming decade, which means we may reach 50 percent resistance of community-acquired E. coli to fluoroquinolones within the next ten to twenty years.

Drug-resistant urinary infections (NHS)

A study in Hong Kong concludes that antibiotic resistance may arise from the overuse of antibiotics in food-producing animals. When researchers examined bacteria resistant to the antibiotic gentamicin, 84% of human samples and 75% of animal samples had an identical gene for antibiotic resistance.

The study, published in the Journal of Medical Microbiology, asserts that “Consumers may acquire antibiotic-resistant bacteria from contaminated food,” and ”Good personal and food hygiene are the best ways to prevent this.”

The National Health Service draws a different conclusion:

This was a small study, which found that resistance to the antibiotic gentamicin was granted by the same gene sampled from both animals and humans. However, it did not look at the possible routes by which this resistance may be transmitted between animals and humans. For example, it could not say whether consuming animals with antibiotic-resistant E. coli in their guts is a possible route of transmission.

Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: systematic review and meta-analysis (British Medical Journal)

This story about urinary tract and pulmonary infections also received a great deal of coverage.

Individuals prescribed an antibiotic in primary care for a respiratory or urinary infection develop bacterial resistance to that antibiotic. The effect is greatest in the month immediately after treatment but may persist for up to 12 months. This effect not only increases the population carriage of organisms resistant to first line antibiotics, but also creates the conditions for increased use of second line antibiotics in the community.

That last sentence means: Not only are more people carrying and spreading resistant bacteria, but, as patients develop resistance, there’s an increased need to use newer and more expensive antibiotics, as opposed to older and less expensive ones. There is more antibiotic resistance to older drugs than to the newer ones, simply because they’re been around longer. Physicians like to limit the use of newer antibiotics, so they will have something effective to use when a patient has an infection that’s resistant to an older drug. This finding is not good news.

Stoking the antibiotic pipeline (British Medical Journal)

If no new antibiotics are developed, this will of course be bad news for anyone who acquires an antibiotic resistant infection. But it will also change many aspects of the practice of medicine. Surgeries with an increased risk of infection – abdominal surgery, for example, or any lengthy, complicated surgery – will no longer be feasible. Chemotherapy, which wipes out the immune system, would be totally inadvisable. Transplants could no longer be performed. Intensive care is only possible because there are effective antibiotics. The chances of surviving burns, automobile accidents, and battlefield injuries would be greatly reduced.

A new drug takes 10 years to develop, costs $1 billion, is used for a short period of time by patients, has a short marketing lifetime as resistance develops, and rapidly becomes obsolete as physicians fear it will no longer be effective. No wonder Big Pharma is not interested in developing new antibiotics.

This BMJ article discusses all of these issues and more, including the obstacles of government regulation and the difficulties of clinical trials. Rising Plague also has an excellent discussion of how pharma has been burned by US government regulations and policy reversals.

Incentives to develop new antibiotics should be designed with some early funding to ignite interest and appropriate rewards for the high risks of research and development. Such action needs to be accompanied by parallel efforts to redress and dismantle incentive structures that lead to overuse of antibiotics, which is currently fuelling the spread of resistant bacteria.

British medical journals cover this topic much more frequently than American journals. Why is that?

Curing the antibiotic issue (The Daily Caller)

What I found interesting about this article was that it appeared in a conservative publication. Maybe it will be possible to address the need for new antibiotics without denialists questioning the science and politicians claiming the issue is part of a liberal agenda. The author makes a good point about the problem posed by clinical trials for antibiotics:

Unlike most new drugs, even narrow-spectrum antimicrobials are often used to treat various types of infection. This results in increased costs because of the requirement for clinical trials for each indication, with enrollment of large numbers of patients to ensure the drug’s safety and to document its effectiveness against specific microbial pathogens. Furthermore, because there are no rapid diagnostic tests for many resistant pathogens, it can be difficult and costly to find suitable patients to enroll in clinical trials.

Risk Factors for Antibiotic-Resistant Escherichia coli Carriage in Young Children in Peru (PDF) (American Journal of Tropical Medicine and Hygiene)

The Galapagos islands provide an ideal setting for investigating the transmission of resistant bacteria in the absence of antibiotics. Peru provides an opportunity to compare the presence of resistant bacteria in two groups of children: Those who eat home-raised, antibiotic-free chicken and those who eat chickens raised on antibiotics. Guess who had more antibiotic resistant bacteria?

In Peru, by the way, antibiotics are available without a physician’s prescription. Even rural villagers can purchase them at the local “bodega.” Children age 3 to 15 are entitled to free antibiotics. So while rural children may be more likely to eat farm-raised chickens, they are not necessarily less exposed to antibiotics than more affluent children who eat store-bought chicken. Recent use of antibiotics, either by the children or other household members, was associated with increased presence of antibiotic resistant E. coli. (Emphasis added in the following quotation)

Residing in a zone where a larger proportion of households served home-raised chicken in the past year protected against carriage of E. coli resistant to all three antibiotic categories [ampicillan, sulfamethoxazole, multiple drugs]. … This study … improves our understanding of the growing global public health threat of antibiotic resistant organisms, and underscores the critical role that antibiotic use in animals plays in contributing to this threat. The vast majority of the tons and tons of antibiotics ingested each year on this planet are administered to livestock and animals. This study clearly shows that such use comes with a very real cost to human health.

And finally, a Voice of America video called Antibiotic Resistance Is a Growing Threat: