High rate of acquisition but short duration of carriage of multidrug-resistant Enterobacteriaceae after travel to the tropics

by Etienne Ruppé, Laurence Armand-Lefèvre, Candice Estellat, Paul-Henri Consigny, Assiya El Mniai, Yacine Boussadia, Catherine Goujon, Pascal Ralaimazava, Pauline Campa, Pierre-Marie Girar9, Benjamin Wyplosz, Daniel Vittecoq, Olivier Bouchaud, Guillaume Le Loup, Gilles Pialoux, Marion Perrier, Ingrid Wieder, Nabila Moussa, Marina Esposito-Farèse, Isabelle Hoffmann, Bruno Coignard, Jean-Christophe Lucet, Antoine Andremont, and Sophie Matheron
Date : July 15, 2015

From : Clinical Infectious Diseases (http://cid.oxfordjournals.org)

> « Background. Multidrug-resistant Enterobacteriaceae (MRE) are widespread in the community, especially in tropical regions. Travelers are at risk of acquiring MRE in these regions, but the precise extent of the problem is not known.


Results. Among 824 participating travelers, 574 provided feces samples before and after travel and were not MRE carriers before departure. Of these, 292 (50.9%) acquired an average of 1.8 MRE. Three travelers (0.5%) acquired carbapenemase-producing Enterobacteriaceae. The acquisition rate was higher in Asia (142/196, 72.4%) than in sub-Saharan Africa (93/195, 47.7%) or Latin America (57/183, 31.1%). MRE acquisition was associated with the type of travel, diarrhea and exposure to beta-lactam during the travel. Three months after return, 4.7% of all the travelers carried MRE. Carriage lasted longer in travelers returning from Asia and in travelers with a high relative abundance of MRE at return.

Conclusions. MRE acquisition is very frequent among travelers to tropical regions. Travel to these regions should be considered a risk factor of MRE carriage during the first 3 months after return, but not beyond. »

Full text (Abstract): http://cid.oxfordjournals.org/content/early/2015/04/21/cid.civ333.abstract?sid=436de09d-3620-494e-b31e-8943e04c572b

We need more than just new antibiotics to fight superbugs

by Tim Leighton,
Professor of Ultrasonics and Underwater Acoustics at University of Southampton

Date : July 15, 2015

From : theconversation.com/uk

> « By 2050, drug resistant diseases could be killing more people than cancer, an extra 10m deaths per year. They could also cause a loss to the global output of US$100 trillion dollars – equivalent to a sum greater than the size of the current global economy.

A potential future catastrophe in healthcare, where even routine surgical procedures and easily treated infections become significantly more hazardous, is commonly attributed to the appearance of new strains of antibiotic-resistant bacteria. It is often argued that the answer is more funding for the development of new antibiotics.


The development of new antimicrobial drugs is an arms race against natural selection that cannot be won: when antimicrobials (not just antibiotics) are applied, microbes of all types (not just bacteria) have proven to be adept at developing resistant strains from the survivors. If the drug kills 99.99% of a population of microbes, it is the genetic makeup of the survivors that goes forward to the next generation. To mitigate against potential catastrophes in healthcare and food production, measures over and above the development of new antibiotics have to be undertaken.

These include two key elements. One is infection prevention. If a dangerous microbe never enters the body, no antimicrobial is required. The development of new microbe-resistant materials and products, as well as the development of minimally invasive procedures in hospitals and clinics, improvements in waste disposal and a revolution in cleaning, are some of the measures already being researched.

The second element to reducing the use of antimicrobials is the removal of environments that encourage resistant strains to develop, for example in the body of the patient or farm animal, with simple measures such as ensuring a full prescription is taken rather than stopping early when symptoms disappear – a practice that encourages the survival of resistant microbes. Other measures include the invention of sensors to detect infection early and identify the specific microbe present, so that targeted antimicrobials can be used in place of broad-spectrum agents, one example of responsible antimicrobial stewardship. »

Full text : http://theconversation.com/we-need-more-than-just-new-antibiotics-to-fight-superbugs-44054

Global Health Threats of the 21st Century: Antibiotic Resistance

by Ramanan Laxminarayan, director of the Center for Disease Dynamics, Economics & Policy and Senior Research Scholar at Princeton University

Date : December 2014

From : Finance & Development, Vol. 51, No. 4

« Antibiotics have transformed the practice of medicine. However, a massive scale-up in their use has resulted in an increase in drug-resistant strains of disease-causing bacteria and a global decline in antibiotic effectiveness. Rising incomes in low- and middle-income countries have generated huge demand for antibiotics, but high infection levels and uncontrolled antibiotic use in these countries are leading to treatment failures for people unable to afford expensive second-line drugs when antibiotics don’t work. In high- and upper-middle-income countries, antibiotic use remains high, particularly in hospitals, and resistance is driving up treatment costs.

Lack of access to antibiotics still kills more people than resistant bacteria, but antibiotics are not a substitute for good public health policy, vaccinations, clean water, and proper sanitation. The infectious disease mortality rates in low- and lower-middle-income countries today vastly exceed those in high-income countries before antibiotics were introduced in 1941.


Resistance—a natural phenomenon—is accelerating because no single patient, physician, hospital, insurer, or pharmaceutical company has an incentive to reduce antibiotic use.


The global burden of resistance is poorly quantified but is likely to be concentrated in three categories: the costs of resistant infections, the costs of antibiotics, and the inability to perform procedures that rely on antibiotics to prevent infection.


New antibiotics have been developed, but the cost of bringing any new drug to market is very high. The rate at which new antibiotic compounds are being discovered is slowing. Fourteen of the 17 classes of antibiotics in use today were discovered before 1970. Most innovation involves reengineering existing compounds rather than finding new mechanisms.­

Public investment in antibiotics is justified because the lack of effective drugs can create public health emergencies. Secondary bacterial infections are big killers during influenza pandemics, for example. The United States and Europe are encouraging the development of new drugs. But unless incentives for drug development are tied to conservation, these initiatives may simply put off till tomorrow a problem that will take a high toll on society.­

Full text : http://www.imf.org/external/pubs/ft/fandd/2014/12/jonas.htm


Antibiotic Restriction Might Facilitate the Emergence of Multi-drug Resistance

by Uri Obolski, Gideon Y. Stein, Lilach Hadany

Date : June 25, 2015

From : PLoS Computational Biology

> « High antibiotic resistance frequencies have become a major public health issue. The decrease in new antibiotics' production, combined with increasing frequencies of multi-drug resistant (MDR) bacteria, cause substantial limitations in treatment options for some bacterial infections. To diminish overall resistance, and especially the occurrence of bacteria that are resistant to all antibiotics, certain drugs are deliberately scarcely used—mainly when other options are exhausted. We use a mathematical model to explore the efficiency of such antibiotic restrictions. We assume two commonly used drugs and one restricted drug. The model is examined for the mixing strategy of antibiotic prescription, in which one of the drugs is randomly assigned to each incoming patient. Data obtained from Rabin medical center, Israel, is used to estimate realistic single and double antibiotic resistance frequencies in incoming patients. We find that broad usage of the hitherto restricted drug can reduce the number of incorrectly treated patients, and reduce the spread of bacteria resistant to both common antibiotics. Such double resistant infections are often eventually treated with the restricted drug, and therefore are prone to become resistant to all three antibiotics. Thus, counterintuitively, a broader usage of a formerly restricted drug can sometimes lead to a decrease in the emergence of bacteria resistant to all drugs. We recommend re-examining restriction of specific drugs, when multiple resistance to the relevant alternative drugs already exists.» ­

Full text : http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1004340


Antibiotic alternatives rev up bacterial arms race

by Sara Reardon

Date : May 27, 2015

From : www.nature.com

> « Few new antibiotics are in development, and overuse of existing ones has created resistant strains of deadly bacteria. "We need a change from what we have," says Stephen Baker, head of medicinal chemistry for antibacterials at Glaxo­SmithKline in College­ville, Pennsylvania.
Baker will talk about some of the alternatives to antibiotics on 2 June at the American Society for Microbiology's annual meeting in New Orleans, Louisiana. Here are a few of the therapies that scientists are exploring.

Predatory bacteria
Bacteria cause infection, but some can also fight it by preying on fellow microbes. Several researchers are beginning to test these predatory bacteria in animal models and cell cultures.
The best-known species, Bdellovibrio bacteriovorus, is found in soil. It attacks prey bacteria by embedding itself between the host's inner and outer cell membranes, and begins to grow filaments and replicate. "It's like going into a restaurant, locking the door and starting to munch away," says Daniel Kadouri, a bacteriologist at Rutgers University in Newark, New Jersey. The host bacterium eventually explodes and releases more B. bacteriovorus into the environment. (...)

Antimicrobial peptides
Plants, animals and fungi have vastly different immune systems, but all make peptides — small proteins — that destroy bacteria. Peptides from creatures such as amphibians and reptiles, which are unusually resistant to infection, could yield new therapeutics.
Peptides with antibacterial activity have been isolated from frogs, alligators and cobras, among others, and some seem to be effective in epithelial cell cultures and at healing wounds in mice. These peptides can be modified to increase their potency, and several are in clinical trials. One, called pexiganan, based on a peptide from frog skin, is now in phase III clinical trials to treat diabetic foot ulcers. (...)

Of all the alternatives to antibiotics, phages — viruses that attack bacteria — have been used the longest in the clinic. Scientists in the Soviet Union began developing phage therapies in the 1920s, and former Soviet countries continue the tradition.
Phages have several advantages over antibiotics. Each type attacks only one type of bacterium, so treatments leave harmless (or beneficial) bacteria unscathed. And because phages are abundant in nature, researchers have ready replacements for any therapeutic strain that bacteria evolve to resist. (...)

Gene-editing enzymes
CRISPR, a gene-editing technique that has taken the scientific world by storm, is based on a strategy that many bacteria use to protect themselves against phages. Researchers are turning that system back on itself to make bacteria kill themselves.
Normally, the bacteria detect and destroy invaders such as phages by generating a short RNA sequence that matches a specific genetic sequence in the foreign body. This RNA snippet guides an enzyme called Cas9 to kill the invader by cutting its DNA.
Scientists are now designing CRISPR sequences that target genomes of specific bacteria, and some are aiming their CRISPR kill switches at the bacterial genes that confer antibiotic resistance.

Metals such as copper and silver are the oldest antimicrobials. They were favoured by Hippocrates in the fourth century bc as a treatment for wounds, and were used even earlier by ancient Persian kings to disinfect food and water. Only now are researchers beginning to understand how metals kill bacteria.
Some groups are exploring the use of metal nanoparticles as antimicrobial treatments, although little research has been done in people. Because metals accumulate in the body and can be highly toxic, their use may be restricted mostly to topical ointments for skin infections. (...) »

Full text: http://www.nature.com/news/antibiotic-alternatives-rev-up-bacterial-arms-race-1.17621