VCU GH2DP Honduras Trip Update: Potpourri

Up early in Olanchito, working on our report for the Health Minister and waiting for the day to ramp up.

Here are a few additional (somewhat random) thoughts on some of the things we saw yesterday. 

One of the key pieces of advice I give my travel clinic patients is to be very careful not to ingest municipal water in developing countries (this is a major risk factor for developing diarrheal illness). This includes not eating fresh vegetables (which likely have been washed in bacterial-contaminated municipal water). The caveat to this is that these foods may be okay to eat if you know they were washed with clean water. 

Here is a picture of the lettuce for yesterday's lunch meeting being washed using a water purification system; I went for it, so far so good. 

Lettuce being washed by water purification system

Picture from local pharmacy

Another thing that always surprises me is how many antibiotics one can buy over the counter at pharmacies here; one can find almost anything, including injectables. You only need money to access these medications: they are available without prescription. 

I have never seen local data on antibiotic resistance, but I imagine it is high (at least in the cities) for some of the most common, cheapest antibiotics (such as amoxicillin, which is available here in supermarket checkout lines, like gum and candy are in the US). 

Beyond driving antibiotic resistance, inappropriate antibiotic use can lead to drug toxicity and treatment failure (prescribing the right antibiotic for the right condition for the right amount of time is often tricky for physicians; if the antibiotic is chosen without professional guidance the likelihood its use will be appropriate is low). 

Some good information from the WHO on the appropriate use of antibiotics (including in developing countries) can be found here.

You can learn more about the VCU Global Health and Health Disparities Program (GH2DP) and our work in Honduras here. 

An Update on Tuberculosis

Here is an excellent article on tuberculosis published in Nature.

Tuberculosis (TB) is caused by a bacteria and is spread largely through the air (when someone with TB in his or her lungs coughs, et cetera). TB commonly causes lung disease, but can involve many other parts of the body, as well. Most people who are exposed to TB do not develop active infection; rather, they develop "latent" infections where they are not infectious and the bacteria are dormant. Although people with latent infections can go on to later develop active infections, the majority do not. If a person develops an immune-system compromising disease (such as HIV) he or she is then much more likely to develop active TB infection. TB is a deadly illness; in 2011 there were 1.4 million TB deaths globally.

It is estimated that one-third of people worldwide are infected with TB.

The Nature article provides a comprehensive overview of what is currently going on with TB globally, and discusses the problem of TB drug resistance in great detail. Identifying drug resistance in TB is time-consuming and difficult and testing for this is far from universal. The article also highlights what has contributed to the emergence of drug-resistant TB, including the breakdown of public health infrastructure and TB control programs.

What are needed are better antibiotics for drug-resistant TB and, the "holy grail" for TB control, a highly effective vaccine. Additionally, tests for drug resistance need to get better, faster and cheaper, and TB control programs need to be supported aggressively.

An Update on Antibiotic Stewardship: From the 22nd European Congress of Clinical Microbiology and Infectious Diseases

Here is a nice article by Canton and Bryan that provides an update on Antibiotic Stewardship as reported at the 22nd European Congress of Clinical Microbiology and Infectious Diseases. The article references several poster presentations from this meeting as well as multiple studies that are already in print.

Infection with antibiotic-resistant organisms
has been associated with an increased
risk of death (cdc.gov)

Antibiotic Stewardship is a field of study and practice focused on decreasing the emergence of antibiotic resistance and optimizing antibiotic use.

A survey project that polled 324 facilities from six continents revealed that over half of these have Antibiotic Stewardship Programs (ASPs), although only 1/3rd had formally assessed these programs' impact. Those programs that had done formal assessments found that stewardship efforts were associated with decreased use of broad-spectrum antibiotics and decreased costs. 

cdc.gov

Targeted interventions in long-term care facilities (a known reservoir of antibiotic resistant organisms) led to decreased antibiotic use in these settings. 

Some countries are better stewards of antibiotics (in the outpatient
setting) than others. Antibiotics are often prescribed for viral
upper respiratory illnesses, a practice that drives antibiotic
resistance and has no affect on these infections (antibiotics are active
against bacteria, not viruses) (cdc.gov)

A study by Denes and colleagues found that there was poor adherence by primary care doctors to guidelines for UTIs in France. 

There are a paucity of new antibiotics in the "pipeline." This is especially true for multi-drug resistant (MRD) gram-negative infections. 

The article (part of a two-part series) by Canton and Bryan is a nice overview of the research presented at the European Congress of Clinical Microbiology and Infectious Diseases. These studies add to the growing Antibiotic Stewardship literature. However, critical questions still remain.  What interventions are best for decreasing the emergence of antibiotic resistance? What interventions are best in certain settings (hospitals/ long-term care facilities/ the general practitioner's office)? We know ASPs can lead to decreased use of broad-spectrum antibiotics and reduce costs, but what really works in terms of decreasing resistance? Robust, high-quality research is needed to answer these critical questions. 

The antibiotic pipeline is "drying up." This is especially
true for drugs to combat resistant gram-negative
infections (cdc.gov)

Beyond this, the future is still bleak in terms of new antibiotics to combat multi-drug resistant gram-negative infections. It is critical we preserve the antibiotics we have and reduce the spread of resistant organisms. 

Combating Antibiotic Resistance: A Call for Collaboration

Methicillin resistant Staphylococcus aureus (MRSA) (cdc.gov)

Here is a nice op-ed article by Carl Nathan that appeared in Sunday's New York Times. Nathan discusses the problem of antibiotic resistance and the challenges to new drug development, including bacteria that rapidly develop resistance to new antibiotics and poor economic incentives for industry to create new drugs.

Nathan highlights novel collaborations between industry, government and the non-profit sector designed to expedite new drug discovery. The Infectious Diseases Society of America has great information on the problem of antibiotic resistance (and potential solutions) that can be found here.

Antibiotic Use in Cattle: Driving Antibiotic Resistance in Humans?

wikipedia.org

Here is a nice article published yesterday in the Kansas City Star that discusses antibiotic use in cattle and its potential effect on antibiotic resistance in humans. I have alluded to this connection in several previous posts; this article provides a comprehensive and balanced overview of this problem. 

Some highlights (my comments appear in italics):  

1) 80% of all antibiotics are used in animals; as antibiotic resistance in large part is related to the selective pressure of antibiotics on bacteria, efforts to combat resistance in humans have to account for the huge amount of antibiotics used in animal husbandry 

2) The beef industry can now bring a calf to slaughter in a little over a year, half the time this process used to take (this is attributed to genetics, antibiotics, growth promoters and hormones); see yesterday's post for comments on how antibiotics may be related to the obesity epidemic in humans

3) Antibiotic resistance in animals has been linked to human illness

4) There are significant barriers to addressing this issue

As outlined in this article, this is a complicated issue. However, to avoid entering the 'post antibiotic era' we need to aggressively preserve the antibiotics we have left-which means using them judiciously in both humans and animals. Articles such as this that raise awareness and provide balanced information are crucial. 

Obesity on the Rise: Related to Antibiotic Use?

Here is a nice NPR piece on the possible link between childhood obesity and antibiotics. This story is from back in August but I figured I'd bring it back up in case anyone missed it; I also alluded to this in an earlier post.

Obesity has become epidemic in the United States. According to the CDC, the prevalence of obesity has exploded over the past few decades: almost one in five children and adolescents (17%) is now obese, as well as over one-third of adults (36%). The obesity prevalence in children has nearly tripled since 1980.

Here is an instance where 'a picture is worth a thousand words.' The following maps illustrate obesity prevalence in US adults in 1990 versus 2010:

These maps are both compelling and disturbing; what has caused the explosion of obesity over the past twenty years?

An intriguing question is whether the increase in obesity prevalence is related to antibiotic use.

Antibiotics have long been used in animal husbandry to "fatten up" food animals. It is not exactly clear why this happens (e.g., why using low levels of antibiotics leads to fatter animals). An important question is whether antibiotic use also drives a similar process in humans.

A study by Cho and colleagues that was published in Nature in August found that the administration of antibiotics to mice was associated with changes in the composition of organisms in the gut that led to changes in fat metabolism and fatter animals. Although this was a mouse model, it does provide 'biologic plausibility' for how antibiotic administration could lead to obesity in humans.

Another article by Blustein and colleagues utilized a database from the UK with data from over 11,000 children born in 1991-1992. These authors found that antibiotic exposure within the first 6 months of life was subsequently associated with increased body mass from 10-38 months of age.

Although the above studies are intriguing, they do not provide definitive evidence that the current obesity epidemic is related to antibiotic exposure. Many things are likely contributing to this epidemic; one thing is clear, however: the prevalence of obesity has increased dramatically and this has had-and will have-enormous implications for our healthcare system and society.

Antibiotics have revolutionized modern medicine: they are critical for helping patients survive cancer therapy, for many complicated surgeries and are life-saving in the setting of many serious infections. However, studies such as those noted above illustrate that antibiotics may have effects beyond their intended purpose, and is further evidence that their use should be targeted and judicious. This is even more important given the widespread problem of antibiotic resistance and the paucity of new antibiotics that are being developed. More research into the link between obesity and antibiotic use is needed.

Antibiotic Resistance: Effect of Length of Therapy

Here is a nice blog piece over at PLOS that provides a nice commentary on the problem of antibiotic resistance in people, and discusses the possible relationship of duration of antibiotic therapy and the emergence of resistance. 

In terms of antibiotic therapy length, this is dependent on the condition (e.g., pneumonia, urinary tract infection, et cetera), person-specific factors (does the infection involve the bladder only? does it involve the kidneys? are there bacteria in the blood?) as well as the specific infecting bacteria. A physician needs to take all of these factors into account when recommending an antibiotic treatment course. 

What is clear is that clinicians should follow consensus guidelines when determining length of therapy for a given patient, that non-bacterial infections should not be treated with antibiotics, and that more studies are needed to assess the optimal length of therapy for many bacterial infections.  

Pork: Contaminated with Antibiotic Resistant Bacteria?

wikipedia.org

Here is a study published in Consumer Reports that looked at the presence of antibiotic resistant bacteria in pork. They tested 198 samples of ground pork and pork chops, all consumer products, and found that 69% were contaminated with Yersinia enterocolitica, 11% were contaminated with Enterococcus, 7% were contaminated with Staphylococcus aureus and 4% were contaminated with Salmonella.

Of the whopping 69% of products contaminated with Yersinia enterocolitica, 39% were resistant to 2-3 antibiotics. Sixty-four percent of the Staphylococcus aureus isolates were resistant to 2-4 antibiotics and 38% of the Salmonella isolates were resistant to 5 antibiotics.

These findings highlight the issue of antibiotic use in the food industry driving antibiotic resistance in general. As antibiotics are used in a population of animals (pigs, for instance), antibiotic susceptible bacteria are killed off (thus 'selecting out' resistant bacteria); these bacteria are then shed into the environment, contaminate fertilizer and can contaminate food products such as the pork noted in this study. Humans then can become colonized or sick when they come in contact with these organisms. A person who ingests undercooked pork contaminated with bacteria such as Yersinia enterocolitica could develop a severe diarrheal illness that would be more difficult to treat as the organism is already resistant to multiple antibiotics.

This report highlights key things consumers can do to protect themselves, such as ensuring meat is cooked appropriately (thus killing any bacterial contaminants), keeping raw meat separate from other foods and good hand washing.

This report is a disturbing real-time reminder that non-human antibiotic use is an important component of the current antibiotic resistance crisis; this is especially important when one considers that approximately 80% of all antibiotics used in the United States are used in food-production animals. Efforts to combat antibiotic resistance must account for the large percentage of antibiotic use in the food industry, and true solutions to this problem will require coordinated efforts across multiple disciplines.

Antibiotic Resistance: Why Is This a Big Deal?

cdc.gov

Here is a nice article published online in American Medical News that provides a very nice overview of the problem of antibiotic resistance. The article also links to a consensus statement by 26 major health groups (including the CDC, Infectious Diseases Society of America and American Academy of Pediatrics, to name a few) that outlines the nature of the problem and commits to begin combatting the issue more aggressively, in a coordinated fashion, via promoting improved utilization of antibiotics, calling for new antibiotics to treat resistant infections and raising awareness about this issue in general. This is an excellent "call to arms" that both raises awareness about this issue and commits to a coordinated approach to addressing it.

Notably missing from the list of organizations that signed this statement, however, are major agricultural groups; as previously discussed, the majority of antibiotics are used in animal husbandry. The problem of antibiotic resistance truly crosses disciplines, and solutions to this issue will accordingly need to involve professionals across diverse fields such as agriculture, medicine, public health, economics, sociology, et cetera (the previously mentioned "One Health" approach to addressing issues with global impact).

A "One Health" Approach to Antibiotic Resistance

cdc.gov

This is a nice post highlighting the recent symposium "A One Health Approach to Antimicrobial Use & Resistance: A Dialogue for a Common Purpose" that was coordinated by the National Institute for Animal Agriculture. This meeting brought together experts in antibiotic resistance from numerous disciplines (following the "One Health" approach that emphasizes interdisciplinary coordination to address global health issues). 

The following were the 'take home points' from the conference: antibiotic resistance is not a new phenomenon, the issue is complex and involves more than just its health implications (also has social, political and economic implications); all communities that use antibiotics are responsible for antimicrobial stewardship; people from all disciplines need to work together to address this important issue. 

The call for a coordinated, interdisciplinary response to antibiotic resistance is sound and necessary; improved antibiotic use in humans is important but the issue must also be addressed in animal populations where the majority of antibiotics are used. The One Health approach emphasizes that experts across the board (veterinarians, physicians, economists, et cetera) and around the globe need to work together to address the issue.

One thing is certain: the time to get aggressive with battling antibiotic resistance is now. We have essentially run out of new antibiotics to combat many resistant infections, and perhaps are nearing the dreaded 'post-antibiotic era.' Although a recent survey by the Pew Health Group indicated that many Americans are aware of the issue of antibiotic resistance, this issue is largely not viewed as a major public health crisis (which it is). 

You can test your knowledge about antibiotics here.