Friday, November 20, 2015

The Crisis of Antibiotic Resistance: Are We Entering the Post-Antibiotic Era?

I had a wonderful opportunity to speak at a hospital in the Richmond community this week about antibiotic resistance and stewardship; I was asked to speak by that health system's Antimicrobial Stewardship Program as part of their activities around "Get Smart About Antibiotics" week. I was asked to write up my talk so they could share it with their health system. My write-up is below. 

The Crisis of Antibiotic Resistance: Are We Entering the Post-Antibiotic Era?

In November we celebrate the CDC’s “Get Smart About Antibiotics Week,” an event designed to raise awareness about the crisis of antibiotic resistance and to outline possible solutions. To answer the question of whether we are entering a post-antibiotic era: in a word, yes. But there is hope.
Antibiotics are potentially life-saving compounds, and their discovery has been critical to many of the medical and surgical advances we have seen in the past 75 years. Without antibiotics patients would not be able to survive the infectious complications of things like chemotherapy, organ transplantation and immune suppression for rheumatologic diseases.

We truly are at a crisis point with antibiotic resistance, especially for multi-drug resistant gram negative rods (MDR GNR). For many patients with MDR GNR infections we have essentially returned to 19th century medicine: in the absence of antibiotics we are left with pursuing aggressive ‘source control’ for infected tissues, when possible. An example would be a patient with a diabetic foot infection: whereas surgery and antibiotics can often cure these infections, a patient with an infection with a pan-resistant GNR may require amputation. This is not a doomsday scenario, this is reality for many of our patients in 2015.

The CDC estimates that 2 million people acquire infections with antibiotic-resistance bacteria yearly and 23,000 die as a direct result of these infections. It is estimated these infections lead to upwards of 35 billion dollars in excess healthcare costs in the United States alone. These statistics do not fully capture the scope of the problem, however, as the morbidity associated with these infections can be significant.

Here is the problem in a nutshell: antibiotic use selects for resistant organisms and the emergence of resistance has outpaced the development of new antibiotics. Most of the antibiotics in use today are natural products that organisms have been using to battle one another for millennia; we have ‘discovered’ these and adopted them for use in humans and animals. The antimicrobial ‘resistome’ (the resistance capacity of organisms to overcome antibiotics) already exists in nature, presumably for most if not all antibiotics. This is why we see resistance emerge fairly rapidly whenever ‘new’ antibiotics are deployed.

Antibiotic use extends far beyond therapeutic use in humans. It is estimated that 70% of antibiotic use is in animals for non-therapeutic use. Antibiotics are often used in the animal industry to grow larger, fatter animals faster. Any solutions to the crisis of antibiotic resistance have to span the continuum of use in both animals and humans.

Our relationship with the microbes who live on and inside is not well understood; there is increasing evidence that there may be a symbiotic relationship with our ‘microbiome,’ however. There are an astounding 10 bacterial cells for every 1 human cell in the human body. There is some intriguing data that suggests altering our microbiome with antibiotics can lead to things like allergies and obesity. Antibiotics should not be seen as innocuous.

It is estimated 50% of all antibiotic use in human medicine is unnecessary. The reasons for this are myriad. Front-line providers need rapid, accurate, affordable tests to diagnose the etiology of things like upper respiratory infections and urinary tract infections. We also need better protocols for treating various infectious conditions informed by properly performed clinical trials. We need better surveillance technologies to identify antibiotic resistance and standardized, risk adjusted data on antibiotic prescribing at the provider level.

Beyond all of the above we need new antibiotics to combat drug-resistant bacteria. To date there is no new anti-GNR compound with a novel mechanism of action in the antibiotic creation ‘pipeline.’ Although the FDA approval mechanism for antibiotics has become more streamlined in recent years, we have seen far fewer antibiotics in development. Many pharmaceutical companies have abandoned antibiotic development altogether.

So what can be done in 2015 to combat this issue by individual providers? First and foremost we should strive to prevent infections. Vaccinate patients according to national guidelines, wash your hands before and after patient contact and use appropriate contact precautions in the inpatient environment. We can also prevent the emergence of antibiotic resistance by optimizing our antibiotic use, especially for inpatient medicine. Record the indication, dose and expected duration when ordering antibiotics. Take a daily ‘time out’ for each patient on antibiotics to re-assess their use and continued need. Be aggressive with diagnostics early on to aid in de-escalation later. And perhaps most importantly partner with your Antimicrobial Stewardship Team. These teams exist to assist you in optimizing antibiotic use and can be a terrific resource.

Many of our patients have already entered the ‘post-antibiotic era.’ The development of antibiotic resistance has outpaced new drug development. The issue is complex but first and foremost we need to be aware of just how dire the problem is and that we all have a role to play in its solution. It has been 75 years since we saw the widespread deployment of antibiotics. Unless major changes occur in antibiotic use and production we are in danger of fully returning to 19th century practice for many of our patients. 

Tuesday, November 10, 2015

PK/PD in Clinical Practice

Multi-drug resistance gram-negative rods (CDC)
There is a great article in the November 1st issue of Clinical Infectious Diseases where Labreche and colleagues discuss recent updates on using pharmacokinetics-pharmacodynamics (PK/PD) in antimicrobial susceptibility testing.

Given the current crisis of gram-negative resistance and the paucity of new drugs in development it is critical that physicians learn to optimize their use of the drugs left in our armamentarium. For most antibiotics/ organisms susceptibility results are simply listed as "S"usceptible, "I"ntermediate, or "R"esistant. Oftentimes the Minimum Inhibitory Concentration (MIC) of the organism is not provided; even when these values are provided they are difficult for most physicians to interpret. What is needed is a better understanding of PK/PD principles as well as how to navigate the complex recommendations of the many organizations providing antibiotic susceptibility cutoffs.

Labreche and colleagues provide a nice overview of core PK/PD principles and also discuss the different agencies that provide breakpoints for different organisms and drugs (FDA, CLSI, EUCAST). For the latter, differences in how the organizations come up with recommendations are highlighted. Several useful examples of recent changes are provided and how these changes can be applied to clinical practice.

Thursday, June 11, 2015

VCU GH2DP Outreach Trip to Yoro, Honduras: Summary

Traveling to La Hicaca
Today we returned to San Pedro Sula after a week up in the mountains in rural Yoro, Honduras.

Since 2005 we have been working with approximately 17 villages with little to no access to medical care.

Medicine Clinic in Lomitas
With the aid of our many local, regional, national and international partners we were able to see approximately 700 patients this week. In addition we distributed approximately 90 water filters (each of which will provide an entire household with clean drinking water for 2 years), helped facilitate cervical cancer screening for 80 women and completed a project focused on assessing knowledge and risk factors for dengue and chikungunya infection as well as projects focused on the effectiveness of a new chlorination system and several novel clean water technologies. 

Assembling water filters

Testing new water catchment device
With Dr. Pat Mason and Dr. Ana Sanchez working on our deworming project

Internal Medicine team, Lomitas

Dr. Jason Cook working on water chlorination system project

GH2DP Outreach Team, La Hicaca

GH2DP Pathway Residents and Student Scholars

Friday, June 5, 2015

GH2DP Outreach Trip: Day 2

Last night we arrived in Olanchito late and spent several hours preparing medications and supplies. Today we leave to go to La Hicaca where our first clinic will be held this afternoon.

A major focus of our health outreach work focuses on de-worming. Last year stool testing revealed a high prevalence of whipworm infection despite de-worming with a single dose of albendazole twice yearly. In addition to continuing surveillance we have changed our de-worming protocol to better target whipworm and have initiated a new de-worming tracking project.

After this morning there will likely be no new posts until we get back from the mountains. Will share more about our trip when we return.

Thursday, June 4, 2015

GH2DP Outreach Trip to Yoro, Honduras

Today is day one of our outreach trip to rural Yoro, Honduras, on a medical and public health outreach trip with VCU's Global Health and Health Disparities Program (GH2DP). 

The U.S. contingent of our group left early this morning and has arrived in San Pedro Sula. In addition to our group we have approximately 950 pounds of gear and supplies we will transport to Olanchito and organize tonight.

Our plan is to meet the rest of our group and transport our team and supplies up to the rural, mountainous village of La Hicaca tomorrow. From here we will stage our medical and public health outreach work.

Tuesday, June 2, 2015

GH2DP Outreach Trip to Rural Yoro, Honduras: June 2015

Students and residents preparing water
filters in Lomitas
Our upcoming outreach trip to rural Yoro, Honduras is fast approaching. Our team, in collaboration with the local Ministry of Health and many local, regional and international partners, helps provide care to approximately 1,200 people from 17 villages. We have been working collaboratively to provide care in this region for the past 10 years.

Our team is once again fairly large and includes attending
physicians (pediatricians and internists), medical and pediatric residents, an attending pharmacist, students from medicine, pharmacy and public health in addition to an undergraduate engineering student and numerous other individuals. We are once again collaborating with colleagues from Brock University and the National Autonomous University of Honduras on a project exploring the local prevalence of soil-transmitted helminth (worm) infection.

Engineers Without Borders students with a novel rain
water catchment device in La Hicaca 
We will also get to see first-hand numerous other projects we have been longitudinally collaborating on: an improved cookstove project we have been working on with a local nonprofit (the Pico Bonito Foundation) as well as the placement of numerous new latrines. We will also get to see the new chlorination systems that were installed this past year. Six of the villages we serve (and approximately 40% of the population we serve) have access to water directly in their homes via a network of pipes that gravity-feed water from five different cisterns which are themselves fed by a river deeper in the mountains. We collaborated with local partners to install chlorination systems that slowly leach chlorine into water at the level of the cistern. We have had a water filter project in the region since 2008 that provides clean drinking water to the entire region. We know from our prior work these locally-created filters are clinically and microbiologically effective. Since the new chlorination systems have replaced the filters for the villages where these were installed we have a project that will look at the microbiologic and clinical effectiveness of these new systems. Additionally, we will also be testing water (at the level of individual homes) for chlorine content.

With colleagues from the National Autonomous University
of Honduras and Brock University
We have once again partnered with VCU's Engineers Without Borders student chapter to trial several novel clean water devices.

We also have a study focused on knowledge, attitudes and risk factors for the mosquito-borne diseases dengue and chikungunya.

In terms of our direct clinical work we have modified our typical clinic schedule somewhat in an attempt to be more accessible to patients in outlying areas. The population we serve is spread across a wide geographic area and some people travel 6 to 7 hours one way by foot to see us; unfortunately the infrastructure only provides a few road access points to facilitate moving our group and supplies. We hope our new schedule will allow us to serve more people.

Testing water for microbiologic contamination 
This year we will also be trialing a new education project focused on our student and resident trainees. This focuses on core content highlighted during the trip (focusing on demography, tropical dermatology, tropical infectious diseases and chronic disease screening).

Clinic in Lomitas 
We have a fantastic group this year who have worked very hard to prepare for this trip. I am absolutely thrilled to work with and learn from this amazing group of students, residents and our many community, regional and international partners.

I will blog about our trip as cellular access allows; we also will be tweeting about the trip (#GH2DP).

Monday, April 20, 2015

3rd Annual VCU Global Health Showcase Recap

Dr. Kerkering speaking on the West Africa Ebola outbreak
Today was VCU's 3rd Annual Global Health Showcase, an opportunity for people around VCU and the greater Richmond community to share and discuss global health projects.

With Dr. Bearman and GH2DP residents and students
The day started with a keynote presentation from Dr. Thomas Kerkering on his work treating Ebola patients in West Africa. Dr. Kerkering is a VCU alumnus and his talk was both moving and compelling. He showed excerpts from a documentary on the early days of the current Ebola outbreak in West Africa (this documentary can be found here).

Subsequently there were several 'break-out'
sessions: one discussing getting involved in global health research, one focused on training opportunities for medical students and residents and one focused on providing healthcare in resource-limited settings.

Viewing posters
There was an excellent poster section exploring global-health related research from around VCU. VCU's Global Health & Health Disparities Program was well represented with our students and residents presenting seven different projects.

The day ended with an excellent session focused on some of the ethical challenges of getting involved in global health work.
With Dr. Bearman and current GH2DP Pathway Residents

Monday, April 13, 2015

3rd Annual VCU Global Health Showcase: Making it Work, Getting it Right

The 3rd annual Virginia Commonwealth University Global Health Showcase is coming up on April 20, 2015. This is an all day event featuring an exciting keynote from Dr. Tom Kerkering discussing his experience with the Ebola outbreak in West Africa, several breakout sessions and a poster session featuring global-health related work from trainees across the university. This year's meeting is called "Making it Work, Getting it Right." The theme of the meeting is giving students and faculty key tools to engage in global health work.

VCU EWB students trailing a novel water catchment device
in Yoro, Honduras, June 2014
Prior showcases have been a wonderful opportunity to network, share ideas and build new relationships. The first showcase led to our program's (the Global Health & Health Disparities Program, GH2DP) current partnership with VCU's Engineers Without Borders (EWB) student chapter. This relationship has led to the development of several novel clean water technologies for use in rural Latin America as well as helped support or ongoing clean water campaign in Yoro, Honduras.

VCU EWB students trailing a new biased filter,
Richmond, VA, 2015
It is not too late to register and come out for the showcase on April 20th! Details about the showcase (including the agenda) can be found here.

Monday, March 23, 2015

Global Health Resources Guidebook for Students, Residents and Fellows

In preparation for a 'breakout' session at the upcoming 3rd Annual Virginia Commonwealth University Global Health Showcase I put together a resource guidebook for students, residents and fellows interested in global health; this can be found here.

This 'book' contains a number of links to great online resources: from lists of post-graduate training programs in global health to international and domestic volunteer opportunities to lists of great global-health related books and journals. Additionally, it links to a number of free (!!) online training resources for global health.

Thursday, March 5, 2015

Special Guest Blog Post from Nadia Masroor: February GH2DP Outreach Trip to Yoro, Honduras

This is a special guest blog post by Nadia Masroor, who has joined us on the last few health outreach trips to Yoro, Honduras, and who recently returned from Honduras: 

Our February trip to Olanchito and La Hicaca provided some excellent feedback on several ongoing projects. On Thursday February 12th, Dr. Bearman and I had the wonderful opportunity to meet with Padre Pedro and the rest of the Catholic priests in Olanchito for lunch.

Afterwards, Dr. Bearman, Padre Pedro, and I met with the Pico Bonito Foundation to discuss their progress on current projects. Pico Bonito has successfully installed chlorination systems in La Hicaca, Chorro Viento, and Puerto Rico. Those living in these three villages are encouraged to use the chlorinated water cisterns for their water supply. In order to determine the efficacy of chlorination, the 2015 brigade team will plate and incubate chlorinated water to assess microbiological growth. As for those who do not have access to the cisterns, an estimated 90-100 filters will need to be distributed in June 2015.

Hike to Chorro Viento
The Pico Bonito Foundation has recently installed new cook stoves in many of the homes in LaHicaca. According to the foundation, each cook stove costs about $100. We plan to continue this project by funding Pico Bonito to install another 15-20 cook stoves this year. Padre Pedro and Rosa, who is the nurse providing care to the people of La Hicaca and surrounding villages, will determine which impoverished homes are most in need of cook stoves. In conjunction with the cook stoves, the Pico Bonito foundation has also agreed to install new latrines for the people in Sector La Hicaca. Approximately 15-20 latrines, which cost $100 each, are projected to be built throughout the village this year. Lastly, in order to replace the deteriorated school latrines, we have requested 4 new latrines to be constructed as well, which have been estimated to cost $800-$1000. To say the least, our meeting with the Pico Bonito Foundation has enlightened us on the plethora of projects we can initiate in order to improve living conditions in La Hicaca and surrounding villages.

Later that day we met with Dr. Alma Nunez from the Ministry of Health to discuss the June 2015 brigade. Historically, La Hicaca has been the clinic site for 3 days and Lomitas has been the clinic site for 2 days. This year, however, Padre has advised spending 2.5 days in La Hicaca and 2.5 days in Lomitas. By increasing clinic time in Lomitas, Dr. Nunez and Padre hope that the brigade will be able to extend its care to more people. The total number of brigade clinic sessions will remain the same. In addition, Padre Pedro will work with the Ministry of Health to provide dental services for 3 days, covering both La Hicaca and Lomitas.

Based on Brock University’s findings from the June 2014 brigade, the majority of the population suffers from Trichura, which cannot be effectively treated with albendazole alone. Thus during this year’s brigade we will be distributing oxantal pamoate in addition to the albendazole to provide enhanced Trichura coverage. Padre Pedro has taken on the task to inquire and purchase both the albendazole and the oxantal pamoate.

Cistern in Chorro Viento
Dr. Nunez has proposed aggressively promoting the brigade via Radio Catolica broadcast in order to increase awareness and participation. Therefore, Padre Pedro will collaborate with Radio Catolica in order to provide the brigade dates and details about the services offered. We hope to see an increase in the number of people who attend the brigade in June.

On Friday February 13th, we traveled to La Hicaca so that could meet with Rosa in el Centro de Salud. Rosa graciously agreed to continue sanitation education and to take on the latrine and cook stove projects with Pico Bonito. She has also requested an additional 300 speculums for cytology exams.

In the afternoon, we had the opportunity to examine the water cisterns with the new chlorination systems in La Hicaca and Chorro Viento. We drove to La Culatta and climbed up to Chorro Viento. The 45-minute hike was definitely not an easy one and made me appreciate the 5-6 hour journeys many people endure to come to the brigade. Below are some pictures of the cisterns and the chlorination system installed.

New chlorination system in Chorro Viento

We attended Mass on Friday evening, traveled back to San Pedro Sula Saturday morning, and flew back to the US on Sunday. Although a short trip, we have gained a substantial amount of knowledge on current programs implemented in La Hicaca and surrounding villages.

I cannot wait to return in June- to see the progress and of course, to see my friends.