Marc Lipsitch

Marc Lipsitch, an assistant professor in the Department of Epidemiology, has been named an Ellison Medical Foundation New Scholar in Global Infectious Disease. The program supports investigators in basic biological and clinical sciences who are conducting research on the molecular and cellular mechanisms of parasitic and infectious diseases of global public health significance. The program provides awards of up to $50,000 per year for a four-year period. Applications are taken by invitation only.

Lipsitch has received funding to research "Antibiotic Resistance in Streptococcus pneumoniae: Transmission Dynamics and Consequences for Public Health." He is working on the project with a student, a post doc, and a lab manager at HSPH, as well as collaborators at the Centers for Disease Control and Prevention (CDC).

"Human use of antibiotics is one major force that affects the prevalence of antibiotic resistance in organisms that cause infections in humans," said Lipsitch. "Because antibiotic resistance is increasing in many organisms, there is a lot of interest in how to reduce resistance or at least how to slow the increase in resistance."

Lipsitch is looking specifically at Streptococcus pneumoniae, a bacterial pathogen that causes more than 100,000 hospitalizations for pneumonia, millions of cases of otitis media (ear infections), and more than 3,000 cases of meningitis annually, according to the CDC.

"The work we propose to do looks at both sides of the questions: how do we affect the bug’s population biology and how does the bug’s population biology affect human health," said Lipsitch.

Lipsitch is trying to understand the relationship between antibiotic use and factors that lead to antibiotic resistance. The drugs kill the pathogens sensitive to antibiotics, sometimes leaving behind antibiotic-resistant pathogens that can multiply and be transmitted. He is also investigating the consequences of using vaccines that may be effective against some strains of pathogens but not against other strains.

Lipsitch has developed a multifaceted research plan. He is collaborating with CDC scientists to test several hypotheses about why antibiotic resistance patterns vary in different parts of the world. For example, in some European countries less than 10 percent of strains of S. pneumoniae are resistant to penicillin compared to 40 to 60 percent in parts of the US. Some of the discrepancy can be explained by discretionary use, as opposed to necessary use, of penicillin and related antibiotics–physicians may feel pressured by patients to prescribe antibiotics, even when the drugs are not called for or are ineffective against a particular illness. Antibiotics, for example, do not work against viruses, such as the ones that cause colds.

"It is not obvious how to change this behavior within a country that has a strong culture of using antibiotics," said Lipsitch.

To conduct research about antibiotic resistance patterns, Lipsitch and his colleagues will initially use data sets from developed countries because the sets are large and systematic. Lipsitch expects the methods he develops to be generalizable to other groups and plans to eventually establish collaborations with investigators in developing countries. He hopes to combine statistical analyses of the data sets with mechanistic mathematical models to project trends in resistance to single and multiple drugs within each of the populations he studies.

Use of a specific antibiotic may undermine the effectiveness of other antibiotics. Lipsitch and HSPH student Alethea McCormick are looking into the relationship between resistance to penicillin and resistance to another antibiotic called erythromycin. Penicillin and erythromycin are in different classes of drugs, yet many strains of S. pneumoniae are resistant to both drugs.

"It may be that if a population uses erythromycin or other members of that class, it will cause an increase in resistance not only to that class but also to penicillin," said Lipsitch.

A key part of Lipsitch’s research is trying to figure out whether decreasing antibiotic use will change antibiotic resistance rates.

"Just because using antibiotics makes resistance go up doesn’t mean that taking antibiotic use away will automatically make resistance go down," said Lipsitch.

He wants to figure out if resistant strains are at any kind of a disadvantage when there are no antibiotics present.

"You might imagine that if being resistant were such a great thing, bacteria would have already been resistant before antibiotics appeared. The bacteria weren’t resistant at first, which leads some people to think that being resistant may present some kind of natural disadvantage," said Lipsitch.

To test the hypothesis, Lipsitch, lab manager Claudette Thompson and postdoctoral fellow Krzysztof Trzcinski are inoculating rats with a mixture of strains of S. pneumoniae; one strain is resistant to specific antibiotics and the other strain is not resistant. Then, they are taking samples from the rats to measure the ratio of the number of resistant bacteria to sensitive bacteria. If the resistant strains start to decrease in number, then there may be an indication that resistance comes with a natural disadvantage, or a cost.

"If that’s generally true, that’s a good thing because that means if you take away the pressure to be resistant, for example if you decrease antibiotic use, there will be something pushing in the other direction, helping antibiotics to remain effective," said Lipsitch.

What if pathogens resistant to antibiotics actually cause less disease than their drug-sensitive counterparts? Recent research has shown that penicillin-resistant strains of S. pneumoniae are considerably less virulent than their drug-susceptible counterparts in animal models. Lipsitch and his colleagues want to test the hypothesis based on human data.

"We want to look at strains causing real disease in real people and compare the sorts of disease that are caused by resistant strains as compared to sensitive strains," said Lipsitch. "There are a lot of methodological problems with that approach because part of what determines if something causes disease is how it responds to treatment. We want to capture disease manifestations before any treatment has happened, and that’s the challenge we’re trying to work through."

Lipsitch is also developing mathematical models to assess how existing antibiotics may be better used to simultaneously optimize treatment success in patients, prevent the emergence and spread of strains resistant to any individual drug, and forestall the appearance of multiple-resistant organisms that are not effectively treated by existing drugs.

In addition to the Ellison Medical Foundation, Lipsitch has been chosen to receive the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) Young Investigator Award from the American Academy of Microbiology. The award is sponsored by Merck and Company and consists of a $2,500 prize to be awarded at the ICAAC on September 1.

It’s time to put the public back into public health," said HSPH’s Dr. Kimberly Thompson when talking about her recently released book, Overkill: How Our Nation’s Abuse of Antibiotics and Other Germ Killers is Hurting Your Health and What You Can Do About It (Rodale Press), written with Debra Fulgham Bruce. Thompson is assistant professor of risk analysis and decision science in the Department of Health Policy and Management.

"Overuse of antibiotics and other germ-killers may be opening the door to a public health crisis, and the solution lies in making sure that individuals become empowered to make better choices when they manage their risks from germs," said Thompson.

As scientists learn more about drug-resistant super-germs that continue to emerge and as they look for new, more powerful, effective pharmaceuticals to fight them, Overkill provides a hands-on guide to germ risks and what to do about them. The book offers a series of questions to help individuals characterize their personal risk profile and then suggests practical steps to take for protection from germs and from the misuse of antibiotics and antibacterial products.

Covering the spectrum of germ-related conditions, Overkill emphasizes a number of strategies that people can employ to protect themselves from germs and prevent illness, as well as ways to treat symptoms. The book also tackles germ myths, encouraging the reader to challenge misperceptions of antibiotics as magic pills that cure all.

Emphasizing basic hygiene and food safety, Overkill devotes an entire chapter to preventing food-borne illnesses, which claim the lives of approximately 5,000 Americans and make one out of every four Americans sick each year, according to the Centers for Disease Control and Prevention.

Recognizing the need for people to appreciate their own personal risks, Overkill provides a chapter with guidance for special situations, such as when caring for babies or immuno-compromised people or when living with many other people in crowded spaces, such as in a dormitory.

For more information, visit Thompson’s "Age of Risk Management" web site at: www.aorm.com.