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Reposted by Madeleine Kline

Department of Immunology and Infectious Diseases, Harvard T.H. C @harvard-iid.bsky.social · Jul 30

In April, we congratulated IID’s Madeleine Kline (“Maddy”) on achieving the Emerging Physician Leader Award and Scholarship from Health Care Without Harm. 👏Learn more about the award and this year’s inspiring recipients here:

🔗 us.noharm.org/initiatives/....

(@mckline98.bsky.social)

Health professional awards, scholarships, & fellowships | Health Care Without Harm - US & Canada

us.noharm.org

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Madeleine Kline @mckline98.bsky.social · Jul 18

Your point about higher starting prevalence settings is also excellent — and an area of ongoing work in the lab!

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Madeleine Kline @mckline98.bsky.social · Jul 18

However, this would effectively mean there is a higher “resistance emergence” probability to those drugs, which we did test in our sensitivity analysis. Our framework could be easily adapted to more specifically look at bystander selection via something like an importation rate parameter.

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Madeleine Kline @mckline98.bsky.social · Jul 18

Thanks so much! It’s true that bystander selection through antibiotic usage for non-gonorrhea infections could occur (especially for ceftriaxone and gepotidacin), and this is not explicitly modeled here.

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Madeleine Kline @mckline98.bsky.social · Jul 3

Our results indicate that distributing selective pressures across the population minimizes the emergence of drug resistance in gonorrhea in US MSM and underscore the importance of disease and context-specific decision-making. [10/10]

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Madeleine Kline @mckline98.bsky.social · Jul 3

It was possible to find combinations of parameters where equal allocation was worse than sequential, but these were rare edge cases that required a combination of unlikely events. Even then, the difference between strategies was not large [9/10]

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Madeleine Kline @mckline98.bsky.social · Jul 3

Equal allocation was still better when we changed the prevalence threshold from 5% to 1% or 10%, and across a wide range of parameter values for parameters that determine underlying model behavior [8/10]

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Madeleine Kline @mckline98.bsky.social · Jul 3

The sequential strategy had met the 5% resistance prevalence threshold i) for each drug individually and ii) for all 3 drugs in at least as many simulations and iii) for at least as many drugs on average compared to the equal allocation strategy [7/10]

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Madeleine Kline @mckline98.bsky.social · Jul 3

We looked at the proportion of simulations had reached 5% prevalence of resistance for each drug and found that the equal allocation strategy 🔴 was better than the sequential strategy 🔵 because: [6/10]

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Madeleine Kline @mckline98.bsky.social · Jul 3

We compared two strategies: equal allocation 🔴, where all 3 drugs are used in random allocation but each individual gets treated with 1 drug, and sequential 🔵, where new drugs are only used once resistance prevalence for the previous drug has reached 5% [5/10]

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Madeleine Kline @mckline98.bsky.social · Jul 3

Here, we used a stochastic compartmental gonorrhea transmission model of US MSM to test introduction strategies with two new available drugs and one currently used drug, aimed at capturing random emergence and extinction dynamics [4/10]

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Madeleine Kline @mckline98.bsky.social · Jul 3

Antibiotic stewardship often urges us to reserve new antibiotics until they are absolutely needed, especially in hospital settings. Past research has shown that for gonorrhea treatment, distributing selective pressures by offering more treatment options at the same time reduces drug resistance[3/10]

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Madeleine Kline @mckline98.bsky.social · Jul 3

There were > half a million notifications for gonorrhea in the US in 2023, and the bacteria that cause the infection have developed resistance to all antibiotics used to treat it. 2 new drugs, zoliflodacin and gepotidacin, had positive phase III trial results and will likely be approved soon [2/10]

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Madeleine Kline @mckline98.bsky.social · Jul 3

⚠️ New preprint ⚠️: Two new antibiotics are likely coming for gonorrhea 💊. How should we deploy them in the US to minimize drug resistance? @kroster.bsky.social @dhelekal.bsky.social Eva Rumpler @yhgrad.bsky.social [1/10]
www.medrxiv.org/content/10.1...

Comparing Strategies to Introduce Two New Antibiotics for Gonorrhea: A Modeling Study

Introduction Drug resistance in Neisseria gonorrhoeae is an urgent public health threat. The anticipated approval of two new antimicrobials for gonorrhea prompts the need for evidence-based rollout st...

www.medrxiv.org

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Madeleine Kline @mckline98.bsky.social · Jul 3

Our results indicate that distributing selective pressures across the population minimizes the emergence of drug resistance in gonorrhea in US MSM and underscore the importance of disease and context-specific decision-making. [10/10]

Madeleine Kline @mckline98.bsky.social · Jul 3

It was possible to find combinations of parameters where equal allocation was worse than sequential, but these were rare edge cases that required a combination of unlikely events. Even then, the difference between strategies was not large [9/10]

1

Madeleine Kline @mckline98.bsky.social · Jul 3

We looked at the proportion of simulations had reached 5% prevalence of resistance for each drug and found that the equal allocation strategy 🔴 was better than the sequential strategy 🔵 because: [6/10]

Madeleine Kline @mckline98.bsky.social · Jul 3

We compared two strategies: equal allocation 🔴, where all 3 drugs are used in random allocation but each individual gets treated with 1 drug, and sequential 🔵, where new drugs are only used once resistance prevalence for the previous drug has reached 5% [5/10]

1

Madeleine Kline @mckline98.bsky.social · Jul 3

Here, we used a stochastic compartmental gonorrhea transmission model of US MSM to test introduction strategies with two new available drugs and one currently used drug, aimed at capturing random emergence and extinction dynamics [4/10]

1

Madeleine Kline @mckline98.bsky.social · Jul 3

Antibiotic stewardship often urges us to reserve new antibiotics until they are absolutely needed, especially in hospital settings. Past research has shown that for gonorrhea treatment, distributing selective pressures by offering more treatment options at the same time reduces drug resistance[3/10]

1

Madeleine Kline @mckline98.bsky.social · Jul 3

There were over 1/2 a million notifications for gonorrhea in the US in 2023, and the bacteria that cause the infection have developed resistance to all antibiotics used to treat it. 2 new drugs, zoliflodacin and gepotidacin, had positive phase III trial results and will likely be approved soon[2/10]

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Reposted by Madeleine Kline

Bailey Bowcutt @baileybowcutt.bsky.social · May 22

I'm a current Harvard graduate student and I found out today that I had my NSF GRFP terminated without notification. I was awarded this individual research fellowship before even choosing Harvard as my graduate school

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Reposted by Madeleine Kline

Kirstin Oliveira Roster @kroster.bsky.social · May 21

New preprint. After years of increases, gonorrhea diagnosis rates dropped in the US in 2022 and 2023. While the news is promising, understanding WHY is key to sustaining progress.
dash.harvard.edu/handle/1/427...

Why are gonorrhea diagnoses declining in the US?

After a decade of rising cases, the US CDC reported a decline in the rate of gonorrhea diagnoses for two years in a row in 2022 and 2023, especially among young adults. Primary and secondary syphilis ...

dash.harvard.edu

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Reposted by Madeleine Kline

Harvard T.H. Chan School of Public Health @hsph.harvard.edu · May 16

With nearly all of Harvard Chan School’s direct federal grants terminated, we are relying on philanthropy to power our research and support our educational programs. Every gift, regardless of size, advances our vision of health, dignity, and justice for every human. Support our work: hsph.me/whygive

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Reposted by Madeleine Kline

Scott Delaney @scott-delaney.bsky.social · May 14

My ongoing request:

If your NSF or NIH grant was terminated--whether at Harvard or elsewhere--please report it here.

NSF: grant-watch.us/submit-nsf.h...

NIH: grant-watch.us/submit-nih.h...

Our trackers are actively used in lawsuits and are often the only record that terminations ever occurred.

Dan Garisto @dangaristo.bsky.social · May 14

NSF appears to be terminating hundreds of its grants to Harvard, per internal sources at NSF and at Harvard. At least one division has had all its grants cut.

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