Marc J. Bonten

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases • March 05, 2025

Angela Huttner, Marc Bonten, Joshua Davis, Leonard Leibovici, Thomas Tängdén, Ilan Schwartz

The views expressed by the authors are their own and do not necessarily reflect those of the European Society for Clinical Microbiology and Infectious Diseases (ESCMID) or Elsevier. Each time a man stands up for an ideal, or acts to improve the lot of others, or strikes out against injustice, he sends forth a tiny ripple of hope. Robert F. Kennedy, Senior Political decisions in the United States of America influence every person on the planet. In the healthcare sphere alone, the first week of President Trump’s return to government has had massive reverberations. The effects of executive orders include: - The withdrawal of the USA from the World Health Organization (WHO), comprising 194 member states and of which it was a founding member. This will position the USA along Lichtenstein as the only members of the United Nations not part of the WHO. - An unprecedented and vaguely worded “pause” on all external communications from the Centers for Disease Control and Prevention (CDC), the National Institutes of Health (NIH), and the Food and Drug Administration (FDA), hampering the ability of these agencies to mount responses to and share alerts on emerging infectious and other health threats, during a period of heightened anxiety regarding human cases and pandemic potential of H5N1. - A 90-day stop-work order and freeze on disbursements of foreign aid, funding that is critical to fighting emerging threats (like Marburg virus in Tanzania), neglected tropical diseases and, via the President’s Emergency Plan for AIDS Relief (PEPFAR), HIV. - The interruption of NIH study sections, effectively disrupting the awarding of biomedical research grants to move evidence-based medicine forward. - A “pause” on all federal grants and loans. - A memo to all employees of Health and Human Services (HHS) and other agencies threatening “adverse consequences” if they do not report within 10 days on colleagues who may have tried to protect government programs aimed at diversity, equity, and inclusion. The Trump executive order to eliminate diversity, equity, and inclusion efforts in government programs will deprioritize research that addresses the social determinants of infectious diseases. As specialist clinicians and scientists, we know that infectious diseases cannot be controlled, prevented or treated optimally without attention to their socio-economic contexts. In the meantime, the Republican-controlled Senate appears poised to confirm as HHS Secretary Robert F. Kennedy, Jr., an anti-vaccine activist who has also questioned germ theory and whether HIV is the cause of AIDS. Mr. Kennedy has long been in the employ of anti-vaccination interest groups, taking in over $10 million this past year alone from them [1]. While he has recently promised to stop collecting fees on some of his vaccine lawsuits involving the U.S. government, he will continue to benefit financially by reportedly collecting referral fees for legal cases not involving the U.S. government: last year he reportedly received over $850,000 from the law firm that sued Merck over the human papillomavirus vaccine [1]. Investment in infectious diseases research is already suffering, but this is merely the beginning. When he was running to become president in 2023, Kennedy declared that “We’re going to give infectious diseases [research] a break for eight years [2].” Even if they say or do nothing going forward, US-based medical journals and their editors may well find themselves in the crosshairs. Mr. Kennedy promised in 2023 that if he were president, he would “order the Justice Department to investigate the editors and publishers of medical journals for ‘lying to the public’” on the safety and efficacy of approved vaccines [3]. These words should be taken seriously. Investigations of journal editors and publishers have been a highly effective means of stifling both free speech and rational scientific inquiry in recent past [4]. Concerned doctors and scientists have raised their voices against Mr. Kennedy’s nomination and these new orders, including 77 Nobel Prize winners who wrote a letter of opposition to the nomination [5]. Over 23,000 doctors have signed another letter opposing it, posted online by the Committee to Protect Health Care [6]. Mr. Kennedy’s spokesperson dismissed the signed statement as “just another grift” that would “bilk donors” to advocacy groups [7]. White is black and day is night. You did not see what you saw; you did not hear what you heard. Our colleagues in the United States have been courageous under uncertainty and significant duress. As physicians and editors, we call on the global infectious disease and clinical microbiology community to amplify their ripples. Letters are a good place to start, but their impact and reach are uncertain in a world whose media are increasingly controlled by profit-driven players bearing ideologies that bend with political winds. We ask for both individual and coordinated resistance. As individuals, we can learn from recent history. The lessons collected by the historian Timothy Snyder become sadly hyper-relevant now: do not obey in advance, defend institutions, stand out, believe in truth, listen for dangerous words…and be as courageous as you can [8]. As a collective in a globalized age, we can organize across borders, speak loudly, and in one voice. We can use open-source and open-protocol digital media to avoid supporting the very groups that are assailing science and evidence-based medicine. We must be available to and engage with general-interest and science journalists, whose work has never been more critical, to correct the falsehoods and provide accurate, conflict-free medical information to an increasingly confused public. Political decisions in a powerful nation influence every person on the planet. And yet personal decisions everywhere, if well coordinated, can too. Medicine—and infections—are more globalized than ever. Let us work together now to keep what we have built across borders.

JAMA Network Open • July 02, 2025

Denise Van Hout, Paul Mouncey, David Harrison, Marc Bonten, Lennie Derde, Aisha Anjum, Djillali Annane, Janis Best Lane, Frank Brunkhorst, Maurizio Cecconi, Stephan Ehrmann, Anthony Gordon, Leanne Hays, Esmee Kester, Niamh Mahon, Colin Mcarthur, Alistair Nichol, Svenja Peters, Sara Pugliese, Kathryn Rowan, Julian Torre Cisneros, Sebastian Weis

Ethical, administrative, regulatory, and logistical (EARL) procedures can hamper clinical trial delivery. Quantification of these hurdles is rare, prohibiting identification of areas for improvement. To identify and quantify EARL hurdles in trial delivery before and during the COVID-19 pandemic. This cohort study used data from the ongoing Randomized Embedded Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia to enable comparison of EARL procedures for multiple protocols across 19 European countries in the pre-COVID-19 pandemic (February 19, 2016 to March 10, 2020) and COVID-19 pandemic (March 11, 2020, to May 4, 2023) periods. Data were analyzed from November 2024 to March 2025 with contracts and protocol submissions as the units of analysis. Time to (1) site contract completion, (2) regulatory and ethical approval (TTA), and (3) first patient in (FPI). The UK was compared with non-UK countries because of its distinct research infrastructure. There were 257 fully signed first contracts with study sites for analysis. In the UK, contract completion times decreased by 97% (95% CI, 95% to 98%), from a median (IQR) of 196 (154 to 250) days in the pre-COVID-19 pandemic period to 5 (1 to 11) days during the COVID-19 pandemic. In non-UK countries, median (IQR) contract completion times were 224 (119 to 412) days and 183 (62 to 291) days before and during the COVID-19 pandemic, respectively (relative difference, -18%; 95% CI, -43% to 52%). In total, 44 interventions in 16 domains were submitted, yielding 232 protocol approvals for analysis. During the COVID-19 pandemic, median (IQR) TTA was 8 (5 to 31) days in the UK and 115 (47 to 103) days in non-UK countries (median difference, 107 days; 95% CI, 76 to 123 days), with large variation across non-UK countries. Time between approval and FPI during the COVID-19 pandemic was, on average, 3 months faster in the UK compared with non-UK countries (median difference, 90 days; 95% CI, 42 to 141 days). This study found that EARL procedures were lengthy and variable between countries, reflecting different interpretations of trial regulations, with faster processes in the UK. These findings underscore the need to streamline processes across European countries to improve trial efficiency, in particular during future public health emergencies such as pandemics.

Nederlands Tijdschrift Voor Geneeskunde • May 20, 2025

Ruud Duijkers, Marc J Bonten, Wim Boersma

Objective: To investigate whether the duration of antibiotic therapy in patients with CAP can be reduced using a biomarker-guided algorithm. Methods: Randomized controlled multicentre study. Methods: A total of 468 non-ICU patients with CAP were randomized after 2-3 days into three groups (ratio 1:1:1): standard treatment, PCT-guided treatment, and CRP-guided treatment. The primary outcome was the total number of days on antibiotic treatment until day 30. Secondary outcomes included new antibiotic prescriptions, time to clinical stability, length of hospital stay, and 30-day mortality. Results: The mean age of 468 participants was 67 years, and a potential pathogen was identified in 64% of cases. The total number of days on antibiotic treatment was reduced by 30% in the CRP group (4 vs. 7 days; p < 0.001) and by 22% in the PCT group (5.5 vs. 7 days; p < 0.001). No significant differences were observed in secondary outcomes between the standard treatment and biomarker-guided treatment groups. Conclusions: Both CRP- and PCT-guided algorithms reduce the duration of antibiotic use in non-ICU patients with CAP. No differences were observed between the three groups in terms of additional antibiotic prescriptions, length of hospital stay, or mortality.

Antimicrobial Agents And Chemotherapy • May 19, 2025

Sahaya Rajakani, Basil Xavier, Ngoc Nguyen, Qiang Lin, Anouk Braspenning, Nienke Plantinga, Bastiaan H Wittekamp, Olympia Zarkotou, Rob Van Houdt, Youri Glupczynski, Spyros Pournaras, Marc J Bonten, Surbhi Malhotra Kumar

Colistin is one of the last-line antibiotics against multi-drug-resistant (MDR) gram-negative pathogens, such as Klebsiella pneumoniae. Using long-read sequencing, we observed remarkable genome-wide transposition events in MDR K. pneumoniae exposed to colistin in patients receiving treatment for respiratory infections or as part of selective decolonization strategies and further confirmed these on in vitro selection experiments. These data add yet another dimension to the role of antibiotics in mediating specific processes in bacteria beyond antibiotic resistance.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT02208154.

Critical Care (London, England) • April 02, 2025

Jelle L Haitsma Mulier, Fleur Van Dijk, Valentijn Schweitzer, Marc J Bonten, Lennie P Derde, Olaf Cremer

Background: Selective Digestive Decontamination (SDD) prevents infections and reduces mortality in the intensive care unit (ICU). Microbiological surveillance is considered essential for effective decontamination and detecting antibiotic resistance. However, its optimal frequency is unclear. We compared microbiological yield and costs of different surveillance intervals during SDD. Methods: In a computational simulation study, using data from a Dutch ICU, three surveillance scenarios were compared: (A) twice-weekly, (B) once-weekly, and (C) no surveillance. The primary outcome was the number of clinically relevant potentially pathogenic microorganisms (PPMs) detected per scenario. Secondary outcomes included detection of colonisation persistence prompting SDD intensification and surveillance costs. Results: We included 8,499 ICU admissions, 52,553 clinical and 75,567 SDD cultures. Scenario A yielded 911 (95% CI 905-917) PPMs per 1,000 days, of which 90 (88-94) were clinically relevant: 9 (9-10) multidrug-resistant microorganisms, 68 (66-71) microorganisms resistant to standard therapy, and 13 (12-14) infection-related microorganisms. Scenarios B and C yielded 85 (82-88) and 77 (75-80) relevant PPMs, respectively (94% and 86% compared to scenario A). Scenario A identified 56 (55-58) cases of colonisation persistence per 1,000 days while scenarios B and C detected 43 (42-45) and 12 (11-12), respectively. Total costs of SDD surveillance were €78,774, €55,208, and €31,522 per 1,000 days for scenarios A, B and C. Conclusions: Compared to twice-weekly surveillance, once-weekly microbiological surveillance reduces costs by 30% with 6% loss in clinically relevant PPM detections. No surveillance reduces costs by 60% with 14% detection loss.