2nd November 2023

Explore the latest Editors’ picks from Journal of Antimicrobial Chemotherapy (JAC) and JAC-Antimicrobial Resistance (JAC-AMR). In JAC, we have support for a new, shorter treatment regimen for visceral leishmaniasis, safety trial results for a new antifungal treatment and a report on remdesivir treatment for COVID-19 patients. And in JAC-AMR, 10 years of data from Peru show a worrying increase in resistance to shigellosis treatments and a report finds reduced cefiderocol activity in Pseudomonas aeruginosa with treatment-emergent resistance to ceftolozane/tazobactam.

Luka Verrest and others, Population pharmacokinetics of a combination of miltefosine and paromomycin in Eastern African children and adults with visceral leishmaniasis. Journal of Antimicrobial Chemotherapy 2023; dkad286, https://doi.org/10.1093/jac/dkad286

Children account for around half of visceral leishmaniasis cases worldwide, so it is important to ensure that new treatment regimens are adapted accordingly. This population pharmacokinetic analysis by Verrest et al. supports the implementation of a shorter 14 day paromomycin + allometric miltefosine combination regimen for visceral leishmaniasis in Eastern Africa, as it provided adequate exposure in both children and adults.

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Oliver A Cornely and others, Phase 1b safety and pharmacokinetics of intravenous and oral fosmanogepix in patients with acute myeloid leukaemia and neutropenia. Journal of Antimicrobial Chemotherapy 2023; dkad269, https://doi.org/10.1093/jac/dkad269

Cornely et al. report results from a Phase 1b trial of fosmanogepix, an antifungal prodrug that inhibits cell wall synthesis, in immunocompromised patients at risk of invasive fungal infections. They found similar safety and pharmacokinetics profiles to those previously observed in healthy volunteer and show that fosmanogepix was safe and well tolerated.

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Karl Hagman and others, Effects of remdesivir on SARS-CoV-2 viral dynamics and mortality in viraemic patients hospitalized for COVID-19. Journal of Antimicrobial Chemotherapy 2023; dkad295, https://doi.org/10.1093/jac/dkad295

In a cohort of viraemic patients hospitalized for COVID-19, Hagman et al. found that remdesivir treatment did not significantly affect SARS-CoV-2 viraemia duration, serum viral load decline, 60 day mortality or in-hospital adverse outcomes in those who’d had symptoms for ≤10 days at admission. However, serum viral load decline was significantly faster in patients with ≤7 days of symptoms at admission, suggesting remdesivir could be beneficial if administered soon after symptoms begin.

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Willi Quino and others, Trends in antimicrobial resistance of Shigella species in Peru, 2011–2020. JAC-Antimicrobial Resistance 2023; dlad110, https://doi.org/10.1093/jacamr/dlad110

Quino et al. report resistance rates and species distribution of Shigella species over the past 10 years in Peru, highlighting a concerning increase in resistance to antibiotics commonly used to treat shigellosis. Shigella sonnei was the most common species, followed by Shigella flexneri, and more than 90% of all isolates tested were resistant to trimethoprim/sulfamethoxazole, with resistance to ciprofloxacin and nalidixic acid also on the rise.

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Ryan K Shields and others, In vitro activity of cefiderocol against Pseudomonas aeruginosa demonstrating evolved resistance to novel β-lactam/β-lactamase inhibitors. JAC-Antimicrobial Resistance 2023; dlad107, https://doi.org/10.1093/jacamr/dlad107

In this study, Shields et al. tested cefiderocol activity against P. aeruginosa collected before and after treatment with β-lactams and new β-lactam/β-lactamase inhibitor combinations. They report cross-resistance between cefiderocol and ceftolozane/tazobactam and highlight the importance of routine cefiderocol susceptibility testing when treatment options are limited.

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