Infectious Diseases

Antibiotic spectrum intensity, not dose or duration, drives ICU carbapenem‑resistant Gram‑negative acquisition

In this prospective four‑ICU cohort of 422 adults, 35.8% acquired carbapenem‑resistant Gram‑negative bacteria during a median 12‑day stay. Higher Antibiotic Spectrum Index per antibiotic day independently increased CR‑GNB risk, with an adjusted hazard ratio of 1.14 per one‑unit increase. The ASI–risk relationship was J‑shaped, indicating even moderate spectrum escalation can substantially raise acquisition risk. Defined Daily Doses and Length of Therapy were not independently associated with CR‑GNB after adjustment despite non‑linear trends. Relative importance analysis identified spectrum intensity as the dominant driver, supporting stewardship that rapidly narrows and de‑escalates coverage. 1

Four‑hour nanopore metagenomics accurately identifies pathogens and resistance in complicated UTIs

Seventy‑eight patients with complicated UTIs underwent 11 preparatory workflows followed by real‑time nanopore metagenomic sequencing. The optimized protocol achieved 99% accuracy for pathogen identification and 90% accuracy with 95% specificity for susceptibility profiling versus culture‑based routines. Pathogens were reliably detected at bacterial loads as low as 32 cells/µL, and 13 culture‑missed pathogens were confirmed by alternative assays. Turnaround from sample collection to informed decision was about four hours and up to 30% cheaper than some existing metagenomic methods. The authors propose using DNA yield and flow cytometry for pre‑screening to triage samples and improve cost‑effectiveness. 2

Aztreonam‑avibactam remains highly active against global MBL‑producing Enterobacterales

This study tested 490 metallo‑β‑lactamase‑producing Enterobacterales from 27 countries, largely NDM‑1, NDM‑5, and VIM‑1 producers. All isolates were susceptible to aztreonam‑avibactam by EUCAST and FDA breakpoints, with MIC50/90 of 0.12/0.5 mg/L. Cefiderocol inhibited 66.7% of isolates by EUCAST and 90.8% by FDA criteria, while cefepime‑taniborbactam was active against fewer than 60%. Tigecycline and colistin inhibited most isolates, but activity was incomplete, with colistin susceptibility only 76.6% by EUCAST. Aztreonam‑avibactam retained activity despite additional resistance mechanisms and PBP3 insertions, supporting its role for severe MBL‑mediated infections. 3

Combination HIV immunotherapy achieves ART‑free control in most participants in a proof‑of‑concept trial

Ten ART‑suppressed adults with HIV received a conserved‑element Gag DNA+IL‑12 prime/MVA boost vaccine plus two broadly neutralizing antibodies and lefitolimod. bNAbs were re‑dosed at analytic treatment interruption, and seven of ten participants maintained post‑intervention viral control off ART. Control appeared independent of residual plasma bNAb levels, implicating vaccine‑primed and TLR9‑stimulated cellular responses. Early expansion of activated CD8+ T cells to rebounding virus correlated with lower median off‑ART viral loads. These data suggest that multi‑component immunotherapy can slow rebound and may inform future cure‑directed strategies. 4