The CDC reported a surge in NDM-CRE, dangerous bacteria that are “resistant to some of the strongest antibiotics.” The U.S. saw a 460% increase in infections of NDM-CRE between 2019 and 2023.

CAB/RPV for people with HIV and persistent viremia in the US would lead to more viral suppression and fewer deaths compared to oral-based ART regimens. Inc

In this phase II trial, reduced-dose flucytosine (60 mg/kg/day) demonstrated inferior cerebrospinal fluid fungal clearance compared to standard dosing in c

Gaza's health-care system has faced widespread destruction during the ongoing Israeli military invasion that began in October, 2023, leading to a proliferation of disease outbreaks.1,2 During this tim...

The Phase 3 ASSEMBLE study investigated aztreonam–avibactam versus best available therapy (BAT) for treatment of complicated intra-abdominal infection (cIAI), complicated urinary tract infection (cUTI), hospital-acquired/ventilator-associated pneumonia (HAP/VAP) or bloodstream infection (BSI) caused by confirmed MBL-producing multidrug-resistant pathogens.MethodsThis prospective, multicentre, randomized, open-label, central assessor-blinded study randomized hospitalized adults 2:1 to aztreonam–avibactam [+ metronidazole (cIAI)] or BAT for 5–14 (cIAI, cUTI and BSI) or 7–14 (HAP/VAP) days. Primary endpoint was clinical cure at test-of-cure (TOC) visit on Day 28  ±  3 [microbiological ITT (micro-ITT) analysis set]. Secondary endpoints included microbiological response at TOC, 28-day mortality and safety. No formal hypothesis testing was planned.ResultsFifteen patients were randomized [aztreonam–avibactam, n = 12; BAT, n = 3 (ITT and micro-ITT analysis sets)]. Most frequent baseline pathogens were Enterobacterales; Klebsiella pneumoniae was most common [aztreonam–avibactam, 6/12 (50%); BAT, 2/3 (67%)]. MBL subtypes/variants identified in the aztreonam–avibactam group were NDM-1 (n = 7), NDM-5 (n = 3), VIM-2 (n = 2) and L1 (n = 3); and for BAT were NDM-1 (n = 2) and NDM-5 (n = 1). Clinical cure rates at TOC were 5/12 (42%) for aztreonam–avibactam and 0/3 (0%) for BAT. Per-patient microbiological responses were generally consistent with clinical responses. Twenty-eight-day all-cause mortality rates for aztreonam–avibactam and BAT were 1/12 (8%) and 1/3 (33%), respectively. Aztreonam–avibactam was generally well-tolerated, with no treatment-related serious adverse events.ConclusionsThese Phase 3 data provide support for aztreonam–avibactam as a potential therapeutic option for difficult-to-treat infections caused by MBL-producing Gram-negative bacteria.

A group of twenty who worked in other areas of healthcare while studying, have now qualified as doctors.

There have been more measles cases in the US this year than any other since the disease was declared eliminated a quarter-century ago.

Antimicrobial resistance is a global public health threat that requires urgent solutions. One strategy to decrease resistance of Gram-negative bacteria (GNB) to β-lactam antibiotics (BL) is their combination with β-lactamase inhibitors (BLI).ObjectivesThis systematic review analyses the outcomes, safety and pharmacokinetics (PK) of recently approved or under clinical development BLI and BL/BLI combinations.MethodsThe systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. PubMed, Embase, and Cochrane electronic databases were used to search for articles from January 2010 to November 2024. The studies were retrieved and screened on the basis of predefined exclusion and inclusion criteria. A quality assessment of the included studies was conducted following the New Castle-Ottawa Scale.ResultsA total of 191 articles addressing clinical research regarding the efficacy, safety, tolerability, and PK of new BL/BLI combinations with avibactam, durlobactam, enmetazobactam, nacubactam, relebactam, taniborbactam, tazobactam, vaborbactam and zidebactam were included. According to the published literature, clinical research supports the novel BL/BLI combinations for the treatment of complicated urinary tract infections, complicated intra-abdominal infections, and hospital-acquired and ventilator-associated pneumonia (HAP/VAP) caused by GNB. In spite of that, the development of new BLI effective for class B metallo-β-lactamases (MBL) is still challenging, being aztreonam/avibactam the only approved combination active against MBL-producing bacteria.ConclusionsAlthough there has been extensive research to develop new BLI and BL/BLI combinations, only a few have reached the market. More evidence of its usefulness in the real world is still needed.

AbstractCases of Candida infection have been on the rise in recent years. A comprehensive and clear understanding of the mechanisms of antifungal resistance is fundamental for developing novel therapies to address the current and emerging threat of fungal diseases. Certain Candida species can cause superficial or invasive infections in immunocompromised hosts, and invasive Candida infections are major contributors to infectious disease deaths. As fungi are eukaryotes like humans, there are only a limited number of unique molecular targets available for antifungal drug development. Until recently, there have only been four primary classes of antifungals used to treat systemic fungal infections. Among these, azole antifungals are globally used because they are both inexpensive and effective. Due to various factors, resistance to antifungal drugs—especially azole antifungals—has developed in many Candida species, posing a significant public health threat. This review discusses the known mechanisms of azole antifungal resistance in Candida albicans, Candida auris, Nakaseomyces glabrata, Candida tropicalis, Candida parapsilosis and explores strategies to overcome the resistance problem.

Among modifiable clinical factors in patients with E. faecium BSI, source control and the execution of follow-up blood cultures demonstrated a protective effect on 30 day mortality.

Background Bacterial prostatitis is a common infection affecting the patient’s quality of life. It is caused by various bacteria, including multidrug-resistant Enterobacterales. Fosfomycin is active a...

Traditional treatment of methicillin-susceptible Staphylococcus aureus (MSSA) native valve endocarditis is based on cloxacillin/cefazolin monotherapy. Antibiotics with high activity against MSSA such as ceftaroline and daptomycin have been marketed last years, but there are no clinical trials evaluating them as monotherapy or combination therapy in patients with MSSA endocarditis.ObjectivesTo compare the efficacy of cloxacillin, ceftaroline and daptomycin monotherapies and daptomycin combinations with beta-lactams in a rabbit model of MSSA endocarditis.MethodsEndocarditis was induced in rabbits using two strains of MSSA. After 24h of infection, they received human-like doses of cloxacillin, ceftaroline or daptomycin or combinations of daptomycin plus either cloxacillin or ceftaroline. Isolates recovered from vegetation, spleen and kidney were retested for daptomycin non-susceptibility (DNS) post-treatment.ResultsMSSA vancomycin MIC did not influence the efficacy of any antibiotic treatment. Cloxacillin, ceftaroline and daptomycin had similar activity (25-50%) in sterilizing vegetations. However, 13% of rabbits treated with daptomycin developed DNS. The addition of daptomycin to cloxacillin or ceftaroline was synergistic and bactericidal, showing significantly more activity and higher rates of sterile vegetations (≥90%) than any monotherapy Combinations also showed better activity in spleens and kidneys compared with daptomycin monotherapy and prevented the development of DNS in all tissues. There were no differences between the two daptomycin combinations.ConclusionsIn the MSSA experimental endocarditis model, daptomycin combinations with beta-lactams had significantly better activity than either their monotherapies in sterilizing valve vegetations and preventing DNS development. These findings support their use in clinical practice and to perform clinical trials.

Los Angeles has declared an outbreak of hepatitis A virus based on “elevated virus levels” in wastewater surveillance and a “sustained increase” in cases over the last year, health officials announced.

Stenotrophomonas maltophilia is an opportunistic pathogen most commonly isolated from patients with complex/life-threatening disease or cystic fibrosi…

This study (China Assessment of Antifungal Therapy in Hematological Diseases [CAESAR 2.0]) aimed to provide updated epidemiological data on invasive fungal disease (IFD) in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT).MethodsThis multicenter, real-world, observational study was conducted at 12 allo-HSCT centers in China between January and December 2021. Consecutive adult patients (aged ≥18 years) who underwent allo-HSCT with antifungal prophylaxis were included. IFD was diagnosed according to the 2019 criteria of the European Organization for Research and Treatment of Cancer and Mycoses Study Group (EORTC/MSG). Follow-up was completed by 31 December 2022.ResultsA total of 2015 patients were included. Mold-active antifungal prophylaxis was used in 76.08%, most of whom received voriconazole (44.37%) or posaconazole (31.71%). The cumulative incidence of IFD (proven or probable) 1 year after allo-HSCT was 6.3%. Pathogens were identified in 47.97% of IFD cases and mainly included Candida spp. (17.89%), Mucorales (13.01%), Aspergillus spp. (8.94%), and Pneumocystis jirovecii (6.5%). Multivariate analysis identified the following factors associated with IFD: disease at advanced stage (hazard ratio, 2.55 [95% confidence interval, 1.58–4.12]; P < .001), absolute neutrophil count engraftment (≤28 days) (0.37 [15–.92]; P = .03), platelet engraftment (≤28 days) (0.41 [.27–.62]; P < .001), and acute graft-vs-host disease grade III–IV (2.97 [1.97–4.49]; P < .001). The IFD-attributable mortality rate was 48.28%.ConclusionsDespite the widespread use of mold-active prophylaxis, the risk of IFD after allo-HSCT remains high. The most common pathogens are Candida spp., Mucorales, Aspergillus spp., and P. jirovecii.

To the  Editor—We read with interest the recent article by Schranz et al [1], which quantified the unbillable time for coordination of outpatient parenteral antimicrobial therapy (OPAT) at 27 minutes per week. We commend them for this seminal and important work, which takes some first steps toward quantifying the necessary time for OPAT services. Due to difficulty billing for remote monitoring services, reports such as this are welcomed and demonstrate some of the resources required to provide OPAT patients with high-quality care. However, the authors did not address the specifics of their OPAT practice model, the antimicrobials used, or the difference in coordination of care with patients on vancomycin as compared to daptomycin.