New data published today in Clinical Infectious Diseases indicates that early implementation of shorter treatment regimens for drug-resistant tuberculosis (TB) in the United States was successful.

The data come from a cohort of 70 US patients who were started on the 6-month, all-oral bedaquiline, pretomanid, and linezolid (BPaL) regimen for rifampin-resistant TB (RR-TB) in October 2019, shortly after the US Food and Drug Administration approved the regimen. The data on treatment outcomes were collected and analyzed by the BPaL Implementation Group (BIG). Because data from several trials indicated a high rate of adverse events with 1,200 milligrams (mg) of linezolid, most of the US patients treated with the BPaL regimen were started with a 600-mg linezolid dose based on the determination of their provider and had the dosage adjusted by therapeutic drug monitoring (TDM).

Of the 70 patients (65.7% male, 90% non–US-born, 77.9% non-White), 68 (97.1%) completed BPaL treatment. Fifty-five patients (80.9%) who completed BPaL had at least 6 months of follow-up without relapse, 36 (52.9%) had at least 12 months, and 19 (27.9%) had at least 24 months. Two patients (2.9%) were lost to follow-up after treatment completion, three (4.4%) after 6 months of treatment, and two (2.9%) experienced relapse.

Using an initial 600-mg linezolid dose daily adjusted by TDM and careful clinical and laboratory monitoring for side effects, supportive care, and expert consultation throughout BPaL treatment, three patients with hematologic toxicity (4.4%) and four with neurotoxicity (5.9%) required a change in linezolid dose or frequency. The median BPaL duration was 6 months.

Early implementation of new tuberculosis treatments is feasible, serving as a model for future innovations.

The study authors say the BPaL regimen has "transformed" treatment for drug-resistant TB in the United States. Previous RR-TB regimens were as long as 24 months, with poorer outcomes. From 2014 through 2018, only 62% of the 618 US patients with RR-TB completed the treatment, with 8% dying before treatment completion.

"The BIG cohort demonstrates that, with collaborative efforts among providers and public health programs, early implementation of new tuberculosis treatments is feasible, serving as a model for future innovations," they wrote.

Implementation of a prospective audit-and-feedback (PAF) intervention combined with an online tool was tied to an almost 10% reduction in carbapenem use at a Spanish hospital without worse patient outcomes, researchers reported today in the Journal of Antimicrobial Chemotherapy.

The study examined carbapenem use at a hospital in Barcelona 2 years before and 2 years after implementation of an online, real-time tool (the SAP business object, SAP-BO) that provides data on antibiotic consumption and helps antimicrobial stewardship programs (ASPs) assess and measure the success of a stewardship intervention. The study was conducted in the hospital's urology department, which was selected due to its high carbapenem usage, with the PAF specifically targeting carbapenem prescriptions. A total of 7,631 patients were included in the study, with 4,092 in the pre-intervention period and 3,359 in the intervention period.

There was a 9% decrease in carbapenem use as assessed by defined daily doses (DDD) per 100 patient-days (PD) in the intervention period (incidence ratio [IR], 0.91; 95% confidence interval [CI], 0.85 to 0.97). Carbapenem days of therapy (DOT)/100 PD also fell during the intervention period, decreasing from 12.4 to 11.0 (– 1.5 DOT/100 PD; IR, 089; 95% CI, 0.83 to 0.94). In addition, overall antibiotic DDD/100 PD fell by 3% (IR, 0.97; 95% CI, 0.94 to 0.99) and DOT/100 PD by 7% (IR, 0.93; 95% CI, 0.91 to 0.95).

Our study demonstrates the usefulness and safety of the implementation of an ASP that combines a [prospective audit-and-feedback] intervention with an electronic tool.

Analysis of the intervention's impact on patient safety found the incidence of infections caused by carbapenemase-producing organisms was similar in the two periods, as was the incidence of Enterococcus faecium bacteremia and Clostridioides difficile–associated diarrhea. The rate of extended-spectrum beta-lactamase incidence decreased, but the difference was not statistically significant. Length of hospital stay, in-hospital all-cause mortality, and 30-day readmission incidence remained unchanged.

"Overall, our study demonstrates the usefulness and safety of the implementation of an ASP that combines a PAF intervention with an electronic tool to reduce carbapenem use," the study authors wrote. "Further studies are needed to explore the ecological impact of similar programmes."

Australian First Nations (FN) people, who, like other indigenous populations, are at high risk for poor COVID-19 outcomes, have robust immune responses to the Pfizer/BioNTech vaccine,  finds a study published yesterday in Nature Immunology.

A University of Melbourne-led team evaluated immune responses in 97 COVID-naïve adults (58 FN people and 39 nonindigenous people from Darwin, Northern Territory) in 2021 or 2022. The researchers performed sampling before the first dose, 6 to 28 days after dose 1, before dose 2, 28 days after dose 2, 6 months after dose 2, and 28 days after dose 3.

Median participant age was 44 years, and 47% and 74% of participants in the Australian FN group and the nonindigenous people, respectively, were women.

Lower response in those with chronic conditions

Australian FN people elicited effective immune responses to vaccination, including neutralizing antibodies, receptor-binding domain (RBD) antibodies, SARS-CoV-2 spike–specific B cells, and CD4⁺ and CD8⁺ T cells.

In FN participants, RBD immunoglobulin G (IgG) antibody levels were correlated with body mass index and negatively correlated with age. Reduced RBD antibodies, spike-specific B cells, and follicular helper T cells were observed in vaccinated participants with chronic conditions such as diabetes and kidney disease and were strongly tied to altered glycosylation of IgG and increased interleukin-18 plasma levels.

We saw high levels of antibodies binding to the virus following two vaccine doses.

These changed immune responses were also seen in nonindigenous people with chronic conditions, which the study authors said indicates the changes were related to the conditions rather than to ethnicity. Vaccine-induced antibody responses against the SARS-CoV-2 Delta and Omicron variants were lower but rose substantially after the third dose, similar to those in previous studies among nonindigenous people.

"We saw high levels of antibodies binding to the virus following two vaccine doses," said lead author Wuji Zhang, a PhD candidate, in a University of Melbourne's Peter Doherty Institute for Infection and Immunity news release. "T cells against the spike protein, which often recognise small sections of the virus and are similar across different variants, were also seen in higher numbers and showed 'memory signatures' following vaccination."