A study of tuberculosis (TB) patients in South Africa found that more than half receiving treatment with a bedaquiline-containing regimen had isolates with bedaquiline resistance, researchers reported last week in The Lancet Microbe.

For the retrospective longitudinal study, a team led by researchers with Stellenbosch University collected and analyzes sputum samples from adults with culture-positive pulmonary TB who received at least 4 months of a bedaquiline-containing regimen from January 20, 2016, to November 20, 2017. Bedaquiline has recently become part of all standard drug-resistant TB regimens globally, but it was introduced for compassionate use in South Africa in 2012. To monitor treatment response and resistance emergence, the researchers conducted phenotypic drug-susceptibility testing for bedaquiline on baseline samples and samples from each month, and performed whole-genome sequencing (WGS).

Bedaquiline resistance gain

Of the 38 patients with isolates assessable for phenotypic drug susceptibility testing, 3 (8%) had bedaquiline resistance at baseline (primary resistance), 18 (47%) gained resistance (due to acquisition or reinfection), and 17 (45%) were susceptible at both baseline and follow-up. WGS revealed that several Rv0678 and pepQ single-nucleotide polymorphisms and indels were associated with resistance, while isolates with Rv0676c, Rv0677c, and Rv1979c variants were seen with both resistant and susceptible isolates. Patients with baseline fluoroquinolone resistance, clofazimine exposure, and four or fewer effective drugs were more likely to have bedaquiline-resistance gain.

Our study highlights risks associated with implementing life-saving new drugs and shows evidence of bedaquiline-resistance transmission.

The authors say the study is one of the first to report individual-level bedaquiline resistance gain over time among patients treated in a programmatic setting with a bedaquiline-containing regimen, and underscores the importance of adequate drug-susceptibility testing capacity.

"Our study highlights risks associated with implementing life-saving new drugs and shows evidence of bedaquiline-resistance transmission," they wrote. "Routine drug susceptibility testing should urgently accompany scale-up of new drugs; however, rapid drug susceptibility testing for bedaquiline remains challenging given the diversity of variants observed."

Implementation of an antimicrobial stewardship program (ASP) was associated with a significant reduction in antibiotic consumption and antimicrobial resistance in children with severe bacterial pneumonia at a pediatric intensive care unit (PICU) in China, researchers reported yesterday in the Journal of Global Antimicrobial Resistance.

In the single-center study, researchers from Beijing Children's Hospital set out to examine the impact of ASP 2018, a set of guidelines issued by China's National Health Commission that emphasize strict control of antibiotic use, particularly for vulnerable populations such as children, the elderly, and pregnant women. Under those guidelines, the hospital created a management team of pharmacists, clinicians, infectious disease specialists, microbiologist, and administrators to regularly inspect the use of antibiotics.

To assess the impact of the ASP, the researchers compared resistance rates, antibiotic consumption, and clinical outcomes among children with severe pneumonia in the PICU before and after implementation of the program. The study evaluated data on 287 children, including 165 before the intervention (May 2016 to April 2018) and 122 after the intervention (May 2018 to April 2020).

Decline in resistance rates, antibiotic consumption

After the ASP implementation, Staphylococcus aureus replaced Streptococcus pneumoniae as the predominant gram-positive bacterium and Klebsiella pneumoniae replaced Pseudomonas aeruginosa as the most common gram-negative bacterium. The resistance of S pneumoniae to clindamycin, erythromycin, and tetracycline was significantly reduced, while S aureus resistance to tetracycline was reduced from 59.1% to 32.5% after ASP implementation.

Resistance rates of K pneumoniae to amoxicillin/clavulanic acid and trimethoprim/sulfamethoxazole (SXT), and Acinetobacter baumannii to cefotaxime and SXT, also declined significantly. The isolation rate of multidrug-resistant strains decreased significantly as well, from a high of 16.8% before intervention to 6.7% after intervention.

Meanwhile, total consumption (defined daily doses [DDD] per 100 patient-days) of five antimicrobials (cephalosporins, carbapenems, macrolides, antifungal agents, and linezolid) decreased by 21.9% overall. No increase in length of hospital stay or mortality was observed.

The study authors say that while only a small number of PICUs in China have the staff to implement the ASP, the experience at their hospital "may provide some references for its promotion and application nationwide."

The population benefit of COVID-19 vaccination via direct and indirect effects was substantial in Tokyo in early 2022 during Omicron, with an estimated 65% reduction in the number of SARS-CoV-2 infections, according to a new model that compared risks between unvaccinated and vaccinated individuals.

The study is published in BMC Infectious Diseases and used data from the sixth wave of COVID-19 cases seen in Tokyo caused by the BA.1 and BA.2 Omicron subvariants from January to May 2022.

To create the statistical model that measured impact, researchers examined data on primary series and booster vaccination coverages and the confirmed cases stratified by vaccination history. Direct effect was how receiving the vaccine prevented illness, hospitalization, or death, and indirect effect was how much the vaccine prevented viral spread among the total population.

Estimated 8.5 million infections indirectly prevented

The investigators calculated that mass vaccination campaigns directly prevented 640,000 COVID-19 cases during the sixth wave, and indirectly prevented as many as 8.5 million infections.

The absolute number of people who benefited from vaccination was highest for adults aged 30 to 39 years in the primary series program, and those 80 years and older in the booster program, with estimates of 86,181 people (95% confidence interval [CI], 84,743 to 87,503) and 37,101 people (95% CI, 35,649 to 38,780), respectively, the authors said.

Although the Omicron variant was challenging to control, vaccination was a critical public health tool for mitigating COVID-19.

"Although the sixth wave from January to May 2022 was the largest in Japan by the end of the study period, we found that the population benefited from both direct and, more importantly, indirect protection," the authors concluded. "Although the Omicron variant was challenging to control, vaccination was a critical public health tool for mitigating COVID-19."

A new study from researchers at the University of Pittsburgh shows adults who suffered childhood abuse or neglect were more likely to be hospitalized for COVID-19 or die from the virus in adulthood. The study was published last week in the Journal of Epidemiology and Community Health.

The study was based on information gleaned from the UK Biobank, which included health information on 151,200 adults of middle age or older who completed the Childhood Trauma Screen prior to the pandemic (January 2020) and were still active in the UK Biobank when hospitalization and mortality data were most recently updated in November 2021.

People who said they had suffered "adversity" in childhood had a significant increased risk for adverse COVID-19 outcomes, including an odds ratio (OR) of 1.23 for COVID hospitalization (95% confidence interval [CI], 1.15 to 1.31) and an OR of 1.25 of a COVID-19–related death (95% CI, 1.11 to 1.42).

Adversity may be linked to inflammation

"While this investigation was unable to speak to potential mechanisms, it is likely that higher levels of inflammation, as well as alterations in the hypothalamic pituitary adrenal axis, related to childhood adversity are connected to the increased mortality and hospitalization observed here,” the authors wrote, noting that childhood adversity has been previously linked to increased rates of cancer, alcoholism, and heart disease.

 It is likely that higher levels of inflammation, as well as alterations in the hypothalamic pituitary adrenal axis, related to childhood adversity are connected to the increased mortality and hospitalization observed here.

"These findings highlight how trauma early in life can have long-lasting impacts on health decades later," said Jamie L. Hanson, PhD, lead study author said in a University of Pittsburgh press release. "We know that COVID-19 is related to excessive hospitalization and death in the UK and in the United States. And there’s emerging research finding that facing adversity, abuse or neglect, early in life, could have sizeable effects on physical health."