Study shows Pseudomonas infections more likely to develop resistance to ceftazidime-avibactam

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Data from a single-center study show that in patients with multidrug-resistant (MDR) Pseudomonas aeruginosa infections, resistance occurred more commonly among those treated with ceftazidime-avibactam (CZA) than those treated with ceftolozane-tazobactam (C/T), researchers reported last week in Clinical Infectious Diseases.

The study, conducted at the University of Pittsburgh Medical Center, included 113 adult patients (median age, 64 years; 63% male) with MDR P aeruginosa pneumonia or bacteremia. The aim of the study was to follow patients for 90 days after treatment with CZA or C/T.

While both are considered first-line agents for MDR P aeruginosa infections, rates of resistance following treatment have not been established. The primary endpoint was development of resistance within 90 days of treatment initiation, defined as a four-fold increase in the minimum inhibitory concentration (MIC) from baseline.

Ninety-three patients in the study received C/T, and 20 received CZA. Patient demographics, severity of illness, and treatment characteristics were similar for patients treated with either agent. Rates of 30-day survival, microbiologic failure, and recurrent infections did not vary between the two groups.

Analysis of 107 patient isolates found a four-fold MIC increase from baseline in 40% (8 of 20) of patients treated with CZA and 10% (9/87) treated with C/T. A planned subgroup analysis of 63 patients treated from 2019 through 2021 showed rates of treatment-emergent resistance of 44% (8/18) in patients treated with CZA and 13% (6/45) in those who received C/T.

Larger studies needed

Whole-genome sequencing showed that CZA resistance was associated with new mutations in ampC and efflux regulatory pathways. The researchers did not identify any clinical factors associated with resistance.

The study authors say their findings, which are limited by the small number of patients treated with CZA and the single-center design of the study, "require validation in real-world multicenter studies aimed to assess the comparative effectiveness of these agents."

Study shows persistence of H5N1 in unpasteurized milk and on milking unit surfaces

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Stephanie Soucheray, MA

A new study in Emerging Infectious Diseases shows the H5N1 virus persists in unpasteurized milk and remains infectious on milking unit surfaces for several hours.

"Information on virus persistence is critical to understanding viral exposure risk to dairy workers during the milking process," the authors explained. "We analyzed the persistence of infectious influenza viruses in unpasteurized milk on surfaces commonly found in milking units, such as rubber inflation liners and stainless steel."

To conduct experiments with infectious strains, the authors used influenza A(H5N1) strain A/dairy cattle/TX/8749001/2024 or a surrogate influenza A(H1N1)pdm09 pandemic influenza virus strain, A/California/07/2009. They compared the diluted virus 1:10 in raw unpasteurized milk with phosphate-buffered saline as a control. Virus samples were collected immediately and after 1, 3, or 5 hours to detect infectious virus.

"To mimic environmental conditions within open-air milking parlors in the Texas panhandle during March–April 2024, when the virus was detected in dairy herds, we conducted persistence studies using 70% relative humidity,” the authors said.

Virus remained infectious past 1 hour

The H5N1 cattle virus remained infectious in unpasteurized milk on stainless steel and rubber inflation lining after 1 hour, and the H5N1 cattle virus had a similar decay rate to the human H5 virus.

"Further experiments examining H1N1 infectiousness over longer periods revealed viral persistence in unpasteurized milk on rubber inflation liner for at least 3 hours and on stainless steel for at least 1 hour," the authors said. "Those results indicate that influenza virus is stable in unpasteurized milk and that influenza A virus deposited on milking equipment could remain infectious for >3 hours."

The authors said the expert results suggest dairy workers should take extra care to wear personal protective equipment such as face shields, masks, and eye protection during milking.

Contaminated rubber inflation liners could be responsible for the cattle-to-cattle spread observed on dairy farms

"In addition, contaminated rubber inflation liners could be responsible for the cattle-to-cattle spread observed on dairy farms," they concluded. "Sanitizing the liners after milking each cow could reduce influenza virus spread between animals on farms and help curb the current outbreak."

Surveillance data show rise in US Powassan virus cases

News brief

Stephanie Soucheray, MA

New passive surveillance of Powassan virus in ticks shows a four-fold rise in the number of US cases from 2014 to 2023 (compared with 2004 to 2013). The surveillance data is published in Clinical Microbiology and Infection.

From 2004 through 2013, 64 cases of human Powassan virus were reported to the Centers for Disease Control and Prevention (CDC), but that number jumped to 270 cases from 2014 to 2023.

The authors said the increase in cases is due to increased awareness but also the geographic expansion of Ixodes scapularis vector ticks, or black-legged ticks. The ticks also carry Borrelia bacteria, which causes Lyme disease.

Powassan virus can have severe outcomes, with up to 50% of case-patients experiencing lasting neurologic symptoms. In about 10% of cases, the virus causes fatal encephalitis, according to the CDC. However, the authors of the study said mild cases of Powassan may be unreported and undetected and cause few, if any, notable symptoms.

The proportion of humans bitten by Powassan-positive ticks that develop disease and the conditions under which neuroinvasive disease develop are still unknown.

"Most Powassan-positive bites may cause non-specific presentations that do not result in healthcare seeking or trigger testing for Powassan virus infection when healthcare is accessed," the authors wrote. "The proportion of humans bitten by Powassan-positive ticks that develop disease and the conditions under which neuroinvasive disease develop are still unknown."