Antibody combo Evusheld did not improve COVID outcomes in small trial

News brief

man drip — Pitchayanan Kongkaew / iStock

Despite a substantial increase in neutralizing antibodies against SARS-CoV-2 at days 3 and 8, the monoclonal antibody combination drug Evusheld did not significantly improve hospitalized COVID-19 patients' clinical status or accelerate viral clearance in a phase 3 DISCOVERY European trial.

The results of the trial were described yesterday in a research letter in the Journal of Infection. Evusheld is composed of tixagevimab and cilgavimab (T-C) monoclonal antibodies (mABs), and the study included 399 participants, 214 of whom received Evusheld. A previous study, ACTIV-3-TICO, showed a significant reduction in mortality at day 15 in patients who received Evusheld as an intramuscular injection.

Though there were no major safety events and no increased cardiovascular risks seen in the present trial, researchers found no significant differences in mortality or hospitalization among participants randomized to receive Evusheld and those who received standard care (not remdesivir).

Study conducted during Omicron

Both controls and cases in the trial had an approximate mortality rate of 15% at day 90.

The researchers said the difference seen between the ACTIV trial and DISCOVERY may be due to variants: 40% of COVID infections in the DISCOVERY trial were caused by the Omicron variant, compared to the ACTIV trial, which was primarily during Delta variant dominance.

The SARS-CoV-2 Omicron variant and its multiple sub-lineages have proven to be more evasive than the ancestral strain or Delta variant to vaccines and therapeutic mABs.

"In the ambulatory setting, and while ancestral strains were circulating, the administration of intramuscular T-C to treat SARS-CoV-2 infections significantly reduced the risk of hospitalization and death in patients at risk for disease progression, compared to placebo," the authors wrote, referring to yet another phase 3 trial, called TACKLE. "The SARS-CoV-2 Omicron variant and its multiple sub-lineages have proven to be more evasive than the ancestral strain or Delta variant to vaccines and therapeutic mABs, including T-C."

US study finds high prevalence of antibiotic resistance in urinary Klebsiella isolates

News brief

Chris Dall, MA

An analysis of Klebsiella isolates from US women treated for uncomplicated urinary tract infections (uUTIs) found a high prevalence of antimicrobial resistance (AMR), researchers reported this week in Antimicrobial Resistance & Infection Control.

In the study, a team of researchers from Rutgers University; GSK; and Becton, Dickinson and Company analyzed Klebsiella pneumoniae and Klebsiella oxytoca urinary isolates from women seeking outpatient care for presumed uUTIs at 304 US hospitals from January 2011 through December 2019. Although Escherichia coli is the most common cause of uUTIs, K pneumoniae causes approximately 6% of cases, and the study authors say that AMR surveillance for uUTIs is needed to enable physicians to provide optimal empiric antibiotic treatment for patients.

AMR prevalence varies by geography, age

A total of 250,719 K pneumoniae isolates and 19,833 K oxytoca isolates were analyzed. The most frequent resistance phenotypes in 2019 were nitrofurantoin-not-susceptible (Klebsiella species, 54.0%; K pneumoniae, 57.3%; K oxytoca, 15.1%) and trimethoprim/sulfamethoxazole-not-susceptible (Klebsiella species, 10.4%; K pneumoniae, 10.6%; K oxytoca, 8.6%). Extended-spectrum-beta-lactamase-positive/not-susceptible prevalence was 5.4%, 5.3%, and 6.8%, respectively.

The prevalence of K pneumoniae resistance phenotype varied by US Census division and by age, and it increased over time (except for the nitrofurantoin-not-susceptible phenotype, which was stable and greater than 50% throughout). AMR prevalence was higher in the south Atlantic, west south central, and east south central divisions and among women 55 and older.

"This study describes a large sample of K. pneumoniae isolates from US outpatients over nine years and provides valuable insights into prevalence of AMR among urine isolates in this setting," the authors wrote. "Ongoing surveillance of community isolates is necessary to ensure that female patients continue to receive effective empiric antibiotic therapy for uUTI."

Postexposure vaccination prevented hepatitis A outbreak, investigators report

News brief

Stephanie Soucheray, MA

A successful targeted vaccine campaign prevented a hepatitis A outbreak in a Los Angeles County jail, according to a study yesterday in Morbidity and Mortality Weekly Report.

On May 30, 2023, the Los Angeles County Jail system was notified that an inmate had received a positive hepatitis A test result, the authors said. The person was a 41-year-old food handler who had been first jailed on April 27, 2023, who reported homelessness, injection drug use, and alcohol use disorder on intake. The patient complained of severe abdominal pain and, upon clinical examination, showed signs of jaundice.

An investigation using electronic health records and immunization history helped identify prison contacts who were eligible for hepatitis A vaccination.

Vaccination began within 48 hours

Within 48 hours, 2,766 persons were offered vaccine, and 1,510 (54.6%) agreed to receive it.

"Contacts who were food handlers without confirmed evidence of immunity and who declined vaccination were removed from food-handling duties for the duration of their potential incubation period," the authors wrote.

No additional cases were identified.

"This exposure response highlights the importance of initiating a rapid response to hepatitis A exposure in a jail setting to minimize risk for transmission and help prevent an outbreak," the authors wrote.

"The prompt vaccine rollout likely helped reduce transmission and prevent an outbreak among the LACJ population, and the enhanced surveillance, which included the monitoring of emergency hospital transfers made because of suspicion of acute hepatitis A, helped identify possible secondary cases or clusters needing further investigation"