A systematic review and meta-analysis found resistance to cefiderocol was low overall but "alarmingly high" among certain types of carbapenem-resistant bacteria, Greek researchers reported late last week in Clinical Microbiology and Infection.

Sold under the brand name Fetroja, cefiderocol is a cephalosporin antibiotic with a novel method of penetrating the tough outer membrane of gram-negative bacteria, including multidrug-resistant pathogens. Approved for the treatment of complicated urinary tract infections by the US Food and Drug Administration (FDA) in 2019 and for the treatment of nosocomial pneumonia in 2020, cefiderocol is considered a last-resort option for carbapenem-resistant bacterial infections.

Higher resistance in certain carbapenem-resistant isolates

With resistance to cefiderocol being increasingly reported, researchers from the University of Crete set out to estimate the global cefiderocol non-susceptibility (CFDC-NS) in clinical isolates of the gram-negative pathogens considered to be among the most serious antimicrobial resistance threats: Enterobacterales, Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia. The 78 studies they reviewed included 82,035 clinical isolates from Europe (50%), the Americas (33%), and the Western Pacific Region (17%).

CFDC-NS was low overall but varied by species, with a rate of 8.8% for A baumannii, 3% for Enterobacterales, 1.4% for P aeruginosa, and 0.4% for S maltophilia. And while cefiderocol appeared to retain relatively good activity against carbapenem-resistant bacteria overall, CFDC-NS was much higher in carbapenem-resistant A baumannii (13.2%) and carbapenem-resistant Enterobacterales (12.4%) and significantly higher in New Delhi metallo-beta-lactamase (NDM)–producing A baumannii (44.7%), NDM–producing Enterobacterales, and cefatazidime/avibactam-resistant Enterobacterales (36.6%).

Among other limitations, the study authors note that CFDC-NS varied by breakpoint definition, with the FDA, Clinical Laboratory Standards Institute (CLSI), and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) all having different susceptibility thresholds.

"Antimicrobial stewardship, infection control and continued surveillance at the local level, as well as regular updating and reporting of global CFDC-NS estimates, are imperative for preventing or delaying emerging resistance against cefiderocol," they wrote. "Harmonization of EUCAST and CLSI breakpoints would help such efforts."

The Virginia Department of Health (VDH) recently reported a statewide meningococcal disease outbreak that has sickened 27 people since June 2022, including five patients who died from complications of their infections.

The illnesses involve Neisseria meningitidis serogroup Y, one of the strains included in the meningococcal conjugate vaccine (MenACWY). In its statement, the health department said the case total so far is three times higher than expected during the period. Twenty of the cases were reported in the eastern region of the state, but infections have also been reported in the southwest (5) and central (2) regions.

Impact on minority populations

So far, health officials haven't identified a common risk factor, though genetic sequencing of the bacteria suggests the infections are highly related. Most patients are Black or African American adults ages 30 to 60. Only one had received the MenACWY vaccine.

The VDH urged parents and healthcare providers to ensure that children receive all recommended vaccines, including MenACWY, which is recommended for adolescents before entering 7th grade, with a booster dose before 12th grade. The vaccine is also recommended for people who are at increased risk from the disease.

Meningococcal disease is rare but serious and is spread by lengthy contact through the exchange of respiratory or throat secretions, such as kissing or sharing cups or water bottles. The VDH said the overall risk to the state's population is low.

Along with the Virginia outbreak, the Centers for Disease Control and Prevention (CDC ) is also tracking a meningococcal disease outbreak involving serogroup C in Florida—primarily in gay and bisexual men—that since 2021 has sickened at least 24 people, 6 of them fatally. About half of the patients are Hispanic men, and some of the patients are living with HIV.

A new research letter in JAMA notes that, compared with 3 months after patient intensive care unit (ICU) hospitalization for acute respiratory distress syndrome (ARDS) caused by COVID-19, at 1 year family members had lower levels of post-traumatic stress disorder (PTSD), anxiety, or depression.

Moreover, ARDS caused by COVID-19 compared to ARDS caused by other illnesses was not associated with any greater psychological distress among family members.

The research was based on patients and families seen in 23 ICUs in France, with follow-up at 3 and 12 months conducted to assess PTSD levels, anxiety levels, and depression prevalence.

About a quarter had PTSD, depression after 1 year

At 12 months, 437 family members completed psychological questionnaires (268 for COVID-19 ARDS and 169 for non–COVID-19 ARDS). There was no significant between-group difference for PTSD symptoms at 12 months, which was present in 25% of family members of patients with COVID-19 ARDS compared to 22% for non–COVID-19 ARDS. Symptoms of depression were also not significantly different (26% in COVID families, 22% in non-COVID family members).

Family members' psychological symptoms may have eased over time as patients recovered.

That compares with a 35% rate of PTSD at 3 months in family members of patients COVID-related ARDS and 19% with non-COVID ARDS, according to the team's earlier findings, published in JAMA in February 2022. A US study in April 2022 found a 48% rate of PTSD in family members of COVID-19 ARDS patients 6 months after ICU discharge.

"Twelve months after patient ICU hospitalization, having ARDS caused by COVID-19 compared with other causes was not significantly associated with increased symptoms of PTSD, anxiety, or depression in family members in contrast with results after 3 months," the authors concluded. "Family members' psychological symptoms may have eased over time as patients recovered."

Of 37 men who have sex with men (MSM) in a global case series focusing on breakthrough mpox, 29 (78.4%) contracted mpox after two appropriately spaced Jynneos vaccine doses, 7 (19.0%) experienced reinfections, and 1 had an infection that met the criteria for both reinfection and infection after vaccination.

For the study, published yesterday in The Lancet Infectious Diseases, an international team led by University of Chicago Medicine researchers mined data on 37 MSM who had a previous mpox infection or two mpox vaccine doses from May 2022 through June 2023. Median patient age was 36 years.

A global outbreak involving a mutated mpox virus strain affecting primarily MSM began in May 2022. Since then, case clusters have been detected in patients with presumed immunity through infection or vaccination, the study authors noted.

Less severe signs, symptoms

Reinfected patients had a shorter illness and less mucosal disease than during their first infection. Vaccinated patients had few lesions and low mucosal involvement and needed little pain relief. No deaths or bacterial superinfections were reported, and only one patient required hospitalization a necrotic neck lesion.

While reinfections and infections after vaccination were mostly mild, "natural immunity and vaccine-induced immunity are not fully protective against mpox infection," the authors wrote.

Natural immunity and vaccine-induced immunity are not fully protective against mpox infection.

In a related commentary, Marc Shamier, MD, of Erasmus Medical Center in the Netherlands, and colleagues called for research into the level and durability of immunity in at-risk groups and long-term vaccine effectiveness. "It is crucial to sustain population immunity, particularly among the younger MSM population at risk," they concluded.

In a separate study in The Medical Journal of Australia, researchers in Sydney describe two vaccinated MSM infected with mpox in May 2023. "Clinicians should be aware of the possibility of breakthrough modified MPXV [mpox virus] infection in patients with epidemiological risk factors and a characteristic vesiculopustular rash, despite a history of vaccination," they wrote.