Drugmaker AbbVie announced late last week that the US Food and Drug Administration (FDA) has approved Emblaveo (aztreonam-avibactam) for treating complicated intra-abdominal infections (cIAIs).

The FDA approved the monobactam/beta-lactamase inhibitor combination for use in combination with metronidazole to treat patients who have limited or no treatment options for cIAIs caused by gram-negative bacteria, including Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae complex, Citrobacter freundii complex, and Serratia marcescens.

The combination of aztreonam with avibactam aims to restore aztreonam's activity against gram-negative bacteria that are becoming increasingly resistant to antibiotics. Specifically, it targets gram-negative pathogens that carry two defense mechanisms—metallo-beta-lactamase (MBL) enzymes and other beta-lactamase enzymes—that confer resistance to nearly all currently available antibiotics. While aztreonam can evade degradation by MBLs on its own, the addition of avibactam helps restore its activity against other beta-lactamases.

As a potential weapon against infections with limited treatment options, Emblaveo was granted Qualified Infectious Disease Product and Fast Track designations by the FDA in 2019 to speed up development and review.

Novel treatment option

"As bacteria evolve, industry, government, and clinical experts must work together to ensure that the infectious disease community has the tools to advance public health," Roopal Thakkar, MD, executive vice president of research & development and chief scientific officer at AbbVie, said in a press release. "We're proud to offer this important novel treatment option to urgently address the significant threat of antimicrobial resistance."

The approval was based on prior findings regarding the safety of aztreonam for treating cIAIs, as well as the results of the phase 3 REVISIT trial, which found that Emblaveo had similar cure rates in patients with cIAI or hospital-acquired or ventilator-associated pneumonia (HAP-VAP) compared with meropenem with or without colistin.

As bacteria evolve, industry, government, and clinical experts must work together to ensure that the infectious disease community has the tools to advance public health.

Emblaveo was jointly developed by Pfizer and AbbVie. In April 2024, the European Medicines Agency approved the drug for treatment of cIAIs, HAP-VAP, and complicated urinary tract infections. AbbVie hold the rights for commercialization in the United States and Canada, while Pfizer holds commercialization rights in all other countries.

The New Hampshire Department of Health and Human Services (DHHS) said a person from Merrimack County has become the first person in the state to be diagnosed as having clade 1 mpox, also known as clade 1b. 

This detection raises the total US clade 1 cases to three. 

The individual recently traveled to Eastern Africa, where there is an ongoing outbreak of clade I mpox.

"The individual recently traveled to Eastern Africa, where there is an ongoing outbreak of clade I mpox, and is currently self-isolating and recovering at home," the DHHS said in a press release issued late last week. "The individual's illness poses no current risk to the public."

The DHHS said there was no evidence of human-to-human transmission in this case, but contacts of the patient are being closely monitored and offered prophylactic (preventive) vaccination. 

The novel clade1b is different from the clade 2 virus that circulated globally in 2022 and 2023, primarily among men who have sex with men.

First clade 1 case in Ireland, possibly in South Sudan 

In related news, Ireland's Health Service Executive (HSE) said an Irish resident has contracted the country's first case of clade 1 mpox. The person had recently traveled to the Democratic Republic of the Congo, where clade 1b mpox was first noted in 2024 is currently circulating in the community at high levels. 

"The HSE is fully prepared to respond to this case, as work has been ongoing since August 2024," the HSA said in a statement. "We have been working alongside international partners and National Health Protection has been monitoring mpox closely since the outbreak in Democratic Republic of Congo first emerged."

Finally, according to a post on ProMed Mail, South Sudan has reported an mpox case, and though the clade isn't mentioned, clade 1b is a strong possibility, given the patient had recently traveled to Uganda.

If the case is confirmed as clade 1b, South Sudan would be the 22nd affected African country.

A series of reports released today by the European Centre for Disease Prevention and Control (ECDC) show sexually transmitted infections (STIs) in Europe continued their upward trajectory in 2023.

The data from the latest ECDC annual epidemiologic reports on STIs show the notification rate for confirmed gonorrhea cases in European Union/European Economic Area countries rose by 31% in 2023 compared with 2022 and has risen by 321% since 2014. The increase was observed across different age groups and demographics but was steepest in women aged 20 to 24 (46%). Men who have sex with men (MSM) accounted for 58% of gonorrhea cases.

The rate of syphilis cases rose 13% from 2022 and has doubled since 2014, with the highest rates seen in men aged 25 to 34 and 72% of cases reported in MSM. The increase in the rate of chlamydia infections slowed to 3% in 2023 after reaching record high notification rates in 2022, but is still up 13% since 2014.

ECDC officials say that while increased STI testing could account for some of the increases, less condom use and higher numbers of sexual partners could also be to blame.

"ECDC emphasises the importance of proactive measures to address the rising STI rates," the agency said in a news release. "Using condoms consistently for vaginal, anal and oral sex is crucial for prevention. Open and honest communication about sexual health with partners can also help reduce the risk of STI transmission."

Continued emergence of drug-resistant gonorrhea

The report also notes the continued emergence of drug-resistant strains of gonorrhea. While resistance to the first-line antibiotic ceftriaxone is rare, 25.2% of isolates analyzed by the European Gonococcal Antimicrobial Surveillance Program in 2022 were resistant to azithromycin, which is frequently used in combination with ceftriaxone. In addition, one multidrug-resistant and one extensively drug-resistant gonorrhea isolate were detected in Germany and Austria, respectively.

"The emergence of drug-resistant strains threatens the effectiveness of current treatments, making it crucial to emphasise prevention and promote responsible antibiotic use," the agency said.

The World Health Organization (WHO) last week released its global research agenda for antimicrobial resistance (AMR) in human health.

Designed to fill the substantial knowledge gaps on AMR that have hampered development of evidence-based policies and interventions and contributed to the stalled progress on national AMR action plans, the agenda includes 33 research priorities for bacterial and fungal infections organized into four themes: Prevention, diagnosis, treatment and care, and cross-cutting. An additional seven research priorities focus on drug-resistant tuberculosis (TB).

"The goal of this research agenda is to identify and give priority to the research topics with the greatest impact on mitigating AMR in the human health sector," the WHO said. "A priority research agenda for AMR is critical in guiding policy-makers, researchers, funders, implementing partners, industry and civil society in generating new evidence to inform AMR policies and interventions."

Priorities need to be translated into 'actionable, implementable' studies

Among the priorities are investigating the impact and contribution of community water, sanitation and hygiene (WASH) and waste management interventions on AMR in healthcare settings and the community; investigating and evaluating rapid point-of-care tests that can distinguish bacterial from viral infections, identify bacterial pathogens, and detect antimicrobial susceptibility; identifying antimicrobial stewardship interventions that are feasible, context-specific, and cost-effective in inpatient and outpatient settings; and studying the epidemiology, morbidity, and mortality of infections caused by WHO bacterial and fungal priority pathogens.

A priority research agenda for AMR is critical in guiding policy-makers, researchers, funders, implementing partners, industry and civil society in generating new evidence to inform AMR policies and interventions.

Research priorities for drug-resistant TB include investigating the impact of TB vaccines on preventing infection and disease, determining optimal diagnostic and treatment delivery modes, and examining more effective and shorter treatment regimens for patients with drug-resistant TB.

The WHO says the research agenda emphasizes the need to translate the research priorities into actionable, implementable studies that can ultimately inform and strengthen AMR policies around the world, particularly in low-resources countries.

Only 1.3% of pregnant US COVID-19 patients received an antiviral drug to reduce the risk of severe illness in winter 2021 to fall 2022, 67% less than their nonpregnant counterparts, finds a study published last week in Clinical Infectious Diseases.

University of California Los Angeles researchers analyzed claims data on antiviral drug prescriptions among 412,755 privately and publicly insured COVID-19 outpatients ages 18 to 49 years who were pregnant (33,855), recently pregnant (2,460), or nonpregnant (376,440) from December 2021 to September 2022. 

"The odds of admission to an intensive care unit and the need for invasive ventilation following COVID-19 illness are 2-fold higher in pregnant and recently pregnant people compared with nonpregnant women of reproductive age," the authors wrote. "Severe COVID-19 illness during pregnancy has been linked to increased risks of preterm birth, cesarean delivery, and fetal growth restriction."

The National Institutes of Health recommend nirmatrelvir-ritonavir (Paxlovid) as first-line treatment for nonhospitalized, high-risk pregnant COVID-19 patients.

Low prescribing even in women with chronic conditions

A total of 6.8% of all participants received an antiviral (1.3% of pregnant, 5.4% of recently pregnant, and 7.3% of nonpregnant women). Paxlovid was prescribed most often (90.9%), followed by molnupiravir (9.1%) and intravenous remdesivir (less than 0.1%).

As with COVID-19 vaccine trials, pregnant people have been excluded from clinical trials evaluating COVID-19 therapeutics.

The rate of antiviral prescriptions was 67% lower in pregnant than in nonpregnant women (prevalence ratio [PR], 0.33), including those with one or more high-risk underlying conditions (PR, 0.29). Prescription rates were also lower among recently pregnant women who had at least one high-risk chronic condition (PR, 0.57).

Antiviral treatment rates rose with age for recently pregnant and nonpregnant—but not pregnant—patients. In total, 64% of recently pregnant and 85% of nonpregnant antiviral recipients had private health insurance, relative to 55% of pregnant women.

"As with COVID-19 vaccine trials, pregnant people have been excluded from clinical trials evaluating COVID-19 therapeutics," the researchers wrote. "The evidence supporting the safety and effectiveness of COVID-19 treatments during pregnancy is therefore limited, which may influence hesitancy to prescribe and/or use antiviral medications during pregnancy and lactation."

• The Spokane Regional Health District (SRHD) last week announced Washington state's first pertussis (whooping cough) death since 2011, which involved a child younger than 5 years old who died in November 2024. The death was recently confirmed by the US Centers for Disease Control and Prevention (CDC), which in early January warned that cases in 2024 were higher than levels seen before the COVID pandemic. The SRHD said though pertussis was the cause of death, the child had other health factors that may have contributed. The child had received some doses of the diphtheria-tetanus-acellular pertussis vaccine (DTaP) vaccine but had not gotten the whole series.
• The Pan American Health Organization (PAHO), one of the World Health Organization's (WHO's) regional offices, issued an epidemiologic alert on February 7 on increased dengue serotype 3 (DENV-3) circulation in the Americas, which could increase the risk from the disease during the peak of the season. It urged member countries to brace for a possible rise in cases and to ensure early diagnosis and timely care to reduce the number of severe illnesses and deaths. The region experienced record dengue activity in 2024, with more than 13 million cases spread over 50 countries and territories. "The reappearance of a serotype that did not circulate in the last decade, such as DENV-3, combined with the increase in the susceptible population, not only increases the probability of severe cases of dengue, but could also cause epidemics that overload health services, exceeding their capacity to respond," PAHO said.
• The CDC recently updated its SARS-CoV-2 variant proportion estimates, which show that, for the 2 weeks ending February 1, the proportion of KP.3.1.1 viruses continued to decline, with XEC holding steady and LP.8.1 rising. The proportion of XEC variants is at 43%, with LP.8.1 as the next most common, at 20%, up slightly from 15% for the period that ended on January 18. LP.8.1 is one of two SARS-CoV-2 variants on the WHO's list of variants under monitoring that are on the rise, according to the WHO's recent risk evaluation. The prevalence of the virus, along with XEC, is increasing globally, but the health risk is considered low. LP.8.1 is a descendant of KP.1.1.3, which is part of the JN.1 lineage and currently makes up 7% of available global sequences.