COVID booster halved severe illness, but some groups still at higher risk

A study of 30 million people in the United Kingdom finds that 0.4% of people who completed their primary COVID-19 vaccine series had severe breakthrough infections, compared with 0.2% of booster recipients, during Omicron variant predominance.

The study, published today in The Lancet, also shows that older adults, men, people with underlying medical conditions, and those with suppressed immunity were remained at elevated risk for hospitalization and death after receiving the booster.

University of St. Andrews researchers in Scotland led the study of 16,208,600 people who completed their primary COVID-19 vaccination series with the Pfizer/BioNTech or AstraZeneca/Oxford vaccines from Dec 8, 2020, to Feb 28, 2022, and 13,836,390 who received a Pfizer or Moderna booster from Dec 20, 2021, to Feb 28, 2022. Participants lived in England, Northern Ireland, Scotland, and Wales.

A total of 0.4% of primary vaccine recipients and 0.2% of those who received a booster had severe COVID-19 outcomes from Dec 20, 2021, through February 2022, with booster-associated risk falling from 8.8 to 7.6 events per 1,000 person-years compared with people who didn't receive boosters.

The risk of severe outcomes remained elevated in older adults (absolute risk reduction [aRR] for 80 years or older vs 18 to 49 years, 3.60), those with chronic conditions (aRR for 5 or more vs no comorbidities, 9.51), men (aRR, 1.23), those taking immunosuppressant drugs (aRR, 5.80), and those with chronic kidney disease (aRR for stage 5, 3.71). Previously COVID-infected people were at lower risk (aRR for infected at least 9 months before booster, 0.41).

The at-risk groups should "be prioritised for additional boosters, including novel optimised versions, and the increasing array of COVID-19 therapeutics," the researchers wrote.

In a related commentary, Stephanie Irving, MHS, of Kaiser Permanente in Oregon, and Maria Sundaram, PhD, MSPH, of the Marshfield Clinic in Wisconsin, called the absolute numbers of severe COVID-19 outcomes "disheartening, translating to life-altering events for more than 26,000 families over the 2-month study period. Protection of the individuals at highest risk must be a priority as we continue to develop and refine response strategies for the COVID-19 pandemic."
Oct 14 Lancet study and commentary

Europe reported 14% decrease in live births 9 months into pandemic

Europe saw a 14% decrease in live births in January 2021, just 9 to 10 months after the first peak of COVID-19, compared to the same timeframes in 2018 and 2019, according to a study published yesterday in Human Reproduction.

The authors say this is likely because of lockdowns and not due to the virus itself or problems as a result of infection, such as deaths, miscarriages, or stillbirths.

"We think that couples’ fears of a health and social crisis at the time of the first wave of COVID-19 contributed to the decrease in live births nine months later," said author Leo Pomar, PhD, a midwife sonographer at Lausanne University Hospital in a press release. "The decline in births nine months after the start of the pandemic appears to be more common in countries where health systems were struggling and capacity in hospitals was exceeded. This led to lockdowns and social distancing measures to try to contain the pandemic."

The authors looked at data from 24 European countries. They adjusted the live birth rates to take into account seasonal variations and found that January 2021 was the only month in which there was a significant drop in live births.

According to the authors, the incidence of COVID-19 during the first wave varied from 0.5% to 5.1% in the countries included in the analysis.

Decreases in birth rates in January 2021 were seen in Belgium (12% decrease), Estonia (-13%), France (-14%), Italy (-17%), Latvia (-15.5%), Lithuania (-28%), Portugal (-18%), Romania (-23%), Russia (-19%), Spain (-23.5%), Ukraine (-24%), England and Wales (-13%), and Scotland (-14%).

"Social distancing measures, fears related to the pathogen and the social/economic crisis may be indirect factors that played a role in the decision of couples to postpone pregnancies and could be investigated in future research," the authors concluded.
Oct 13 Hum Reprod study
Oct 13 Hum Reprod press release

Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans

Concerning rise found in last-resort antibiotic use in European hospitals

A study of antibiotic consumption in European hospitals found increasing use of antibiotics reserved for the most difficult-to-treat infections, researchers reported yesterday in Eurosurveillance.

Using data from the European Centre for Disease Prevention and Control, researchers from Hungary, Croatia, and Norway investigated hospital-sector antibiotic consumption in the United Kingdom and in European Union/European Economic Activity countries from 2010 to 2018. They focused on the use of antibiotics classified by the World Health Organization (WHO) as Reserve group antibiotics, which includes antibiotics and antibiotic classes that are intended as "last-resort" treatments for multidrug-resistant infections.

A total of 23 countries provided data on hospital-sector antibiotic consumption. In 2018, a total of 7,025,162 defined daily doses (DDD) of Reserve antibiotics were consumed in the hospital sector in the 23 reporting countries, for an average of 0.050 DDD per 1,000 inhabitants per day, up from 0.017 DDD per 1,000 inhabitants per day in 2010.

There was considerable variation in consumption of Reserve antibiotics among countries, with higher consumption observed in southern European countries. A significant increase in the consumption of Reserve antibiotics was observed in 15 of the 23 countries, and none of the countries showed a decrease.

Of the antibiotics in the Reserve group, four (tigecycline, colistin, linezolid, and daptomycin) accounted for 91% of the consumption.

"The significantly increasing trends in the consumption of reserve antibiotics in most of countries, raises concerns," the study authors concluded. "The observed findings might reflect the real burden of AMR [antimicrobial resistance] among pathogens or inappropriate use, which would both need to be addressed." 
Oct 13 Eurosurveill study

Report: Carbapenemase-producing Enterobacterales rose in Latin America

Originally published by CIDRAP News Oct 12

A report today in Emerging Infectious Diseases highlights increased detection of carbapenemase-producing Enterobacterales (CPE) in Latin America and the Caribbean during the COVID-19 pandemic.

The report, by researchers with the Pan American Health Organization and several national laboratories in the region, notes that while several countries had reported detection of CPE prior to the pandemic, detection of Enterobacterales harboring multiple carbapenemase genes was limited.

But during the pandemic, national laboratories in Argentina, Brazil, Colombia, Guatemala, Paraguay, Peru, Uruguay, Venezuela, Ecuador, and Costa Rica reported the emergence or increased detection of carbapenemase combinations—mainly the carbapenemase genes bla_KPC and bla_NDM—while Belize, Dominica, and Chile reported the emergence of carbapenemase genes that had not previously been detected.

Among the countries reporting increased CPE detection, Colombia reported more than twice the number of CPE strains from January 2020 through December 2021 compared with 2018-2019, while data from hospitals in five Brazilian states showed a 42.8% increase in CPE isolates during the pandemic (March 2020 to October 2021) compared with 20 months before.

The authors say that the reported increases in CPE detection during the pandemic were likely caused by a variety of pandemic-related factors.

"The pandemic might have accelerated the problem of resistance to the limited antimicrobial arsenal in the region because of antimicrobial drug misuse, prolonged hospital stays, and a high rate of antimicrobial prescriptions in hospital settings, such as medical wards and ICUs, where a high number of patients with COVID-19 were hospitalized during the first pandemic wave," they write.

They also point out that many countries in the region do not have access to the newly developed antibiotics for treating the multidrug-resistant infections caused by CPE, which has resulted in increased use of last-resort antibiotics like polymyxins.

They conclude, "In an ideal scenario, access to newly developed and approved antimicrobials and tools to guide their prudent use should be guaranteed for the entire world in parallel with current local AMR [antimicrobial resistance] prevention and control strategies, including the prioritization of antimicrobial stewardship and rapid AMR detection."
Oct 12 Emerg Infect Dis report

Non-preferred antibiotics often used for urinary infections at VA hospitals

Originally published by CIDRAP News Oct 12

A study of Veterans Affairs (VA) medical centers found that clinicians prescribed the preferred antibiotic for patients with positive urine cultures less than half of the time, researchers reported today in Antimicrobial Stewardship & Healthcare Epidemiology.

For the study, which aimed to analyze how urinary tract infection management can be improved in VA outpatients, VA researchers extracted data on positive urine cultures collected at 31 VA medical centers from 2016 through 2019.

Cases were classified as cystitis, pyelonephritis, or asymptomatic bacteriuria (ASB) based on documented signs and symptoms, and preferred therapy definitions were applied for each subdiagnosis: ASB (no antibiotics), cystitis (trimethoprim-sulfamethoxazole, nitrofurantoin, and beta-lactams), and pyelonephritis (trimethoprim-sulfamethoxazole and fluoroquinolone). The researchers assessed whether preferred antibiotics were chosen for each subdiagnosis and whether the duration was appropriate. Outcomes included 30-day clinical failure or hospitalization. 

Of 3,255 cases reviewed, ASB was identified in 1,628 cases (50%), cystitis was identified in 1,156 cases (36%), and pyelonephritis was identified in 471 cases (15%). Antibiotics were prescribed in 43% of these cases, including 40% with ASB. Of 2,831 cases analyzed, 1,298 (46%) received the preferred therapy selection and duration for cases where it could be defined. The most common antibiotic class prescribed was fluoroquinolones (34%).

Patients prescribed preferred therapy had lower odds of clinical failure than those who received non-preferred therapy (8% vs 10%; unadjusted odds ratio [OR], 0.74; 95% confidence interval [CI], 0.58 to 0.95). They also had lower odds of 30-day hospitalization (3% vs 5%; unadjusted OR, 0.55; 95% CI, 0.37 to 0.81). Odds of clinical treatment failure or hospitalization were higher for beta-lactams relative to ciprofloxacin (unadjusted OR, 1.89; 95% CI, 1.23 to 2.90).

"These findings suggest clinicians could benefit from educational and interventional strategies that target appropriate selection and duration of therapy," the study authors concluded.
Oct 12 Antimicrob Steward Healthc Epidemiology study

Non-prescription antibiotic dispensing common in Ethiopian pharmacies

Originally published by CIDRAP News Oct 10

A simulated client study in Ethiopia found a high rate of non-prescription antibiotic dispensing at community pharmacies, researchers reported today in the Journal of Antimicrobial Chemotherapy.

For the study, postgraduate and graduate pharmacy students from the University of Gondar were selected to visit community drug retail outlets (CDROs) in the Amhara region of Ethiopia, with a focus on small towns. They visited each CDRO in pairs, with one presenting a pre-prepared clinical case scenario and the other recording the interaction, and they visited each CDRO twice, presenting the case scenario in the first visit and directly requesting antibiotics in the second. The simulated case scenarios were acute childhood diarrhea, acute childhood upper respiratory tract infection, and adult urinary tract infection.

The study had 450 interactions across the two visits. Non-prescribed antibiotics were obtained in 198 of the 225 (88%) clinical case scenario-based visits and in 205 of the 225 (91%) direct antibiotic request visits. Of those CDROs that dispensed antibiotics, 84% provided them at the first level of demand in the clinical case scenario-based visit, and 95% provided them on the first direct antibiotic request. CDRO staff members requested additional information about the patient or the case in 40% of the clinical case scenario-based visits and 30% of the direct antibiotic request visits.

The study authors note that, despite Ethiopia's prescription-only antibiotic dispensing legislation, the rate of non-prescription dispensing found in the study is higher than pooled estimates in sub-Saharan Africa (69%) and a previous simulated patient study conducted in community pharmacies in Addis Adaba, Ethiopia's capital.

"Our findings suggest the need for immediate and sustained measures to address this issue," they wrote. "These could include stricter enforcement of regulations that restrict antibiotics to prescription-only use, imposing heavier penalties for those who contravene the rules, and enhancing regular CDRO supervision."
Oct 10 J Antimicrob Chemother study

Phage therapy clinical trial launches for cystic fibrosis patients

Originally published by CIDRAP News Oct 10

The National Institutes of Health (NIH) announced last week that enrollment has begun on an early-stage clinical trial to evaluate bacteriophage therapy in cystic fibrosis (CF) patients who carry Pseudomonas aeruginosa in their lungs.

The trial will evaluate the safety and microbiologic activity of WRAIR-PAM-CF1, an experimental phage cocktail manufactured by Adaptive Phage Therapeutics of Gaithersburg, Maryland. The cocktail contains four species of bacteriophage—bacteria-killing viruses—that specifically target P aeruginosa, a frequently multidrug-resistant bacterium that colonizes the lungs of CF patients and is the most common cause of CF exacerbations. The hope is that the cocktail will reduce the amount of P aeruginosa in the lungs.

The trial, which will begin as a phase 1b trial and expand to a phase 2 trial, aims to enroll up to 72 adult CF patients, who will receive a single intravenous infusion of the cocktail at three dosage levels. Investigators with the Antibacterial Resistance Leadership Group will assess the safety and microbiologic activity of the cocktail after eight participants have completed each dosage, and that assessment will determine which dosage level will be given in the next stage of the trial. They'll also be looking at how the phages function in the body and how they affect patients' lung activity.

"The prevalence of antibiotic resistance is concerning, and the need for more effective therapeutics for vulnerable populations, such as people with cystic fibrosis, is especially urgent," National Institute of Allergy and Infectious Diseases Director Anthony S. Fauci, MD, said in an NIH press release. "Although research on bacteriophage therapy may still be in its infancy in the United States, we hope that this study, and others like it, could open the doors to a new type of therapy for difficult-to-treat bacterial infections." 
Oct 4 NIH press release

Surveys indicate many French GPs feel pressure to prescribe antibiotics

Originally published by CIDRAP News Oct 10

Telephone surveys of the general public and general practitioners (GPs) revealed that, despite an overall decline in antibiotic use in France over the past decade, more than a third of clinicians report pressure to prescribe antibiotics, researchers reported last week in Antimicrobial Resistance & Infection Control.

To help inform future national awareness campaigns on antimicrobial resistance, researchers with Public Health France conducted two telephone surveys in 2019 and 2020. The first explored antibiotic consumption and knowledge and beliefs about antibiotic resistance among a representative sample of the general public ages 15 years and older. The second explored the evolution of prescribing practices and attitudes toward patient demands for antibiotics among a representative sample of 388 GPs.

In the general public survey, 27% of respondents said they had received antibiotics during the previous 12 months, and 54% of those with a child aged 6 years and under said their child had received an antibiotic during the same period.

In the GP survey, 65% declared they had reduced their antibiotic prescribing over the previous 5 years, and 64% said they did not automatically prescribe antibiotics but advised patients to contact them in 2 or 3 days if symptoms persisted. Among GPs, 33% said they often have patients who insist on having antibiotics, and that elderly patients with comorbidities were among the most demanding. Only 3% of the general public said they put pressure on their GP to prescribe an antibiotic.

The vast majority of respondents in the general public survey expressed trust in their GP regardless of whether they had prescribed them antibiotics (89%) or not (91%). Only half of respondents said they knew antibiotics only act on bacteria, and 38% said they understood exactly what antibiotic resistance is.

A 2020 study by Public Health France found that, from 2009 to 2019, the number of antibiotic prescriptions fell by 18% among all age-groups except the elderly.

The authors say a forthcoming public awareness campaign will take the survey results into account.
Oct 6 Antimicrob Resist Infect Control study