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

Study: US C difficile prevalence fell during COVID-19 pandemic

The prevalence of Clostridioides difficile infection (CDI) in the United States declined during the COVID-19 pandemic, but inpatient mortality and treatment costs were higher, according to a paper published yesterday in Open Forum Infectious Diseases.

Using data from the Premier Healthcare Database, researchers with the University of Texas and Texas A&M compared CDI prevalence and inpatient outcomes in the pre-COVID (April 2019 to March 2020) and COVID (April 2020 to March 2021) periods. Overall, a total of 25,991 inpatients and outpatients with a laboratory-confirmed CDI diagnosis were included in the analysis. The investigators analyzed data on 22,130 unique patients, who were predominantly older (median age, 68 years), female (57.5%), and White (79.5%).

CDI prevalence significantly decreased from the pre-COVID to the COVID period (12.2 CDI cases per 10,000 encounters vs 8.9 per 10,000), driven primarily by a reduction in inpatient CDI prevalence (57.8 per 10,000 vs 49.4 per 10,000), though outpatient CDI prevalence fell as well (2.2 per 10,000 vs 1.5 per 10,000). But an interrupted time series analysis found no significant difference in the rate ratio (RR) from the pre-COVID to the COVID period for all encounters (RR, 1.04; 95% CI, 0.90 to 1.20) or inpatient encounters (RR, 1.08; 95% confidence interval [CI], 0.98 to 1.19).

Patient costs increased by an average of approximately $2,000 from the pre-COVID to the COVID period. Among inpatients only, all-cause mortality increased from 5.5% in the pre-COVID period to 7.4% in the COVID period. Costs and mortality were higher for those with severe CDI.

The study authors say the similar rate of decline in the pre-COVID and COVID period is an indication that CDI prevalence was falling before the pandemic. But better adherence to infection control practice in hospitals (eg, improved hand hygiene, donning of personal protective equipment) and new practices in outpatient settings (eg, masking, social distancing) during the pandemic may have helped further limit CDI transmission.

"Further studies are needed to identify the specific factors that contributed to changes in CDI prevalence and health outcomes, such that targeted interventions can be maintained or created in the future to prevent and treat CDI effectively," they concluded.
Aug 25 Open Forum Infect Dis abstract

Study links recent azithromycin use with resistant gonorrhea infections

Originally published by CIDRAP News Aug 25

A study of patients at a sexual health clinic in Seattle found that recent treatment with azithromycin was associated with subsequent azithromycin-resistant gonococcal infections, researchers reported yesterday in Clinical Infectious Diseases.

To explore the relationship between individual-level azithromycin exposure for sexually transmitted infections and subsequent azithromycin resistance in people with Neisseria gonorrhoeae infections, researchers with the University of Washington and Public Health-Seattle & King County (PHSKC) analyzed data collected data on patients treated for gonorrhea at the PHSKC Sexual Health Clinic from 2012 through 2019. Azithromycin is one of the last two antibiotics recommended for treatment of uncomplicated gonorrhea, which has progressively developed resistance to all antibiotics used for its treatment, but azithromycin-resistant gonorrhea infections have been rising worldwide in recent years.

During the study period, 2,155 unique patients were diagnosed with 2,828 culture-positive gonorrhea infections, 156 (5.5%) of which were caused by azithromycin-resistant N gonorrhoeae. Of those 156 patients, 4 (2.6%) had received an azithromycin prescription in the 29 days prior to their gonorrhea diagnosis, and 37 (24%) had received azithromycin the prior 30 to 365 days.

After the researchers adjusted for clinical, demographic, and risk behavior characteristics, they found that an azithromycin-resistant N gonorrhoeae infection was strongly associated with receipt of azithromycin in the prior 29 days (adjusted odds ratio [aOR], 6.76; 95% CI, 1.76 to 25.90), but not with receipt of azithromycin in the prior 30 to 365 days.

The researchers also found that azithromycin minimum inhibitory concentration levels—a measurement of how much antibiotic is needed to prevent growth of bacteria—were associated with the number of azithromycin prescriptions in the prior 30 days.

The study authors say the findings suggest that the long half-life and persistence of subtherapeutic levels of azithromycin in people who've recently been exposed to the antibiotic may result in the selection of azithromycin-resistant gonorrhea strains.
Aug 24 Clin Infect Dis abstract

Global survey highlights factors in non-prescription antibiotic dispensing

Originally published by CIDRAP News Aug 24

A global survey of pharmacists found that, despite good knowledge about antibiotics and antimicrobial resistance (AMR), nearly two-thirds had dispensed antibiotics without a prescription at least once, and those who did were much likely to come from lower-income countries, researchers reported today in JAC-Antimicrobial Resistance.

The survey, disseminated by the Commonwealth Pharmacists' Association during the World Health Organization's World Antibiotic Awareness Week, asked respondents about antibiotic supply practices, knowledge, and beliefs about AMR. A total of 546 pharmacists from 59 countries responded, with Africa (41%), Asia (26%) and Oceania (22%) most represented. Forty-four percent were from low-income countries, and most practiced in nations with antibiotic prescribing regulations (94%), and had 10 or more years of experience (51%).

Participants reported supplying a mean of 46 antibiotic prescriptions per week (standard deviation, 81), of which 73% ± 35% were given in response to a prescription. Overall, 227 respondents (60.2%) dispensed antibiotics at least once without a prescription. Respondents scored well in the knowledge section of the survey, with mean knowledge scores of 9.6 ± 1.3 (out of 12), and held positive beliefs about the importance of addressing AMR, with a mean score of 3.5 ± 0.6 (out of 5).

Further analysis found that the better knowledge that respondents had about antibiotics, the fewer misperceptions they had relating to AMR. Also, having more positive beliefs about addressing AMR was associated with lower odds of supplying antibiotics without a prescription (aOR, 0.91; 95% CI, 0.86 to 0.95). But the odds of supplying antibiotics without a prescription were 7.4 times higher among respondents from lower-income countries (aOR, 7.4; 95% CI, 4.16 to 13.24), and the respondents from lower-income countries had lower scores for beliefs about AMR compared with respondents from higher-income countries.

"This finding has important implications when considering the development of global health policies relating to AMR as this could have implications for public access to necessary antimicrobials even though stricter regulation could reduce unnecessary antimicrobial use," the study authors wrote. "AMS [antimicrobial stewardship] initiatives should consider a pharmacist's individual beliefs about AMR but also the country context in which pharmacists practise."
Aug 24 JAC-Antimicrob Resist study

Trial finds no impact on trachoma from mass azithromycin distribution

Originally published by CIDRAP News Aug 23

A randomized clinical trial in Niger found that mass distribution of azithromycin to preschool-aged children was no more effective at reducing incidence of trachoma than placebo, researchers reported today in JAMA Network Open.

The cluster-randomized trial, conducted by investigators with the Macrolides Oraux pout Réduire les Décés Avec un Oeil sur la Resistance (MORDOR)-Niger Study Group, assessed the effects of biannual mass azithromycin distribution to children ages 1 to 59 months in 30 villages in a region of Niger thought to have hypoendemic trachoma. The World Health Organization (WHO) recommends mass distribution of azithromycin for districts with trachoma, the world's leading infectious cause of blindness, but concerns that mass antibiotic administration to entire communities could promote antibiotic resistance has led researchers to ask whether targeted distribution might be a better strategy.

A total of 4,756 children in 30 communities were included, with 1,695 children enrolled in 15 azithromycin communities and 3,031 in 15 placebo communities. Enrolled children received a single dose of oral azithromycin or oral placebo every 6 months over 24 months. The primary outcome of the trial was the incidence of trachomatous inflammation-follicular (TF).

The mean prevalence of TF at baseline was 1.9% (95% CI, 0.5% to 3.5%) in the azithromycin group and 0.9% (95% CI, 0 to 1.9%) in the placebo group. At 24 months, TF prevalence was 0.2% (95% CI, 0 to 0.5%) in the azithromycin group and 0.8% (95% CI, 0.2% to 1.6%) in the placebo group. The lower incidence of TF in the azithromycin group was not considered statistically significant (incidence rate ratio adjusted for baseline: 0.18 [95% CI, 0.01 to 1.20]).

The study authors say that the low baseline prevalence of trachoma in the communities makes it difficult to determine whether targeted mass distribution of azithromycin to preschool-aged children could be an effective strategy for trachoma elimination. It also suggests trachoma may have been eliminated as a public health problem in those communities.

"It remains unclear whether azithromycin distributions to preschool-aged children would be effective in other areas with hypoendemic trachoma that have slightly more infection than those assessed in the present study," they wrote.
Aug 23 JAMA Netw Open study

Multidrug-resistant TB treatment more effective than thought

Originally published by CIDRAP News Aug 23

A systematic review and meta-analysis of studies from countries in Central and West Africa found higher-than-expected treatment success rates for multidrug-resistant and rifampicin-resistant tuberculosis (MDR/RR-TB), researchers reported yesterday in the International Journal of Infectious Diseases.

The analysis of 14 studies from 14 countries in the two regions, published from 2005 through 2020 and including 4,268 people, found the overall treatment success was 74.6% (95% confidence interval [CI], 65% to 82.2%), with a pooled success rate of 80.8% (95% CI, 56% to 93.3%) for the Central African subgroup and 69.3% for the West African subgroup (95% CI, 56.3% to 79.7%). The estimated proportion of successfully treated MDR/RR-TB patients was significantly higher than the WHO's estimate of 59% and reaches the WHO's 2015 target of 75% treatment success for MDR-TB.

The findings are surprising because the studies were conducted while countries in the region were using the standard MDR-TB regimen, which lasts 18 to 24 months and includes injectable drugs. Poor adherence to that regimen has been associated with low treatment success rates. The authors note the findings may be explained by early introduction of a 9- to 11-month regimen in many of the included countries, along with the absence of data from 12 countries in the region.

"Whether this reflects the true rate of treatment success or whether the rate is skewed due to underreporting remains unknown," they wrote. 

In 2022, the WHO endorsed a 6-month all-oral regimen for MDR-TB that experts hope will lead to even better treatment outcomes.
Aug 22 Int J Infect Dis study

Study highlights impact of stewardship steps in severely ill COVID patients

Originally published by CIDRAP News Aug 22

A study conducted at two hospitals in Thailand found that implementing a procalcitonin (PCT) and Clinical Pulmonary Infection Score (CPIS) was associated with reduced inappropriate antibiotic use, multidrug-resistant organisms (MDROs), and invasive fungal infections (IFIs) in severely-to-critically ill COVID-19 patients, researchers reported today in Infection Control & Hospital Epidemiology.

In the quasi-experimental study, conducted from March 2020 through February 2022, Thai and US researchers evaluated the role of PCT-CPIS in two hospitals in which severely-to-critically ill COVID-19 patients were treated in intensive care units. They compared inappropriate antibiotic use during the 1-year pre-implementation period (period 1: March 2020 through February 2021), when no antibiotic protocols were available for COVID-19 patients at either hospital, and the 1-year post-implementation period (period 2: March 2021 through February 2022).

During period 2, antibiotics were not initiated, or were discontinued on day 3, for patients with a CPIS score of less than 6 and PCT of less than 0.5 micrograms per liter (μg/L).

In total, 192 patients were included in period 1 and 214 in period 2. Their median age was 62 years, 52.0% were severely ill, and 23.6% were critically ill. Compared with period 1, overall inappropriate antibiotic use in period 2 fell significantly, from 63.5% to 31.3%, driven mainly by reduced inappropriate antibiotic use in severely-to-critically ill COVID-19 patients (80.8% in period 1 vs 39.1% in period 2). But it was not reduced among mildly-to-moderately ill COVID-19 patients (8.7% vs 7.5%).

In period 2, researchers also observed a significantly lower incidence of MDRO-IFIs (25% vs 16.8%) and MDR Acinetobacter baumannii (16.1% vs 9.3%), as well as significantly shorter antibiotic duration (7 days vs 0 days) and shorter hospitalizations (13 days vs 10 days). There was no difference in 30-day mortality between the two periods.

"Our findings suggest that the PCT-CPIS strategy could be beneficial to severely-to-critically ill COVID-19 patients," the authors concluded.
Aug 22 Infect Control Hosp Epidemiol abstract