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

Study shows pre-pandemic global decline in antimicrobial use

An analysis of prescribing data from more than 80 countries found that global antimicrobial consumption declined prior to the COVID-19 pandemic, researchers reported today in the Journal of Antimicrobial Chemotherapy.

For the cross-sectional time-series analysis, researchers from the University of Pittsburgh and the University of Toronto obtained data on global monthly purchases of antimicrobials (antibiotics, antivirals, and antifungals) from 2014 through 2020 from the IQVIA MIDAS database, which contains monthly drug data for 84 countries. Their aim was to evaluate antimicrobial consumption pre-pandemic and assess the impact of the World Health Organization (WHO) Global Action Plan on Antimicrobial Resistance (GAP-AMR), which was adopted in 2015 to encourage countries to develop national AMR action plans.

Over the study period, the worldwide monthly antimicrobial purchase rate averaged 112.9 units per 1,000 population, with antibiotics accounting for 88.7% of antimicrobial consumption. Prior to the pandemic, the average monthly antimicrobial consumption rate in developed countries changed by –8.4%, compared with –1.2% in developing countries. Among countries with an AMR national action plan, all but five experienced a decline in average monthly antibiotic consumption pre-pandemic.

Global antimicrobial consumption increased by 11.2% from March 2019 to March 2020. The greatest increase was for antivirals in both developed (48.2%) and developing countries (110%), followed by antibiotics (6.9% and 5.9%, respectively). But from April to August 2020, antimicrobial consumption decreased worldwide by 18.7% compared with the previous year, with antibiotic consumption declining in both developed (–28%) and developing (–16.8%) countries.

The study authors say the findings show a promising decline in antimicrobial consumption pre-pandemic. And the decline in antibiotic use after the initial months of the pandemic, when it became clear that antibiotics were not effective against COVID-19, suggests that antibiotic stewardship efforts have not been derailed by the pandemic. But they warn that increases in antiviral use require attention.

"Antimicrobial consumption was decreasing across the globe pre-pandemic, especially for antibiotics, suggesting a positive impact of the WHO GAP-AMR," the study authors write. "AMR plans should include specific measures to ensure continued AMR efforts are fully implemented and continued during health crises such as the COVID-19 pandemic."
Feb 18 J Antimicrob Chemother study

Studies find lower antibiotic use in COVID patients in Hong Kong, Japan

Two new studies of COVID-19 patients in Japan and Hong Kong found low rates of concurrent bacterial infections and lower rates of antibiotic use than have been previously reported.

While previous studies have found low rates of bacterial co-infections in COVID-19 patients throughout the pandemic, they have also found high rates of antibiotic use, particularly in the early months of the pandemic. A meta-analysis of 24 studies found that roughly 72% of COVID-19 patients treated from Dec 25, 2019, through Mar 31, 2020, received antibiotics. Secondary bacterial infection was found in 14.3% of patients.

But in a letter published yesterday in the Journal of Infection, researchers reported that, among 11,004 COVID-19 patients hospitalized in Hong Kong from the beginning of the pandemic through Mar 3, 2021, 29.1% were treated with antibiotics, and only 1.84% had bacterial co-infections. Antibiotic use was common in patients without any co-infection (66.1%) or when co-infection was uncertain (13.7%). The authors note that antibiotic use may have been lower than found in previous studies because Hong Kong uses hospitalization as an isolation strategy, and many of the patients had mild or asymptomatic cases.

In a study of patients treated at Japan's National Hospital Organization Tochigi Medical Center from Nov 1, 2020, through Oct 9, 2021, published today in JAMA Network Open, researchers found that of 1,056 patients analyzed, only 18 (1.7%) received any antibiotics during hospitalization. Of these 18 patients, 15 used antibiotics for treatment and 3 used them as a prophylaxis.

Most of the patients (80%) had mild or moderate COVID-19. Seven microbiologically confirmed infectious diseases other than COVID-19 were detected in 6 patients (0.6%) during hospitalization.

"Given that most patients with noncritical severity recovered without antimicrobial drugs, the use of most antimicrobial drugs to treat noncritical cases in many hospitals might be unnecessary," the authors write. "Antimicrobial drugs should be used cautiously to treat patients with COVID-19 infection."
Feb 17 J Infect letter
Feb 18 JAMA Netw Open research letter

Chinese study highlights spread of MCR-1 colistin resistance gene in E coli

Originally published by CIDRAP News Feb 17

A study of fecal samples from patients at hospitals in Shanghai found the mobile colistin resistance gene MCR-1 in nearly 4% of Escherichia coli strains, most of them from children, Chinese researchers reported today in the Journal of Global Antimicrobial Resistance.

In the study, researchers from China's Center for Disease Control and Prevention collected fecal samples from patients with diarrhea and healthy individuals treated at Shanghai hospitals from 2012 through 2015. They isolated E coli bacteria from the samples, then screened the E coli strains, using polymerase chain reaction, to detect MCR-1, a gene that was first discovered in China in 2015 and is known to be widely distributed in E coli and other pathogens that cause diarrhea. They also conducted whole-genome sequencing (WGS) and antimicrobial susceptibility testing on the isolates.

A total of 1,204 E coli strains were isolated from the fecal samples, and 40 strains (3.9%) carried MCR-1. The MCR-1–positive rates climbed from 1.20% in 2012 to 3.94% in 2015. Most strains harboring MCR-1 were isolated from children younger than 7 years of age, and the gene was found in four types of E coli: atypical enteropathogenic, typical enteropathogenic, enterotoxigenic, and enteroaggregative.

Antimicrobial susceptibility testing found that all 40 strains carrying MCR-1 were resistant to colistin, 36 were resistant to three or more antibiotic classes, and 27 were resistant to five or more classes. WGS revealed that nearly half of the strains also carried quinolone-resistance genes or beta-lactam–resistance genes and were multidrug-resistant (MDR). The predominant type of plasmid in MCR-1­–positive E coli was IncX4 and IncI12.

"These results indicate that more attention should be paid to the spread of mcr-1 in various types of E. coli," the study authors wrote. "Strengthening the surveillance of mcr-1-positive strains and investigating their prevalence and distribution will help us actively respond to the challenge of MDR gram-negative Enterobacteriaceae."
Feb 17 J Glob Antimicrob Resist study

Previously approved antibiotic could be used against plague, melioidosis

Originally published by CIDRAP News Feb 17

The UK government says its scientists, working in collaboration with industry and academia, have found that a fluoroquinolone antibiotic used to treat ear infections may also work against plague and melioidosis.

The antibiotic, finafloxacin, was approved by the US Food and Drug Administration in 2014 for the treatment of acute otitis externa (infection of the outer ear canal) and is also in clinical trials for use in patients with complicated urinary tract infections. But German pharmaceutical company Merlion Pharma says finafloxacin has also demonstrated efficacy against Burkholderia pseudomallei, the bacterium that causes melioidosis, and Yersinia pestis, which causes plague, in mouse models of infection.

In a project funded by the US Defense Threat Reduction Agency (DTRA), scientists from the UK's Defence Science and Technology Laboratory (Dstl) have been working with MerLion to further investigate whether finafloxacin can be used to treat infections caused by these pathogens, which are endemic in several parts of the world but are also considered potential bioweapons.

"Finding an antibiotic that works against a range of pathogens is really exciting," Dstl associate professor Sarah Harding, PhD, said in a news release. "It has been almost 10 years of research, which would not have been possible without the collaboration between Dstl, MerLion Pharmaceuticals and DTRA."
Feb 17 UK.gov news release 

Pharmacist-developed app aims to improve antimicrobial prescribing

Originally published by CIDRAP News Feb 15

The Commonwealth Pharmacists Association (CPA) last week announced a new program to improve surveillance and prescribing of antimicrobials in low- and middle-income countries (LMICs).

The Surveillance and Prescribing support for Antimicrobial Stewardship Resource Capacity Building (SPARC) program will re-develop and expand the availability of an antimicrobial prescribing smartphone app, adding updated core prescribing guidance and information on additional good stewardship practices. Veterinary antimicrobial prescribing and stewardship guidance will also be added to the app, which was developed and launched a few years ago by CPA.

"We aim to provide increased support for antimicrobial use surveillance in human health and empower frontline clinicians with improved access to their national standard treatment guidelines as well as internationally recognized antimicrobial stewardship guidelines through the development and rollout of an antimicrobial prescribing and stewardship smartphone app for human and animal health," CPA Technical Program Lead Diane Ashiru-Oredope, PhD, said in a press release.

The program will be funded through the UK Department of Health and Social Care's Fleming Fund. The app will be available in 22 LMICs in Africa and Asia where the Fleming Fund is active.

SPARC also aims to develop workshops and provide practical assistance for up to six countries to carry out a global point-prevalence survey to track antimicrobial use. 
Feb 9 CPA press release

US surveillance study finds high incidence of ESBL-E infections

Originally published by CIDRAP News Feb 14

An active laboratory- and population-based surveillance study conducted at five US sites found a high incidence of infections caused by extended-spectrum beta-lactamase–producing Enterobacterales (ESBL-E), researchers reported today in Infection Control & Hospital Epidemiology.

The pilot study, led by researchers with the Centers for Disease Control and Prevention (CDC), identified incident ESBL-E cases at five Emerging Infections Program (EIP) sites in New York, Georgia, Tennessee, Colorado, and New Mexico over a 3-month period (October to December 2017).

An incident ESBL-E case was defined as an E coli, Klebsiella pneumoniae, or Klebsiella oxytoca isolate resistant to at least one extended-spectrum cephalosporin and non-resistant to carbapenems. Antimicrobial susceptibility testing and whole-genome sequencing was conducted on a convenience sample of case isolates.

The researchers identified 884 ESBL-E incident cases among 815 patients. Of the 884 cases, 790 (89%) were E coli bacteremia, and 94 (11%) were K pneumoniae bacteremia. The estimated annual incidence in the three sites conducting population-based surveillance (New York, New Mexico, and Tennessee) was 199.7 per 100,000 population. Among the cases, 393 (47%) were classified epidemiologically as community-associated, 282 (34%) as healthcare-associated community-onset, and 40 (5%) as hospital-onset.

Among 136 isolates (15%) tested at the CDC, 122 (90%) met the surveillance definition phenotype; 114 (93%) of 122 were shown to be ESBL producers by clavulanate testing. In total, 111 (97%) of confirmed ESBL producers harbored a bla _CTX-M gene. Among ESBL-producing E coli isolates, 52 (54%) were sequence type ST131; 44% of these cases were community-associated.

The study authors say the findings are concerning not only because the incidence of ESBL-E infections in the United States appears to be much higher than previously established estimates for other resistant phenotypes, such as carbapenem-resistant Enterobacterales (2.93 infections per 100,000) but also because only 30% occurred in hospitalized patients. The CDC has previously highlighted ESBL-E as a serious antibiotic resistance threat.

"In conclusion, ESBL-E causes a high burden of infections in the community and in healthcare, and additional data are needed to further characterize risk factors and sources of acquisition to focus prevention efforts," they write.

The EIP has implemented ongoing ESBL-E surveillance at six US sites based on the findings.
Feb 14 Infect Control Hosp Epidemiol abstract

VA study highlights inappropriate asymptomatic bacteriuria treatment

Origianally published by CIDRAP News Feb 14

An in-depth review of provider documentation at eight Veterans Affairs (VA) sites found that more than a quarter of asymptomatic bacteriuria (ASB) cases were inappropriately treated with antibiotics, researchers reported last week in the American Journal of Infection Control.

In the case-control study, a team led by researchers from Baylor College of Medicine reviewed a random sample of 10 positive urine cultures per month, per facility, classifying them as urinary tract infection or ASB and as treated or untreated. They then reviewed provider-documented text from medical charts that was associated with urine culture ordering to identify symptoms and factors associated with inappropriate ASB treatment.

Out of 960 cultures analyzed from October 2018 through September 2018, 575 were ASB cases. Of these, 158 (27.5%) were inappropriately treated with antibiotics. After controlling for known predictors of ASB treatment, the researchers found that abdominal pain, confusion, decreased urine output, falls, urine characteristics, abnormal vital signs, laboratory values, and voiding issues were all significantly associated with inappropriate ASB treatment. Misleading symptoms with the strongest effect included falls (odds ratio [OR], 3.19), abnormal vital signs (OR, 3.18), and abdominal pain (OR, 2.44).

ASB-treated patients received an average of 1.4 antibiotics, with cephalosporins (41%) and fluoroquinolones (21%) being the most common classes prescribed.

The study authors say the findings suggest a role for diagnostic stewardship to accompany antibiotic stewardship and that future research should examine the factors associated with inappropriate ASB treatment.

"Teasing out these unique cues can help improve our understanding behind improper ASB treatment and should be incorporated into teaching vignettes used in antibiotic stewardship interventions," they wrote.
Feb 11 Am J Infect Control abstract

Risk of severe disease much lower with Omicron COVID variant than Delta

The risk of hospitalization, intensive care unit (ICU) admission, and death was much lower among more than 9,000 Canadian COVID-19 patients infected with the Omicron variant than among matched Delta patients, according to a study published yesterday in JAMA.

The risk of hospitalization or death with Omicron was 41% of—and the risk of death was one-tenth of—that of Delta.

Public Health Ontario researchers retrospectively studied the outcomes of all COVID-19 patients in the province with illness onset from Nov 22 to Dec 24, 2021, amid the Omicron surge but before the emergence of the Omicron BA.2 subvariant. Median follow-up was 24 days.

Omicron cases were identified using whole-genome sequencing or S gene target failure testing, and Delta cases were identified through these methods or as those not identified as Omicron.

Among 37,296 Omicron cases, 9,087 were matched in a 1:1 ratio with Delta cases. Fifty-three Omicron patients (0.6%) were hospitalized, and 3 (0.3%) died, compared with 129 hospitalizations (1.4%) and 26 deaths (0.3%) among Delta patients.

The hazard ratio (HR) for hospitalization or death among Omicron patients relative to Delta patients was 0.41 (95% confidence interval [CI], 0.30 to 0.55) (0.33 in a sensitivity analysis [95% CI, 0.19 to 0.56]). The HR for ICU admission or death was 0.19 (95% CI, 0.09 to 0.39), while it was 0.12 (95% CI, 0.04 to 0.37) for death.

Estimates of Omicron severity stratified by age, sex, and vaccination status all indicated decreased severity.

"The results align with findings from South Africa, Scotland, and England, all of which have demonstrated substantial decreases in risk associated with Omicron," the researchers wrote. "While severity may be reduced among Omicron cases, the absolute number of hospitalizations and the effects on health care systems are likely to be significant due to the elevated incidence of Omicron."
Feb 17 JAMA research letter

California reports H1N2v flu case

California has reported a variant H1N2 (H1N2v) flu case in an adult who had direct contact with pigs, the US Centers for Disease Control and Prevention (CDC) said today in its weekly FluView report.

The patient wasn't hospitalized and has recovered. Some respiratory illnesses were reported in some of the patient's contacts, but the CDC said the events occurred during a period of high respiratory illness activity, and no specimens were collected for testing. No ongoing human-to-human transmission of H1N2v has been linked to the case.

So far, three novel influenza A cases have been reported to the CDC this flu season. Earlier reports involved an H3N2v case in Ohio and an H1v (neuraminidase not determined) case in Oklahoma.

In other US flu developments, flu activity increased in some parts of the country last week, though the percentage of outpatient visits for flulike illness remained below the national baseline.

The CDC said overall, sporadic activity continues across the nation, with H3N2 as the dominant strain. Eight states are reporting low flu activity, another marker for clinic visits for flulike illness. Hospitalization rates increased slightly, and no new pediatric flu deaths were reported, keeping the season's total at five.
Feb 18 CDC FluView report

Four babies infected with Salmonella, Cronobacter tied to infant formula

At least four babies have been infected with Salmonella Newport or Cronobacter sakazakii and one has died after drinking infant formula made from a powder produced at Abbott Nutrition's Sturgis, Michigan, facility, the Food and Drug Administration (FDA) said in a news release and outbreak update yesterday.

Three babies tested positive for C sakazakii infections and one for Salmonella, and all were hospitalized. The FDA said, "Cronobacter may have contributed to a death in one case."

The formula from Abbott's Sturgis facility was bought from Sep 6 to Dec 18, 2021, the babies' families reported. The FDA is advising people not to use Similac, Alimentum, or EleCare powdered infant formulas if the first two digits of the product code are 22 through 37 and the code on the container contains K8, SH, or Z2 and the expiration date is Apr 1, 2022, or later.

Scientists with the FDA and CDC are partnering with local officials to investigate the outbreak. "This is an ongoing investigation, and the firm is working with the FDA to initiate a voluntary recall of potentially affected product," the FDA said. "FDA is continuing to investigate and will update this advisory should additional consumer safety information become available."

So far investigators have reported several C sakazakii detections in environmental samples taken at the Sturgis plant. A review of the company's records also indicates environmental contamination with the pathogen and the company's destruction of product because of Cronobacter contamination. 

"As this is a product used as the sole source of nutrition for many of our nation's newborns and infants, the FDA is deeply concerned about these reports of bacterial infections," said Frank Yiannas, MPH, FDA deputy commissioner for food policy and response, in the news release. "We want to reassure the public that we're working diligently with our partners to investigate complaints related to these products."
Feb 17 FDA news release and outbreak update

Malawi reports wild poliovirus case linked to Pakistan

In a worrying development, a wild poliovirus type 1 (WPV1) case has been detected in a child in Malawi, Africa's first such case since 2016.

In a statement yesterday, the Global Polio Eradication Initiative (GPEI) said the case involves a 3-year-old girl from Lilongwe, the country's capital, whose paralysis symptoms began on Nov 19, 2021. Tests done by South Africa's National Institute for Communicable Diseases and the US CDC confirmed the WPV1 finding. Sequencing shows that the virus is genetically linked to a WPV1 strain detected in Pakistan's Sindh province.

The case is considered an imported case from Pakistan and does not affect the World Health Organization African region's poliovirus-free certification, which it received in August 2020.

The GPEI is supporting Malawi's response, which includes enhanced surveillance to identify undetected transmission and urgent immunization activities.
Feb 18 GPEI statement

In other polio developments, three countries reported more vaccine-derived polio cases last week: Mozambique, Nigeria, and Somalia. All involved circulating vaccine-derived poliovirus type 2 (cVDPV2).

Mozambique reported two cases, one each in Nampula and Cabo Delgado provinces. Both had onsets in 2021 and are included in its total for last year. Nigeria reported 16 more cases in six states, lifting its total for 2021 to 413. And Somalia reported one new case, which involves a patient from Banadir province, marking its first case of 2022.
Feb 17 GPEI update

USDA reports waterfowl H5 avian flu, including in Connecticut, Georgia

The US Department of Agriculture (USDA) reported 108 more highly pathogenic H5 detections from wild bird surveillance, all on the East Coast, with first detections reported from Connecticut and Georgia.

The USDA's Animal and Plant Health Inspection Service (APHIS) has now reported 247 detections in waterfowl as officials track the virus sampling of both live and hunter-harvested birds. Connecticut's detections are in New London and Middlesex Counties, located in the south-central part of the state. Georgia's detections were from Hart County, in the northeastern part of the state on the South Carolina border.

Other detections include previously affected states, along with newly affected counties within those state, such as Currituck and Craven counties in North Carolina.

Some of the highly pathogenic H5N1 detections on the eastern seaboard have been confirmed as Eurasian H5N1, the strain that is affecting wild birds and poultry in multiple parts of the world. The virus is also confirmed or suspected as triggering outbreaks on five poultry farms in three states, three of them in Indiana.

The USDA said last week that it has expanded surveillance of the virus to all four of the migratory bird flyways that span the US mainland.
APHIS list of highly pathogenic avian flu detections in wild birds