Over 40% of COVID patient stool samples had viral RNA but no live virus

Over 40% of 79 stool samples from COVID-19 patients admitted to one of four hospitals in Spain contained SARS-CoV-2 RNA but no live virus, suggesting a negligible ability to replicate in this medium and a very low likelihood of fecal-oral viral transmission, finds a study published yesterday in Scientific Reports.

Researchers from the University of Seville collected stool samples from 62 adult COVID-19 patients at hospital admission and/or follow-up at up to 4 months from March 2020 to February 2021. Median patient age was 59 years, 61.2% were men, and 30.6% had chronic conditions, the most common of which was solid-organ transplant (73.6%).

The team detected SARS-CoV-2 genetic material in 27 of 62 patients (43.5%). In the first week after illness onset, 7 of 19 (36.8%) patients excreted fecal viral RNA, compared with 9 of 28 (32.1%) in the second week. A subset of patients, mostly solid-organ transplant recipients, excreted RNA until week 16. There were no differences by age, sex, or chronic conditions in the presence or absence of viral RNA in stool samples. 

No live virus was found on culture, and fecal viral RNA was not tied to gastrointestinal symptoms or illness severity.

"Our study suggests that the fecal–oral transmission of SARS-CoV-2 if any is negligible as an alternative infection route," the researchers wrote. "Moreover, in our experience, the detection of SARS-CoV-2 RNA in feces at the beginning of the disease is not associated with any clinical factor nor with unfavorable clinical outcome."
May 5 Sci Rep study

Crowded homes, low income tied to higher risk of COVID-19 in pregnancy

Pregnant women living in low-income neighborhoods and homes that are crowded were more likely to contract COVID-19 during the pre-vaccination period of the pandemic, according to a study yesterday in Obstetrics & Gynecology.

To conduct the study, researchers from Children's Hospital of Philadelphia (CHOP) used serum samples from 5,991 pregnant patients who gave birth at two hospitals in Philadelphia from Apr 13 to Dec 31, 2020. The investigators looked for antibodies indicative of a previous COVID-19 infection.

Participants also provided race address information, which the researchers geocoded with census data. The researchers classified neighborhoods using three criteria: community deprivation, determined by how many residents live below the federal poverty line; racial segregation of the neighborhood; and crowding, defined as more people than rooms in a home.

A total of 9.4% of women included in the study had antibodies to SARS-CoV-2. Hispanic women had the highest prevalence (19.3%), followed by Black (14%) patients, with Asian (3.2%) and White (2.7%) patients having much lower rates.

Deprivation (adjusted odds ratio [aOR], 1.16; 95% confidence interval [CI], 1.02 to 1.32) and crowding (aOR, 1.15; 95% CI 1.05 to 1.26) were associated with increased rates of COVID-19, but racial segregation was not (aOR, 0.90; 95% CI 0.78 to 1.04).

"By now it is well understood that the COVID-19 pandemic has disproportionately affected Hispanic and Black communities in the United States, and our study identifies potential factors that contribute to this phenomenon in pregnancy," said Heather H Burris, MD, MPH, the first author of the study, in a CHOP press release. 
May 5 Obstet Gynecol study
May 5 CHOP press release

Avian flu appears in more US flocks, detected in Canadian foxes

The US Department of Agriculture (USDA) Animal and Plant Health Inspection Service (APHIS) reported a few more highly pathogenic avian flu outbreaks in poultry, all involving backyard birds, as well as 50 more detections in wild birds, mostly in the Midwest, with North Dakota noting deaths from the virus in crows.

South Dakota had two more poultry outbreaks, in Day and Hamlin counties in the eastern part of the state. Minnesota reported one more outbreak, bringing its total to 69. The virus struck a location in Carver County, just west of Minneapolis.

So far, activity involving the Eurasian H5N1 strain has led to the loss of 37.6 million birds across 33 states, according to the USDA.

The 50 new H5N1 detections from wild bird surveillance raise the total to 1,006. Most of the new listings are from the Midwest, including North Dakota, Wisconsin, and South Dakota. Most involved waterfowl and raptors; however, North Dakota reported several detections in crows found dead.

Outside of the Midwest, there were a few detections in Wyoming, Colorado, and Maryland.
USDA APHIS poultry avian flu page
USDA APHIS wild bird avian flu page

In related developments, the Canadian Wildlife Health Cooperative (CWHC) this week announced the identification of the first Eurasian H5N1 in wild mammals in the Americas.

The virus was found in wild fox kits in Ontario on May 2. They were found together in St. Mary's and submitted to a wildlife rehabilitation center. One was dead and one had severe neurologic symptoms and died shortly after admission. H5N1 was found in brain tissue samples, and officials said the virus was likely the cause of death.

The strain had been previously found in a few mammals in Europe and in two people, one in the United Kingdom and another in Colorado, raising concerns about zoonotic potential.
May 4 CWHC blog post

Pakistan confirms its second wild poliovirus case of the year

Pakistani officials have reported one more wild poliovirus type 1 (WPV1) case, its second of the year, and Nigeria has confirmed three more circulating vaccine-derived poliovirus type 2 (cVDPV2) cases, the Global Polio Eradication Initiative (GPEI) said in its weekly update.

Pakistan's WPV1 case was in Khyber Pakhtunkhwa province, the GPEI said, but it provided no information on when the person first exhibited symptoms. Last year the country reported one WPV1 case. It has also had eight cVDPV2 cases this year.

Nigeria's 3 new cVDPV2 cases are in Niger, Katsina, and Zamfara states, bringing the number of 2022 cases to 20. The country had 415 cVDPV2 cases in 2021.
May 5 GPEI update

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

WHO report highlights global toll of healthcare-associated infections

The World Health Organization (WHO) today issued a report highlighting the threat of healthcare-associated infections (HAIs) and the role that infection prevention and control (IPC) programs can play in reducing that threat.

According to the report, out of every 100 patients in acute care hospitals, 7 patients in high-income countries and 15 in low- and middle-income countries (LMICs) will acquire on average at least one HAI during their stay, and up to 30% of patients in intensive care units will acquire one. Nearly one quarter (23.6%) of hospital-treated sepsis cases are healthcare-associated.

The impact is not limited to acute care hospitals. Data show that 4.4 million HAIs occur in long-term care facilities every year in European countries, while 1 out of every 43 US nursing home residents has an HAI.

The problem is exacerbated by antimicrobial resistance (AMR), with data showing that mortality is at least two to three times higher among those with HAIs caused by resistant microorganisms.

Meanwhile, progress on implementing and funding national IPC programs has been slow, particularly in LMICs. While recent WHO surveys show that 61.3% of countries have a national IPC program, only 54.7% of them have an active, functioning program with annual work plans and a budget, and only 4 of the 106 countries (3.8%) have met all minimum requirements for an IPC program. Compared to LMICs, high-income countries were five to eight times more likely to have a more advanced IPC implementation status.

The report suggests that implementing a range of IPC interventions, such as hand hygiene and enhanced environmental hygiene, could reduce HAI rates by 35% to 70%, halve the risk of dying from an HAI caused by a resistant pathogen, and decrease the associated long-term complications and health burden of AMR by 40%.

"WHO is calling on all countries around the globe to increase their investment in IPC programmes to ensure quality of care and patient and health workers' safety," the agency said in a press release. "This will not only protect their populations, increased investment in IPC has also demonstrated to improve health outcomes and reduce health-care costs and out-of-pocket expenses."
May 6 WHO report on infection prevention and control
May 6 WHO press release

Drug-resistant gonorrhea surveillance lacking, researchers warn

Two reports published yesterday in Eurosurveillance stress the need for better surveillance, control, and management of drug-resistant gonorrhea.

In a systematic review of literature on surveillance systems targeting AMR in gonorrhea, a team of Australian researchers found 40 records describing 32 country-level Neisseria gonorrhoeae surveillance system and 10 records describing four regional surveillance systems. The proportion of countries with surveillance systems in each of the WHO's six regions ranged from 1 of 22 countries in the Eastern Mediterranean and 5 of 54 in Africa, to 3 of 11 countries in Southeast Asia.

Only four countries (Australia, New Zealand, Canada, and the United Kingdom) had gonorrhea AMR surveillance systems that were both comprehensive (covering all culture-evaluable gonorrhea diagnoses) and national (covering more than 50% of jurisdictions. Most striking, the study authors noted, was the lack of surveillance in LMICs that have a high burden of gonorrhea.

"We have found that in most WHO regions, information on adequate systems was only available from a few countries," they wrote. "We also found major gaps in coverage, comprehensiveness and representativeness as well as wide variation in the methodology. These gaps indicate serious vulnerability in countries' capacity to detect, accurately monitor and respond to N. gonorrhoeae AMR and represents a global health risk in a world connected through travel."

In the other report, researchers from the WHO, European Centre for Disease Prevention and Control (ECDC), and the UK Health Security Agency note that since the ECDC issued its response plan to control and manage multidrug-resistant N gonorrhoeae in Europe in 2012, several strains of extensively drug-resistant gonorrhea have emerged, prompting an update to the plan in 2019, including strengthened surveillance and treatment failure monitoring. The authors conclude that the plan should be reviewed every 2 years to identify and address areas for improvement

"Along with prevention, diagnostic, treatment and epidemiological surveillance strategies, AMR surveillance is essential for effective control of gonorrhoea," they wrote. 
May 5 Eurosurveill systematic review
May 5 Eurosurveill perspective

Pseudomonas outbreak in Norway linked to disposable washcloths

In another report published yesterday in Eurosurveillance, Norwegian researchers described a nationwide Pseudomonas aeruginosa outbreak in Norway linked to disposable washcloths.

The outbreak began in November 2021, when the Norwegian Institute of Public Health was notified by the University Hospital of North-Norway of three patients hospitalized with severe COVID-19 who had died from bloodstream infections caused by indistinguishable P aeruginosa strains, only a few days apart. Whole-genome sequencing (WGS) revealed the infections were caused by the novel sequence type ST3875.

Additional cases caused by P aeruginosa ST3875 were then rapidly detected in hospitals in all four regions of Norway, strongly indicating a common source of infection. By Apr 25, 2022, the outbreak included 339 cases at 38 hospitals. While most patients were colonized or had mild urinary tract or wound infections, 53 patients (15.3%) died, with 7 of the deaths (2.1%) directly attributable to P aeruginosa.

On Mar 18, Oslo University Hospital detected P aeruginosa—which thrives in warm, moist environments—in disposable pre-moistened washcloths after systematic testing of several hundred different products that were used on the hospital wards that treated identified cases. Subsequent polymerase chain reaction (PCR) testing and WGS identified the P aeruginosa isolates from the washcloths as the outbreak strain, ST387. After use of the washcloths was stopped, there was a rapid decline in cases over the next 4 weeks. Screening for further cases is ongoing.

On Mar 23, the Norwegian Food Safety Authority banned contaminated lots of the product from the Norwegian market and on Apr 9 issued a warning in Norway against use of all products from the manufacturer. But investigators warn that the washcloths have been sold and used in many countries, and that the outbreak may be ongoing and undetected in EU countries and beyond.

"Consequently, it is prudent to advise further investigations of P. aeruginosa ST3875 infections, and when identified, investigate if they are linked to the same product," they wrote.
May 5 Eurosurveill rapid communication

Nanoparticle drug for MRSA receives FDA go-ahead for human trial

Originally published by CIDRAP News May 5

Biotechnology startup Cellics Therapeutics announced yesterday that the Food and Drug Administration has allowed the investigational new drug (IND) application for CTI-005, an experimental blood cell membrane drug that targets methicillin-resistant and methicillin-susceptible Staphylococcus aureus (MRSA and MSSA).

The IND authorization will allow Cellics to start a multicenter, randomized phase 1b/2a trial investigating the safety and efficacy of CTI-005 in MRSA and MSSA pneumonia patients. CTI-005 consists of red blood cell membrane nanoparticles, or "nanosponges," that neutralize toxins emitted by MRSA and MSSA, enabling the immune system to kill the bacteria. MRSA and MSSA pneumonia is traditionally treated with the antibiotics vancomycin and linezolid.

CTI-005 is one of several drugs Cellics is developing through its Cellular Nanoparticle (CNP) technology.

"This IND allowance is an important milestone for Cellics Therapeutics and also for the CNP Technology," Cellics founder Liangfang Zhang, PhD, said in a company press release. "The CNP Technology creates a new therapeutic modality, Cellular Nanosponge, which uses human cell membranes as drug substance to treat infectious diseases and inflammatory diseases." 
May 3 Cellics Therapeutics press release

Stewardship steps help Singapore hospital cut broad-spectrum antibiotics

Originally published by CIDRAP News May 5

A study conducted in a hospital with high rates of antibiotic resistance in Singapore found that sequential implementation of two antimicrobial stewardship interventions was associated with reduced use of broad-spectrum antibiotics, researchers reported yesterday in JAMA Network Open.

To examine the outcomes associated with the sequential implementation of prospective review and feedback (PRF) with computerized decision support systems (CDSS) at a university teaching hospital in Singapore, researchers conducted an interrupted time series analysis of antibiotic use, multidrug-resistant organism incidence, and other unintended outcomes at the hospital from 2007 through 2018.

Daily real-time PRF of piperacillin-tazobactam and carbapenems (intervention 1) was introduced at the hospital in 2009, and a CDDS that covered 52 infective syndromes and followed hospital empiric antibiotic guidelines (intervention 2) was introduced in 2011.

After implementation of intervention 1, the use of piperacillin-tazobactam and carbapenems increased at a slower trend of 0.33 (95% confidence interval [CI], 0.18 to 0.48) more defined daily doses (DDDs) per 1,000 patient-days per month, while use of other broad-spectrum antibiotics fell by –11.05 (95% CI, –15.55 to –6.55) fewer DDDs per 1,000 patient-days per month.

After intervention 2, there were −0.22 (95% CI, −0.33 to −0.10) fewer DDDs per 1,000 patient-days per month of piperacillin-tazobactam and carbapenems and −2.10 (95% CI, −3.13 to −1.07) fewer DDDs per 1,000 patient-days per month for other broad-spectrum antibiotics. Also after intervention 2, incidence of Clostridioides difficile decreased by –0.02 (95% CI, –0.03 to –0.01) cases per 1,000 patient-days per month.

The study also found that when compulsory use of CDDS for piperacillin-tazobactam and carbapenems was lifted in half of the hospital wards in March 2017 (intervention 3), use of the two antibiotics increased by 0.28 (95% CI, 0.02 to 0.55) DDDs per 1,000 patient-days per month.

"This cohort study found that implementation of PRF and CDSS was associated with limiting the use of piperacillin-tazobactam and carbapenems while reducing use of other broad-spectrum antibiotics in a hospital with high antibiotic resistance rates," the study authors wrote. "The continued use of CDSS was needed to sustain the decrease in use of piperacillin-tazobactam and carbapenem."
May 3 JAMA Netw Open study

Approval of tebipenem HBr in doubt, Spero says

Originally published by CIDRAP News May 5

Biopharmaceutical company Spero Therapeutics announced yesterday that it will immediately defer current commercialization activities for tebipenem pivoxil hydrobromide (HBr), an oral carbapenem currently under review by the FDA, after the agency cast doubt on approval of the drug.

The FDA has been reviewing Spero's New Drug Application (NDA) for tebipenem HBr for the treatment of complicated urinary tract infections (cUTIs) caused by certain microorganisms in patients with limited treatment options, with an approval decision initially expected in late June. The application included data from a phase 3 trial that found that 7 to 10 days of tebipenem HBr was non-inferior to 7 to 10 days of intravenous (IV) ertapenem, with a similar safety profile.

But in a press release, Spero said that the FDA informed company officials in a recent meeting that a new analysis of the trial's microbiological intention-to-treat population found that pre-specified non-inferiority margin of –12.5% was not met, and that the data in the review package "may be insufficient to support approval during this review cycle."

"We are disappointed that the FDA has identified substantive review issues, and we strongly believe that tebipenem HBr would offer healthcare providers, payers and patients an important oral antibiotic alternative to IV treatment for cUTI for patients with limited oral treatment options," said Spero CEO Ankit Mahadevia, MD.

The company said it will continue to work with the FDA on a path forward for tebipenem HBr, but will "immediately refrain from investment in near-term commercialization activities."

Spero also announced it will reduce its workforce by 75% and restructure operations to reduce costs.
May 3 Spero Therapeutics press release

Colombian hospital stewardship tied to reduced antibiotics, resistance

Originally published by CIDRAP News May 3

A study conducted in hospitals in Colombia found that implementation of antimicrobial stewardship programs (ASPs) was associated with a decline in antibiotic consumption and antibiotic resistance, researchers reported yesterday in BMC Infectious Diseases.

In the retrospective observational study, Colombian researchers measured antibiotic consumption over 48 months at four high-complexity hospitals (institutions A-D) from 2009 to 2012, comparing the 24 months before ASP implementation and 24 months after through an interrupted time series analysis.

They also measured the incidence of meropenem-resistant Acinetobacter baumannii, ceftriaxone-resistant Escherichia coli, ertapenem-resistant Klebsiella pneumoniae, meropenem-resistant P aeruginosa, and oxacillin-resistant S aureus. Common features of the ASPs included a multidisciplinary ASP team, antimicrobial guidelines for the most prevalent infections, and prospective audits and feedback.

Prior to implementation of the ASPs, the four hospitals showed trends toward an increase in broad-spectrum antibiotic consumption (ceftriaxone, cefepime, piperacillin/tazobactam, ertapenem, meropenem, and vancomycin). After ASP implementation, all hospitals saw decreased antibiotic consumption, with the greatest reduction observed in institution B (45%), followed by institution A (29%), D (28%), and C (20%).

The use of ertapenem and meropenem declined in hospital wards, while a decrease in the use of ceftriaxone, cefepime, piperacillin/tazobactam, meropenem, and vancomycin was observed in intensive care units.

In addition, the trend toward an increase of oxacillin-resistant S aureus, ceftriaxone-resistant E coli, and meropenem-resistant P aeruginosa was reversed.

"In our study, we showed that ASPs are a key strategy in tackling the emerging threat of AMR and have a positive impact on antibiotic consumption and resistance," the study authors concluded.
May 2 BMC Infect Dis study

Multimodal stewardship intervention linked to fewer outpatient antibiotics

Originally published by CIDRAP News May 2

A multimodal intervention at primary care practices in a large healthcare system in North Carolina was associated with significant decreases in inappropriate outpatient antibiotic prescribing for upper respiratory tract infections, researchers reported today in Infection Control & Hospital Epidemiology.

The interventions included in the Carolinas Healthcare Outpatient Antimicrobial Stewardship Outpatient Network (CHOSEN) included an antimicrobial stewardship health education campaign for patients and providers, and an interactive reporting dashboard for comparing antibiotic prescribing among providers, practices, and organizational groupings. In the study, researchers evaluated the impact of the initiative before (April 2016 to October 2017) and after (May 2018 to March 2020) it was implanted at 162 ambulatory family medicine, internal medicine, pediatric medicine, and urgent care facilities. The primary outcome of interest was inappropriate antibiotic prescribing for upper respiratory infections by primary-care service line.

Overall, the proportion of encounters with antibiotics inappropriately prescribed fell from 47.5% in the pre-intervention period (286,580 antibiotic prescriptions in 404,248 encounters) to 38.7% during the intervention period (277,177 prescriptions in 832,200 encounters). The relative difference in prescribing rates was –18.5%. Comparison of monthly antibiotic prescribing rates showed that after CHOSEN was implemented, encounters in family medicine showed the largest relative decrease in the proportion of visits with inappropriate antibiotic prescribing (–20.4%), followed by internal medicine (–19.5%), pediatric medicine (–17.2%), and urgent care (–16.6%).

The study authors say the key factors in the success of the CHOSEN intervention included diverse stakeholder engagement in design and implementation, unified messaging and tools across all service lines and practices, senior leadership support, and timely performance feedback and data transparency. The intervention has since been expanded to the emergency division, school-based care practices, and virtual visits.

"Detailed evaluations of changes in prescribing by indications, provider characteristics, practice type, and antibiotic classes, along with their interactions, are planned for future analysis," they wrote.
May 2 Infect Control Hosp Epidemiol study

Follow-up blood cultures tied to longer hospital stays, antibiotic duration

Originally published by CIDRAP News May 2

In a study published late last week in the same journal, researchers found that follow-up blood culture (FUBC) practices for gram-negative bacilli (GNB) bacteremia were associated with prolonged length of hospital stay and duration of antibiotic treatment.

To evaluate the value of routine FUBC for GNB bacteremia, which has been questioned because of the increased risk of false-positive results, researchers conducted a retrospective observational study at four acute-care hospitals in New York City, comparing length of hospital stay, antibiotic duration, and in-hospital mortality in patients with GNB bacteremia who had FUBCs performed and those who didn't. Of the 376 hospitalized patients with GNB bacteremia who met eligibility, 271 (72%) had FUBCs performed.

After propensity score matching, the researcher analyzed 87 pairs of patients with and without FUBCs. The median length of stay was longer among patients with FUBCs than patients without FUBCs (9 days vs 7 days; P = .017). The median duration of antibiotic treatment was also longer among patients with FUBCs than patients without (8 vs 6 days; P = .007). No statistically significant difference was observed in in-hospital mortality between patients with and without an FUBC (odds ratio, 0.37; 95% confidence interval [CI], 0.08 to 1.36).

"In conclusion, current clinical practices of obtaining FUBCs in patients with GNB bacteremia may be associated with prolonged length of stay and duration of in-hospital antimicrobial therapy," the study authors wrote. "Thus, the development of validated selection criteria for identifying subgroups in which FUBCs are likely to have a higher or lower yield is essential to optimizing clinical outcomes and resource utilization."
Apr 29 Infect Control Hosp Epidemiol study