Stewardship / Resistance Scan for Aug 07, 2020

News brief

Survey finds widespread broad-spectrum antibiotic use in COVID patients

A web-based survey of physicians in 23 countries indicates widespread broad-spectrum antibiotic use in COVID-19 patients, an international team of researchers reported today in the Journal of Antimicrobial Chemotherapy.

The 16-question survey, which was completed by 166 physicians at 82 hospitals, asked respondents about what influenced their decision to provide antibiotic treatment to COVID-19 patients, the local antibiotic guidelines in relation to COVID-19, the antibiotics most commonly chosen for empiric treatment, and duration of therapy. The questions on the decision for antibiotic therapy used a 5-point grading scale (1 = least important and 5 = most important), while specific pathogen coverage used a 4-point (1 = strongly disagree and 4 = strongly agree) bi-modal scale.

Most of the respondents worked in university-affiliated hospitals (71.7%), over three quarters (78.2%) were involved in direct care of COVID-19 patients, and more than half (50.3%) were specialists in infectious diseases.

The existence of local guidelines for antibiotic use in COVID-19 patients were reported by 61.8% of participants, and 82.9% said the guidelines did not differ from those for community-acquired pneumonia. Clinical presentation was recognized as the most important reason for the start of antibiotics (mean score = 4.07; standard deviation [SD] = 1.095). On the bi-modal 4-point score, most respondents rated as the highest the need for coverage of atypical pathogens (mean score = 2.8; SD = 0.99), followed by Staphylococcus aureus (mean score = 2.67; SD = 1.05) and Pseudomonas aeruginosa (mean score = 2.13; SD = 1.07).

Less than one third of participants (29.1%) said they chose not to prescribe any antibiotic for patients on the ward, while 52.4% reported prescribing a combination of beta-lactams and macrolides or fluoroquinolones. For patients in the intensive care unit, 63% of respondents prescribed piperacillin/tazobactam. The mean reported duration of antibiotic treatment was 7.12 days (SD = 2.44).

"This study is a real-time and first-hand picture of what is going on in antibiotic prescribing in COVID-19 patients and a stimulus for much-needed research in this field," the authors wrote.
Aug 7 J Antimicrob Chemother study

 

Scientists in Taiwan detect MCR genes in human Klebsiella isolates

Scientists in Taiwan have detected colistin-resistance genes in human Klebsiella pneumoniae isolates, according to research today in Clinical Microbiology and Infection.

In a letter to the editor, scientists from Taiwan's National Institute of Infectious Diseases and Vaccinology report the detection of MCR-1, MCR-3, and MCR-8 genes in six clinical isolates from elderly, hospitalized patients collected by the Taiwan Surveillance of Antimicrobial Resistance program in 2018. Sanger sequencing revealed they were MCR-1.1, MCR-3.5, and MCR-8.2. All isolates were resistant to multiple antibiotics but susceptible to carbapenems and amikacin.

Whole-genome sequencing indicated that the plasmids carrying the genes are similar to those that have been found in different species of Enterobacteriaceae in animals and humans in Taiwan, and carried several other antibiotic resistance genes.

The authors of the study note that while MCR genes have been detected in Escherichia coli from humans, animals, and the environment in several countries, there have been few reports of MCR genes in K pneumoniae.

"In conclusion, plasmids carrying either mcr-1mcr-3, or mcr-8 have spread to several clinical K. pneumoniae isolates from different regions of Taiwan," the authors wrote. "Their transferability, persistence, potential to spread, ongoing evolution and concomitant multiple antimicrobial resistance genes necessitate continuous monitoring."
Aug 7 Clin Microbiol Infect abstract

News Scan for Aug 07, 2020

News brief

Asymptomatic and symptomatic COVID-19 patients show similar shedding patterns

Patients with confirmed asymptomatic COVID-19 infections shed virus at similar levels to those who are experiencing symptoms, underscoring the importance of public health actions to control the spread of the virus, researchers from South Korea reported yesterday in JAMA Internal Medicine.

Their cohort study involved 303 patients who were isolated at a community treatment center in Cheonan in March. Health workers carefully tracked patients' symptoms during isolation. Among the group, 193 (63.7%) had symptoms at the start of isolation and 21 (19.1%) of the asymptomatic patients went on the develop symptoms. Also, the health workers conducted reverse transcription polymerase chain reaction (RT-PCR) tests on lower and upper respiratory tract samples on multiple days at doctor discretion.

Cycle threshold values for SARS-CoV-2 were similar for both asymptomatic and symptomatic patients. Viral shedding lasted about 17 days in asymptomatic patients and 19.5 days for symptomatic and presymptomatic patients.

Researchers noted that the testing method didn't gauge infectiousness but said people with confirmed infections should be isolated regardless of symptoms, and they emphasized that symptom-based screening may substantially underreport cases.
Aug 6 JAMA Intern Med abstract

 

Ebola infects 3 more in latest DRC outbreak, 77 total, with 33 deaths

Three more Ebola cases have been confirmed in the Democratic Republic of Congo (DRC) Equateur province outbreak, raising the total to 77, the World Health Organization (WHO) African regional office said today on Twitter.

One more death was reported, lifting the fatality count to 33. It's unclear if the death involved one of the latest confirmed patients.

The outbreak, the country's 11th involving Ebola, was first detected in early June and is occurring in the same area as a 2018 outbreak that lasted a few months and totaled 54 cases, 33 of them fatal. The WHO said the latest outbreak is concerning, because it is occurring across a wide geographic area with some of the illnesses occurring in Mbandaka, the provincial capital that has travel connections to Kinshasa and neighboring countries.

In the African regional office's weekly health emergencies and outbreaks report, the WHO said the outbreak response is challenged by a lack of resources for investigations in Mbandaka and case management in hard-to-reach places. It noted that the treatment facility in Bikoro is full, and that six confirmed cases in four different locations remain in the community. So far, more than 18,800 people have been vaccinated.
Aug 7 WHO African regional office tweet
Aug 6 WHO African regional office weekly report

 

Four countries report more polio cases

Four countries reported more polio cases last week, including Pakistan, Cameroon, Chad, and the Democratic Republic of Congo (DRC), according to the latest weekly update from the Global Polio Eradication Initiative (GPEI).

Pakistan reported three more wild poliovirus type 1 (WPV1) cases, one each from Khyber Pakhtoon, Punjab, and Sindh provinces, raising the total for the year to 63.

In Africa, Cameroon reported one circulating vaccine-derived poliovirus type 2 (cVDPV2) case, its fourth ever. The case was detected in Est province, marking its third polio case of 2020.

Chad reported three more cVDPV2 cases, one each from Ndjamena, Sila, and Tandjile provinces, raising the country's number for 2020 to 62 from two different outbreaks. One of them is linked to Nigeria's Jigawa state outbreak.

Meanwhile, the DRC reported two more cVDPV2 cases, one from Kwango province and one from Kwilu province, putting the country's total for the year at 22.
Aug 7 GPEI weekly update

 

Avian flu outbreaks hit poultry in Australia, Russia, and Vietnam

Three countries reported new highly pathogenic avian influenza outbreaks, which involved three different strains: H7N7, H5N8, and H5N1, according to the latest notifications from the World Organization for Animal Health (OIE).

Australia, which recently reported H7N7 on a layer farm in Lethbridge in Victoria, reported the virus at a second layer farm in the same area. The latest outbreak began on Aug 5, killing 190 of 355,000 susceptible birds, which included free-range, caged, and barn-based poultry. Depopulation is under way. So far the source isn't known, but contact with wild species may have played a role.

Elsewhere, Russia reported two outbreaks involving H5N8 in backyard poultry. The investigation also turned up the virus in a wild duck found at a lake near the village right before the outbreaks began. The virus struck flocks at two different sites in Chelyabinskaya oblast in events that began on July 28. The virus killed 129 of 186 susceptible birds, and the birds—including chicken, ducks, and geese—were slated for culling. Russia reported its last outbreak involving the strain in 2005.

And in Asia, Vietnam reported a new outbreak involving H5N1, which began on July 23 and affected village birds in Tra Vinh province, killing 200 of 1,040 poultry. The surviving birds were destroyed to curb the spread of the virus. Vietnam reported its last outbreak in early June.
Aug 7 OIE report on H7N7 in Australia
Aug 4 OIE report on H5N8 in Russia
Aug 7 OIE report on H5N1 in Vietnam

ASP Scan (Weekly) for Aug 07, 2020

News brief

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

Survey finds widespread broad-spectrum antibiotic use in COVID patients

A web-based survey of physicians in 23 countries indicates widespread broad-spectrum antibiotic use in COVID-19 patients, an international team of researchers reported today in the Journal of Antimicrobial Chemotherapy.

The 16-question survey, which was completed by 166 physicians at 82 hospitals, asked respondents about what influenced their decision to provide antibiotic treatment to COVID-19 patients, the local antibiotic guidelines in relation to COVID-19, the antibiotics most commonly chosen for empiric treatment, and duration of therapy. The questions on the decision for antibiotic therapy used a 5-point grading scale (1 = least important and 5 = most important), while specific pathogen coverage used a 4-point (1 = strongly disagree and 4 = strongly agree) bi-modal scale.

Most of the respondents worked in university-affiliated hospitals (71.7%), over three quarters (78.2%) were involved in direct care of COVID-19 patients, and more than half (50.3%) were specialists in infectious diseases.

The existence of local guidelines for antibiotic use in COVID-19 patients were reported by 61.8% of participants, and 82.9% said the guidelines did not differ from those for community-acquired pneumonia. Clinical presentation was recognized as the most important reason for the start of antibiotics (mean score = 4.07; standard deviation [SD] = 1.095). On the bi-modal 4-point score, most respondents rated as the highest the need for coverage of atypical pathogens (mean score = 2.8; SD = 0.99), followed by Staphylococcus aureus (mean score = 2.67; SD = 1.05) and Pseudomonas aeruginosa (mean score = 2.13; SD = 1.07).

Less than one third of participants (29.1%) said they chose not to prescribe any antibiotic for patients on the ward, while 52.4% reported prescribing a combination of beta-lactams and macrolides or fluoroquinolones. For patients in the intensive care unit, 63% of respondents prescribed piperacillin/tazobactam. The mean reported duration of antibiotic treatment was 7.12 days (SD = 2.44).

"This study is a real-time and first-hand picture of what is going on in antibiotic prescribing in COVID-19 patients and a stimulus for much-needed research in this field," the authors wrote.
Aug 7 J Antimicrob Chemother study

 

Scientists in Taiwan detect MCR genes in human Klebsiella isolates

Scientists in Taiwan have detected colistin-resistance genes in human Klebsiella pneumoniae isolates, according to research today in Clinical Microbiology and Infection.

In a letter to the editor, scientists from Taiwan's National Institute of Infectious Diseases and Vaccinology report the detection of MCR-1, MCR-3, and MCR-8 genes in six clinical isolates from elderly, hospitalized patients collected by the Taiwan Surveillance of Antimicrobial Resistance program in 2018. Sanger sequencing revealed they were MCR-1.1, MCR-3.5, and MCR-8.2. All isolates were resistant to multiple antibiotics but susceptible to carbapenems and amikacin.

Whole-genome sequencing indicated that the plasmids carrying the genes are similar to those that have been found in different species of Enterobacteriaceae in animals and humans in Taiwan, and carried several other antibiotic resistance genes.

The authors of the study note that while MCR genes have been detected in Escherichia coli from humans, animals, and the environment in several countries, there have been few reports of MCR genes in K pneumoniae.

"In conclusion, plasmids carrying either mcr-1mcr-3, or mcr-8 have spread to several clinical K. pneumoniae isolates from different regions of Taiwan," the authors wrote. "Their transferability, persistence, potential to spread, ongoing evolution and concomitant multiple antimicrobial resistance genes necessitate continuous monitoring."
Aug 7 Clin Microbiol Infect abstract

 

Penicillin allergy delabeling linked to more appropriate antibiotic use

Originally published by CIDRAP News Aug 6

A combination of direct delabeling and oral penicillin challenge in patients with reported penicillin allergies resulted in improved antibiotic prescribing at two Australian hospitals, Australian researchers reported yesterday in Clinical Infectious Diseases.

In the study, patients with a reported penicillin allergy were offered a single-dose oral penicillin challenge or direct removal of the penicillin allergy label based on their history. The primary end point of the study was the proportion of patients delabeled. The secondary end points were the use of narrow-spectrum penicillins, restricted antibiotics, and appropriate antibiotics in delabeled patients compared with both the pre-testing period and non-delabeled patients.

During the study period (January through August 2019), investigators at the two hospitals assessed 1,779 patients reporting 2,135 allergies and found 1,272 with a penicillin allergy. Of the 1,225 patients analyzed, 355 were delabeled: 161 by direct delabeling and 194 by oral challenge. Ninety-seven percent (194 of 200) of patients were negative upon oral challenge.

In the delabeled patients, the investigators observed an increase in narrow-spectrum penicillin usage (adjusted odds ratio [OR], 10.51; 95% confidence interval [CI], 5.39 to 20.48), improved antibiotic prescribing (adjusted OR, 2.13; 95% CI, 1.45 to 2.13), and a reduction in restricted antibiotic usage (adjusted OR, 0.38; 95% CI, 0.27 to 0.54) in the post-testing period compared with the pre-testing period.

In the propensity score analysis, they noted an increase in narrow-spectrum penicillins (OR, 10.89; 95% CI, 5.09 to 23.31) and beta-lactam/beta-lactamase inhibitors (OR, 6.68; 95% CI, 3.94 to 11.35) and a reduction in restricted antibiotic use (OR, 0.52; 95% CI, 0.36 to 0.74) and inappropriate prescriptions (relative risk ratio, 0.43; 95% CI, 0.26 to 0.72) in the delabeled group compared with the patients who retained their allergy label.

"Our study in hospitalized inpatients demonstrated, at an individual and propensity-adjusted level, a dramatic increase in appropriate and narrow-spectrum penicillin use in those delabeled, without an increase in total antibiotic consumption," the authors of the study wrote. "The strategy provided here should enable clinicians globally to implement and incorporate similar antibiotic allergy delabeling programs into their health service as a novel medication safety and AMS [antimicrobial stewardship] intervention with minimal additional resources."
Aug 5 Clin Infect Dis abstract

 

German data show significant drop in pediatric antibiotic prescribing

Originally published by CIDRAP News Aug 6

An analysis of national outpatient antibiotic prescribing data in Germany shows a significant reduction in antibiotic prescribing for children and adolescents over the last decade, German researchers reported today in Eurosurveillance.

In a cross-sectional analysis of annual antibiotic prescription rates among insured children ages 0 to 14 from 2010 through 2018, researchers from Germany's Central Research Institute of Ambulatory Health Care found that the age-standardized antibiotic prescription rate fell by 43%, from 746 prescriptions per 1,000 people in 2010 to 428 per 1,000 in 2018 (P < 0.001). The highest reductions were observed in children ages 0 to 1 (49%) and 2 to 5 (44%). The 2-to-5 age-group had the highest prescription rate, with 683 prescriptions per 1,000 people in 2018, while children ages 10 to 14 had the lowest, with 273 prescriptions per 1,000. Rates declined strongly in all regions of the country.

With the exception of penicillins with a beta-lactamase inhibitor, prescription rates of all antibiotic subgroups decreased markedly. But second- and third-generation cephalosporins accounted for 32% of prescribed antibiotics, which is high compared with other European countries.

The authors of the study say the reductions may have been driven by rising public awareness of antibiotic resistance in Germany, an increasingly critical view of the use of antibiotics, and an increasing focus on judicious prescribing among German physicians. But they also note that there is room for improvement, as the antibiotic prescribing rate in German children remains roughly 70% higher than it is in Norway and the Netherlands.
Aug 6 Eurosurveill study

 

NIH awards $19 million for new gonorrhea diagnostic test

Originally published by CIDRAP News Aug 5

The National Institutes of Health (NIH) today awarded $19 million for a new diagnostic test that can detect gonorrhea in under 30 minutes—and determine if the infection is susceptible to a single-dose antibiotic. The test is made by Visby Medical, Inc.

The award is part of the NIH's Antimicrobial Resistance Diagnostic Challenge, which aims to improve diagnostics for the more than 2.8 million antibiotic-resistant infections in the United States each year. Those infections kill more than 35,000 people annually, the NIH said in a news release.

"Challenge prizes spur innovation, and we saw many innovative concepts throughout this competition. I want to congratulate Visby Medical for their winning technology, which could help reduce the unnecessary use of antibiotics, a major driver of antimicrobial resistance," said NIH Director Francis S. Collins, MD, PhD.

Visby's device is a palm-sized, disposable test that allows clinicians to treat patients immediately with antibiotics likely to cure their infections.

Gonorrhea, one of the most common sexually transmitted infections in the world, has grown increasingly resistant to antibiotics in recent years. According to the Centers for Disease Control and Prevention, there were more than 580,000 US gonorrhea cases in 2018, a 63% increase from 2014.
Aug 5 NIH press release 

 

Analysis finds Staph bacteremia mortality rises sharply after 2 days

Originally published by CIDRAP News Aug 6

A secondary analysis of patients with S aureus bacteremia suggests that the best cutoff to predict mortality is a duration of 2 days despite active antibiotic therapy, an international team of researchers reported yesterday in The Lancet Infectious Diseases.

In the largest study to date evaluating the risk associated with increasing duration of S aureusbacteremia, researchers with the International Staphylococcus aureus collaboration study group and European Society of Clinical Microbiology and Infectious Diseases Study Group for Bloodstream Infections, Endocarditis and Sepsis assessed outcomes on adults hospitalized for S aureusbacteremia at 17 European hospitals from January 2013 through April 2015. The primary outcome was 90-day mortality. The duration of bacteremia was defined as bacteremic days under active antibiotic therapy, counting the first day as 1.

Of the 1,588 patients assessed for eligibility, 987 were included in the analysis, with a median age of 65 years. Overall, death within 90 days occurred in 273 patients (28%). The 315 patients (32%) with more than 1 day of bacteremia had higher Charlson comorbidity index and sequential organ failure assessment scores and a longer interval from first symptom to first blood culture.

Analysis of the primary outcome found that crude mortality increased from 22% (148 of 672) with 1 day of bacteremia to 39% (85 of 218) with 2 to 4 days, 43% (30 of 69) with 5 to 7 days, and 36% (10 of 28) with more than 7 days of bacteremia. In addition, metastatic infections developed in 6% of patients (39 of 672) with 1 day of bacteremia compared with 13% of patients (40 of 315) who had bacteremia for at least 2 days. The second day of bacteremia had the highest hazard ratio and earliest cutoff significantly associated with mortality (adjusted hazard ratio, 1.93; 95% confidence interval, 1.51 to 2.46; P < 0.0001).

The findings are noteworthy because persistent bacteremia is poorly defined, and applied cutoff durations to define it vary from 2 days to more than 7 days.

"We believe that the second day of bacteraemia after starting active antibiotic therapy represents the most meaningful clinical cutoff to define persistent bacteraemia and to consider the implementation of additional diagnostic and therapeutic measures to reduce the high mortality in S aureus bacteraemia," the authors wrote.
Aug 4 Lancet Infect Dis abstract

 

Artemisinin resistance mutations detected in Rwandan malaria parasites

Originally published by CIDRAP News Aug 5

Researchers from Rwanda, France, and the United States have detected the emergence and expansion of an indigenous lineage of artemisinin resistant (ART-R) malaria parasites in Rwanda, according to a new study in Nature Medicine.

The researchers conducted an in-depth genetic analysis of Plasmodium falciparum samples collected at six Rwandan sites from 2012 to 2015 and performed gene-editing studies to evaluate the in vitro resistance phenotypes of parasites harboring mutations in the propeller domain of the Pfkelch13 gene, which can mediate artemisinin resistance. Resistance to artemisinin-based combination therapy (ACT) for malaria is widespread in Southeast Asia, particularly in the Greater Mekong Subregion, and has also been identified in Latin America, but to date has not been reported in Africa.

The scientists performed Pfkelch13 propeller domain genotyping on 534 pretreatment samples collected from patients who participated in clinical trials to assess the efficacy of artemether-lumefantrine and dihydroartemisinin-piperaquine for treating uncomplicated P falciparum malaria. While the cure rates in both treatment arms of these trials were above 95%, a Pfkelch13 R561H mutation—previously associated with delayed parasite clearance following ART monotherapy or ACT treatment in the Greater Mekong Subregion—was observed in 19 of 257 samples (7.4%) at the trial site in Masaka.

Gene editing using CRISPR-Cas9 confirmed the Pfkelch13 R561H mutation conferred artemisinin resistance in vitro, and phylogenetic analysis showed a clear separation between the Pfkelch13 R561H mutants found in Rwanda and those found in Southeast Asia and Latin America.

"This study clearly shows the early warning signs of ART-R in Rwanda," the authors wrote. "Genetic analyses indicate that Rwandan Pfkelch13 561H mutants are the product of de novo local emergence."

The authors add that if the spread of ART-R cannot be contained in Rwanda and neighboring countries, a rise in resistance to ACT partner drugs could result, leading to high treatment failure.
Aug 3 Nat Med study

 

Online program tied to less inappropriate antibiotic use for pediatric ARTIs

Originally published by CIDRAP News Aug 3

As many as one third of outpatient antibiotic prescriptions written for pediatric acute respiratory tract infections (ARTIs) are inappropriate, but a distance learning course consisting of three program modules aimed at family clinicians was associated with a 7% drop in overall antibiotic prescribing rates for all ARTI visits, according to a study published today in Pediatrics.

The study took place in 19 pediatric practices in 2015 to 2019, and visits for acute otitis media, bronchitis, pharyngitis, sinusitis, and upper respiratory infection for children 6 months to 11 years without recent antibiotic use were included.

Clinicians were assigned to use the Dialogue Around Respiratory Illness Treatment (DART) Quality Improvement Program—an evidence-based online communication skills and antibiotic prescribing education training program developed by the authors. The program focuses on how clinicians can communicate their decision not to prescribe antibiotics to a patient's family, as well as more generally on antibiotic overuse.

A total of 72,723 ARTI visits by 29,762 patients were included in the study. Antibiotic prescribing declined by 7% 2 to 8 months after physicians completed DART. The program resulted in sustained reductions in antibiotic prescribing during viral ARTI visits and sustained decreases in second-line antibiotic prescribing during streptococcal pharyngitis and sinusitis visits, but it did not result in sustained reductions in antibiotic prescribing during all pharyngitis visits, the authors said.

In an accompanying commentary, US experts not involved in the study said the DART program tackles one of the biggest hurdles in pediatric antibiotic overuse: parents. "The reasons for inappropriate antibiotic prescribing in ambulatory pediatrics are multifactorial, including patient pressures and demand, actual or perceived parental satisfaction, provider knowledge, and provider time constraints," they said. "An effective approach to decreasing inappropriate antibiotic prescribing must therefore address each of these contributing factors."
Aug 3 Pediatrics study
Aug 3 Pediatrics commentary

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