News Scan for Mar 06, 2020

News brief

For third week in a row, US flu activity declines

For the third week in a row, US flu levels dropped last week, the Centers for Disease Control and Prevention (CDC) said today in its weekly FluView report. But the CDC said the flu season continues to be tough on children, as 11 new pediatric flu-related deaths were confirmed.

"Pneumonia and influenza mortality has been low, but 136 influenza-associated deaths in children have been reported so far this season," the CDC said. "This number is higher for the same time period than in every season since reporting began in 2004-05, except for the 2009 pandemic." The pediatric death toll was 144 in the 2018-2019 flu season.

All regions are still reporting elevated flu activity, but rates of outpatient visits for influenza-like illness (ILI) dropped last week, from 5.5% to 5.3%. The percentage of specimens positively identified as influenza also dropped, from 28% to 24.3%.

The number of jurisdictions reporting high ILI activity included New York City, Puerto Rico, and 40 states, down from 43 states last week. The number of jurisdictions reporting regional or widespread flu increased, however, from 48 to 51.

The cumulative hospitalization rate rose from 52.7 to 57.9 per 100,000 population last week. Children ages 0 to 4 years were hospitalized at a rate of 84.9 per 100,000 population, and those 65 or older were hospitalized at a rate of 147.5 per 100,000 population.
Mar 6 CDC FluView report

DRC starts countdown to Ebola outbreak end

In its weekly snapshot on the Democratic Republic of the Congo (DRC) Ebola outbreak yesterday, the World Health Organization (WHO) said the country hasn't reported a new case since Feb 17. The agency added that, on Mar 3, the last patient confirmed with the disease was discharged from an Ebola treatment center.

The WHO said that although the events marked an important milestone, there's still a high risk of recurrence and it's critical to maintain response operations. A country must pass 42 days, which equals two incubation periods, after the last infected person tests negative a second time.

As of Mar 3, the country's overall outbreak total stood at 3,444, which includes 134 probable cases and 2,264 deaths. The WHO praised the international community for covering about half of the $83 million price tag for battling the virus from January through June of this year, but it still needs $40 million in support to continue response activities.

Ebola virus can persist in some body fluids in protected parts of the body, such the eyes or testes, and cases linked to survivors in past outbreaks have triggered new transmission chains. Early in the outbreak, the DRC and its partners established a national program for Ebola survivors. The WHO said 1,160 people have survived the disease, about three fourths of them adults.

In published remarks, Ibrahima Soce Fall, MD, the WHO's assistant director for emergency response, today said the last patient to leave treatment was a woman in Beni. "This is why it's critical to maintain surveillance and rapid response capacities. And that's what we are doing. We're still in full response mode."
Mar 5 WHO update
Mar 6 WHO comments on last case
WHO online Ebola dashboard

Study finds wide variability in antibiotic use at US children's hospitals

A cross-sectional examination of antibiotic use in US children's hospitals has found that, on any given day, more than a third of hospitalized children are receiving an antibiotic, and 1 in 8 are receiving a broad-spectrum antibiotic, US researchers reported today in Infection Control and Hospital Epidemiology.

The study, conducted by researchers from Vanderbilt University Medical Center, looked at antibiotic prescribing at 51 US children's hospitals that participate in the Children's Hospital Association's Pediatric Health Information System. Single-day assessments of antibiotic use among all patients at the hospitals were conducted on May 3, 2017; Aug 2, 2017; Oct 25, 2017; and Jan 31, 2018. The main outcome of interest was receipt of an oral, intravenous, or inhalation antibiotic on the study day.

Of 52,769 total hospitalized children, 19,174 (36.3%) received antibiotics on the study day and 6,575 (12.5%) received broad-spectrum antibiotics. The overall prevalence of antibiotic use varied across hospitals, ranging from 22.3% to 51.9%, and did not appear to be explained by the clinical complexity of patients. Antibiotic use prevalence was 29.2% among medical patients and 47.7% among surgical patients.

Although there was no significant seasonal variation in antibiotic use, regional prevalence varied, ranging from 32.7% in the Midwest to 40.2% in the West (P < .001). Among hospital units, pediatric intensive care unit patients had the highest prevalence of both overall and broad-spectrum antibiotic use, at 58.3% and 26.6%, respectively (P < .001).

The authors of the study say further exploration of the main drivers of inpatient antibiotic use variability could help inform antibiotic stewardship efforts.
Mar 6 Infect Control Hosp Epidemiol abstract

New polio cases reported in Pakistan, Afghanistan, African countries

The latest weekly update from the Global Polio Eradication Initiative (GPEI) today shows six counties reporting new cases, with Afghanistan and Pakistan reporting new wild polio virus type 1 (WPV1) infections and four African nations reporting vaccine-derived cases.

The two WPV1 cases in Afghanistan, one each in Helmand and Zabul provinces, are the country's first cases of 2020. In 2019, Afghanistan reported 29. The four WPV1 infections in Pakistan—one each in Punjab, Khyber Pakhtunkhwa, Sindh, and Balochistan provinces—bring the country's 2020 total to 21, compared with 146 WPV1 cases in all of 2019.

The circulating vaccine-derived polio virus type 2 (cVDPV2) cases reported in Africa include 1 in Angola in Benguela province; 4 in Chad's Ouaddai, Chari Baguirmi, Batha, and Logone Oriental provinces; 2 in the DRC's Lualaba and Tshopo provinces; and 1 case in Ethiopia's Oromyia province. In addition, Angola reported two cVDPV2-positive environmental samples, and Somalia and Ivory Coast each reported one cVDPV2-positive environmental sample. Malaysia reported thee cVDPV2-positive environmental samples.

GPEI says the risk of further cVDPV2 spread across the Lake Chad subregion remains high.

The update also noted that Iran has been removed from the list of outbreak countries after months of consultations and a high level of poliovirus surveillance sensitivity, triggered by the May 2019 isolation of WPV1 in a sewage sample from Sistan and Balochistan province.
Mar 6 GPEI weekly update

WHO study shows uptick in global measles incidence

Global measles incidence increased from 2013 through 2018, and while reasons for the rise are multifactorial and vary by country, inadequate immunization is a key factor, researchers from the World Health Organization (WHO) reported yesterday in the Journal of Infectious Diseases.

The analysis of case-based measles surveillance data reported to the WHO, World Bank country income status, and estimates of national immunization coverage found that a total of 1,495,559 suspected measles cases were reported from 2013 through 2018, and 899,800 were eventually classified as measles. Global annual incidence for 2018 was 46 cases per million persons, the highest annual incidence in the study period. Of the 899,800 measles patients, 45% never received the measles vaccine, 12% received one dose, and 30% had an unknown vaccination history.

Lower- and middle-income countries accounted for 66% of cases, with 70% coming from Nigeria, India, Philippines, Ukraine, and Pakistan. Seventy-seven percent of patients were under the age of 15, with the incidence highest in those under the age of 1. The median age of patients increased by country income status, and in high-income countries with historically stronger vaccination programs, patients had higher median ages.

The analysis also found that high-income countries have many cases in people 15 and older who were unvaccinated or undervaccinated. That's a shift from the prevaccine era, when 95% were immune by age 15, the authors of the study note, and a finding that could help guide measles elimination efforts in those countries.

"To achieve elimination, immunization programs and primary care services must be strengthened, and strategies targeting those outside the age of most routine immunization services also need to be undertaken in some countries to close remaining immunity gaps," the authors wrote. They also urged countries to improve case-based surveillance.
Mar 5 J Infect Dis study

ASP Scan (Weekly) for Mar 06, 2020

News brief

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

Study finds wide variability in antibiotic use at US children's hospitals

The authors of the study say further exploration of the main drivers of inpatient antibiotic use variability could help inform antibiotic stewardship efforts.
Mar 6 Infect Control Hosp Epidemiol abstract

Trial demonstrates effectiveness of highly-resistant TB regimen

Originally published by CIDRAP News Mar 5

The results of the clinical trial that helped pave the way for US Food and Drug Administration (FDA) approval of the new tuberculosis drug pretomanid appeared today in the New England Journal of Medicine.

The phase 3 Nix-TB trial, conducted at three sites in South Africa by a team of British, South African, and US researchers from April 2015 through November 2017, evaluated the safety and efficacy of 26 weeks of combined treatment with oral pretomanid, bedaquiline, and linezolid in patients with extensively drug-resistant tuberculosis (XDR-TB) and multidrug-resistant tuberculosis (MDR-TB) that was not responsive to treatment. The primary end point was incidence of an unfavorable outcome, defined as treatment failure or relapse during follow-up, at 6 months after the end of treatment.

Of the 109 patients enrolled in the trial, 11 (10%) had an unfavorable outcome and 98 patients (90%; 95% confidence interval [CI], 83% to 95%) had a favorable outcome at 6 months after the end of therapy. Among the 71 patients with XDR-TB, 63 (89%; 95% CI, 79% to 95%) had a favorable outcome, and 35 of 38 MDR-TB patients (92%; 95% CI, 79% to 98%) had a favorable outcome. Peripheral neuropathy occurred in 88 patients (81%) and myelosuppression in 52 patients (48%). Both adverse effects were linked to linezolid.

The FDA approved pretomanid—which was developed by the nonprofit TB Alliance, as part of the three-drug combination for patients with XDR- and MDR-TB—in August 2019. The 6-month regimen is significantly shorter than current treatment regimens for highly drug-resistant TB, which last 18 to 24 months, involve as many as eight drugs, and have low cure rates.

"For both individual patients with tuberculosis and national tuberculosis programs, a shorter duration of treatment that is effective is beneficial," the authors of the study wrote.

A secondary end point of treatment failure at 24 months after end of treatment is currently being measured. The authors note that there has been only one additional relapse among the 47 patients who have reached this point in the study.
Mar 5 N Engl J Med study
Aug 14, 2019, CIDRAP News story "FDA approves new drug for highly resistant tuberculosis"

Study: New urine culture order tied to less testing, antibiotic use

Originally published by CIDRAP News Mar 5

The addition of a new order set for urine cultures at five Texas hospitals was associated with decreases in the number of urine cultures performed and days of antibiotic therapy and substantial financial savings, researchers reported today in Infection Control and Hospital Epidemiology.

The study, led by researchers from Baylor College of Medicine, analyzed a newly added order set in the electronic health record at the five hospitals that requires practitioners to choose an indication for the type of urine culture being ordered. The main goal for implementing the new order set was to reduce unnecessary testing and antibiotic treatment in patients with asymptomatic bacteriuria.

The primary outcome was the number of urine cultures performed at the hospitals before and after implementation of the new order set, adjusted for the number of total patient-days. The researchers also assessed antibiotic days of therapy (DOT), catheter-associated urinary tract infection (CAUTI) rate, and the overall financial impact.

The total number of urine cultures at the five hospitals decreased from 32,598 before the new order set (June 2017 through May 2018) to 20,064 after (July 2018 through June 2019). Adjusted per patient-days, urine cultures decreased from 1,175.8 per 10,000 patient-days to 701.4 after the intervention (a 40.4% reduction). Antibiotic DOT for patients with a urinary tract infection fell from 102.5 to 86.9 per 1,000 patient-days (a 15.2% reduction), the CAUTI rate dropped from 11.5 to 9.3 per 10,000 catheter-days, and the estimated yearly savings following the intervention was $535,181.

The authors note that the results suggest the order set is not always being used correctly and that a follow-up quality improvement study may be warranted.
Mar 5 Infect Control Hosp Epidemiol abstract

Review finds high antibiotic use, resistance on African farms

Originally published by CIDRAP News Mar 5

A meta-analysis of previously published research has found high levels of antibiotic use and resistance in food-producing animals and the environment in Africa, a team of Tanzanian researchers reported in Antimicrobial Resistance and Infection Control.

The researchers reviewed and analyzed 176 articles published from 2005 through 2018 and found that the percentage of farms using antibiotics ranged from 77.6% in Nigeria to 100% in Tanazania, Cameroon, Zambia, Ghana, and Egypt. In total, 14 different classes of antibiotics were used, mainly tetracyclines, aminoglycosides, and penicillins. The prevalence of multidrug-resistant (MDR) Escherichia coli isolates in food-animals ranged from 20% in Nigeria to 100% in South Africa, Zimbabwe, and Tunisia, while the prevalence of MDR E coli in environmental samples ranged from 33.3% in South Africa to 100% in Algeria. Environmental E coli exhibited resistance to 16 different antibiotics.

The review also found that none of the countries studied had documented antibiotic use or antibiotic resistance surveillance programs specific for animals or the environment.

The authors of the study say the high levels of antibiotic use and resistance found in animal production systems in Africa is likely to escalate the already high prevalence of antibiotic resistance on the continent.

"This, coupled with weak regulations and antimicrobial resistance surveillance systems in the region is a great concern to the animals, environment and humans as well," they wrote.
Mar 3 Antimicrob Resist Infect Control study

Study: Inappropriate presurgical antibiotic use common in children

Originally published by CIDRAP News Mar 4

A point-prevalence study of 32 US children's hospitals found that prophylactic (preventive) antibiotics were inappropriately given in 33.0% of pediatric surgical patients. The study, published today in Infection Control & Hospital Epidemiology, was led by members of the SHARPS Collaborative based at Washington University in St. Louis.

The researchers collected chart data from the hospitals' electronic medical records from September 2016 to December 2017, identifying 1,324 children receiving antibiotics (cefazolin, clindamycin, vancomycin, cefoxitin, and piperacillin/tazobactam) for surgical prophylaxis.

Overall, 485 prophylactic antibiotics were classified as inappropriate because of administration longer than 24 hours (n = 387, 79.8%), no indication for prophylaxis (32, 6.6%), and the use of antibiotics that were too broad spectrum (29, 6.0%).

National guidelines give procedure-specific recommendations for antibiotic prophylaxis, including drug and dosing, to prevent surgical-site infections. "The 2017 Centers for Disease Control and Prevention (CDC) guideline recommends only a single dose of perioperative prophylaxis for clean and clean-contaminated cases," the authors wrote. "Despite these guidelines, inappropriate surgical prophylaxis use continues to be common."

Inappropriate surgical prophylaxis was highest in otolaryngologic patients (62.7%; 95% CI, 52.6% to 72.1%), cosmetic or reconstructive surgery patients (40.7%; 95% CI, 30.0% to 52.2%), and neurosurgery patients (40.3%; 95% CI, 34.2% to 46.6%).

Of the 485 prescriptions deemed inappropriate, 258 (53.2%) would not have been routinely reviewed by the hospitals' antimicrobial surgical programs, according to the authors. The hospitals' use of inappropriate prophylaxis varied significantly, from 0.0% to 62.8%.

The study likely underestimated the percentages of inappropriate use, considering the new CDC recommendation of no antibiotics for low-risk procedures, the investigators said. They called for more studies to better estimate the inappropriate prophylaxis rate, identify contributing factors, and determine the best ways to optimize prophylactic use of antibiotics.
Mar 4 Infect Control Hosp Epidemiol study

Study: De-escalation rates low in hospitalized pneumonia patients

Originally published by CIDRAP News Mar 4

An analysis of adults with pneumonia at 164 US hospitals has found that less than 15% of those treated with broad-spectrum antibiotics had their coverage de-escalated by day 4, researchers reported today in Clinical Infectious Diseases.

The study, conducted by researchers with Cleveland Clinic and the University of Massachusetts Medical School, aimed to assess de-escalation practices in a cohort of hospitalized pneumonia patients after negative cultures for methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa.

New guidelines from the American Thoracic Society and the Infectious Disease Society of America recommend switching from broad-spectrum to narrower-spectrum antibiotics at 48 hours if microbial cultures do not reveal these multidrug-resistant pathogens and the patient is improving. The researchers wanted to know to what degree hospitals will have to change their practices to adhere to this recommendation.

The study’s primary outcome was de-escalation on hospital day 4. The researchers also looked at the association of de-escalation with all-cause mortality, transfer to an intensive care unit (ICU), length of hospital stay, and costs.

Of the 14,170 pneumonia patients treated with one anti-MRSA and at least one anti-pseudomonal antibiotic from 2010 through 2015, both antibiotics were de-escalated in 1,924 patients (13%) by day 4. Hospital de-escalation rates ranged from 2% to 35% and varied across regions, but de-escalation was more common in large teaching hospitals.

At hospitals in the top quartile of de-escalation, rates of de-escalation were less than 50%—even in patients at lowest risk for death. In propensity-adjusted analysis, patients with de-escalation had lower odds of subsequent transfer to the ICU (adjusted odds ratio, 0.38; 95% CI, 0.18 to 0.79), shorter hospital stays (adjusted ratio of means, 0.76; 95% CI, 0.75 to 0.78), and costs (adjusted ratio of means, 0.74; 95% CI, 0.72 to 0.76).

The authors of the study concluded that, in order to adhere to the new guidelines, physicians will need to substantially change their response to negative cultures for most non-critically ill patients. "Since antibiotics are not benign, and antimicrobial stewardship is an important priority, hospital antibiotic stewardship programs should emphasize de-escalation following negative cultures as an opportunity to reduce exposure to broad-spectrum antibiotics, improving both antimicrobial stewardship and medication safety by substitution of lower-toxicity agents," they wrote.
Mar 4 Clin Infect Dis abstract

Stewardship intervention tied to improved prescribing for kids' UTIs

Originally published by CIDRAP News Mar 3

A study conducted in a large healthcare system in Colorado found that a multicomponent intervention was associated with increased use of first-line antibiotics among children with uncomplicated urinary tract infections (UTIs), researchers reported today in Pediatrics.

The intervention at Kaiser Permanente Colorado (KPCO), instituted in April 2017 after a gap analysis identified frequent use of broad-spectrum antibiotics in the treatment of pediatric UTIs, involved several educational and process improvements aimed at key drivers of prescribing practices. In addition to developing new local clinical practice guidelines for pediatric UTIs that recommended the narrow-spectrum antibiotics cephalexin or sulfamethoxazole and trimethoprim as initial therapy, KPCO conducted a 2-hour educational session on the new guidelines, added them to a searchable online repository, and added a pediatric UTI algorithm and order set to the electronic health record.

To determine the impact of the intervention on prescribing for pediatric UTIs, KPCO researchers conducted an interrupted time-series analysis to compare prescribing before and after the implementation date (January 2014 to September 2018).

Among the 2,142 outpatient UTIs identified (1,636 pre-intervention and 506 post-intervention), after adjusting for clustering of UTIs within treating clinicians, the analysis found that the proportion of UTIs treated with first-line antibiotics increased from 43.4% pre-intervention to 62.4% post-intervention (P < .0001). Use of cephalexin increased from 28.9% to 53% (P < .0001), while use of the second-line antibiotic cefexime decreased from 17.3% to 2.6% (P < .0001). The changes were sustained for 1 year after the intervention. Researchers also observed a decrease in the average antibiotic treatment duration.

The authors note that the design of the study prevents them from inferring that the intervention caused the change in prescribing, and that it's not possible to determine which components were associated with the improvements.

They conclude, "Despite the limitations inherent in a nonexperimental study design, the methods and interventions developed in the current study may be informative to other learning health systems and other content areas when conducting organization-wide quality improvement initiatives."
Mar 3 Pediatrics abstract

Funding for new drug-resistant malaria treatments announced

Originally published by CIDRAP News Mar 3

The European & Developing Countries Clinical Trials Partnership (EDCTP) announced today that it will invest €21.9 million (US $24.5 million) to combat drug-resistant malaria in Africa and address other areas of urgent need in malaria treatment.

The EDCTP grant, awarded to the new PAMAfrica consortium led by the Medicines for Malaria Venture (MMV), will support a clinical trial for new combinations of compounds for treating complicated and uncomplicated malaria that fully active against artemisinin-resistant strains. Two other trials will assess a rapid-acting treatment for severe malaria and a new malaria treatment for malnourished babies.

MMV, drug maker Novartis, and other partners will provide an additional €22 million (US $24.6 million) over 5 years.

"Antimalarial drug resistance, originally seen in Southeast Asia, is being reported in Africa and may threaten current treatments," MMV Chief Scientific Officer Timothy Wells, PhD, said in a joint news release from EDCTP, MMV, and Novartis. "It is important to have new therapies that are active against this emerging threat of resistance."

The PAMAfrica consortium includes Novartis and research organizations from Burkina Faso, Gabon, Germany, Mozambique, Spain, and Uganda.
Mar 3 EDCTP, MMV, Novartis news release

Study: Delaying antibiotics OK in mild to moderate bacterial infections

Originally published by CIDRAP News Mar 2

Withholding antibiotic therapy until diagnosis of bacterial infections (ie, 4 to 8 hours) seems acceptable in patients other than those who may have septic shock or bacterial meningitis and may be a sound antibiotic stewardship approach, according to a meta-analysis of 60 studies published in Clinical Microbiology and Infection.

European researchers explored the effect of time to antibiotic initiation on clinical outcomes in patients in emergency departments (EDs) who had bacterial infections of different severities and sources.

Initiating antibiotic treatment quickly—within 3 hours—is considered crucial in patients with severe bacterial infections such as septic shock and meningitis, but the researchers sought to better understand which patients could withstand delayed treatment in order to improve antibiotic stewardship. Many patients in the ED have common community-acquired infections caused by bacteria sensitive to narrow-spectrum antibiotics, the researchers wrote.

"We conclude that the literature supports prompt administration of effective antibiotics for septic shock and meningitis, but there is no clear evidence showing that a delayed start of therapy is associated with worse outcome for less severe infectious syndromes," the investigators said. "This approach promotes the use of ecologically favourable antibiotics in the ED, reducing the risks of side effects and selection of resistance."

The researchers, who found few studies in the literature on mild to moderate infections, called for stronger evidence from prospective clinical trials.
Feb 28 Clin Microbiol Infect abstract

Combo antibiotic for resistant UTIs shows promise in phase 3 trial

Originally published by CIDRAP News Mar 2

French biopharmaceutical company Allecra Therapeutics announced last week that its investigational combination drug Exblifep met the US FDA and European Medicines Agency's pre-specified primary end point and demonstrated superiority over piperacillin-tazobactam in a phase 3 trial of patients who had complicated urinary tract infections (cUTIs).

The topline results from the phase 3 ALLIUM trial showed that the overall success of Exblifep in cUTI patients was 79.1%, compared with 58.9% for piperacillin-tazobactam. The primary end point in the randomized trial was a combination of clinical cure and microbiologic eradication. The drug was also well tolerated, with 4.3% of patients reporting adverse events, compared with 3.7% of piperacillin-tazobactam patients.

Exblifep is a combination of the novel beta-lactamase inhibitor enmetazobactam with the fourth-generation cephalosporin cefepime. It's intended for treatment of infections caused by multidrug-resistant strains of Enterobacteriaceae and Pseudomonas aeruginosa.

"The superiority demonstrated in the primary endpoint, at test of cure, combined with a comparable safety profile to that of well tolerated and widely used piperacillin-tazobactam support the potential use of cefepime-enmetazobactam as a new empiric and carbapenem- sparing treatment for multi-drug resistant Gram-negative infections," Allecra Chief Medical Officer Patrick Velicitat, MD, said in a company press release.
Feb 25 Allecra Therapeutics press release