Stewardship / Resistance Scan for Jan 11, 2021

News brief

High burden, increased resistance noted in invasive E coli infections

A new study led by researchers with Pfizer shows a substantial burden of extraintestinal invasive Escherichia coli infections (IEIs) in the United States, with increasing resistance to extended-spectrum cephalosporins.

In the study, published late last week in Clinical Infectious Diseases, researchers examined data from the Premier Healthcare Database, looking at all adult inpatient and hospital-based outpatient visits with continuous microbiology data submission from Jan 1, 2009, through Dec 31, 2016, for IEI events, which were defined as having a positive E coli culture from blood, urine, cerebrospinal fluid, or other normally sterile sites. The main outcome variables included count and prevalence of IEI events, risk of IEI occurrence, and the antibiotic resistance pattern of related IEI isolates.

The researchers analyzed more than 144.9 million hospital visits among more than 37.2 million patients during the study period and found that 71,909 IEI events occurred among 67,583 patients, corresponding to an IEI prevalence of 0.50 events per 1,000 visits and 1.82/1,000 patients. Among IEI patients identified, 58,168 (86%) were inpatients.

Prevalence among adults increased with age, ranging from 0.23/1,000 among patients 18 to 49 years to 1.3/1,000 among those 85 and over. Overall, 26.9/1,000 patients with IEI had a recurrent IEI in the 12 months following their initial infection. Urosepsis was the most common IEI, accounting for 66% of all infections, followed by bloodstream infections (22.1%).

Among all IEI cases with antibiotic susceptibility testing, 28.22% were resistant to fluoroquinolones, 9.18% were resistant to extended-spectrum cephalosporins, and 0.14% were resistant to carbapenems. Resistance to extended-spectrum cephalosporins increased from 5.46% to 12.97% during the study period.

"This high burden and acuity indicate that additional strategies for prevention are needed for IEI," the authors of the study wrote. "More research is needed to find effective ways to prevent these potentially deadly infections."
Jan 9 Clin Infect Dis study

Trial: Oral antibiotics alone not enough for uncomplicated appendicitis

The results of a randomized clinical trial involving adults with uncomplicated appendicitis show that treatment with oral antibiotics alone met the prespecified threshold for treatment success but failed to demonstrate noninferiority to intravenous (IV) antibiotics followed by oral antibiotics, researchers in Finland reported today in JAMA.

The open-label, noninferiority randomized trial was conducted from April 2017 to November 2018 in nine Finnish hospitals and included 599 patients with computed tomography–confirmed uncomplicated acute appendicitis. The purpose of the trial was to see whether oral antibiotics, which can be taken on an outpatient basis, could be an alternative to a combination of oral and IV antibiotics, which require hospital administration to ensure patient safety. An oral antibiotic regimen would shorten hospital stays and could enhance cost savings and patient satisfaction.

During the trial, a total of 295 patients received oral moxifloxacin for 7 days and 288 received IV ertapenem for 2 days followed by oral levofloxacin for 5 days. The primary end point was treatment success of greater than 65% for both groups. Treatment success was defined as hospital discharge without surgery and recurrent appendicitis during 1-year follow-up. The noninferiority margin was -6%.

The results showed that the treatment success rate was 70.2% among patients in the oral antibiotics group and 73.8% for patients treated with IV followed by oral antibiotics, for a difference of -3.6%. The confidence interval of the difference (-9.7%) exceeded the predefined noninferiority definition of a lower limit of -6%.

Despite the results, the authors of the study suggest the treatment success rate for oral antibiotics be considered during the COVID-19 pandemic in order to free up hospital resources at a time of bed capacity shortages and to reduce the risk of COVID-19 exposure for patients with uncomplicated appendicitis.

In an accompanying commentary, two experts with Nationwide Children's Hospital in Columbus, Ohio, wrote, "Additional studies related to nonoperative management of appendicitis no longer need to focus on the effectiveness of the treatment, but on further defining optimal treatment strategies. This includes antibiotic duration, mode of antibiotic delivery, the need for in-patient observation, and how to disseminate and promote implementation of nonoperative treatment choices across various practice types and patient demographics.
Jan 11 JAMA study
Jan 11 JAMA commentary

News Scan for Jan 11, 2021

News brief

Report highlights delirium, comas in sedated COVID-19 ICU patients

In COVID-19 patients admitted to intensive care units (ICUs) early in the pandemic, 82% were in a comatose state at some point and 55% experienced delirium, reports a Lancet study published late last week. Previous studies have connected ICU delirium to higher costs, greater mortality risk, and long-term dementia.

Patient data from 14 countries showed that 54.9% of 2,088 patients admitted to ICUs prior to Apr 28, 2020, developed delirium for a median of 3 days and 81.6% were in a coma for a median of 10 days.

"This is double what is seen in non-COVID ICU patients," said Brenda Pun, DNP, RN, of Vanderbilt University Medical Center, co-first author of the study, in a Vanderbilt news release. "It is clear in our findings that many ICUs reverted to sedation practices that are not in line with best practice guidelines," Pun added.

Sixty-four percent of patients were given benzodiazepines and 70.9% were given propofol, both for a median of 7 days. Patients who experienced delirium or coma on one day were 17.84 and 6.34 times more likely to develop it the next day, respectively.

Acute brain dysfunction—defined as either coma or delirium—occurred for a median of 12 days.

While benzodiazepine sedative infusions were associated with a 59% higher risk of delirium, the physical or digital presence of family was associated with a 27% decrease.

Other factors associated with acute brain dysfunction included antipsychotic use (odds ratio [OR] 1.59), invasive mechanical ventilation (OR, 1.48), continuous opioid infusions (1.39), smoking or alcohol abuse (1.37), restraint use (1.32), vasopressor use (1.25), older age (1.13), and a higher Simplified Acute Physiology Score II score (1.17), which measures the likelihood of ICU mortality.

"Although SARS-CoV-2 infection was initially hypothesised to contribute directly to neurological symptoms, it seems more likely that neurological effects are caused indirectly by factors such as low blood-oxygen levels, coagulopathy, exposure to sedative and analgesic drugs, isolation, and immobility," write the researchers.

Scientists need to explore the reasons behind sedation practice with COVID-19, writes Valeria Page, MB BCh, in a Lancet commentary. "What was the extent of proning patients or use of muscle relaxants, both of which require deep sedation? What was the impact of a reduction in trained staff? 30% of ICUs had a shortage of personal protective equipment for care providers, which alone might have influenced the decision not to reduce a patient's sedation."
Jan 8 Lancet study
Jan 8 Vanderbilt University press release
Jan 8 Lancet commentary

Early oseltamivir for severe flu tied to fewer hospital readmissions

A new Australian study published in the International Journal of Infectious Diseases shows early administration with the antiviral drug oseltamivir (Tamiflu) was tied to reduced 30-day readmissions and length of hospital stay, but not to 30-day mortality in patients hospitalized with severe influenza.

The retrospective study was based on outcomes of adult patients administered oseltamivir either within 48 hours or after 48 hours of hospitalization due to severe flu. The 1,828 patients were admitted to two major tertiary hospitals in South Australia from January 2016 to March 2020.

The mean age of patients was 66.4, and 52.9% were women. Patients also had a high comorbidity burden, including 32.4% with a history of chronic pulmonary disease. The overall mortality rate was 4.3%, and the readmission rate was 13.5%.

Both 30-days readmissions and the composite outcome of 30-days readmissions or death were significantly reduced among patients who received oseltamivir (P < 0.05) less than 48 hours after compared with the delayed-treatment group, the authors said.

"The beneficial effect of Oseltamivir in reducing readmissions could be related to a reduction in the incidence of secondary complications of influenza such as bacterial pneumonia or fewer exacerbations of underlying chronic medical conditions," the authors concluded.
Jan 9 Intl J Infect Dis study

H5N8 avian flu hits poultry in Northern Ireland, Hungary, and India

Northern Ireland and Hungary are the latest countries in Europe to report the appearance of highly pathogenic H5N8 avian flu in poultry, according to the latest notifications from the World Organization for Animal Health (OIE).

Northern Ireland's outbreak began on Dec 27 at a layer farm in Clough, the first event in poultry involving the strain in the country, which is part of the United Kingdom, since 2017. The virus killed 197 of 32,347 birds.

Hungary reported two H5N8 outbreaks at commercial turkey farms in Kamarom-Esztergom County in the northwest, its first involving the strain since June 2020. The events began on Jan 4, and, taken together, the virus killed 150 of 84,572 birds. Hungarian officials also reported detecting the H5N8 virus in an egret that was found dead on Dec 22 at a nature park in the same county.

In other developments, India, where the government recently reported avian flu outbreaks in four states, reported five H5N8 events at poultry farms in Kerala state, beginning from Dec 21 to Dec 28. Among the events, the virus killed 25,265 of 82,952 susceptible birds.
Jan 8 OIE report on H5N8 in Northern Ireland
Jan 11 OIE report on H5N8 in Hungarian poultry
Jan 11 OIE report on H5N8 in Hungarian wild birds
Jan 9 OIE report on H5N8 in India