Stewardship / Resistance Scan for Oct 25, 2021

News brief

PAHO issues alert on carbapenemase-producing Enterobacterales

The Pan American Health Organization (PAHO) is calling for increased surveillance and investigation of carbapenemase-producing Enterobacterales in Latin America and the Caribbean.

In an alert issued late last week, PAHO noted the emergence and increase in new combinations of carbapenemase-producing Enterobacterales in the region since the COVID-19 pandemic began, along with the detection of carbapenemases that have not previously been detected.

While pathogens carrying these enzymes, which confer resistance to carbapenem antibiotics, were on the rise in the region prior to the pandemic, PAHO said the increasing incidence of these multidrug-resistant organisms may be tied to rising use of broad-spectrum antibiotics during the pandemic and increases in the healthcare- and device-associated infections among COVID-19 patients.

In particular, Argentina in November 2020 reported that isolates containing both KPC (Klebsiella pneumoniae carbapenemase) and NDM (New Delhi metallo-beta-lactamase)—a combination not previously seen in the country—were the most prevalent among carbapenem-resistant Enterobacteriaceae received in the national reference laboratory.

Uruguay also reported an increase in isolates harboring KPC and NDM, while Ecuador, Paraguay, and Guatemala all reported their first isolates carrying both carbapenemases. In addition, Belize reported its first NDM-carrying Enterobacterales isolate, and Chile and Guatemala reported their first isolates carrying the OXA-48 (oxacillinase) enzyme.

These carbapenemases are particularly concerning because they are carried on mobile pieces of DNA called plasmids and can easily be shared with other bacteria.

"Due to the plasmid nature of the genes encoding these enzymes and the multi-resistant phenotype of these clinical enterobacteria, the probability of dissemination of these resistance mechanisms is very high," PAHO said. "Their emergence, resulting in a significant increase in resistance to carbapenems in Enterobacterales, along with the co-existence of resistance mechanisms to polymyxins, limits the antimicrobial treatment for these pathogens."

To guide timely control measures, the alert urges countries to increase the participation of clinical laboratories in surveillance, calls on laboratories to immediately notify public health authorities and hospital infection control committees when they detect new resistance mechanisms and/or combinations of mechanisms, and recommends that labs develop tools to detect organisms with two or more carbapenemases. It also urges hospitals to implement strict infection prevention and control measures to limit the spread of carbapenemase-producing pathogens.
Oct 22 PAHO epidemiologic alert

Patients who take antibiotics for appendicitis may still need surgery

A team of US researchers reported today in the New England Journal of Medicine that long-term follow-up of a randomized trial showed an increase in the percentage of appendicitis patients who underwent subsequent appendectomy after initial treatment with antibiotics.

The initial results of the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial, reported in the same journal in November 2020, found that 29% of appendicitis patients randomly assigned treatment with antibiotics had undergone appendectomy by 90 days. Based on a general measure of health at 30 days in these patients, investigators determined that antibiotics were non-inferior to appendectomy for the treatment of appendicitis. The findings were noteworthy at a time when many medical procedures were being delayed due to the COVID-19 pandemic.

But in a letter to journal editors today, the investigators reported that data collection on patients up to 4 years after enrollment in the trial revealed that among the patients who received antibiotics, the percentage who underwent subsequent appendectomy rose to 40% at 1 year and 46% at 2 years. The percentage rose to 49% at 3 and 4 years, based on limited follow-up.

At 30 days after randomization, the risk of appendectomy was 27%. Appendectomy was more common among patients who had an appendicolith (calcified deposit in the appendix), but the greater risk was attenuated with time.

"Although some clinicians and patients may determine that these longer-term rates of appendectomy make antibiotics a less desirable treatment than early appendectomy, substantial numbers of patients report a preference for antibiotics, even if appendectomy may ultimately be necessary," the authors wrote. "The present data will further inform shared decision making between clinicians and their patients with appendicitis, including those with an appendicolith."
Oct 25 N Engl J Med abstract

Study: FDA warnings tied to decline in outpatient fluoroquinolones

Analysis of US ambulatory visits shows that the significant decline in the use of fluoroquinolone antibiotics in recent years is linked to Food and Drug Administration (FDA) safety advisories issued in 2016, researchers reported last week in Open Forum Infectious Diseases.

Since 2008, the FDA has issued a series of safety alerts, warnings, and label changes for fluoroquinolones in response to increasing reports of associated adverse events, including tendon rupture, peripheral neuropathy, and central nervous system disorders.

To determine whether these advisories have had an impact on outpatient fluoroquinolone prescribing, researchers from Johns Hopkins Bloomberg School of Public Health analyzed quarterly data from IQVIA's National Disease and Therapeutic Index (NDTI) for 2015 through 2019. NDTI is a monthly audit of office-based physicians that provides information on patterns and treatment of disease.

The researchers looked at fluoroquinolone prescribing trends by provider type and diagnosis over the study period and conducted an interrupted time series (ITS) analysis to assess the impact of FDA advisories issued in May and July 2016 that recommended limiting or even avoiding the use of fluoroquinolones in acute uncomplicated infections.

From 2015 through 2019, fluoroquinolone use declined overall by 36.5%, with declines in annual use of 78%, 31%, and 31% for respiratory, urogenital, and gastrointestinal conditions, respectively. The decline in fluoroquinolone prescribing was dramatic among younger clinicians, falling by 191% among clinicians 44 years of age and younger while remaining stable among clinicians 65 years and older.

The ITS analysis showed that before the 2016 FDA advisories, fluoroquinolone use was approximately 4.8 million treatment visits per quarter, then fell to 4.1 million treatment visits per quarter in the post-advisory period. The pre-advisory and post-advisory trends showed a statistically significant difference of 44,539 visits per quarter.

The study authors note that even with this sizable decline in fluoroquinolone use, 13.7 million treatment visits in 2019 involved fluoroquinolones.

"Despite the decrease, the volume of prescribing continues to be high, raising concerns regarding the potential for continued overuse of these products in settings where they may have an unfavorable risk/benefit balance," they wrote.
Oct 23 Open Forum Infect Dis abstract

News Scan for Oct 25, 2021

News brief

First responders may have higher COVID-19 risk than healthcare workers

First responders' risk for COVID-19 infection is about 60% more than other essential workers, including healthcare workers (HCWs), according to a study published late last week in JAMA Health Forum.

In Arizona, 1,766 HCWs, first responders, and other essential workers took weekly COVID-19 tests from July 2020 to March 2021 (23,393 person-weeks). First responder infection incidence was 13.2 per 1,000 person-weeks, versus 6.7 in HCWs and 7.4 in other essential workers. Compared with HCWs, first responders' adjusted incidence rate ratio (IRR) was 1.60 (95% CI, 1.07 to 2.83), with similar results when compared with other essential workers.

Age was also an independent risk factor, according to the data, with every 10-year increase associated with a 19% reduction in risk (IRR, 0.81; 95% CI, 0.70 to 0.95). This was consistent with Arizona's COVID-19 case trends during the test period.

The cohort consisted of 22.4% first responders (eg, firefighters, correctional officers, emergency medical services personnel), 44.2% HCWs, and 33.4% other essential workers (eg, teachers, operators). The median age was 43.8 years.

While 61.9% were women, the researchers noted that fewer women were first responders (37.0%) compared with healthcare personnel (69.7%) or other essential workers (68.3%). Household income was also distributed unevenly, with 25.0% of HCWs reporting household income of $200,000 per year or more compared with 5.8% of first responders and 6.9% of other essential workers.

"This analysis of the AZ HEROES study data shows that we need to do more to help protect our first responders, their families and the communities they serve," said first author Kate Ellingson, PhD, in a University of Arizona press release. "Specifically, we need to better understand the risk factors driving infection among first responders and to tailor mitigation strategies accordingly, including vaccine promotion."
Oct 22 JAMA Health Forum study
Oct 22 University of Arizona press release

Non-COVID deaths lower in COVID vaccine recipients, study says

COVID-19 vaccine recipients had lower non-COVID death rates than those who were not vaccinated against COVID-19, according to a large study published in Morbidity & Mortality Weekly Report (MMWR) late last week.

The researchers used data from seven US health systems from Dec 14, 2020, to Jul 31, 2021, and matched 6.4 million COVID-vaccinated people with 4.6 million unvaccinated people. About 3.5 million people received the Pfizer/BioNTech vaccine, 2.6 million the Moderna vaccine, and 342,169 the Johnson & Johnson vaccine, and to account for healthcare-seeking behavior, vaccinated and unvaccinated participants were included only if they had at least one dose of flu vaccine in the past 2 years.

The study involved about 11 million people total.

The adjusted relative risk (aRR) of non-COVID deaths per year was 0.41% and 0.34% after the first and second dose of Pfizer, respectively; 0.34% and 0.31% after the first and second dose of Moderna, respectively; and 0.54% after the single dose of Johnson & Johnson. That compares with annual rates ranging from 1.11% to 1.47% in unvaccinated peers.

Among Pfizer recipients 12 to 17 years old, mortality risk did not differ between the vaccinated and unvaccinated cohort, which the researchers say could be due to more similar risk factors in this age-group compared with adults. The researchers also found that mortality rates among Johnson & Johnson vaccine recipients were higher than those who received an mRNA vaccine, which they say could be due to underlying health status and risk behavior differences.

"Despite numerous studies showing the safety of COVID-19 vaccines, some people have remained hesitant to get vaccinated," said lead author Stanley Xu, PhD, in a Kaiser Permanente press release. "This study provides reassurance that the vaccines are very safe, and, in fact, people who received COVID-19 vaccines in the United States had a lower death rate than those who didn't, even if you don't count COVID deaths."
Oct 22 MMWR study
Oct 22 Kaiser Permanente press release

Ebola sickens 1 more in DR Congo flare-up

One more Ebola virus case was confirmed in the Democratic Republic of the Congo (DRC) outbreak, raising the total to six, the World Health Organization (WHO) DRC office said in an Oct 23 Twitter post. The number of deaths remains at three.

Few details were available about the latest case, but the WHO said all are from the same Butsili health area within the Beni health zone of North Kivu province. The six cases include two fatalities of people who died in community settings, which raise the risk of disease spread.

In an update today, the WHO African Region said on Twitter that, of 544 contacts identified so far, 478 are being monitored.

The DRC is experiencing its 13th Ebola outbreak, which began earlier this month with the death of a young boy, whose fatal illness was confirmed, and the earlier suspicious deaths of three neighbors. Early sequencing testing suggests that the source of the current flare-up may be linked to the DRC's large outbreak of 2018-2020. Survivors have been known to harbor the virus in immune-protected parts of the body for a much longer time than the 6 months previously thought.
Oct 23 WHO DRC office tweet
Oct 25 WHO tweet

New CWD detection expands Pennsylvania management areas

The Pennsylvania Game Commission (PGC) recently announced new rules to curb the spread of chronic wasting disease (CWD) after tests on a roadkill deer in Jefferson County were positive.

Officials expanded the states disease management area (DMA) 3 and created a new one: DMA 6, which contains portions of Clearfield, Elk, and Jefferson counties.

The changes were triggered by the discovery of the dead buck near the northern boundary of DMA 3 and and within 2 miles of Pennsylvania's elk management area. The creation of DMA 6 will prevent high-risk animal parts from DMA 3 being moved into the elk management area.

The carcass was collected as part of ongoing CWD surveillance.

In a step to boost surveillance, the state also created another deer management assistance program (DMAP) unit, which will add more than 1,300 permits that allow hunters to take up to two more antlerless deer in the area. Along with the extra hunting opportunities, officials are asking hunters to submit harvested deer heads for CWD testing to determine the extent of infection.

CWD is a fatal prion disease in cervids like deer, elk, and moose that spreads among animals through contact with infected fluids or contaminated environments. Though infections have not yet been detected in humans, the Centers for Disease Control and Prevention (CDC) recommends that people avoid eating meat of CWD-positive deer.
Oct 22 PGC press release

New multistate Salmonella outbreak linked to salami sticks

The CDC announced over the weekend a new Salmonella outbreak linked to salami sticks sold at Trader Joe's grocery stores.

So far 20 people have been sickened in 8 states, including 3 who needed hospitalization. No deaths have been reported. Patients range in age from 2 to 75 years, with a median age of 11.

Eight of nine people interviewed by the CDC as part of the outbreak investigation said they ate Citterio brand Premium Italian-Style Salame Sticks, which are sold at Trader Joe's and other grocery stores.

"Investigators are still working to determine if additional products may be contaminated," the CDC said. "Do not eat Citterio brand Premium Italian-Style Salame Sticks with any best-by date. Throw them away."

California has reported the most cases with 8, Minnesota and Michigan each have 3, Illinois has 2 cases, and New York, New Jersey, Virginia, and Kansas each have a single case. According to the CDC, patients first developed symptoms from Sep 18 to and Oct 3.
Oct 23 CDC report