Stewardship / Resistance Scan for Oct 25, 2021

Carbapenemases in Latin America
Antibiotics for appendicitis
Less outpatient fluoroquinolone use

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

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