Patients with recent cancer therapy at higher risk of poor COVID outcomes

Cancer patients who received systemic treatment like chemotherapy or radiation in the 3 months before testing positive for COVID-19 were at increased risk of death, admission to an intensive care unit (ICU), and hospitalization, according to a study yesterday in JAMA Oncology.

Researchers from the University of Texas MD Anderson Cancer Center analyzed the clinical outcomes in the electronic health records of 507,307 US adults with and without a diagnosis of cancer who tested positive for COVID-19 from Jan 1 to Dec 31, 2020.

Among the patients, 14,287 (2.8%) had cancer, while 493,020 (97.2%) did not. Of the cancer patients, 4,296 (30.1%) had received recent treatment and 9,991 (69%) had not. Average patient age was 48.4 years, and 55.4% were women. Cancer patients were significantly older than non-cancer patients (median age, 67 vs 48 years) and had higher Charlson-Deyo Comorbidity Index scores, an indicator of poorer survival.

Regardless of treatment status, cancer patients were more likely than non-cancer patients to die (7.8% of cancer patients with recent treatment, 5.0% of cancer patients without recent treatment, and 1.6% of non-cancer patients).

In an adjusted analysis, compared with non-cancer patients, cancer patients without recent treatment had similar or superior outcomes (odds ratio [OR] for death, 0.93; OR for mechanical ventilation, 0.61).

But cancer patients who received recent treatment were at higher risk for death (OR, 1.74) and hospitalization (OR, 1.19). And, relative to patients with nonmetastatic solid tumors, patients with metastatic tumors or hematologic (blood) cancers had an OR for death of 2.36 and an OR for mechanical ventilation of 0.87.

Rates of COVID-19 death, mechanical ventilation, ICU stay, and hospitalization all fell during 2020. In the first quarter of the year, patients with recent cancer treatment had a death rate of 11.5%, which fell to 8.4% in the last quarter.
Oct 28 JAMA Oncol study

GAO proposes 16 new recommendations on COVID-19 relief efforts

In its eighth report of COVID-19 relief under the CARES Act, the US Government Accountability Office (GAO) this week made 16 new recommendations to strengthen the government’s pandemic response in the areas of healthcare worker relief, recovery funds, unemployment insurance fraud, and worker safety.

"The government must remain vigilant and agile to address the evolving COVID-19 pandemic and its cascading impacts," the GAO said in the report. "Furthermore, as the administration implements the provisions in the COVID-19 relief laws, the size and scope of these efforts—from distributing funding to implementing new programs—demand strong accountability and oversight."

Since June 2020, the GAO has made 209 recommendations in its COVID-19 reports, and, as of Sep 30, agencies have addressed 33 of them and partially addressed another 48.

As an example of 1 of the 16 new recommendations, the GAO recommends that the Occupational Safety and Health Administration (OSHA) assess various challenges related to resources, communication, and guidance that the agency has faced in its response to COVID-19 and take actions as warranted.

"The progress in vaccinating the country is heartening, but GAO's review makes clear how much remains to be done to help the nation fully rebound from the pandemic," said Gene L. Dodaro, US comptroller general and head of the GAO, in a GAO news release. "If swiftly and effectively implemented, GAO's new and previous suggestions can help support the recovery and put us in a stronger position to deal with future health emergencies."
Oct 27 GAO report
Oct 27 GAO news release

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

Rapid test linked to improved antibiotic therapy for bloodstream infections

Originally published by CIDRAP News Oct 28

Use of a rapid diagnostic test in patients with bloodstream infections (BSIs) was associated with shorter times to optimal antibiotic therapy and antibiotic de-escalation, researchers reported yesterday in Clinical Infectious Diseases.

In the quasi-experimental, multicenter Improving Outcome and Antimicrobial Stewardship (IOAS) study, researchers compared clinical and antimicrobial stewardship metrics in BSI patients at 5 US hospitals before and after implementation of Accelerate PhenoTest BC Kit (AXDX) testing.

AXDX is a rapid diagnostic platform that provides pathogen identification and antibiotic susceptibility test (ID/AST) results from positive blood cultures up to 40 hours earlier than traditional methods. The primary outcomes were time to optimal therapy (TTOT) within 96 hours of blood culture positivity and 30-day mortality.

A total of 854 patients with BSI (435 pre-AXDX, 419 post-AXDX) were included in the study. Patient demographics, co-existing conditions, and baseline clinical characteristics were similar between the two groups.

Median TTOT was 17.2 hours shorter in the post-AXDX arm (23.7 hours) compared with the pre-AXDX arm (40.9 hours). Median time to first antimicrobial modification (24.2 vs 13.9 hours) and first antimicrobial de-escalation (36 vs 27.2 hours) were also shorter in the post-AXDX arm.

There was no statistical difference in 30-day mortality (8.7% pre-AXDX vs 6.0% post-AXDX) between in the two arms, or in the secondary clinical outcomes of length of stay and adverse events. Length of stay was shorter in the post-AXDX arm (5.4 vs 6.4 days) among patients with gram-negative bacteremia.

"This multicenter, real-world study suggests early ID/AST via AXDX has a significant impact on optimizing antimicrobial utilization and outcomes for patients with BSIs," the study authors wrote. "While challenging to demonstrate definitively, the value of early antimicrobial optimization is likely associated with widespread patient and societal benefits such as limiting the emergence of antimicrobial resistance and reduced harm from unnecessary antimicrobial exposures."
Oct 27 Clin Infect Dis abstract

Infant formula linked to more antibiotic resistance genes

Originally published by CIDRAP News Oct 27

Formula feeding is associated with a 70% increase in antibiotic resistance gene (ARG) abundance in the gut microbiome of infants compared with breast milk, US and Finnish researchers reported this week in the American Journal of Clinical Nutrition.

To determine the impact of early exposure to infant formula on the ARG load in newborns and infants born either pre- or full-term, the researchers cross-sectionally sampled the gut metagenomes of 46 infants born prematurely to build a generalized linear model and collected extensive data on the infants' diet during the first month of life.

They then cross-validated the model using 242 infant gut metagenomes from public databases. Their hypothesis was that diet causes a selective pressure that influences the microbial community of the infant gut and that formula might carry an abundance of bacterial species that carry ARGs.

The researchers found that formula-feeding increases the ARG load compared with an exclusively human milk diet. The relative abundance of ARGs carried by gut bacteria was 69% higher in infants receiving formula (fold change, 1.69; 95% confidence interval [CI], 1.12 to 2.55) compared with those who received human milk only. Several ARGs in formula-fed infants were enriched, including extended-spectrum beta-lactamase (ESBL) genes and genes encoding resistance to methicillin and erythromycin in Staphylococcus aureus.

Formula-fed infants also had a higher relative abundance of opportunistic pathogens, including S aureus, Staphylococcus epidermis, Klebsiella pneumoniae, Klebsiella oxytoca, and Clostridioides difficile, and significantly less bacterial species typically found in the gut, such as bifidobacteriaceae.

The study authors note that they did not follow up on the infants to determine whether those who were fed formula or had higher ARG abundance had more infections caused by antibiotic-resistant bacteria and that they could not confirm whether the ARGs were functional. But they say the findings suggest that the changes in formula-fed infants' intestinal environment may result in more ARG-carrying bacteria.

"Infants born prematurely are at particular risk of acquiring severe and life-threatening infections," they wrote. "Thus, increased ARG loads in formula-fed infants and the enrichment of potentially pathogenic bacteria are concerning."
Oct 22 Am J Clin Nutr abstract

Urinary antigen testing may help target antibiotics for pneumonia

Originally published by CIDRAP News Oct 26

Positive pneumococcal urinary antigen testing (PUAT) results among patients hospitalized with community-acquired pneumonia (CAP) was associated with earlier time to de-escalation of antibiotics, according to a single-center study published last week in Open Forum Infectious Diseases.

In the retrospective study, conducted at New York University Langone Health, researchers analyzed hospitalized CAP patients who had PUAT performed in 2019, comparing antibiotic de-escalation and outcomes in those who tested positive and negative. PUAT is a rapid, non-invasive assay that can aid in the diagnosis of CAP caused by Streptococcus pneumoniae. It has also been viewed as a potential antibiotic stewardship tool that might improve time to targeted, narrow-spectrum antibiotics and reduce use of broad-spectrum agents.

Of the 910 patients included in the analysis, 121 (13.3%) had a positive PUAT result and 789 (86.7%) had a negative result. Initial antibiotic de-escalation from a broad-spectrum antibiotic to a narrow-spectrum agent was similar in the PUAT-positive and -negative groups (82.9% vs 81.2%), but median time to de-escalation (interquartile range [IQR]) was similar in the PUAT-positive group (1 [IQR, 0 to 2] day vs 1 [IQR, 1 to 2] day). Within 24 hours of PUAT, more patients in the PUAT-positive group had atypical coverage discontinued (61.3% vs 47.2%). Patients with positive PUAT results were also less likely to have antibiotics escalated.

Among the PUAT-positive group, unadjusted analysis showed a shorter length of stay in patients who were de-escalated compared to those who were not de-escalated or required escalation (6 [IQR 4-10] days vs 8 [IQR 7-12]) days), with no difference in the incidence of Clostridioides difficile, in-hospital mortality, or 30-day infection-related readmission.   

The authors say the findings support the use of PUAT in conjunction with additional stewardship interventions.

"In order to have the greatest impact, testing should be considered on all patients admitted with a diagnosis of CAP, and coordinated efforts should be made with microbiology personnel to ensure appropriate workflows are established for timely PUAT results," they wrote.
Oct 22 Open Forum Infect Dis abstract

PAHO issues alert on carbapenemase-producing Enterobacterales

Originally published by CIDRAP News Oct 25

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

Originally published by CIDRAP News Oct 25

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

Originally published by CIDRAP News Oct 25

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