Stewardship / Resistance Scan for Jul 12, 2021

News brief

Non-antibiotic drugs may be a risk for resistant bacteria

A study of hospital patients in Israel found a link between multidrug-resistant gut bacteria and exposure to commonly used non-antimicrobial drugs (NAMDs), researchers reported last week at the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID).

Out of 1,807 patients admitted to Tel Aviv Medical Center from Jan 1, 2017, to Apr 18, 2019, who had upper urinary tract infection, positive urine or blood culture growing Enterobacterales, and exposure to any of 19 NAMDs prior to admission, 994 patient samples (52.2%) contained drug resistant organisms and 431 (23.8%) had multidrug-resistant organisms (MDROs). Univariate analysis found that exposure to seven drug classes was associated with a resistant organism, and three drug classes—proton-pump inhibitors (PPIs), beta-blockers, and antimetabolites—were significantly associated with MDROs.

A multivariable logistics regression analysis that included previous antibiotic exposure and hospitalization found that exposure to beta-blockers, PPIs, and antimetabolites was significantly associated with resistance to third-generation cephalosporins, trimethoprim-sulfamethoxazole, and fluoroquinolones, with antimetabolites having the greatest impact on antibiotic resistance.

"Our findings highlight the importance of non-antimicrobial drug exposure as a risk factor for antibiotic resistance," lead author Meital Elbaz, MD, of Tel Aviv Medical Center, said in a European Society of Clinical Microbiology and Infectious Diseases (ESCMID)press release. "We urgently need larger studies with more drug classes to confirm the discovery and to clarify the biological link between common prescription drugs and antibiotic resistance."
Jul 9 ECCMID abstract
Jul 9 ESCMID press release


Resistant bacteria found in more than half of dog food samples

In another study presented at ECCMID last week, researchers from Portugal reported that samples of commercially available dog food contained MDR Enterococci, including isolates that were genetically identical to bacteria isolated from hospital patients.

The researchers analyzed 55 samples of dog food (22 wet, 8 dry, 4 semi-wet, 7 treats, and 14 raw-frozen) and found that 30 samples (54%) contained Enterococci that expressed resistance to erythromycin (73%), tetracycline (63%), quinupristin-dalfopristin (60%), streptomycin (53%), chloramphenicol (50%), ampicillin or ciprofloxacin (47% each), gentamycin (40%), linezolid (23%), or vancomycin and teicplanin (2% each). MDR isolates were found in all the raw-frozen samples and three of the non-raw samples.

Genetic sequencing revealed that some of the MDR Enterococcus faecium isolates in the dog-food samples were identical to isolates found in hospital patients in the United Kingdom, Germany, and the Netherlands, as well as to isolates from livestock and wastewater in the United Kingdom.

The researchers also conducted experiments that showed resistance genes from the dog food could be transferred to other types of bacteria, which suggests the potential for spread to people.

"The close contact of humans with dogs and the commercialisation of the studied brands in different countries poses an international public health risk," lead author Ana Freitas, PhD, of the University of Porto, said in an ESCMID press release. "Dog owners should always wash their hands with soap and water right after handling pet food and after picking up faeces."
Jul 9 ECCMID abstract
Jul 10 ESCMID press release


Azithromycin doesn't help mild-to-moderate COVID-19, study finds

A randomized clinical trial conducted in the United Kingdom found that use of the antibiotic azithromycin in patients with mild-to-moderate COVID-19 did not reduce the risk of subsequent hospital admission or death. The results were presented last week at ECCMID and published simultaneously in The Lancet Respiratory Medicine.

In the open-label, randomized trial conducted at 19 UK hospitals from Jun 3, 2020, to Jan 29, 2021, adult COVID-19 patients considered suitable for initial ambulatory management were assigned to receive either standard care plus 500 milligrams of azithromycin once a day for 14 days or standard care alone. The primary outcome was hospital admission or death from any cause within 28 days of randomization.

A total of 298 patients were enrolled, and the primary outcome was assessed in 292. The mean age of patients 45.9 years. Fifteen of 145 patients (10%) randomly assigned to azithromycin were admitted to hospital or died, compared with 17 of 147 (12%) who received standard care alone, for an adjusted odds ratio of 0.91 (95% confidence interval [CI], 0.43 to 1.92). Unadjusted and fully adjusted analyses (further adjusted for age, chronic pulmonary disease, and presence of cancer) demonstrated no significant differences between treatment groups.

This is the latest clinical trial to find no benefit for azithromycin in treating COVID-19 patients, either alone or combined with the antimalaria drug hydroxychloroquine. The previous trials have mainly involved hospitalized patients with late-stage, severe disease, or patients in the early stages of disease with minimal symptoms, while this study focused on patients in the early stages of disease who were at high risk for deterioration. Another distinction of the study was that patients received a high dose of azithromycin for a long duration, so that antiviral, antibacterial, and anti-inflammatory benefits could be assessed.

"In conclusion, our findings in mild-to-moderate COVID-19 managed in ambulatory care, taken together with trials in early disease in primary care and from trials in patients admitted to hospital with severe disease, suggest that azithromycin does not reduce hospital admissions, respiratory failure, or death compared with standard care, and should not be used in the treatment of COVID-19," the study authors wrote.
Jul 9 Lancet Respir Med study

News Scan for Jul 12, 2021

News brief

Flu vaccine linked to better COVID-19 symptoms

People who received the flu vaccine prior to having COVID-19 had less risk of sepsis, stroke, deep vein thrombosis (DVT), and disease requiring emergency or intensive care, according to a study presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) this year.

The researchers looked at 74,754 patients in the international TriNetX research database: All had been diagnosed as having COVID-19, but half had received flu shots 2 weeks to 6 months prior to the infection. Patients were matched across COVID risk factors (eg, age, ethnicity, health conditions) and followed up at 30, 60, 90, and 120 days post-diagnosis.

The group that did receive the flu shot had significantly lower risk for sepsis (risk ratio [RR], 1.36 to 1.45; 95% confidence interval [CI], 1.12 to 1.70) and stroke (RR, 1.45 to 1.58; 95% CI, 1.08 to 2.03) across all time points. While intensive care unit (ICU) admissions did not show a significant association for 60 days, for the other time points, it was tied to a risk ratio of 1.17 to 1.20 (95% CI, 1.00 to 1.39).

Patients who received the flu vaccine also had significantly fewer DVTs 60 to 120 days post-diagnosis (RR, 1.41 to 1.53; 95% CI, 1.08 to 2.08) and, from days 90 to 120 post-diagnosis, significantly fewer emergency department visits (RR, 1.20 to 1.58; 95% CI, 1.05 to 1.48).

Flu vaccine was not linked with reduced risk of death.

"Only a small fraction of the world has been fully vaccinated against COVID-19 to date and, with all the devastation that has occurred due to the pandemic, the global community still needs to find solutions to reduce morbidity and mortality," said senior author Devinder Singh, MD, in a European Society of Clinical Microbiology and Infectious Disease (ESCMID) press release. This does not mean, however, that the flu vaccine can act as a replacement for COVID-19 vaccination, the researchers add.
Jul 11 ECCMID abstract
press release


Single dose of COVID vaccines provides good protection in elderly

A single dose of an mRNA-based COVID-19 vaccine reduced SARS-CoV-2 infection risk by about two-thirds in the elderly, according to a Clinical Infectious Diseases study late last week.

The researchers looked at 16,993 sample specimens from British Columbia residents 70 years or older during the area's spring wave (Apr 4 to May 1). Of the samples, 7.2% tested positive, of which 92% (1,131) were genetically characterized and consisted of 45% Alpha (B117), 14% Gamma (P1), and 14% non-variants of concern (non-VOCs). Participants were considered vaccinated if they had received their first dose of either the Pfizer/BioNTech vaccine or the Moderna vaccine at least 21 days prior to specimen collection.

Overall, vaccine effectiveness (VE) for a single mRNA dose at 21 or more days post-vaccination was 65% (95% confidence interval [CI], 58% to 71%). VE was highest against non-VOCs (72%; 95% CI, 58% to 81%), but it was still high against Alpha and Gamma (respectively, 67%; 95% CI, 57% to 75%, and 61%; 95% CI, 45% to 72%).

Prior to 21 days after vaccination, VE was lower: At days 0 to 13, VE was considered negligible at 14%, and from days 14 to 20, it was 43%. After day 21, however, the researchers note that single-dose VE increased to 75% (95% CI, 58 to 83; days 35 to 41 days).

"Substantial single-dose protection in older adults reinforces the option to defer second doses when vaccine supply is scarce and broader first-dose coverage is rapidly needed," write the researchers. "Such strategy, however, warrants further evaluation to assess duration of protection over a longer period and against additional VOC."
Jul 9 Clin Infect Dis study

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