Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans
VA study finds faster receipt of antibiotics in sepsis patients
Originally published by CIDRAP News Sep 9
A study of US veterans hospitalized with community-acquired sepsis shows an overall decline in time-to-antibiotics, with significant variation across hospitals, researchers reported this week in JAMA Network Open.
The observational cohort study examined the time from presentation to antibiotic administration in sepsis patients admitted to 130 Veterans Affairs (VA) hospitals from 2013 to 2018. Faster receipt of antibiotics has been associated with improved survival in sepsis patients, and sepsis quality improvement programs have resulted in faster administration of antibiotics, but it’s unclear if antibiotic timing for sepsis has improved outside of formal performance incentive programs.
Among a total of 111,385 sepsis hospitalizations identified during the study period, 7,574 patients (6.8%) died in the hospital and 13,855 (12.4%) died within 30 days. Median time-to-antibiotics was 3.9 (2.4 to 6.5) hours, declining from 4.5 hours during 2013-2014 to 3.5 hours during 2017-2018—an absolute change of 54.6 minutes and a relative change of 22.2%. After adjusting for patient characteristics, median time-to-antibiotics declined by 9 minutes per year.
Analysis of hospital-level variation in time-to-antibiotics showed that the magnitude of decrease varied across hospitals, with hospitals that had faster baseline time-to-antibiotics experiencing less change over time. Hospitals in the slowest tertile decreased time to antibiotics by 16.6 minutes per year, while hospitals in the fastest tertile saw time-to-antibiotics decline by 7.2 minutes per year. Median time-to-antibiotics varied by 118.2% across hospitals during 2017-2018, ranging from 3.1 to 6.7 hours.
“This variation persisted after adjustment for granular patient characteristics, suggesting that sepsis practice patterns truly differ across hospitals,” the study authors wrote. “This may represent a potential opportunity for practice improvement going forward, but the benefits of further accelerating time-to-antibiotics must be balanced against the risk of driving antibiotic overuse in patients with noninfectious illness.”
Sep 7 JAMA Netw Open study
Trial data support shorter antibiotic course for bloodstream infections
Originally published by CIDRAP News Sep 9
The results of a randomized controlled trial conducted in Spain suggest that a 7-day course of antibiotics for Enterobacterales bloodstream infections (eBSIs) is preferable to 14 days, researchers reported yesterday in Clinical Microbiology and Infection.
The open-label, multi-center study enrolled patients diagnosed with eBSI from five Spanish hospitals to receive either 7 days (the experimental arm) or 14 days of antibiotic treatment (the control arm). Patients were followed for 28 days after stopping antibiotic treatment. The primary end point was days of treatment at the end of follow-up, and clinical outcomes were assessed through relapse of eBSI, relapse of fever, and clinical cure (resolution of all signs and symptoms of infection).
Secondary end points included crude mortality, superinfections, and adverse events. A superiority margin of 3 days was set for the primary end point, and a non-inferiority margin of 10% for clinical outcomes.
Of the 248 patients enrolled, 119 were assigned to 7 days of antibiotics and 129 to 14 days. The median length of antibiotic treatment in the intention-to-treat population was 7 days in the experimental arm and 14 in the control arm. No significant differences were observed for the other end points at the end of the 28-day follow-up, including mortality, relapse of eBSI, relapse of fever, superinfections, or drug-related adverse events. The non-inferiority margin was met for all clinical outcomes except relapse of fever, which was more frequent in the 7-day group (difference in absolute risk, —0.2%).
A Desirability of Outcome Ranking and Response Adjusted for Duration of Antibiotic Risk (DOOR/RADAR) analysis showed that patients receiving 7 days of treatment had a 77.7% greater probability of achieving better results compared with those who received 14 days of treatment.
The study authors say the findings on relapse of fever suggest some patients may need more than 7 days of antibiotics, but that the overall benefit of shorter antibiotic treatments is clear.
“In conclusion, this trial points to 7-day course of antibiotics as the preferential treatment for eBSI, as long as the source is properly controlled,” they wrote. “The potential impact of implementing this recommendation into clinical practice would be significant in the fight against bacterial resistance.”
Sep 8 Clin Microbiol Infect study
Study describes impact of XDR typhoid on young children
Originally published by CIDRAP News Sep 7
A new study by researchers in Pakistan details the impact and response to treatment among children diagnosed as having extensively drug-resistant (XDR) typhoid infections.
The study, published late last week in BMC Infectious Diseases, reviewed the records of 680 children who had culture-proven XDR Salmonella enterica serovar Typhi infections and were treated at a hospital in Karachi at any point from July 2017 to December 2018.
The World Health Organization estimates that there were 5,247 cases of XDR Salmonella Typhi—which is resistant to five classes of antibiotics—in Karachi from November 2016 to December 2019, but data on clinical features and response to treatment among children has been scarce. The estimated incidence of enteric fever in Pakistan is 413 cases per 100,000 population among children ages 2 to 4, and 573 cases/100,000 population in children ages 5 to 15.
The median age of the patients was 5, and 57.5% were boys. Of the 270 patients with recorded outcomes, 234 (86.7%) were cured within 14 days, while a delayed response to antibiotics was noted in 32 (11.9%). Four children died. Seventy-six children (29%) recovered after treatment with a combination of meropenem and azithromycin, 72% were successfully treated with azithromycin alone, and 15 (6%) responded to meropenem alone.
The study authors note that literature from other parts of Pakistan has also reported a higher frequency of infection among children aged 5 years or younger, which could be explained by the fact that children have lower immunity and require lower bacterial doses to develop infection.
“This study confirms that XDR S. Typhi is common in children under 5 years of age,” they wrote. “We advocate increasing nationwide awareness about the consumption of safe water, antibiotic stewardship and immunisation practices of children.”
Sep 3 BMC Infect Dis study
Indian surveillance report highlights rising carbapenem resistance
Originally published by CIDRAP News Sep 7
The latest antimicrobial resistance (AMR) surveillance data from India shows an increase in carbapenem-resistant Enterobacterales and a rise in fungal infections among hospitalized patients.
The 2020 report from the Indian Council of Medical Research (ICMR) Antimicrobial Resistance Research and Surveillance Network shows that Escherichia coli was the most commonly isolated bacterial pathogen among 65,561 isolates collected from tertiary care hospitals, followed by Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, and Staphylococcus aureus.
Among the E coli isolates, susceptibility to imipenem was 72%, down from 86% in 2016 but up from 63% in 2019. K pneumoniae susceptibility fell from 65% in 2016 to 45% in 2020. The authors of the report say the lower susceptibility to imipenem is reflective of the increase in carbapenem use in India over the past two decades.
The ICMR also reported reduced susceptibility in A baumannii and P aeruginosa. Among A baumannii isolates, reduced susceptibility of 10% to 20% was observed against carbapenems, cephalosporins, monobactams, and beta-lactam/beta-lactamase inhibitor combinations. Only 40% of P aeruginosa isolates were susceptible to fluoroquinolones, and 60% to 70% were susceptible to carbapenems, cephalosporins, and aminoglycosides.
Among the increasing number of fungal infections observed in Indian hospitals, the ICMR reported that the multidrug-resistant yeast Candida auris was consistently isolated from regional hospitals across India. Most C auris isolates were resistant to fluconazole, and the incidence of echinocandin resistance is on the rise.
“Systematic collection, evaluation, and analysis of resistance data of specific pathogens for [the] last five years have highlighted that certain pathogens have become highly drug resistant and have become clinicians’ dilemma,” the report noted. “Aggressive action for prevention, containment, and treatment are needed at the national level.”
Sep 2 ICMR surveillance report