Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans
Review suggests mortality benefit for extended beta-lactam infusion
A meta-analysis of randomized controlled trials and observational studies found that extended infusion of antipseudomonal beta-lactam antibiotics in critically ill patients who had respiratory infections was associated with reduced mortality but not with clinical success, Japanese and Egyptian researchers reported yesterday in the International Journal of Infectious Diseases.
The researchers analyzed nine studies involving 1,058 patients that compared extended infusion (more than 3 hours) of beta-lactam antibiotics with intermittent infusion in critically ill patients. While several studies have demonstrated that prolonged infusion of beta-lactams results in higher clinical cure rates, lower mortality, and shorter hospital stays than intermittent infusion, a meta-analysis approach has not been used to examine the clinical efficiency of extended infusion in critically ill patients with predominant respiratory infections.
The primary outcome of the meta-analysis was all-cause mortality, and secondary outcomes included clinical success (based on pre-defined criteria specific to the infection in each study), hospital length of stay (LOS), intensive care unit (ICU) LOS, and antibiotic duration.
The results showed that mortality was lower for extended infusion than for intermittent infusion, with 126 deaths among 735 patients in the extended-infusion arm compared with 195 deaths among 773 patients in intermittent-infusion arm (risk difference [RD], – 0.10; 95% confidence interval [CI], –0.15 to –0.04). But no significant differences were observed for clinical success (RD, 0.11; 95% CI, –0.09 to 0.30), hospital LOS (RD, –1.68; 95% CI, –3.85 to 0.48), ICU LOS (RD, –2.37; 95% CI, –5.17 to 0.42) or antibiotic duration (RD, 0.05; 95% CI, –1.80 to 1.90) between the two groups.
The authors of the study say well-designed randomized controlled trials are needed to confirm the findings.
Jun 11 Int J Infect Dis abstract
Surveys show little change in antibiotic use in US hospitals
A comparison of surveys of antibiotic use in US hospitals shows little change from 2011 through 2015, US researchers reported this week in Clinical Infectious Diseases.
In 2011, the Centers for Disease Control and Prevention's (CDC's) Emerging Infections Program (EIP) hospital prevalence survey of healthcare-associated infections and antimicrobial use found that 50% of hospitalized patients received antibiotics. The 2015 survey was conducted in hospitals from 10 states that participate in the EIP using similar methods, with each hospital selecting a survey date from May to September 2015, and patients randomly selected from the hospital's morning census on the survey date.
Researchers from the EIP Hospital Prevalence Survey Team reviewed patient records to collect data on antibiotics on the survey date or day before, then compared the percentage of patients on antibiotics with the 2011 results.
Of the 12,299 patients from 199 hospitals, 6,084 (49.5%) received antibiotics on the survey date or the day before (95% CI, 48.6% to 50.4%). Comparison of the 148 hospitals in both surveys found similar rates of antibiotic use, with 4,606 of 9,283 patients (49.6%; 95% CI, 48.6% to 50.6%) receiving antibiotics in 2015 and 4,590 of 9,169 patients (50.1%; 95% CI, 49% to 51.1%) receiving antibiotics in 2011. But the percentage of neonatal critical care patients on antibiotics was lower in 2015 than in 2011 (22.8% vs 32%, P = 0.06).
The results also showed that fluoroquinolone use was lower in 2015 than in 2011 (10.1% vs 11.9%, P < 0.001), while third- and fourth-generation cephalosporin use (12.2% vs 10.7%, P = 0.02) and carbapenem use (3.7% vs 2.7%, P < 0.001) was higher. Pneumonia or respiratory infection was the most common reason for antibiotic use in both surveys.
The authors of the study said the lower prevalence of antibiotic use in neonatal critical care units and reduced use of fluoroquinolones in 2015 are encouraging signs that could provide evidence of the impact of antibiotic stewardship, but noted that the higher use of extended-spectrum cephalosporins and carbapenems is concerning.
Jun 10 Clin Infect Dis abstract
Think tank calls for more US leadership on AMR
A new paper from the Center for Strategic and International Studies (CSIS) is calling for the US government to provide more resources and attention to combating antimicrobial resistance (AMR).
Among the actions recommended in the CSIS brief are the inclusion of AMR funding in any coronavirus legislation to support research and enhance Medicare payments for antibiotic treatments, increased US funding for international AMR monitoring and reduction strategies, development of a concrete action plan to create incentives for developing and sustainably marketing new antibiotics, creation of more effective Medicare reimbursement mechanisms that confer appropriate value to antibiotics, and more federal support for antibiotic research and development.
The paper also calls for the US government to exercise significant global leadership around the issue.
"The U.S. government, in addition to improving infection control and antibiotic stewardship at home, should play a lead role in developing mechanisms to sustain antibiotic development and spur creation of innovative alternatives," CSIS senior associate Nellie Bristol, MPH, writes. "Further, as a public health leader globally, the United States should actively formulate, support, and advance global efforts to reduce AMR to help protect Americans at home and abroad."
Jun 9 CSIS brief
Study supports shorter antibiotic course for pneumonia in children
Originally published by CIDRAP News Jun 11
A study of children hospitalized for community-acquired pneumonia (CAP) found that a shorter course of antibiotics did not increase the odds of treatment failure compared with a longer course, US researchers reported today in the Journal of the Pediatric Infectious Diseases Society.
The retrospective cohort study looked at children older than 6 months who were hospitalized with CAP at the Johns Hopkins Hospital from 2012 through 2018. Guidelines at the hospital have recommended 5 days of antibiotics for children with CAP since 2012, based on published data in the adult population, but variability in prescribing still exists.
To evaluate whether children who received a shorter course of antibiotics are at increased risk of treatment failure, the researchers compared their outcomes with those of children who received a prolonged course. Treatment failure was a composite of unanticipated emergency department visits, outpatient visits, hospital readmissions, or death within 30 days of discontinuing antibiotics.
Of the 439 patients included in the study, 168 (38%) received short-course therapy (median, 6 days), and 271 (62%) received prolonged-course therapy (median, 10 days). Overall, 20 children (4%) experienced treatment failure, and there was no difference in treatment failure between the children who received short-course (3%) versus prolonged-course (6%) therapy (odds ratio [OR], 0.48; 95% CI, 0.18 to 1.30).
Three patients (2%) in the short-course group compared with 8 patients (3%) in the prolonged-course group experienced an unplanned emergency department or outpatient visit related to CAP (OR, 0.54; 95% CI, 0.14 to 2.07), and 2 patients (2%) and 7 patients (3%) in the short- and prolonged-course groups, respectively, required hospital readmission (OR, 0.43; 95% CI, 0.11 to 1.74).
Although they acknowledge that a multicenter randomized controlled trial would provide the best evidence for evaluating antibiotic therapy for CAP in children, the authors of the study say the findings provide additional evidence for the "less-is-more" approach to antibiotic treatment for bacterial infections.
"We believe that the results of our study, when combined with the abundant randomized, controlled trial data in adults, suggest that hospitalized children with uncomplicated CAP can be safely and effectively treated with approximately 5 days of antibiotics," they write. "Because CAP is one of the most common causes of hospitalization and antibiotic prescription in children, decreasing the duration of therapy could have an important public health impact."
Jun 11 J Pediatric Infect Dis Soc abstract
Early antibiotics for COVID-19 found to have no impact on death, infections
Originally published by CIDRAP News Jun 10
A small study of COVID-19 patients treated at a community hospital in southern Switzerland found that early administration of antibiotics did not significantly impact mortality or hospital-acquired infections in critically ill patients, Swiss researchers reported in a letter to the Journal of Infection.
The retrospective study looked at 48 intensive care unit (ICU) patients who had COVID-19, 19 (40%) of whom received antibiotics before ICU admission because of suspected bacterial co-infection. In general, the characteristics of the patients in the antibiotic and non-antibiotic groups were similar, with cardiovascular disease more frequently observed in the non-antibiotic patients. The most frequently used antibiotic was amoxicillin-clavulanate.
Analysis of outcomes showed that mortality was similar between the two groups (24% without antibiotics vs 26% with antibiotics, P = 0.86) and that no difference was observed in the overall number of delayed hospital-acquired infections during ICU stay, though urinary tract infections were more frequently seen in the non-antibiotic patients, and candidemia cases appeared more often in the antibiotic group.
Although the low number of patients in the study did not allow the researchers to draw a firm conclusion from the results, they said the findings "call into question the utility of early treatment of a presumptive bacterial superinfection in COVID-19 patients."
"Large multi-centric studies are urgently needed to investigate the impact of early antibiotics therapy on mortality, subsequent healthcare associated infections and ICU complications (i.e., duration of mechanical ventilation)," they wrote.
Jun 4 J Infect letter
Mass distribution of azithromycin linked to resistant strep in Africa
Originally published by CIDRAP News Jun 9
The addition of the antibiotic azithromycin to seasonal malaria chemoprevention (SMC) was associated with an increase in azithromycin-resistant serotypes of Streptococcus pneumoniae in children in Burkina Faso, researchers reported yesterday in The American Journal of Tropical Medicine and Hygiene.
To better understand whether mass distribution of azithromycin was associated with the emergence of resistance in S pneumoniae, the researchers collected and analyzed nasopharyngeal samples from 400 children enrolled in a large trial investigating whether adding the antibiotic to SMC had an effect on child mortality and morbidity. In the trial, children 3 to 59 months received four courses a year of SMC and azithromycin or a placebo over a period of 3 years (2014 through 2016). The researchers analyzed the nasopharyngeal samples for S pneumoniae carriage before and after treatments in each year of the study, and conducted antibiotic susceptibility tests and serotyping on S pneumoniaeisolates.
Of the 1,468 S pneumoniae isolates obtained, 698 randomly selected isolates were tested and serotyped. A total of 56 serotypes were detected by polymerase chain reaction, but serotypes 6A, 19A, 19F, 23F, and 35B persisted in all the pre- and post-treatment surveys, both in children who received azithromycin and in those who received placebo. An increase in azithromycin-resistant strains of S pneumoniae was observed in all these serotypes following exposure to the antibiotic.
"In conclusion, this study has shown that the increase in the resistance of nasopharyngeal isolates of S. pneumoniae noted following MDA [mass drug administration] with AZ [azithromycin] used in association with SMC was probably not associated with the emergence of a single resistant clone but due to the emergence of resistance in pneumococci belonging to several different serotypes," the authors of the study wrote.
Jun 8 Am J Trop Med Hygiene abstract
Study finds high rate of antibiotic prescribing for sinusitis
Originally published by CIDRAP News Jun 9
An analysis of antibiotic prescribing for acute sinusitis found that half of the patients visiting an integrated health system in Chicago for the disease met the criteria for antibiotics, but the actual prescribing rate was much higher, researchers from Northwestern University Feinberg School of Medicine reported yesterday in Clinical Infectious Diseases.
For the study, the researchers analyzed data on adult visits to Northwestern Medicine for acute sinusitis in 2017 and selected 500 distinct visits for manual chart review, looking for which patients received an antibiotic. To meet the criteria for antibiotics, patients had to have persistent, severe, or worsening symptoms—the clinical criteria defined by the Infectious Diseases Society of America for treatment of bacterial sinusitis.
Of the 500 visits, 425 met all the inclusion criteria, and 214 patients (50%) met the criteria for antibiotic prescribing, with the most common symptom criteria being persistent symptoms. Clinicians prescribed antibiotics for 205 (96%) of these patients, but they also prescribed antibiotics for 193 of the 211 patients (92%) who did not meet the criteria for antibiotics.
The most commonly prescribed antibiotics were amoxicillin-clavulanate (46% of prescriptions), azithromycin (20%), amoxicillin (12%), and cefdinir (6%). The median duration of treatment was 10 days. Guidelines recommend amoxicillin-clavulanate and amoxicillin as first-line antibiotics for acute sinusitis, and specifically recommend against macrolides and third-generation cephalosporins.
The authors of the study also noted that, because their assessment of guideline-concordant antibiotic-appropriateness was very forgiving, the proportion of patients who met the criteria "likely represents the upper bound of appropriateness."
"Ambulatory stewardship measures have generally addressed only antibiotic-inappropriate diagnoses, such as non-specific upper respiratory tract infections, or the requirement for streptococcal testing with a diagnosis of pharyngitis," the authors wrote. "To meaningfully reduce inappropriate antibiotic prescribing, future stewardship efforts should address the diagnosis of and appropriateness of antibiotic prescribing for sinusitis."
Jun 8 Clin Infect Dis abstract
Behavioral interventions tied to less urgent care antibiotic use
Originally published by CIDRAP News Jun 8
Implementation of behavioral "nudges" targeting non–guideline-concordant antibiotic prescribing helped reduce inappropriate prescribing for respiratory tract infections at three California urgent care centers (UCCs), researchers reported last week in Open Forum Infectious Diseases.
The study by researchers from Eisenhower Health, the University of California-Davis, and the University of Southern California Keck School of Medicine looked at prescribing rates for acute respiratory tract infections (ARTIs) at the high-volume rural UCCs before and after the implementation of three behavioral interventions: physician/patient education, public commitment, and peer comparison. The peer comparison intervention involved sending individual prescribing data and a blinded ranking email to providers.
The interventions were based on work from the MITIGATE study, which found that stewardship interventions tailored to the local site and setting reduced antibiotic prescribing for ARTIs by a third. An interrupted time series analysis (ITS) compared prescribing for ARTIs at the urgent care centers over a 16-month period before the intervention and 6 months during the intervention, a period that covered two flu seasons.
The analysis found a lower percentage of antibiotic-inappropriate prescribing during the intervention-period (58.5%) flu season (2018-19) than during the pre–intervention-period (73%) flu season (2017-18), resulting in an absolute 14.5% decrease in inappropriate prescribing for ARTIs, or about 981 prescriptions averted. The ITS analysis revealed that the estimated mean percent of antibiotic-inappropriate prescribing for ARTI decreased by 2.2% per month during the intervention period, compared with –0.71% during the pre-intervention period.
"The observed decrease in antibiotic-inappropriate prescribing for ARTI in this study suggests that utilizing a behavioral science approach may improve judicious use of antibiotics in community UCCs," the authors concluded.
Jun 6 Open Forum Infect Dis abstract
Higher US flu vaccine coverage linked to lower antibiotic prescribing
Originally published by CIDRAP News Jun 8
In another new study in Open Forum Infectious Diseases, researchers from the Center for Disease Dynamics, Economics & Policy in Washington, DC, and the University of Maryland School of Medicine in Baltimore found that increased influenza vaccination uptake was associated with state-level reductions in antibiotic use.
Using state-level monthly data on the number of dispensed antibiotic prescriptions from a large prescription drug database and seasonal flu vaccination coverage data from the CDC's FluVaxView database, the researchers conducted a retrospective analysis of US flu vaccination coverage and antibiotic prescribing rates from 2010 through 2017. They used a fixed-effects regression analysis to analyze the relationship between vaccine coverage rates and the number of antibiotic prescriptions per 1,000 residents from January to March of each year. They also looked at the impact of vaccination on prescribing by age-group.
After controlling for access to healthcare, socioeconomic differences, vaccine effectiveness, climate, and state-level differences, the researchers found a significant negative association between increased influenza vaccination rates and antibiotic use rates.
A ten-percentage point increase in vaccine coverage was associated with 6.5% reduction in prescription rates, equivalent to 14.2 fewer antibiotic prescriptions per 1,000 individuals (95% CI, 6.0 to 22.4, P = 0.001). Increased vaccination coverage reduced prescribing rates in the pediatric population (0 to 18 years) by 6.0% or 15.2 prescriptions per 1,000 individuals (95% CI, 9.0 to 21.3; P < 0.001), and in those over 65 years by 5.2% or 12.8 prescriptions per 1,000 individuals (95% CI, 6.5 to 19.2, P < 0.001).
"Substantially boosting seasonal influenza vaccination coverage should be a central element of efforts to reduce use of antibiotics," the authors of the study wrote.
Jun 6 Open Forum Infect Dis abstract
