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

Wide healthcare transmission of carbapenem-resistant Klebsiella noted

A multicenter US study identified widespread nosocomial transmission of carbapenem-resistant Klebsiella pneumoniae (CRKP) within and between healthcare settings, researchers reported yesterday in Clinical Infectious Diseases.

Using data from patients enrolled in the prospective Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacterales (CRACKLE-2) study, which includes patients with at least one clinical culture of carbapenem-resistant Enterobacterales (CRE), a team of US researchers created a cohort of patients with clonal group (CG) 258 CRKP who had been enrolled from April 2016 through August 2017.

To better understand CRKP transmission, they used whole-genome sequencing and phylogenetic analysis to evaluate static (defined by genetically related isolates with a most recent common ancestor) and dynamic (incorporating genetic distance, spatial distance, and transmission events) CRKP clusters within and between healthcare systems.

Most patients were admitted from home (150, 43%) or a long-term care facility (115, 33%). In total, 55 static and 47 dynamics clusters were identified involving 210 of 350 (60%) and 194 of 350 (55%) patients, respectively. About half of static clusters were identical to dynamic clusters. Static clusters consisted of 33 (60%) intra-system and 22 (40%) inter-system clusters. Dynamic clusters consisted of 32 (68%) intra-system and 15 (32%) inter-system clusters and had fewer single nucleotide polymorphism (SNP) differences compared to static clusters (8 vs 9). Dynamic inter-system clusters contained more patients than dynamic intra-system clusters (median, 4 vs 2).

"Most patients had a CRKp isolate that could be genetically linked to an isolate of at least one other patient, regardless of the method used to assign clusters," the study authors wrote. "Most patients were part of clusters with patients from the same healthcare system, but about a third of clusters showed evidence of transmission across healthcare systems."

The authors say these observations "emphasize that successful control of multidrug-resistant organisms requires infection prevention measures at both local and regional levels."
Sep 29 Clin Infect Dis abstract

Inappropriate antibiotics common in private practice in South Africa

Analysis of health insurance data found a high rate of inappropriate antibiotic prescribing by private-sector general practitioners (GPs) in South Africa, researchers reported today in JAC-Antimicrobial Resistance.

The analysis of February 2018 prescribing data from the claims database of a private health insurer by researchers from the University of Kwa-Zulu, Natal categorized antibiotic prescriptions as "appropriate," "potentially appropriate," and "inappropriate" based on International Classification of Disease (ICD-10) codes. Further assessments of antibiotic choice, dosage, and duration of treatment were carried out to determine the appropriateness of prescriptions in comparison with treatment guidelines.   

A total of 188,141 antibiotics were prescribed for 174,889 patients who consulted private-sector GPs in February 2018. Penicillins were the most frequently prescribed antibiotic class, accounting for 40.7% of all prescriptions, and amoxicillin-clavulanic acid was the most frequently prescribed antibiotic, making up 28.6% of all antibiotics prescribed—even though it was rarely recommended in guidelines. Respiratory diseases generated the most prescriptions, accounting for 46.1% of all diagnoses.

Of all prescriptions, 8.8% were appropriate, 32% were potentially appropriate, 45.4% were inappropriate, and 13.8% could not be assessed. Of those prescriptions deemed appropriate and potentially appropriate, 30.8% were the correct antibiotic, and of the correctly selected antibiotics, 57.7% had correct doses. Of the antibiotics with correct doses, 76.7% had correct dosage frequencies and durations of treatment.

"This is of concern, as under-dosing and over-dosing, even when the antibiotic choices are correct, puts patients at risk of treatment failure and at risk of developing adverse effects, respectively," the study authors wrote.

They concluded, "This study revealed that a substantial number of antibiotics are inappropriately prescribed by GPs in the private primary healthcare sector in South Africa, necessitating urgent stewardship interventions to sustain the efficacy of existing antibiotics, contain antibiotic resistance, improve the standard of care and reduce unnecessary healthcare expenditure by health insurers."
Sep 30 JAC-Antimicrob Resist study

UK report shows rise in resistant, sexually transmitted Shigella

Originally published by CIDRAP News Sep 29

A report yesterday from the United Kingdom's Health Security Agency (HSA) shows sexually transmitted Shigella infections are rising again in England after falling during the COVID-19 pandemic.

Analysis of data from two surveillance databases, the Second Generation Surveillance System (SGSS) and the Gastrointestinal Data Warehouse (GDW), shows Shigella infections climbed by 189% in SGSS and 172% in GDW from the third quarter of 2021 to the second quarter of 2022.

The number of travel- and non–travel-related Shigella cases began to climb following the easing of COVID-19 restrictions and is now nearing prepandemic levels. The increase was most notable (127%) in men who have sex with men (MSM), and the highest proportion of diagnoses among presumptive MSM was in London.

The report also found that among presumptive MSM, antimicrobial resistance is consistently high in Shigella flexneri and Shigella sonnei isolates, with 96% and 92% of isolates classified as multidrug-resistant (MDR) or extensively drug-resistant (XDR), respectively. A sustained increase in the proportion of XDR S sonnei has been driven by a resurgence of an S sonnei clade 5 outbreak strain.

In a recent study published in The Lancet Infectious Diseases, HSA investigators reported that of 72 confirmed cases Shigella cases identified in the United Kingdom from Sep 1, 2021, to Feb 9, 2022, all belonged to clade 5 and all were genotypically MDR or XDR.

While shigellosis is often associated with exposure to contaminated food and water, it can be transmitted through oral and anal sex and is considered a sexually transmitted disease. A report in February from the European Centre for Disease Prevention and Control (ECDC) noted an increase in XDR S sonnei infections in the United Kingdom and elsewhere in Europe and warned that the risk of spread among networks of MSM who engage in high-risk sexual practices, such as oral-anal contact, could be high in the coming months.
Sep 28 UK HSA report
Jul 6 Lancet Infect Dis study
Feb 23 ECDC rapid risk assessment

Randomized trial finds no impact from antibiotic prescribing feedback

Originally published by CIDRAP News Sep 29

A randomized trial conducted in Scottish primary care practices found that general practice-level feedback had no effect on antibiotic prescribing, researchers reported today in the Journal of Antimicrobial Chemotherapy.

For the Feedback on Antibiotic Prescribing in Primary Care (FAPCC) trial, 340 Scottish general practices were randomized to receive four quarterly antibiotic-prescribing feedback reports (the intervention group) or not (the control group) from the second quarter of 2016 to the first quarter of 2017. The reports included different clinical topics, benchmarking against national and health board prescribing rates, behavioral messaging with improvement techniques, and educational resources. The primary outcome was total antibiotic prescribing rate.

The baseline total antibiotic prescribing rate in the 181 intervention hospitals and 159 control hospitals was 1.93 prescriptions and 1.98 prescriptions per 1,000 patients per day, respectively. Total antibiotic prescribing rates were falling in both arms prior to the study, and the downward trend continued during the study period, falling to 1.83 (intervention) and 1.90 (control) prescriptions per 1,000 patients per day at the main analysis timepoint (1 year after the last feedback report was issued).

There was no evidence of intervention effect (adjusted rate ratio, 0.98; 95% confidence interval (CI), 0.94 to 1.02). There was also no evidence of effect on secondary prescribing or hospital admission outcomes.

The study authors hypothesize that the feedback had no impact on prescribing because it added little to existing antibiotic stewardship interventions that had been applied over the previous 14 years and had resulted in steady and substantial reductions in antibiotic prescribing in Scottish primary care. They suggest that focusing future feedback interventions on the highest prescribers may have a better return on investment, but say further research is needed.

"This well-designed, real-world, practice-level antibiotic prescribing feedback had minimal additional effects in the context of decreasing antibiotic prescribing and an established national stewardship program," they wrote. "Designing and implementing effective feedback interventions remains a priority to support challenging targets for reductions in antibiotic prescribing."
Sep 29 J Antimicrob Chemother study

Trial supports protocol for reducing antibiotics in suspected sepsis cases

Originally published by CIDRAP News Sep 28

An opt-out protocol for antibiotic de-escalation in patients with suspected sepsis resulted in more antibiotic discontinuations and less exposure to broad-spectrum antibiotics, with no evidence of harm, according to the results of a randomized controlled trial published today in Clinical Infectious Diseases.

The trial, conducted in 10 US acute care hospitals from September 2018 through May 2020, aimed to quantify the effect of an antibiotic opt-out program targeting low-risk patients in whom systemic infection was not confirmed or who recovered quickly and were therefore candidates for antibiotic de-escalation.

Eligible patients were randomly assigned to the opt-out protocol versus usual care. In the intervention arm, the clinician responsible for antibiotic treatment was encouraged to stop antibiotics based on an initial safety screen that determined the patient was not likely to have sepsis. If the clinician decided to continue antibiotics, a study team member initiated a guided antibiotic de-escalation discussion. The primary outcome of the trial was 30-day post-enrollment antibacterial days of therapy (DOT).

Among 9,606 patients screened, 767 were enrolled. Patients in the intervention arm had 32% lower odds of antibiotic continuation (79% vs 84; odds ratio [OR], 0.68; 95% CI, 0.47 to 0.98). Among those who had antibiotics continued, DOT (mean, 10.4 vs 9.9; ratio of means, 1.06; 95% CI, 0.88 to 1.26) were not different. Fewer intervention patients were exposed to extended-spectrum antibiotics (36% vs 44%). Thirty-day safety events were similar in both arms.

The most common rationales for continuing antibiotics were treatment of localized infection (76%) and belief that stopping antibiotics was unsafe (31%).

The study authors suggest the screening tools and standardized opt-out language and questions were critical factors in the success of the intervention.

"The opt-out language set expectations for antibiotic discontinuation based on patient-specific review and screening criteria," they wrote. "Thus, it sped up decisions to stop antibiotics among patients who ultimately may have had antibiotics stopped at a later timepoint in the absence of an intervention."
Sep 28 Clin Infect Dis abstract

Report: Resistant Campylobacter common in UK chicken

Originally published by CIDRAP News Sep 28

A new report from the United Kingdom's Food Safety Agency (FSA) finds that antimicrobial resistance (AMR) in Campylobacter bacteria isolated from retail chicken meat and chicken at slaughter is common but appears to have plateaued since 2014.

The analysis of AMR trends in Campylobacter, which causes an estimated 500,000 cases of foodborne illness annually in the United Kingdom, found that resistance to quinolones (ciprofloxacin), nalidixic acid, and tetracycline is common in Campylobacter jejuni and Campylobacter coli in UK broiler chickens.

The prevalence of ciprofloxacin resistance in C jejuni rose from 13% in 2001 to 2005 to 47% in 2011 to 2018, while ciprofloxacin resistance in C coli rose from 18% in the years 2001 to 2005 to 48% in 2016 to 2018. But for both species, there has been no significant change in resistance to ciprofloxacin since 2014.

Similar trends were observed for resistance to tetracycline, with resistance climbing from 27% in 2001 to 66% in 2018 among C jejuni isolates and from 23% in 2001 to 55% post-2013 in C coli, but no significant changes were observed since 2014. Rates of resistance to nalidixic acid rose from 16% in 2001 to 52% in 2018 in C jejuni, and from 16% in 2001 to 50% in 2017 in C coli, but resistance has declined post-2014.

Rates of resistance to erythromycin, gentamicin, and streptomycin were low, as were multidrug-resistant phenotypes.

"It is possible that this is related to the significant reductions in usage of antimicrobials (AMU) undertaken by the poultry industry in the past decade," the report states. "However, more data is required to provide convincing evidence that historical increases in the prevalence of quinolone and tetracycline resistance have ceased."

The authors say monitoring of AMR in C jejuni and C coli from chicken should continue and that further research should investigate the impact of other variables, including the effect of production system and seasonality on the incidence of resistance in Campylobacter.
Sep 28 FSA report

Trial: Fecal microbiota transplantation superior to antibiotics for C difficile

Originally published by CIDRAP News Sep 27

A randomized clinical trial conducted in Denmark found that, in patients with a first or second Clostridioides difficile infection, fecal microbiota transplantation (FMT) was superior to standard-of-care antibiotic treatment in achieving sustained resolution of symptoms, researchers reported last week in The Lancet Gastroenterology & Hepatology.

Conducted at a university hospital in Aarhus, Denmark, the double-blind, placebo-controlled trial enrolled adult patients with a first or second C difficile infection and randomly assigned them to receive either FMT or placebo after receiving 10 days of vancomycin, the standard antibiotic treatment. Treatments were administered on day 1 and between days 3 and 7, and patients were followed for 8 weeks or until recurrence. The primary outcome was resolution of C difficile–associated diarrhea (CDAD) after 8 weeks.

A total of 42 patients were assigned to FMT (21) or placebo (21) from Jun 21, 2021, to Apr 1, 2022. Interim analysis on Apr 7 showed that 19 of 21 patients in the FMT group had resolution of CDAD at 8 weeks, compared with 7 of 21 in the placebo group, for an absolute risk reduction of 57%. Because of the significantly lower resolution rate in the placebo group, the trial was stopped for ethical reasons.

"In rare cases, it can happen that you discover that the treatment you are investigating is so effective that it is ethically indefensible to continue," first author Simon Mark Dahl Baunwall, MD, said in a press release from Aarhus University. "Our study is one example, in that the new FMT treatment is so much better than the standard treatment with antibiotics that it would be unethical to continue, because the patients in the control group would risk not receiving the FMT treatment."

Overall, 204 adverse events were reported, with one or more reported in 20 of 21 patients in the FMT group and all 21 in the placebo group. The most common adverse events were diarrhea and abdominal pain.
Sep 21 Lancet Gastroenterol Hepatol abstract
Sep 26 Aarhus University press release

Wide healthcare transmission of carbapenem-resistant Klebsiella noted

A multicenter US study identified widespread nosocomial transmission of carbapenem-resistant Klebsiella pneumoniae (CRKP) within and between healthcare settings, researchers reported yesterday in Clinical Infectious Diseases.

Using data from patients enrolled in the prospective Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacterales (CRACKLE-2) study, which includes patients with at least one clinical culture of carbapenem-resistant Enterobacterales (CRE), a team of US researchers created a cohort of patients with clonal group (CG) 258 CRKP who had been enrolled from April 2016 through August 2017.

To better understand CRKP transmission, they used whole-genome sequencing and phylogenetic analysis to evaluate static (defined by genetically related isolates with a most recent common ancestor) and dynamic (incorporating genetic distance, spatial distance, and transmission events) CRKP clusters within and between healthcare systems.

Most patients were admitted from home (150, 43%) or a long-term care facility (115, 33%). In total, 55 static and 47 dynamics clusters were identified involving 210 of 350 (60%) and 194 of 350 (55%) patients, respectively. About half of static clusters were identical to dynamic clusters. Static clusters consisted of 33 (60%) intra-system and 22 (40%) inter-system clusters. Dynamic clusters consisted of 32 (68%) intra-system and 15 (32%) inter-system clusters and had fewer single nucleotide polymorphism (SNP) differences compared to static clusters (8 vs 9). Dynamic inter-system clusters contained more patients than dynamic intra-system clusters (median, 4 vs 2).

"Most patients had a CRKp isolate that could be genetically linked to an isolate of at least one other patient, regardless of the method used to assign clusters," the study authors wrote. "Most patients were part of clusters with patients from the same healthcare system, but about a third of clusters showed evidence of transmission across healthcare systems."

The authors say these observations "emphasize that successful control of multidrug-resistant organisms requires infection prevention measures at both local and regional levels."
Sep 29 Clin Infect Dis abstract

Inappropriate antibiotics common in private practice in South Africa

Analysis of health insurance data found a high rate of inappropriate antibiotic prescribing by private-sector general practitioners (GPs) in South Africa, researchers reported today in JAC-Antimicrobial Resistance.

The analysis of February 2018 prescribing data from the claims database of a private health insurer by researchers from the University of Kwa-Zulu, Natal categorized antibiotic prescriptions as "appropriate," "potentially appropriate," and "inappropriate" based on International Classification of Disease (ICD-10) codes. Further assessments of antibiotic choice, dosage, and duration of treatment were carried out to determine the appropriateness of prescriptions in comparison with treatment guidelines.   

A total of 188,141 antibiotics were prescribed for 174,889 patients who consulted private-sector GPs in February 2018. Penicillins were the most frequently prescribed antibiotic class, accounting for 40.7% of all prescriptions, and amoxicillin-clavulanic acid was the most frequently prescribed antibiotic, making up 28.6% of all antibiotics prescribed—even though it was rarely recommended in guidelines. Respiratory diseases generated the most prescriptions, accounting for 46.1% of all diagnoses.

Of all prescriptions, 8.8% were appropriate, 32% were potentially appropriate, 45.4% were inappropriate, and 13.8% could not be assessed. Of those prescriptions deemed appropriate and potentially appropriate, 30.8% were the correct antibiotic, and of the correctly selected antibiotics, 57.7% had correct doses. Of the antibiotics with correct doses, 76.7% had correct dosage frequencies and durations of treatment.

"This is of concern, as under-dosing and over-dosing, even when the antibiotic choices are correct, puts patients at risk of treatment failure and at risk of developing adverse effects, respectively," the study authors wrote.

They concluded, "This study revealed that a substantial number of antibiotics are inappropriately prescribed by GPs in the private primary healthcare sector in South Africa, necessitating urgent stewardship interventions to sustain the efficacy of existing antibiotics, contain antibiotic resistance, improve the standard of care and reduce unnecessary healthcare expenditure by health insurers."
Sep 30 JAC-Antimicrob Resist study