Impact of selective reporting of antibiotic susceptibility testing results on meropenem prescriptions for the treatment of Pseudomonas aeruginosa infections after 2020 EUCAST criteria update: an observational study in a university hospital
Antimicrobial Resistance & Infection Control volume 11, Article number: 165 (2022)
We previously reported an increase in meropenem prescriptions for Pseudomonas aeruginosa infections in our hospital after the implementation of the 10th version of the EUCAST breakpoints table for P. aeruginosa in January 2020. As a consequence, antibiotic susceptibility testing results were adapted by masking meropenem for P. aeruginosa isolates susceptible to either ceftazidime, cefepime or piperacillin-tazobactam. We aimed to assess the changes in meropenem prescriptions after the implementation of the selective reporting.
In this retrospective single-centre observational study, we analysed antimicrobial therapies prescribed for P. aeruginosa infections after the susceptibility testing results have been made available over three periods: “before EUCAST update”, “after EUCAST update without selective reporting” and “after EUCAST update with selective reporting”, at Lausanne University Hospital, Switzerland. We collected epidemiological, microbiological and clinical data. The primary outcome was the prescription of meropenem to treat P. aeruginosa infections after the release of susceptibility testing results. Secondary outcomes were the use of increased dosage of non-meropenem anti-pseudomonal drugs, and IDs’ consultations rates after the release of susceptibility testing results.
Among the 457 patients included, 65 (14.2%) received meropenem: 5/148 (3.4%) before EUCAST update, 51/202 (25.3%) after EUCAST update without selective reporting, and 9/107 (8.4%) after EUCAST update with selective reporting. Supervision and counselling from IDs as well as the use of increased dosages of non-carbapenem antibiotics increased in both periods after EUCAST update, compared to the first period, respectively: 40.5% (60/148) versus 61.4% (124/202) versus 51.4% (55/107) (P < 0.001), and 57.9% (84/148) versus 91.1% (183/202) versus 90.7% (97/107) (P < 0.001).
Selective reporting of antibiotic susceptibility testing results might decrease unnecessary meropenem prescriptions for the treatment of P. aeruginosa infections and could be part of multimodal antibiotic stewardship interventions.
In January 2019, the 10th version of breakpoints table for Pseudomonas aeruginosa was updated by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) . As a result, wild-type P. aeruginosa isolates previously labelled “S” were labelled “I” for ceftazidime, cefepime and piperacillin-tazobactam, but remained “S” for meropenem. Since the implementation in our hospital of the new EUCAST criteria in January 2020, we reported increased odds of meropenem prescriptions .
Following this observation, the internal antibiotic stewardship committee decided to change the report of antimicrobial susceptibility testing results using the “selective reporting”, also known as “cascade reporting”, an antibiotic stewardship strategy of reporting susceptibilities of broad-spectrum agents only when the isolate is resistant to more narrow-spectrum agents [3,4,5]. Practically, since December 21, 2020, meropenem is no longer reported for patients with a P. aeruginosa isolate that is susceptible (“I”—“susceptible, increased exposure”) to at least one beta-lactam among ceftazidime, cefepime and piperacillin-tazobactam. However, if the isolate is resistant to meropenem, it is reported on the susceptibility testing results. Of note, clinicians can always ask the microbiology department to unmask meropenem if needed, in particular in polymicrobial infections or in case of allergy.
In the present study, we aimed to evaluate the impact of this selective reporting on meropenem prescriptions for Pseudomonas aeruginosa infections at Lausanne University Hospital.
Study design and setting
This study is the continuation of a first study that took place at Lausanne University Hospital, a 1500-bed tertiary university hospital in Lausanne, Switzerland. The study setting has been previously described in details elsewhere .
Study design and participants
We conducted a retrospective observational single-center study. All consecutive adult patients with P. aeruginosa isolated from a clinical sample between 01.08.2019 and 31.07.2021 were identified. Those who received an antibiotic for a P. aeruginosa infection and that could be treated either by ceftazidime, cefepime and/or piperacillin-tazobactam based on susceptibility testing results available in the Electronic Medical Record (EMR) were included in the study. We excluded patients with a P. aeruginosa isolate resistant to meropenem, and those with a P. aeruginosa infection that could not be treated by ceftazidime, cefepime or piperacillin-tazobactam due to allergy. We also excluded patients with a polymicrobial infection requiring a treatment with a carbapenem, including ESBL-producing Enterobacterales co-infections.
Three periods were defined: the first from 01.08.2019 to 26.01.2020-patients treated “before EUCAST update” (period 1), the second from 27.01.2020 to 20.12.2020—patients treated “after EUCAST update without selective reporting” (period 2) and the third from 21.12.2020 to 31.07.2021—patients treated “after EUCAST update with selective reporting” (period 3).
Epidemiological, clinical and microbiological data were extracted from the EMR. Data collection for patients meeting the same criteria from 01.08.2019 to 31.07.2020 had been done in the previous study . Epidemiological data included age, sex, and relevant comorbidities. We also collected data on microbiology results, antimicrobial therapy, stay in intensive care, infectious diseases specialist (IDs) consultations, and other clinical aspects: site and severity of infection, community versus healthcare-associated infection—including vascular catheter-associated infections, catheter-associated urinary tract infections, ventilator-associated pneumonia, surgical site infections and infections occurring more than 48 h after admission to hospital. We entered all the data in an electronic clinical report form (eCRF) using the Redcap® platform (Research Electronic Data Capture v10.3.3, Vanderbilt University, Tennessee, USA).
In case of multiple episodes of P. aeruginosa infection, patients included a first time before the implementation of selective reporting could be included once again after selective reporting.
The primary outcome was meropenem prescription as targeted treatment (i.e. after P. aeruginosa susceptibility testing release). We took into consideration the antipseudomonal antibiotic initiated after the susceptibility testing results have been made available. For patients receiving empiric antipseudomonal antibiotic therapy initiated before susceptibility testing results, we took into consideration the ongoing antipseudomonal antibiotic 24 h after the susceptibility testing results have been made available.
Secondary outcomes were the use of increased dosage for non-meropenem anti-pseudomonal drugs, and IDs consultation rates after susceptibility testing results have been made available.
For the descriptive analysis, we summarized categorical variables as numbers (percentages), normally distributed continuous variables as mean ± standard deviation (SD), and continuous variables with a skewed distribution as median [interquartile range (IQR)]. Between-group comparisons were performed using chi-square or Fisher’s exact test for qualitative variables, and Student’s t-test, analysis of variance or Kruskal–Wallis test for quantitative variables.
Analyses for our primary outcome were performed through uni- and multivariable logistic regression models. Models were built manually, adding demographic, and clinical characteristics. We then added variables with a P value below < 0.2 from our univariable analysis. Models were built based on Akaike Information and Bayesian Information Criteria. We calculated Odds ratio (OR) with 95% confidence interval (95% CI) to determine the weight of risks factors for meropenem prescription. P values < 0.05 were considered as statistically significant. Due to the important number of dependent events and the small number of meropenem prescriptions, especially for period 1, these models did not allow us to perform a robust analysis. Therefore, we report only descriptive results. We used Stata SE 17.0 (StataCorp, College Station, TX) for all analyses.
Among 1329 patients with P. aeruginosa documented in a clinical sample between 01.08.2019 and 31.07.2021, 457 patients met inclusion criteria: 148 in the first period, 202 in the second period and 107 in the third period (Additional file 1: Supplementary figure 1). Demographic, clinical and microbiological characteristics of included patients are presented in Table 1.
The proportion of meropenem prescriptions after the susceptibility testing results have been made available varied during the three periods as followed: 3.4% (5/148) before EUCAST update, 25.3% (51/202) after EUCAST update without selective reporting and 8.4% (9/107) after EUCAST update with selective reporting (P < 0.001). The request for IDs consultations was higher in the second and third periods than before EUCAST update (40.5% (60/148) versus 61.4% (124/202) versus 51.4% (55/107), P =< 0.001), as well as the use of increased dosages of non-carbapenems anti-pseudomonal antibiotics (57.9% (84/148) versus 91.1% (183/202) versus 90.7% (97/107), P = < 0.001).
Compared with the reference period before EUCAST update (period 1), there was a significant difference in the odds of targeted meropenem prescriptions for patients included after EUCAST update without selective reporting (period 2) (OR 9.65, 95% CI [3.74–24.89]), and after EUCAST update with selective reporting (period 3) (OR 2.62 [0.85–8.07]), P < 0.001 (Table 2).
Patients with a history of ESBL infection or colonisation (positive sample prior to the current episode of infection within the last six months), a sepsis or septic shock, a Gram-negative rod co-infection, a rapid or ultimately fatal disease, a low respiratory tract infection or a healthcare-associated infections, were also more likely to receive meropenem in unadjusted models.
The primary aim of EUCAST revised definitions of susceptibility test categories was to eliminate the ambiguity associated with the old “intermediate (I)” category . The new “I” category represents a second susceptible category, defined as “susceptible – increased exposure”. However, this change was not always clear for clinicians who preferentially continued to select antibiotics reported as susceptible (S). Regarding wild-type P. aeruginosa, anti-pseudomonal antibiotics are now systematically reported as “I”, except for meropenem as the standard dosage allows reporting wild-type strains as “S”. We previously reported that the change to 2020 EUCAST criteria might be associated with an increase of meropenem prescriptions for the treatment of P. aeruginosa infections. These over-prescriptions were mainly switches of empiric therapy to meropenem after receiving the susceptibility testing results, stressing the need of prescribers' education and the importance of antibiotic stewardship interventions . In the present study, we observed a decrease of meropenem prescriptions after the implementation of selective reporting, although the rates of meropenem prescriptions were still higher than in the first period (8.4% vs 3.4%). One explanation could be the higher rate of healthcare-associated infections in the third period compared to the first one which seems to be a risk of prescribing meropenem as empirical therapy without systematic de-escalation. It also highlights the fact that selective reporting should be associated with training and other antibiotic stewardship measures for clinicians.
The introduction of 2020 EUCAST criteria was also associated with a higher proportion of IDs consultations for P. aeruginosa infections in the second and third periods without and with selective reporting. These findings suggest that masking meropenem combined with infectious diseases consultations prevent over-prescription of meropenem.
Selective reporting of antibiotic susceptibility testing results has been described as a promising antibiotic stewardship tool to reduce inappropriate antibiotic prescriptions [4, 5, 7]. In the specific case of infections due to P. aeruginosa, this easy-to-implement strategy should be promoted to reduce meropenem over-prescriptions, regardless of the size of the hospital and the availability of IDs consultations.
As reported in our first study, we still observed a trend for higher use of adequate targeted antibiotic dosage for ceftazidime, cefepime and piperacillin-tazobactam after EUCAST criteria update (periods 2 and 3).
Our study has several limitations. First, it is a retrospective observational monocentric study with a small sample size and limited external validity. Second, since only 65 patients in total had a meropenem prescription after the susceptibility testing results have been made available, with only five prescriptions before the new EUCAST criteria were implemented, this did not allow us to perform a robust adjusted analysis. Hence, we cannot formally conclude that “selective reporting” was the main cause of reduction in meropenem prescriptions in the third period. Third, many IDs consultations are given orally and not documented in the EMR with a potential underestimation of IDs consultations and their impact on reducing inappropriate prescriptions. Furthermore, the three study periods were not equivalent in duration and in seasons with different epidemiological characteristics, which makes them not perfectly comparable. Another limitation is that we designed our study to evaluate the over-prescription of meropenem as a marker of the quality of care delivered. We did not collect and provide data on patient’s outcome. Finally, we have no data on phone calls to the microbiology laboratory to ask for meropenem susceptibility results if masked.
Despite these limitations, we observed a marked increase in meropenem prescriptions in our hospital after the implementation of the new EUCAST criteria, followed by a decrease after the setting up of the selective reporting. A learning effect and IDs consultations might also have played a role in this decrease. As mentioned by Turnidge et al., these results stress the importance of education and multimodal antibiotic stewardship strategies, as the selective reporting, to improve appropriate prescriptions after the introduction of revised definitions and breakpoint updates .
In conclusion, multimodal antibiotic stewardship interventions with selective reporting of antibiotic susceptibility testing results for Pseudomonas aeruginosa and access to IDs consultations might have reduced the proportion of meropenem over-prescriptions after the 10th version of EUCAST breakpoint table updates in our hospital. These results suggest that selective reporting could be an interesting, easy-to-implement and cheap tool to reduce inappropriate broad-spectrum antibiotics prescriptions.
Availability of data and materials
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
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We thank the doctors and nurses from the department of Infection prevention and control disease for all their work and support. We thank also the infectious diseases and microbiology departments for their shared enthusiasm and valuable support.
No external funding was received.
Ethics approval and consent to participate
As this study was part of the analysis of current clinical care practices, the local ethic committee (La Commission cantonale (VD) d'éthique de la recherche sur l'être humain (CER-VD), Switzerland) stated that this retrospective project was out of the scope of the Swiss Human Research Act and did not required an ethical approval.
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Munting, A., Damas, J., Viala, B. et al. Impact of selective reporting of antibiotic susceptibility testing results on meropenem prescriptions for the treatment of Pseudomonas aeruginosa infections after 2020 EUCAST criteria update: an observational study in a university hospital. Antimicrob Resist Infect Control 11, 165 (2022). https://doi.org/10.1186/s13756-022-01203-x