Antibiotic appropriateness and adherence to local guidelines in perioperative prophylaxis: results from an antimicrobial stewardship intervention

Antimicrobial resistance is considered a global threat for both human health and economic development [1]. In both low-income and high-income countries, resistant microorganisms are the main causative agents of healthcare-associated infections (HAIs) and, among those, surgical site infections (SSIs) are the most reported and surveyed type of HAI, the accounting for up to 20% of all hospital acquired infections [2].. SSIs are defined as postoperative infections occurring within 30 days from a surgical procedure, or within 1 year from a permanent implant [3].

The European Centre for Disease Prevention and Control (ECDC) reports an in-hospital incidence ranging from 0.1 to 5.7 surgical site infections per 1000 post-operative patient-days. Cumulative incidence depends greatly on the type of surgical procedure, with highest rates described for open and laparoscopic colorectal operations (respectively 10.1 and 6.4%), followed by open cholecystectomy (3.9%) and coronary artery bypass graft (2.6%) [3]. Once occurred, surgical site infections are associated with a 2- to 11- fold increased risk of mortality, and the average length of stay is extended of 7–11 days [1, 4, 5]. Excess in healthcare cost is driven by prolonged hospitalization, treatment, additional diagnostic tests and re-operations [6]. The prevention of these infections is complex and it requires the integration of a range of measures before, during and after surgery [7].

Antimicrobial stewardship (AMS) programs play an increasingly important role in patient care and hospital policies [8]. They are widely recognized as a key intervention in reducing the burden of healthcare associated infections and costs, by both improving antimicrobial prescriptive habits and limiting the spread of resistance. Of note, 2016 guidelines by the World Health Organization highlighted the role of unnecessary prolongation of surgical antibiotic prophylaxis (SAP) in developing of antimicrobial resistance [7], and the implementation of AMS plan has recently been included among the Joint Commission Standards of Care [9].

The present study aims to report the results of an educational, participative, long-term continuing AMS intervention conducted between 2013 and 2019 on an Italian University Hospital performing more than 40.000 surgical interventions per year.

We analyzed a total of 789 SAP prescriptions administered to 735 patients, respectively 407 and 382 in pre- and post-interventional surveys (2013 and 2019). Demographic factors and admitting surgical departments are summarized in Table 1. Mean age was 56.7 year (± 17.8y), and 58.3% (n = 433) of included patients were female. 13.3% (n = 104) of all surveyed cases involved contaminated or dirty operative wounds

In 2013, inappropriateness was almost entirely multi-dimensional (Table 2): 98.8% of inappropriate antimicrobial prescriptions were non adherent to local guidelines for at least two dimensions. Before the intervention, the most common reason of inappropriateness were mistakes in indication: 169 (41.5%) of surveyed cases were either prescribed when unnecessary or were not administered prior to procedures with defined SAP indication. In addition, the same amount of patients didn’t receive the correct antimicrobial agent for SAP, or they an inappropriate dose. Furthermore, 118 (29%) of the surveyed baseline cases were inappropriately prolonged after the completion of the surgical procedure (for more than 48 h in case of open-heart surgery, or more than 24 h for all other surgeries). Of note, in 2013, in all surveyed cases of prolonged SAP prescription there was at least one additional reason of inappropriateness.

In the post-interventional survey, appropriateness in duration shifted from 71 to 80.1% (P <  0.0001) of SAP prescriptions, while appropriateness in indication passed from 58.5 to 93.2% (P <  0.0001). A significant increase (P <  0.05) in prescriptive appropriateness was detected also for the other categories included in the study: the correct antimicrobial agent was prescribed in 80.6% of post-intervention cases versus 58.5% of the baseline cases, and surgical prophylaxis was administered at the recommended timing in 97.6% vs 92.4% of cases. Overall, guideline adherence was 46.9% (n = 370), improving from 36.6% (n = 149) at baseline to 57.9% (n = 221) post-intervention (P <  0.0001). Overall and dimension-specific drop in inappropriateness is showed in Fig. 1.

Hospital-associated infections and antimicrobial resistance are a public health priority, and there is a considerable amount of evidence assessing the efficacy of AMS interventions in decreasing the burden of antimicrobial resistance [14]. According to the existing body of evidence, both restrictive and enabling interventions demonstrated to be effective in increasing compliance with antibiotic policies without an increase in mortality, hospital length-of-stay or rate of drug-related adverse events [15]. Still, suboptimal use of antimicrobial for surgical prophylaxis is a common phenomenon [16].

In our study, overall inappropriateness dropped from 63.4 to 42.1%, thus lowering post-interventional results to values reported in countries with low-rates of antimicrobial resistance [17, 18]. However, it should be noted that few studies addressed multiple outcomes of SAP guidelines adherence (indication, antimicrobial selection and dosing, timing, duration) targeting several surgical specialties. Furthermore, in our work, the total guideline adherence rates are affected form the fact that we defined as “overall appropriate” only prescriptions in which all the dimensions were respected.

At baseline, inappropriateness was largely multidimensional: in 70.5% of pre-interventional non-adherent prescriptions, at least two reasons of inappropriateness were recorded, while this percentage fell to 24.2% in 2019.

In the latter, it persisted almost exclusively for urologic and ENT surgical procedures, departments that were identified as main drivers of post-interventional overall inaccuracy. This leads to two considerations. First, that without AMS team guidance, SAP prescriptions tend to be more chaotic, being selection and dosing and duration the two most commonly associated types of inappropriateness (wrong choice/dosing of the antimicrobial agent plus prolonged administration); in contrast, after enablement, only a small proportion of non-compliant departments fail to follow system processes and guidelines. Second, that the same enabling intervention didn’t affect all departments with the same strength. This may be due to inner difficulties in shifting from old, unsupported practices to new prescriptive behaviors, or it may be due to a wider, department-specific deregulation of SAP prescribing. However, a detailed investigation of the reasons behind lack of compliance fall outside the aim of this work.

As recently stated from a Cochrane Library editorial [15], the effectiveness of antimicrobial stewardship needs to be assessed in reason of long-term outcomes, in order to differentiate the impact of a specific intervention with the unintended effects of other concurrent factors. Furthermore, evaluation of sustainability is particularly attractive, because unmaintained results prevent AMS resources to focus towards new priorities. Restriction is relatively low cost, but evidence exist that removal of restrictive measures could lead to reversal of intervention effects [19, 20], probably in reason of a loss of trust and guidance between SAP prescribers and AMS team. More concerning, however, are the findings that enablement fail to achieve a sustained effect after implementation [21]. In our study, 6 years after the baseline evaluation, SAP prescribing still showed a substantial improvement (Fig. 1), highlighting the effectiveness of enablement (review and recommend change) also in terms of sustainability.

The present study evaluates the impact of a continuous, enabling intervention 6 years after its implementation, focusing exclusively on surgical prophylaxis guideline compliance. In our analysis we didn’t include secondary outcomes (e.g. mortality, length of stay) or other clinical (e.g. surgical site infection or acute kidney injury) and microbial outcomes (CDI, colonization or infection with antimicrobial-resistant bacteria), which could have represented an unintended consequence of a generalized improvement in clinical care, rather than a direct measure of the effectiveness of our intervention.

Our study has several limitations. First, our intervention didn’t include explicit goal setting and action planning. Second, we didn’t include a control group, as this was considered unethical. Third, the lack of secondary clinical outcomes and of microbial data didn’t allow us to determine the actual impact of the SAP prescriptive improvement.

Finally, in 2019, appropriateness in duration was still far to be optimal, being the most reported reason of non-compliant prescribing in the post-interventional survey, as well as the dimension with the lowest relative improvement rate (from 71% in 2013 to 80,1% in 2019; P = 0.002). However, this is not an exclusive finding of this work. While all current guidelines recommend SAP discontinuation within 24 h from incision, globally, surgeons still have a tendency to routinely continue SAP several days after surgery [22, 23]. This behavior is likely sustained by the belief that prolonged antimicrobial administration is safe and more efficient in reducing SSI incidence [24, 25], this despite evidence of SAP ineffectiveness beyond 24 h [7, 11]. Conversely, as highlighted by the World Health Organization, prolongation of antibiotic prophylaxis is one of the major determinants of antimicrobial resistance [7, 26].

Antibiotic resistance is a major public health concern. Antibiotic stewardship programs are changing the entire healthcare landscape, having largely demonstrated to be effective and safe. In surgery, proper administration of antibiotic prophylaxis is crucial in preventing the incidence of SSI, but it requires constant effort and close collaboration among SAP prescribers and AMS team. Due to its toxicity and to its probable impact on local ecology, future AMS intervention will need to prioritize SAP prolongation improvement rates.