Drug-related problems associated to antibiotic use in cesarean delivery: a retrospective analysis in a secondary care hospital.

Introduction

A drug-related problem (DRP) is an event or circumstance involving drug therapy that actually or potentially interferes with desired health outcomes.¹ DRPs account for 21% of hospital readmissions, 69% of such problems being preventable.²

Different tools have been agreed on and validated by expert panels to identify and categorize DRPs and their causes.^1,3,4 One of them is the Pharmaceutical Care Network Europe (PCNE) DRP Classification, which has been revised several times, the last version being 9.1 (March 2020). Its validity and reproducibility has been tested^5,6 and it has also been used in many recent studies.^7–9

Antibiotics are one of the most commonly used pharmacological groups and, despite being a key element in the treatment of infectious diseases and in the practice of numerous medical procedures, they can be associated with adverse events that may be life-threatening.¹⁰ Their beneficial effect is compromised by the rapid escalation of antimicrobial resistance, which is mainly the result of irrational use of antibiotics.¹¹ The implementation of clinical guidelines on the use of antibiotics could optimize treatment results.¹²

Therapy optimization and review by a clinical pharmacist includes the identifying and solving DRPs associated with treatments administered to specific patients with the purpose of maximizing benefits and minimizing drug-related risks.¹³

The pharmacist is responsible for promoting adequate use of antibiotics and is therefore expected to provide patients, caregivers and healthcare professionals with the appropriate information, thus playing a prominent role in this regard.^14,15

According to the World Health Organization (WHO), only 10-15% of pregnancies require cesarean delivery for medical reasons.¹⁶ However, in 2018, 60% of 169 countries exceeded these figures, Ecuador standing out among them with 45.5% deliveries using this method.¹⁷ In this country there are Clinical Practice Guidelines for the Assistance of Cesarean Section Deliveries, which address preoperative antibiotic prophylaxis (PAP) but fail to establish specific protocols for antibiotic use.¹⁸

In light of the above, the aim of this study is to identify and categorize the DRPs associated with the use of antibiotics in women undergoing cesarean delivery in a secondary-care hospital in Ecuador and to analyze the causes of these problems, making an improvement proposal on PAP use in accordance with the international guidelines.

Methods

Results

Participants and DRP identification

Participants were aged between 16 and 48 years (30.87 ± 5.50) and 66.83% came from urban areas. Regarding the procedures, 31.33% were scheduled and 68.67% were emergency surgeries (Table 1).

Table 1. Distribution of DPRs identified in the study.

Variables	Patients No (%)	DRPs/patients
		1 DRP No (%)	2 DRP No (%)	3 DRP No (%)	4 DRP No (%)
Age (years)
16-19	16 (1.97)	9 (0.8)	7 (0.62)	-	-
20-34	584 (71.74)	381 (33.87)	195 (17.33)	8 (0.71)	-
≥35	214 (26.29)	126 (11.2)	84 (7.47)	3 (0.27)	1 (0.12)
Type of surgery
Emergency	559 (68.67)	327 (40.17)	225 (27.64)	7 (0.86)	-
Scheduled	255 (31.33)	189 (23.22)	61 (7.50)	4 (0.49)	1 (0.12)

As shown in Figure 1, 30.10% of the patients did not receive PAP, although they all received antibiotics after surgery. 13 different antibiotics were used in the reviewed treatments, the most common being cefazolin and cefalexin. Cefazolin was administered as prophylaxis in 98.07% of the PAP (68.55% of the total sample), and as postsurgery therapy in 79.36% of the total number of cases, while cefalexin was always used postoperatively (in 71.45% of the cases). Cefazolin was commonly used during admission, it was continued for one or two days, and treatment with cefalexin was used after discharge. The rest of antibiotics were used less frequently. The duration of postoperative treatment was 7 days (median 7; interquartile range 1 day).

Figure 1. Antibiotics involved in DRPs.

PAP was administered to a higher percentage of patients in scheduled caesarean sections (83.14%) than in emergency caesarean sections (63.83%) (OR=2.79, p=0.000).

DRPs were identified in 100% of the patients (Table 1), with a total of 1125 DRPs and an average of 1.38 DRP per patient (516 patients with one DRP, 286 with two, and the rest with three or more). A total of 798 DRPs (1.43 DRP per patient) were reported in emergency surgeries, and 327 DRPs (1.28 DRP per patient) in scheduled procedures.

For 28 patients (3.44%), the duration of the surgery was ≥ 4h (245 min - 405 min) and, additionally, two of them lost more than 1.5L of blood. Of these 28 surgeries, 19 were emergency (67.86%) and 9 scheduled (32.14%). None of the 28 patients suffered SSI or adverse drug reactions (ADR), and as regards PAP use, the antibiotic treatment regimens they received were similar to those of the rest of the study sample (cefazolin 2 g, or clindamycin 600 mg in case of penicillin allergy) and 11 of them did not receive PAP. As with the rest of the patients in the study, antibiotic treatment lasted 7 days (median 7 and interquartile range 0.5). At least one DRP was identified in every patient, and two DRPs were reported in 11 patients (1.39 DRP per patient), similar to that obtained for the total population.

Discussion

Although there is research on inappropriate use of antibiotics, few authors analyze the DRPs associated with the use of antibiotics in surgery

In our research, 100% of the patients presented DRPs associated with surgical antibiotic prophylaxis, which is mainly due to the fact that all patients received postoperative antibiotic treatment (either as monotherapy or as combinations of several antibiotics) despite disagreement with guideline recommendations. Other related studies show a prevalence of inappropriate antibiotic use that ranges from 40% to more than 88%.^21–25 In a work based on different surgery specialties, 30.8% of the identified DRPs occurred in obstetric and gynecological surgery.²⁶

However, although the average of 1.38 DRP per patient obtained in this research was high, it is in line with data reported in other studies carried out in countries with limited resources, where values ranged between 0.3 and 1.4 DRP/patient.^25,27,28

Most of the DRPs detected in this study correspond to subdomain P3.1, “Unnecessary drug-treatment”. The reason for this unnecessary prolongation of antibiotic therapy could be that the local guideline for cesarean delivery does not specify what antibiotics should be used, when and for how long, and that the hospital where this study was conducted lacks its own policy for antibiotic use, thus leading to the use of different treatment schemes according to each physician’s individual judgment. This result is consistent with the findings of other studies where adherence to international guidelines was poor and prolonged antibiotic therapy was identified as the main problem.^{21,24,28–30}

Clinical guidelines on antibiotic prophylaxis for cesarean sections recommend using a single dose within the first hour prior to surgery, except when blood losses exceed 1,500 mL or when the surgical procedure lasts more than 4 hours where a second dose is recommended. Evidence also shows that there are no significant differences in the incidence rate of SSI between single and multiple dose administration.^15,31 In these cases, rather than having a beneficial effect, overuse of antibiotics could favor the onset of adverse reactions and the intensification of antimicrobial resistance, while also increasing the associated costs, since patients are given all the prescribed medication free of charge at hospital discharge.

DRPs in subdomain P1.3 “Untreated symptoms or indication” were identified in a smaller number of patients (21.78%), as were DRPs in subdomain P1.2 “Effect of drug treatment not optimal” (3.82%), and they corresponded to patients who had not received PAP but had been treated with antibiotics after surgery, and to the group of patients who received preoperative doses lower than those required (cefazolin 1g), non-recommended antibiotics (ampicillin/sulbactam), or incomplete treatments (clindamycin without the addition of gentamicin in patients with a history of beta-lactam allergies), respectively. Other studies also revealed fewer problems regarding compliance with these three variables (timing of PAP administration, antibiotic choice and dose).^25,31,32

The guidelines considered suggest that antibiotic administration should be initiated within 60 minutes prior to incision. The recommended antibiotic should be a first-generation cephalosporin (generally, cefazolin) and, in cases of severe allergic reactions to cephalosporins, clindamycin combined with an aminoglycoside.^15,33

As regards the remaining DRPs detected, those in subdomain P2.1 correspond to 11 patients who were at potential risk for adverse reactions when receiving beta-lactam therapy despite being allergic to penicillin, and one patient who developed rash after the administration of cefazolin. The DRPs belonging to subdomain P1.1, for their part, correspond to the 11 patients who developed SSI (seven of whom had received PAP). Similar studies also reported failure to comply with PAP administration, as well as a low incidence of ADR and SSI.^34,35

No data have been found in the literature to corroborate the differences observed in the use of PAP between emergency and scheduled procedures.

As explained above, DRPs associated with the use of antibiotics in surgery are frequent, can damage a patient’s health, entail an increase in healthcare costs and could be prevented in most cases by adhering to clinical guidelines.³⁶

The DRPs identified in this study could have been prevented if the five key points for appropriate PAP recommended in the clinical guidelines had been complied with.^{15,19,20,37,38} Such points, shown in Table 4, are as follows: choice of appropriate antibiotic, dose, route and timing of administration and duration of PAP; bearing in mind that PAP is indicated in all cesarean sections except when the patient is already under antibiotic treatment for an active infection.³³ In view of the preceding, we recommend the implementation of a protocol agreed to by all the healthcare professionals involved.

Different studies have proved how incorporating the pharmacist into the healthcare team improves the use of antibiotics both in hospital and in community settings, with the consequent clinical and economic benefits.^39,40 The design and implementation of therapeutic protocols and early identification of DRPs by a clinical pharmacist could contribute to the optimization of antibiotic use. This would reduce microbial resistance, adverse effects and institutional costs, leading to an improvement in the quality of medical care.

One of the limitations of the study is its retrospective nature, which made it impossible to solve the identified problems, although the research objectives were achieved. Another limitation of retrospective studies is the possible presence of bias as a result of not being able to detect any errors in clinical histories. On the other hand, we believe that one of the strengths of the study is that it has revealed the need for the institution to implement protocols that may allow a unified criterion for the use of antibiotics in cesarean sections, which will enable the design of new work strategies.

Conclusions

DRPs were detected in all the patients in the study, mainly associated with the failure to administer PAP and to the use of unnecessary post-surgery antibiotic. The implementation of therapeutic protocols and early identification of DRPs is proposed to optimize the use of antibiotics in the institution. PCN Classification V 9.1 has allowed us to categorize DRPs and their causes, thereby facilitating reporting of results to the professionals involved.

Author contributions

Conceptualization, KRV, AST, MVRM and AM-S.; methodology, KRV, AST, AB, MVRM and AM-S.; software, KRV, AST, AB, MVRM and AM-S.; validation, KRV, AST, AB, MVRM and AM-S.; formal analysis, KRV, AST, AB, MVRM and AM-S.; investigation, KRV and AST.; resources, KRV, AST, MVRM and AM-S.; data curation, KRV, AST, AB, MVRM and AM-S.; writing—original draft preparation, KRV.; writing—review and editing, KRV, AST, AB, MVRM and AM-S.; visualization, KRV, AST, AB, MVRM and AM-S.; supervision, MVRM and AM-S.; project administration, MVRM and AM-S.; funding acquisition, none. All authors have read and agreed to the published version of the manuscript.

Ethics and consent

The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Institutional Review Board of Ambato General Hospital (Protocol code: IESS-HG-AM-DIN-2019-0013-MFDQ and date of approval Jan 29, 2019).

Informed consent statement

Patient consent was waived due to the fact that data were obtained retrospectively from the clinical history, guaranteeing the anonymity of the patients.