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Korean J Intern Med > Volume 24(4); 2009 > Article
Lee, Jung, Yeom, Son, Jung, Kim, Kim, Chang, Kim, Ki, Moon, Chung, Peck, Song, and Woo: Evaluation of Ceftriaxone Utilization at Multicenter Study

Abstract

Background/Aims

As bacterial resistance to antimicrobial agents has grown due to the increasing use of antimicrobial agents, we sought to evaluate the suitability of ceftriaxone usage (representative of third generation cephalosporins) at 10 university hospitals in Korea.

Methods

We prospectively evaluated the appropriateness of antibiotic usage in 400 adult patients who received ceftriaxone between February 1, 2006 and June 30, 2006. Drug utilization evaluation (DUE) methods were based on standards set forth by the American Society of Hospital Pharmacists. The DUE criteria used in this study were modified to be more suitable in our hospital setting: justification of drug use, critical and process indications, complications, and outcome measures.

Results

The average patient age was 64.4 years. The utilization of ceftriaxone was appropriate in 262 cases (65.5%) for the justification of use, while inappropriate use was observed in 138 cases (34.5%). Common reasons for inappropriate use of ceftriaxone included continued empiric use for presumed infections, prophylactic perioperative injection, and empiric therapy for fever. Most of the critical indications showed a high rate of suitability (66.5-98.5%). Complications occurred in 37 cases (9.3%). With respect to outcome measures, clinical responses were observed in 60.7% of cases, while only 15.7% of cases showed evidence of infection eradication via negative cultures.

Conclusions

Appropriate use (65.5%) of ceftriaxone was higher than inappropriate use (34.5%) at university hospitals in Korea. Inappropriate utilization, however, including continued empiric use for presumed infections and prophylactic perioperative injection remained high. Intensification of educational programs and antibiotic control systems for ceftriaxone is needed to improve the suitability of antimicrobial use.

INTRODUCTION

Bacterial resistance to antimicrobial agents due to the increasing use of antimicrobial agents has become a worldwide concern. Over the past several decades, the increased prevalence of known resistant organisms and the emergence of newly resistant organisms such as penicillin-resistant pneumococci, methicillin-resistant Staphyloccus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase-producing Escherichia coli, Klebsiella pneumoniae, and imipenem-resistant gram-negative bacilli, have resulted in delays in effective therapy and the length of hospitalization, and have led to increased costs for patients [1]. Compared to infections caused by susceptible pathogens, those caused by resistant pathogens are associated with higher rates of morbidity and mortality [2,3]. Furthermore, antimicrobial drug resistance has been projected to add between $100 million and $30 billion annually to health-care costs [4]. During the past several years, the problem of antibiotic resistance has noticeably worsened in Korea [5]. With gradual increases in expensive antimicrobial agents, the cost of antimicrobial agents relative to total medical insurance expenses has reached 33.1% [6]. When considering that misuse of antimicrobial agents is the most important cause of antibiotic resistance, the logical first step is to evaluate the suitability of antibiotic usage.
Only one usage analysis of cephalosporins and aminoglycosides for surgical prophylaxis has been conducted at a university hospital in Korea, and most reports examining the appropriateness of antibiotic use have been individual studies [7-12]. Antibiotic use evaluations are a basic measure for evaluating the appropriate usage of antimicrobial agents; however, data gathered from individual hospitals have limited benefits for policy-making. For this reason, we examined antibiotic use status and evaluated the appropriateness of the antibiotic usage in 10 university hospitals in Korea. Specifically, in the present study, we evaluated the use of a specific antibiotic (ceftriaxone, a representative of third-generation cephalosporin) and attempted to compile basic data outlining the appropriate use of antibiotics.

METHODS

The criteria used for antibiotic selection included the following: antibiotics with a risk of abuse, those that were being used in high amounts in Korean hospitals, antibiotics that were likely causing resistance due to increased usage, and those that were not being controlled by an antibiotic prescribing restriction system. Ceftriaxone, a broad-spectrum parenteral cephalosporin, was selected as representative of unrestricted antibiotics. A drug utilization evaluation (DUE) was conducted to determine whether ceftriaxone was being used appropriately based on the "Criteria for Drug Use Evaluation" of the American Society of Hospital Pharmacists [13]. The criteria for DUE used in this study were modified based on their suitability in the Korean hospital setting: justification of drug use, critical and process indications, complications, and outcome measures. A DUE was performed prospectively by reviewing medical records for a total of 400 patients (10 hospitals with 40 patients each) who received ceftriaxone during hospitalization between February 1, 2006 and June 30, 2006, and these data were used in this study. Medical records were examined for the diagnosis, the reason for initiating and discontinuing therapy, gender, dose, frequency of administration, culture and sensitivity (C&S) results, renal function, and duration of antibiotic therapy. All medical records were examined for compliance to the clinical indicators listed above.
Indications for which ceftriaxone was deemed either acceptable or unacceptable are shown in Table 1. Any patients for whom therapy was deemed unacceptable were reviewed with criteria established at the onset of the DUE. Enrolled hospitals were Dong-A University Hospital, Kangbuk Samsung Hospital, Samsung Medical Center, Chungbuk National University Hospital, Chonnam National University Hospital, Chungnam National University Hospital, Seoul Veterans Hospital, Kyungpook National University Hospital, Konkuk University Hospital, and Inje University Paik Hospital.

RESULTS

In total, 400 patients (247 men, 153 women) with a mean age of 64.4 years (range, 3 to 93; 95% CI, 32.4 to 96.4) were reviewed, with 10 cases at each of the 10 institutions. Most cases involved the department of internal medicine (58%); the remainders were in neurosurgery (12%), surgery (7.5%), orthopedic surgery (3.7%), thoracic surgery (3.7%), urology (2.7%), otolaryngology (2%), neurology (2%), and others (4.3%). Ceftriaxone dosing regimens are presented in Table 2. In 340 cases (85%), ceftriaxone was dosed as 2 g/day (range, 1 to 4). The mean duration of ceftriaxone use was 10.3 days (range, 1 to 61).

Justification of ceftriaxone use

The use of ceftriaxone was appropriate in 262 cases (65.5%), and inappropriate in 138 cases (34.5%; Fig. 1). The causes of inappropriate ceftriaxone use included routine perioperative prophylaxis (50%), inappropriate empirical therapy (>5 days) for presumed infections (34.8%), and systemic prophylaxis for infection or colonization (15.2%, Table 3).

Critical (process) indicators

Most of the critical and process indications showed high rates of appropriateness (84.2-98.5%), excluding inappropriate C&S tests prior to the initial ceftriaxone dose (33.5%) and inappropriate duration of therapy (42.8%, Table 4).

Complications

Hepatotoxicity occurred in 16 cases (43.2%), gastrointestinal trouble in 12 cases (32.4%), cutaneous reaction in 6 cases (16.2%), bleeding disturbances in 2 cases (5.5%), and peripheral neuropathy in 1 case (2.7%, Table 5). Each case was managed appropriately.

Outcome measures

Clinical improvement was noted in 243 patients (60.7%), while documentation of microbiological eradication evidenced by negative cultures 72 hours after discontinuation of ceftriaxone was inappropriate in 337 patients (84.3%).

DISCUSSION

The goal of antibiotic therapy is to achieve the best possible clinical outcomes while consuming the least amount of hospital resources. Health-care systems are under intense pressure to increase the quality of care and at the same time reduce costs. Pressure to reduce the cost of antimicrobial therapy is especially intense because these drugs may account for a large portion of a hospital's pharmacy budget. According to previous investigations on antibiotic use, antibiotics might account for 33.1% of the medical insurance budget in Korea, and 20-50% of these cases are suspected to have been abuse [6]. In many cases, antibiotics were prescribed for prophylaxis rather than for treatment [6,7]. Antibiotic abuse such as this in the community and hospitals fuels the crisis of antibiotic resistance, which ultimately results in virtually all pathogenic bacteria becoming resistant to older antibiotics. During the past several years, the problem of antibiotic resistance has noticeably worsened in Korea [5].
We performed a DUE for a specific antibiotic and attempted to gather basic data to examine the appropriate use of antibiotics. Furthermore, we sought to prevent antibiotic misuse and reduce unnecessary medical costs. The one limitation of previous studies for DUE is that most were retrospective and focused on a specific department. To overcome this problem, we prospectively evaluated the appropriate use of ceftriaxone usage (representative of thirdgeneration cephalosporins) at 10 university hospitals in Korea. Ceftriaxone is major drug that is used in the treatment of many important infections due to its high antibacterial potency, wide spectrum of activity, and low potential for toxicity. Its superior activity against Enterobacteriaceae, however, is being challenged by the increasing frequency of beta-lactamase-mediated resistance. Kim et al. [8] reported that 47% of cases met the criteria for justified use in a retrospective study at a university hospital in 1999. In contrast, our study showed that the appropriate use of ceftriaxone was relatively higher (65.5%) as compared to other studies. This difference may be attributable to the fact that the justification of use criteria were stricter and our study allowed more acceptable cases for empirical therapy. Although the appropriateness (65.5%) of ceftriaxone usage was higher than inappropriateness (34.5%) in tertiary care hospitals in Korea, unsuitable utilization such as continued empiric use for presumed infections and prophylactic perioperative injection remained high. Furthermore, appropriate selection of an antibiotic according to C&S was relatively low. Of the critical indications, a lack of C&S prior to initial ceftriaxone dose and an inappropriate duration of therapy were most common. Others showed quite high rates of appropriateness (84.2-98.5%, Table 4). Ceftriaxone is considered to be low in side effects. Among the complications, hepatotoxicity (16 cases, 4%) and GI difficulties (12 cases, 3%) were most common (Table 5). Each case was managed appropriately.
Outcome analyses showed a relatively high clinical improvement rate of 60.7%, while microbiological documentation by follow-up culture was poor (84.3%). These results show that ceftriaxone, when used empirically, should be reevaluated within 72 hours of initiating therapy and when C&S data are reported. Therapy should be discontinued if the C&S report demonstrates that the organisms are sensitive to equally efficacious, less costly antibiotics. According to data generated by this DUE, a combination of physician education programs and feedback control systems directed toward rational ceftriaxone use is suggested for proper medical treatment.

References

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13. American Society of Hospital Pharmacist. Criteria for Drug use Evaluation. 1993;Vol. 4:Bethesda: American Society of Hospital Pharmacist.

Figure 1
Justification of the use of ceftriaxone.
kjim-24-374-g001.jpg
Table 1
Criteria elements for the drug utilization evaluation of ceftriaxone
kjim-24-374-i001.jpg
Table 2
Distribution of ceftriaxone daily dosage
kjim-24-374-i002.jpg
Table 3
Causes of inappropriate ceftriaxone use
kjim-24-374-i003.jpg

Values are number (%).

Table 4
Ceftriaxone drug utilization evaluation: critical (process) indicators
kjim-24-374-i004.jpg

Values are frequency (%).

Table 5
Ceftriaxone drug utilization evaluation: complications
kjim-24-374-i005.jpg

Values are number (%).

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