Summary
Introduction: The primary aim of this study was to evaluate whether there was a difference between outpatient parenteral antibiotic therapy (OPAT) and inpatient parenteral antibiotic therapy (IPAT) costs of ertapenem for urinary tract infections (UTI"s) due to extended-spectrum beta-lactamase (ESBL)-producing Gram-negative bacilli, and to discuss suitability of ertapenem for OPAT programme of Turkey for the near future.
Materials and Methods: A total of 53 patients hospitalized with the diagnosis of UTI and treated with ertapenem were retrospectively evaluated. The cost of ertapenem treatment as IPAT was actual costs retrieved from the hospital records. The estimated cost of the same antibiotic for the same patients as an OPAT programme was then calculated and the costs were compared.
Results: The cost difference between IPAT and OPAT was 12.305 (€ 5783). Outpatient parenteral antibiotic therapy programme would provide an estimated 20% reduction in treatment costs. The estimated number of bed days saved, if the patients had received the treatment as OPAT, was calculated to be 583 days, which constitutes about 5% of the total number of hospitalization days.
Conclusion: Applying ertapenem therapy through OPAT programme for UTIs caused by ESBL-producing Gram-negative bacilli will decrease the financial burden of health expenditures and the number of inpatient bed days in Turkey.
Introduction
Decision for an appropriate antibiotherapy should be made according to isolated organism, results of the antibiotic susceptibility test and the potential pharmacokinetic and pharmacodynamic features of the drug. Outpatient parenteral antibiotic therapy (OPAT) is generally used to refer to the provision of parenteral antimicrobial therapy in at least 2 doses on different days without intervening hospitalization[3]. Outpatient parenteral antibiotic therapy practice will decrease the costs of staffing and maintenance services compared to hospitalization. Consequently, this will allow vacancy of beds for other patients who need hospitalization[4]. Among carbapenems, ertapenem is a good alternative with its pharmacokinetic features and bactericidal activity. Additionally, it can be administered daily as a single intramuscular, subcutaneous, or intravenous injection and, therefore, it is suitable for OPAT[5-7]. Various studies in different countries have shown that OPAT was efficient, reliable and costeffective[8-11]. However, ertapenem has not yet been approved for OPAT programme in Turkey.
The primary aim of this study was to evaluate whether there is a difference between OPAT and inpatient parenteral antibiotic therapy (IPAT) costs of ertapenem for UTIs due to ESBL-producing Gram-negative bacilli, and to discuss suitability of ertapenem for OPAT programme of Turkey for the near future.
Methods
The cost of ertapenem treatment as IPAT was retrieved from the actual hospital records. The estimated cost of the OPAT was calculated with following assumptions:
1) Same duration of antibiotic treatment given as IPAT; and,
2) Same antibiotic treatment used as IPAT given to the same patient.
Then the actual IPAT cost was compared with estimated OPAT cost. The total actual hospitalization cost was retrieved from the hospital registration system in a cost breakdown format. Using the total cost, calculations were made to include only the cost components attributed to the treatment of UTI. Following cost components were taken into consideration in order to calculate the cost of IPAT including bed fees, escort fees, and intravenous access, intravenous injection, intravenous cannula, isotonic solution, ertapenem (1 gram per day) and, urine analysis (UA) charges. For calculation of costs of OPAT, it was assumed that actual costs of the following cost components had to be included: ertapenem 1 gram vial, intramuscular injection (for which the cost is the same with intravenous injection) and UA fees. The difference between the two costs was then calculated. Costs of tests in common both for outpatients and inpatients, such as complete blood count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), urea, creatinine, UA, urine culture, and urinary tract ultrasound examinations, were excluded from the calculation for cost analysis. Similarly, laboratory examinations, consultations and treatments for other comorbid diseases during hospitalization were also excluded. Saved inpatient bed days were calculated using the total number of patients in our clinic and the inpatient bed days during the study period.
Cost Analysis Method
The activity-based cost analysis method was used in this study. All the cost calculations were based on actual costs retrieved from the hospital records of the Department of Finance. The costs were calculated from the Republic of Turkey Social Security Institute perspective. In this study, cost figures were converted to a hard currency in order to eliminate inflationary impacts and to show the value of the costs. All the calculations were made using the prices in Turkish Liras ( ) in 2008-2010 and the Central Bank of Turkey exchange rates were used for converting to Euros (€). The average to € currency exchange rate was 0.47 for the given period (Central Bank of Turkey foreign currency exchange rates archive: Web site: http: // www.tcmb.gov.tr / wps / wcm / connect / TCMB + TR / TCMB + TR / Main + Menu / Istatistikler / Doviz + Kurlari / Gosterge + Niteligindeki + Merkez + Bankasi + Kurlarii, Access date: 12.10.2014). All costs were presented with mean values and standard deviations.
Ethical Declaration
Ethics Committee of İzmir Katip Çelebi University Atatürk Training and Research Hospital (Ethics Committee Approval Number: 53, Date: 19th October 2012) approved the study.
Results
Cost Analysis
The total inpatient cost of 53 patients was 74.084 (€ 34819); the calculated cost of IPAT was 62.447 (€ 29350). The difference [ 11.637 (€ 5469)] was due to comorbid disorders, additional examinations, or treatment consultation fees. The total estimated cost of OPAT (if the patients were to receive the same agent as OPAT) was found to be 50.142 (€ 23566). The cost difference between IPAT and OPAT was 12.305 (€ 5783) and it was 20% less than IPAT cost. Treatment costs for IPAT and OPAT by age and gender per patient are shown in Table 1. The number of productive-age patients (ages 20-65) was almost twice the number of patients older than 65 years. Detailed cost components for IPAT and OPAT per patient are presented in Table 2. During the study period, 1.089 patients were hospitalized for 11.124 days in the clinic where this study was conducted. The estimated number of bed days saved, if the patients had received the treatment as OPAT, was calculated to be 583 days, which constitutes about 5% of the total number of hospitalization days.
Discussion
In different parts of the world, as well as in Turkey, a significant increase has been observed in the burden of both complicated and non-complicated community- or hospital-acquired UTIs due to ESBL-producing E. coli. Treatment of these patients is more complicated and expensive[14-18].
In a recent study, which examined risk factors for ESBL-production in uropathogenic E. coli isolated from community-acquired UTIs from four different geographical regions, it was observed that the production of ESBL was at alarming rates, especially in patients with complicated UTIs (17.4%). The main risk factors were more than three UTI episodes in the preceding year, usage of beta-lactam antibiotics in the preceding 3 months, and prostatic disease[19]. In a study carried out in a tertiary training hospital in Switzerland, the analysis of risk factors of UTI occurring due to community-acquired ESBL-producing E. coli were older age, female gender, diabetes mellitus, recurrent UTI, invasive urological procedures, and prior use of antibiotics such as aminopenicillins, cephalosporins or fluoroquinolones[14]. In our study, uro-genital interventions or diseases and diabetes mellitus were found to be the most important risk factors. Failing to detect any risk factors in 21% of patients might be due to not being able to get a detailed history about the prior use of antibiotics.
The rate of antibiotic resistance and ESBL production increased in recent years both in Turkey and all over the world. This causes difficulties in treating patients with UTIs. More patients need hospitalization. Treatments are getting more complicated.
Morbidity and mortality rates and treatment costs have increased. In a study from our country, which compared community-onset healthcare-associated and hospital-acquired UTIs caused by ESBL-producing E. coli, no resistance was found to carbapenems or fosfomycin. The rate of sensitivity to nitrofurantoin, amikacin, trimethoprim sulfamethoxazole and quinolons was 97.6%, 89%, 29.4% and 17.9%, respectively. In both groups, similar rates of antibiotic resistance were found[20]. In our study, the rate of sensitivity to carbapenems was similar but the rate of sensitivity to other antibiotics was much lower.
In a study in which clinical and microbiological outcomes of ertapenem in OPAT for complicated UTIs was investigated, microbiological and clinical cure rates were 67% and 92%, retrospectively. In this study, it was demostrated that ertapenem was a good alternative to broader-spectrum carbapenems for the treatment of complicated UTIs. As well as being safe and effective, it has adventages of having a narrower spectrum and once daily dosing[21]. In another study, clinical efficacy of ertapenem in the treatment of recurrent cystitis caused by ESBL-producing E. coli in female outpatients was retrospectively reviewed and ertapenem treatment was found to be effective and well-tolerated[22].In our study, clinical and microbiological cure was sustained in all patients receiving ertapenem therapy and no side effect was observed. This shows that ertapenem therapy is efficient and safe in OPAT and it is estimated that use of ertapenem in OPAT may increase patient satisfaction.
Today, indications for OPAT programs, which are successfully used, differ among countries[23, 24]. In a study which analyzed the cost of OPAT in adult patients in a tertiary training hospital in Canada between 1995 and 1998, different parenteral antibiotics were administered for different types of infections, such as bone and joint, skin and soft tissue, endocarditis and others. This study showed that OPAT programme provided an economically attractive alternative to continued hospitalization for selected adult patients with infections requiring parenteral antimicrobial treatment. Also from the hospital perspective, the cost of therapy through the OPAT programme was approximately 13% of the cost estimated if the patient was to continue to be managed in hospital settings[23]. In another study from UK, clinical efficacy and cost-effectiveness of OPAT in 334 episodes (skin and soft tissue infections, cardiovascular infections, central nervous system infections, genito-urinary infections, etc.) between 2006 and 2008 was evaluated. It was found that OPAT cost was 41% of equivalent inpatient cost for an infectious diseases unit and, over the 2-year period, the total number of bed days saved through OPAT activity was 4034. As a result, they concluded that OPAT was safe and clinically effective, with low rates of complications/ readmissions and high levels of patient satisfaction, and also OPAT was found to be cost-effective when compared with equivalent inpatient care[24]. In these two studies, OPAT programme was found more cost-effective than in our study. This can be attributed to longer duration of OPAT needed for the treatment of infections such as bone and joint infections, endocarditis, skin and soft tissue infections, central nevous system infections (mean duration: 23 days) in these studies. Another reason might be differences in health-care expenditures for inpatients between countries. In another retrospective study of patients treated for UTIs caused by ESBL-producing organisms through OPAT over a 4-year period, 24 OPAT episodes involving 11 patients were reviewed. Six patients had an underlying urological abnormality and all patients were treated with parenteral ertapenem. There were no adverse effects related to ertapenem requiring cessation of a course earlier than planned. The mean duration of the OPAT episodes was 9.9 days and a total of 238 inpatient bed days were avoided. As a result, they concluded that ertapenem administration through OPAT may help decrease the costs associated with ESBL infections by reducing the number of inpatient bed days[8].
In our study, all patients were treated with ertapenem and the mean duration of the treatment was 10.7±2.5 days and there were no serious side effects during the treatment. At the end of the treatment, clinical improvement and microbiological eradication were achieved in all patients, and ertapenem therapy was found to be safe and effective. It was predicted that if ertapenem therapy had been applied as OPAT programme, there would have been an estimated 20% savings of the existent inpatient cost. During this 2-year period, the total number of bed days that could have been saved through OPAT was 583 (5% of the total number of bed days). Most of the patients were in economically productive age groups and the changes in opportunity costs due to missed work days were not included in our study, hence the difference in costs between two treatment options might be underestimated.
The findings of this study should be evaluated within its limitations. This is a retrospective study. A limited number of patients were evaluated in this study. This study shows data from a tertiary-care training hospital in Turkey, thus, it demonstrates only local data which can limit generalisability of the findings. The patients were not stratified according to whether the infection was community-acquired or nosocomial. During the study period, nitrofurantoin and fosfomycin could not be included in the antibiotic susceptibility test. Opportunity costs were not evaluated in this study, therefore, the actual cost differences might be higher than our estimates. Multicenter studies about cost analysis of ertapenem therapy for UTIs and assesment of its suitability for OPAT programme are needed in Turkey.
Conclusion
Acknowledgements
Special thanks to Çiçek Kopraman for the contribution to this study through analyzing the cost calculations (Deputy Managing Director of a leading dairy company operating in Turkey; Bachelor"s Degree in Business Administration).
Ethics
Ethics Committee Approval: This study was approved by the Ethics Committee of İzmir Katip Çelebi University Atatürk Training and Research Hospital (Ethics Committee Approval Number: 53, Date: 19th October 2012).Informed Consent: The consent form is not needed for this submission.
Peer-review: Externally and internally peer-reviewed.
Authorship Contributions
Medical Practices: B.Ö., N.T., Z.K., N.S., Concept: B.Ö., N.T., Design: B.Ö., N.T., F.K., Data Collection or Processing: Z.K., N.S., Analysis or interpretation: M.K.S., Literature Search: N.S., T.D., Z.K., Writing: B.Ö., N.T., F.K., T.D.
Conflict of Interest: No conflict of interest was declared by the authors.
Financial Disclosure: This study was undertaken as part of our routine clinical activity and did not receive additional funding.
