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Evaluation of antibiotic use in a hospital with an antibiotic restriction policy
International Journal of Antimicrobial Agents 21 (2003) 308 /312 www.ischemo.org
Evaluation of antibiotic use in a hospital with an antibiotic restriction policy Ays¸e Erbay a,*, Aylin C ¸ olpan a, Hu¨rrem Bodur a, Mustafa A. C ¸ evik a, Matthew ¨ nder Ergo¨nu¨l b H. Samore b, O a b
Ankara Numune Education and Research Hospital, Department of Infectious Diseases and Clinical Microbiology, Ankara, Turkey University of Utah, School of Medicine, Department of Internal Medicine, Division of Clinical Epidemiology, Salt Lake, UT, USA Received 14 May 2002; accepted 29 August 2002
Abstract The study was designed to evaluate rational antibiotic use in relation to diagnosis and bacteriological findings. All hospitalized patients who received antibiotics were evaluated by a cross-sectional study. Of the 713 patients hospitalized, 281 (39.4%) patients received 377 antibiotics. Among 30 different antibiotics the most frequently requested were first generation cephalosporins (19.9%), ampicillin /sulbactam (19.1%) and aminoglycosides (11.7%). Antibiotic use was appropriate in 64.2% of antibiotic requests. In analysis of appropriate use, a request after an infectious diseases consultation was a frequent reason (OR /14, P B/0.001, CI/ 0.02 /0.24). Antibiotics requested in conjunction with susceptibility results were found to be more appropriate than those ordered empirically (OR /4.5, P/0.017, CI/0.06 /0.76). Inappropriate antibiotic use was significantly higher among unrestricted antibiotics than restricted ones (P B/0.001). Irrational antibiotic use was high for unrestricted antibiotics. Additional interventions such as postgraduate training programmes and elaboration of local guidelines could be beneficial. # 2003 Elsevier Science B.V. and the International Society of Chemotherapy. All rights reserved. Keywords: Antibiotic use; Appropriateness; Restriction policies
1. Introduction Antibiotics are one of the most frequently prescribed drugs for hospitalized patients. Studies indicate that about one third of all hospitalized patients receive antimicrobial therapy [1 /4]. Excessive and inappropriate use of antibiotics causes emergence and dissemination of resistant organisms, significant adverse effects and increased costs [1 /7]. The potential for the misuse and abuse of antibiotics were recognized shortly after their introduction [1,8]. Because of increasing concern and awareness of antibiotic resistance problems and inappropriate use of
* Corresponding author. Present address: Esat cad. 140/16, Kucukesat, Ankara 06700, Turkey. E-mail address: [email protected] (A.v.c. Erbay).
antimicrobial agents in hospitals, these drugs have often been the targets of attempts to restrict and control their use [9,10]. Few hospitals have a restriction policy for antimicrobial use in Turkey. Before 1999, in Ankara Numune Education and Research Hospital (ANERH), all physicians from any specialities were free to prescribe any antibiotic they wished. Due to the high resistance rates and excessive use of broad-spectrum antibiotics, the Antibiotic Control Committee decided to initiate an antibiotic restriction policy in 1999, the aim of this antibiotic policy being to ensure the correct and restrictive use of broad-spectrum antibiotics. The aim of this study was to assess the appropriateness of antibiotic use associated with diagnosis and bacteriological findings in a tertiary hospital with an antibiotic restriction policy.
0924-8579/03/$30 # 2003 Elsevier Science B.V. and the International Society of Chemotherapy. All rights reserved. doi:10.1016/S0924-8579(02)00392-8
A.v.c. Erbay et al. / International Journal of Antimicrobial Agents 21 (2003) 308 /312
2. Materials and methods 2.1. The hospital setting ANERH is an 1100-bed referral and tertiary-care hospital in Turkey. The mean annual number of discharges in 1996 /2000 was 36 655 and the mean duration of hospital stay was 8.4 days. The nosocomial infection rate was 3.3% in general wards and 8.8% in the intensive care units (ICU). In general, the resistance of microorganisms to antibiotics is high (Table 1). 2.2. Antibiotic policy An antibiotic restriction policy was initiated in ANERH in January 1999. There were two levels. The Antibiotic Control Committee decides the purchase of antibiotics to the hospital pharmacy based on cost and annual resistance rates; therefore all antibiotics are not available in hospital pharmacy. The second level of restriction is on the requests for certain antibiotics; a prior consultation with an infectious diseases (ID) specialist is required for ceftazidime, cefepime, imipenem, meropenem, ticarcillin /clavulanate, piperacillin / tazobactam and intravenous formulations of quinolones, vancomycin and teicoplanin. 2.3. Collection of data and assessment of antibiotic appropriateness Antibiotic orders of all the hospitalized patients were evaluated in July 2001 by a cross-sectional study. Two ID specialists assessed the ordered antibiotics according to history, physical examination, imaging, microbiology and serology test results. For each patient receiving antibiotic treatment, demographic data, diagnosis, results from microbiological specimens, details of antibiotic administration, indication for treatment or prophylaxis, dosage, dose frequency, administration route and their appropriateness were recorded on individual forms.
Investigators communicated with the physicians responsible when necessary. Disagreements between investigators were solved by discussion and review of published guidelines [11]. Each antibiotic was assessed appropriate or not according to a modification of the criteria of Kunin et al. [12]. The following categories were used to describe inappropriate antibiotic use: 1) Agree with choice of antibiotic, but dosage was inappropriate per literature 2) Disagree with choice of antibiotics because the spectrum of the antibiotics were overlapped 3) Disagree with choice of antibiotic because the spectrum was not broad enough 4) Disagree with choice of antibiotic because the spectrum was overly broad 5) Disagree with choice of antibiotic because an equally effective drug was available at a lower cost 6) Disagree with need for an antibiotic. Antibiotics were judged unnecessary when the patient had no evidence of infection or indication for prophylaxis. Broad-spectrum antibiotic coverage was considered appropriate if there was no available culture and susceptibility result. If a more effective antibiotic was available based on either culture and susceptibility result of the isolated pathogen or identity of the expected pathogen, the antibiotic given was judged inappropriate. An antibiotic was judged expensive when a substantial difference in cost was not accompanied by a significant therapeutic advantage. 2.4. Statistical analysis Logistic regression (LR) and x2-tests were performed, a P value of B/0.05 was accepted as significant. The difference of inappropriate antibiotic use between surgical and medical wards, and restricted and unrestricted antibiotics were examined using the x2-test. For the analysis of inappropriate use, LR was modelled. Inappropriate use was defined as outcome and gender, age, administration route, antibiotic recommendations
Table 1 Resistance rates of some Gram-negative microorganisms in ANERH in 2000
Cefotaxime Ceftazidime Cefoperazone /sulbactam Ticarcillin /clavulanate Piperacillin /tazobactam Cefepime Imipenem Gentamicin Amikacin Ciprofloxacin
309
Klebsiella spp. (%)
E. coli (%)
Pseudomonas spp. (%)
Acinetobacter spp. (%)
80.0 76.3 59.4 84.8 57.1 56.9 6.9 66.6 45.7 56.6
56.0 49.3 50.0 81.4 25.7 39.5 2.4 58.0 20.0 57.6
93.4 62.6 50.0 76.7 42.6 57.1 31.4 65.2 36.9 46.5
100 96.3 50.0 85.7 82.8 71.9 39.2 88.0 70.3 80.0
5 6 4 4 7 0 0 9 5 2 4 2 0 8 56 0 1 1 0 14 0 0 2 2 1 1 1 0 1 24 0 0 1 0 5 2 1 2 1 5 9 0 0 0 26 0 4 6 0 3 0 0 4 1 3 0 7 0 1 29 0 0 0 0 1 0 6 4 19 2 0 0 2 1 35 0 29 0 0 1 0 4 3 0 0 0 0 0 0 37 UTI, urinary tract infection; LRTI, lower respiratory tract infection.
2 7 1 0 12 2 3 14 8 14 7 11 0 3 84 1 28 1 0 29 0 7 6 7 0 0 3 2 2 86
Surgical prophylaxis Skin and soft tissue No evidence of infection or prophylaxis Table 2 Use of antibiotics by diagnosis
Of the 713 patients hospitalized on the prevalence day, 281 (39.4%) patients received 377 antibiotics; 107 (38%) were women. The mean age was 44.59/22 years. One antibiotic was prescribed for 207 (73.6%) patients, 2 antibiotics for 55 (19.6%) patients, 3 antibiotics for 16 (5.7%) patients and 4 antibiotics for 3 (1.1%) patients. Of 30 different antibiotics, the most frequently prescribed were first generation cephalosporins (19.9%), ampicillin /sulbactam (19.1%), aminoglycosides (11.7%), quinolones (11.1%) and carbapenems (7.2%). Skin and soft tissue infections lead to antibiotic use in 22.3% of patients and urinary tract infections in 9.3% of the patients. Surgical prophylaxis accounted for 9.8% of antibiotic use (Table 2). Fifty-eight (20.6%) patients received antibiotics for treatment of hospital-acquired infections. Most of the antibiotics (76%) were given in parenteral form. The dosages of 34 (9%) antibiotics were lower than those recommended. ID specialists recommended 25% of all antibiotics. The most recommended antibiotics of these were glycopeptides (21%), carbapenems (19%), aminoglycosides (19%) and quinolones (10%). Fifty-one percent of these recommendations were based on susceptibility test results. Glycopeptides were used in 76% of patients with to susceptibility results. Carbapenems were given in 13 (48%) patients according to susceptibility result. Antibiotic use was inappropriate in 35.8% (Table 3). Inappropriate antibiotic use was significantly higher among unrestricted antibiotics than restricted ones (P B/0.001) (Table 4). In multivariable analysis of inappropriate use, age, gender, administration route, ID consultation and culture result were included in the model as independent variables. Age and gender of the patients and administration route were not significant for inappropriate antibiotic use (P /0.05). At the final step ID consultation and a positive culture were included in the model. Antibiotic request without an ID consultation was found to be more inappropriate (OR /14, P B/0.001, CI /0.02 /0.24). Antibiotics ordered empirically were found less appropriate than those ordered with of culture and susceptibility results (OR /4.5, P /0.017, CI /0.06 /0.76). Eighty-six antibiotics were administered to 75 (27%) patients who had no evidence of an infection or indication of prophylaxis. Unnecessary antibiotic use
UTI Abdominal infection
3. Results
Penicillin Cephalosporin 1st generation Cephalosporin 3rd generation Cephalalosporin 4th generation Ampicillin /sulbactam Piperacillin /tazobactam Cephaperazone /sulbactam Aminoglycosides Quinolones Carbapenems Glycopeptides Metronidazole TMP /SMZ Other Total
Septicaemia
by ID consultants and prescription based on susceptibility results were defined as independent variables. The model was constructed by backward selection of independent variables. Software package STATA 7.0 (College station, TX) was used for the analysis.
8 75 14 4 72 4 21 44 43 27 21 24 4 16 377
A.v.c. Erbay et al. / International Journal of Antimicrobial Agents 21 (2003) 308 /312 LRTI Other Total
310
A.v.c. Erbay et al. / International Journal of Antimicrobial Agents 21 (2003) 308 /312 Table 3 Categories of inappropriate antibiotic use
311
Table 5 Appropriateness of antibiotic use in different wards
Categories of inappropriate antibiotic use
n
%
Ward
Unnecessary use (no evidence of an infection or indication 86 63.7 of prophylaxis) Overly broad 15 11.1 Not broad enough 12 8.9 Agree with choice of antibiotic, but dosage was inap12 8.9 propriate Overlap of spectrum ( /1 agents used at the same time) 8 5.9 More expensive than the equivalent 2 1.5 Total 135 100
ICUs Medical Surgical Total
Appropriate use
Inappropriate use
Total
n
%
n
%
n
%
22 77 143 242
68.8 80.2 57.4 64.2
10 19 106 135
31.2 19.8 42.6 35.8
32 96 249 377
100 100 100 100
In our study appropriate antibiotic use was 64.2% and rational use was 95% in restricted antibiotics but 58.2% in unrestricted antibiotics (P B/0.001). Previous studies evaluating antibiotic use in hospitals have reported that 28 /65% of prescriptions can be inappropriate [9,13 /15]. Specific rates of inappropriateness reported in the literature vary widely because of the diversity of the methods used to make such assessment. Although prospective studies are robust in evaluation of antibiotic decision and appropriateness of antibiotic use in hospitals, cross-sectional studies are more feasible for the surveillance allowing antibiotic policy to be assessed. The unnecessary use of antibiotics was the most common reason for inappropriateness in our study. This antibiotic misuse was highest on surgical wards and probably based on the consideration that potential or possible bacterial infection is more hazardous to the patient than the risk from use of antibiotics. Various studies have demonstrated that administration of antibiotics to uninfected patients accounts for 32 /60% of irrational antibiotic use [13,16]. In our study, the doses of 34 (9%) antibiotics were incorrect and this situation might have lead to increased morbidity, prolonged hospital stay and the need for more broad-spectrum and expensive drugs. There were only two cases where an antibiotic was judged inappropriate because of the availability of a less expensive drug, and this was probably the outcome of antibiotic restriction policy at ANERH. The principle aim of antibiotic policies is to bring a change in prescribing which will lead to reduction of resistance, decreased cost and improved quality of antibiotic usage [17]. Approaches that have been taken include educational programmes, development of prescribing guidelines, monitoring of drug resistance pat-
was 30% in surgical wards, 12% in ICU and 8% in medical wards. Ampicillin /sulbactam and first generation cephalosporins were the most frequently unnecessarily used antibiotics (35 and 31%, respectively). Antibiotic orders in surgical wards were found to be significantly more inappropriate than medical wards (P B/0.001) (Table 5). Rational antibiotic use was highest when the results of bacteriological samples were positive. Bacteriological samples had been taken before the antibiotic request in 114 (40.6%) patients. Seventeen percent of the antibiotics were requested because of the susceptibility test result. The most common isolated microorganisms were methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli and Klebsiella pneumoniae (Table 6). Antibiotic prescriptions were switched to another antibiotic in 43 (15%) patients; the main reason was susceptibility test result (44.6%) followed by clinical unresponsiveness to the antibiotic used (29.2%), unnecessary switch (24.6%) and antibiotic side effects (1.5%). In 60% of patients, ID specialists switched the antibiotics.
4. Discussion Antibiotics are the most commonly used drugs in Turkey [13] and only few hospitals have antibiotic restriction policies. Due to the high resistance rates and excessive use of broad-spectrum antibiotics, an antibiotic restriction policy was initiated in ANERH. Table 4 Appropriate and inappropriate use in restricted and unrestricted antibiotics Appropriate use
Restricted antibiotics Unrestricted antibiotics Total
Inappropriate use
Total
n
%
n
%
n
%
58 184 242
95.0 58.2 64.2
3 132 135
5.0 41.8 35.8
61 316 377
100 100 100
312
A.v.c. Erbay et al. / International Journal of Antimicrobial Agents 21 (2003) 308 /312
Table 6 Isolated microorganisms and culture sites Wound
Urine
Blood
Tracheal aspirate
Intraabdominal fluid
Other
Total n
MRSA E. coli K. pneumoniae MSSA P. aeruginosa Acinetobacter spp. Other
11 3 5 6 5 3 3
0 7 4 0 1 0 2
7 1 0 2 0 1 2
0 1 0 0 2 1 0
0 0 1 0 0 1 0
0 0 0 0 0 0 2
18 12 10 8 8 6 9
Total
36
14
13
4
2
2
71
terns, development of restrictive hospital formulary, limitation on reports of sensitivity tests, regulation of interactions between pharmaceutical representatives, and requirement for expert approval before or after prescribing some drugs [9,17 /20]. Education programmes have been successful in facilitating more appropriate antibiotic usage; the critical problem is the re-emergence of misuse without continuous education [1,21]. It was reported that requiring prior approval of an ID specialist for the use of restricted antibiotics seems to be the most effective control method [22]. In our study antibiotic recommendations by ID consultation was found to be significantly appropriate. Since it is impossible to restrict the use of all antibiotics, preparation of local guidelines, interventional studies and encouraging physicians to ask for more ID consultations are other important measures. Surgeons might be a suitable primary target for our interventional studies at ANERH. The panel discussions including different specialities, conferences, and seminars on antimicrobial decision making will be planned. Posters and pamphlets will be disseminated to the residents and specialists. To conclude; a combination of both restriction, continuous education of physicians and elaboration of local guidelines appear to be necessary to improve antibiotic use.
References [1] Fishman NO. Antimicrobial management and cost containment. In: Mandell GL, Bennett JE, Dolin R, editors. Principles and practice of infectious diseases, 5th ed.. Philadelphia: Churchill Livingstone Inc, 2000. [2] Thomas M, Govil S, Moses BV, Joseph A. Monitoring of antibiotic use in a primary and tertiary care hospital. J Clin Epidemiol 1996;49(2):251 /4. [3] Singh N, Yu VL. Rational empiric antibiotic prescription in the ICU. Chest 2000;117(5):1496 /9. [4] Nathwani D, Davey P. Antibiotic prescribing */are there lessons for physicians. QJM 1999;92(5):287 /92. [5] McGowan JE, Jr., Gerding DN. Does antibiotic restriction prevent resistance. New Horiz 1996;4(3):370 /6.
% 25.4 16.9 14.1 11.3 11.3 8.4 12.6 100
[6] Emmerson M. Antibiotic usage and prescribing policies in the intensive care unit. Intensive Care Med 2000;26(Suppl 1):S26 /30. [7] Gould IM. A review of the role of antibiotic policies in the control of antibiotic resistance. J Antimicrob Chemother 1999;43(4):459 / 65. [8] Ma M, Rho JP. Considerations in antimicrobial prescribing. Med Clin North Am 1995;79(3):537 /49. [9] Thuong M, Shortgen F, Zazempa V, Girou E, Soussy CJ, BrunBuisson C. Appropriate use of restricted antimicrobial agents in hospitals: the importance of empirical therapy and assisted reevaluation. J Antimicrob Chemother 2000;46(3):501 /8. [10] Couper MR. Strategies for the rational use of antimicrobials. Clin Infect Dis 1997;24(Suppl 1):S154 /6. [11] Gilbert DN, Moellering RC, Sande MA, editors. The Sanford guide to antimicrobial therapy, 31st ed.. Antimicrobial Therapy Inc, 2001. [12] Kunin CM, Tupasi T, Craig WA. Use of antibiotics. A brief exposition of the problem and some tentative solutions. Ann Intern Med 1973;79(4):555 /60. ¨ , Dinc¸ G, Ozbakkaloglu B, Atman UC, Algun U. [13] Tu¨nger O Evaluation of rational antibiotic use. Int J Antimicrob Agents 2000;15(2):131 /5. [14] Maki DG, Schuna AA. A study of antimicrobial misuse in a university hospital. Am J Med Sci 1978;275(3):271 /82. [15] Dunagan WC, Woodward RS, Medoff G, et al. Antimicrobial misuse in patients with positive blood cultures. Am J Med 1989;87(3):253 /9. [16] Dunagan WC, Woodward RS, et al. Antibiotic misuse in two clinical situations: positive blood culture and administration of aminoglycosides. Rev Infect Dis 1991;13(3):405 /12. [17] Nathwani D. How do you measure the impact of an antibiotic policy. J Hosp Infect 1999;43(Suppl):S265 /8. [18] Vlahovic-Palcevski V, Morovic M, Palcevski G. Antibiotic utilization at the university hospital after introducing an antibiotic policy. Eur J Clin Pharmacol 2000;56:97 /101. [19] Crowe HM, Quintiliani R. Antibiotic formulary selection. Med Clin North Am 1995;79(3):463 /76. [20] Marr JJ, Moffet HL, Kunin CM. Guidelines for improving the use of antimicrobial agents in hospitals. A statement by the Infectious Diseases Society of America. J Infect Dis 1987;157(5):869 /76. [21] Gross PA. The potential for clinical guidelines to impact appropriate antimicrobial agent use. Infect Dis Clin North Am 1997;11(4):803 /12. [22] Hirschman SZ, Meyers BR, Bradbury K, Mehl B, Gendelman S, Kimelblatt B. Use of antimicrobial agents in a university teaching hospital. Evolution of a comprehensive control program. Arch Intern Med 1988;148(9):2001 /7.
Evaluation of antibiotic use in a hospital with an antibiotic restriction policy Ays¸e Erbay a,*, Aylin C ¸ olpan a, Hu¨rrem Bodur a, Mustafa A. C ¸ evik a, Matthew ¨ nder Ergo¨nu¨l b H. Samore b, O a b
Ankara Numune Education and Research Hospital, Department of Infectious Diseases and Clinical Microbiology, Ankara, Turkey University of Utah, School of Medicine, Department of Internal Medicine, Division of Clinical Epidemiology, Salt Lake, UT, USA Received 14 May 2002; accepted 29 August 2002
Abstract The study was designed to evaluate rational antibiotic use in relation to diagnosis and bacteriological findings. All hospitalized patients who received antibiotics were evaluated by a cross-sectional study. Of the 713 patients hospitalized, 281 (39.4%) patients received 377 antibiotics. Among 30 different antibiotics the most frequently requested were first generation cephalosporins (19.9%), ampicillin /sulbactam (19.1%) and aminoglycosides (11.7%). Antibiotic use was appropriate in 64.2% of antibiotic requests. In analysis of appropriate use, a request after an infectious diseases consultation was a frequent reason (OR /14, P B/0.001, CI/ 0.02 /0.24). Antibiotics requested in conjunction with susceptibility results were found to be more appropriate than those ordered empirically (OR /4.5, P/0.017, CI/0.06 /0.76). Inappropriate antibiotic use was significantly higher among unrestricted antibiotics than restricted ones (P B/0.001). Irrational antibiotic use was high for unrestricted antibiotics. Additional interventions such as postgraduate training programmes and elaboration of local guidelines could be beneficial. # 2003 Elsevier Science B.V. and the International Society of Chemotherapy. All rights reserved. Keywords: Antibiotic use; Appropriateness; Restriction policies
1. Introduction Antibiotics are one of the most frequently prescribed drugs for hospitalized patients. Studies indicate that about one third of all hospitalized patients receive antimicrobial therapy [1 /4]. Excessive and inappropriate use of antibiotics causes emergence and dissemination of resistant organisms, significant adverse effects and increased costs [1 /7]. The potential for the misuse and abuse of antibiotics were recognized shortly after their introduction [1,8]. Because of increasing concern and awareness of antibiotic resistance problems and inappropriate use of
* Corresponding author. Present address: Esat cad. 140/16, Kucukesat, Ankara 06700, Turkey. E-mail address: [email protected] (A.v.c. Erbay).
antimicrobial agents in hospitals, these drugs have often been the targets of attempts to restrict and control their use [9,10]. Few hospitals have a restriction policy for antimicrobial use in Turkey. Before 1999, in Ankara Numune Education and Research Hospital (ANERH), all physicians from any specialities were free to prescribe any antibiotic they wished. Due to the high resistance rates and excessive use of broad-spectrum antibiotics, the Antibiotic Control Committee decided to initiate an antibiotic restriction policy in 1999, the aim of this antibiotic policy being to ensure the correct and restrictive use of broad-spectrum antibiotics. The aim of this study was to assess the appropriateness of antibiotic use associated with diagnosis and bacteriological findings in a tertiary hospital with an antibiotic restriction policy.
0924-8579/03/$30 # 2003 Elsevier Science B.V. and the International Society of Chemotherapy. All rights reserved. doi:10.1016/S0924-8579(02)00392-8
A.v.c. Erbay et al. / International Journal of Antimicrobial Agents 21 (2003) 308 /312
2. Materials and methods 2.1. The hospital setting ANERH is an 1100-bed referral and tertiary-care hospital in Turkey. The mean annual number of discharges in 1996 /2000 was 36 655 and the mean duration of hospital stay was 8.4 days. The nosocomial infection rate was 3.3% in general wards and 8.8% in the intensive care units (ICU). In general, the resistance of microorganisms to antibiotics is high (Table 1). 2.2. Antibiotic policy An antibiotic restriction policy was initiated in ANERH in January 1999. There were two levels. The Antibiotic Control Committee decides the purchase of antibiotics to the hospital pharmacy based on cost and annual resistance rates; therefore all antibiotics are not available in hospital pharmacy. The second level of restriction is on the requests for certain antibiotics; a prior consultation with an infectious diseases (ID) specialist is required for ceftazidime, cefepime, imipenem, meropenem, ticarcillin /clavulanate, piperacillin / tazobactam and intravenous formulations of quinolones, vancomycin and teicoplanin. 2.3. Collection of data and assessment of antibiotic appropriateness Antibiotic orders of all the hospitalized patients were evaluated in July 2001 by a cross-sectional study. Two ID specialists assessed the ordered antibiotics according to history, physical examination, imaging, microbiology and serology test results. For each patient receiving antibiotic treatment, demographic data, diagnosis, results from microbiological specimens, details of antibiotic administration, indication for treatment or prophylaxis, dosage, dose frequency, administration route and their appropriateness were recorded on individual forms.
Investigators communicated with the physicians responsible when necessary. Disagreements between investigators were solved by discussion and review of published guidelines [11]. Each antibiotic was assessed appropriate or not according to a modification of the criteria of Kunin et al. [12]. The following categories were used to describe inappropriate antibiotic use: 1) Agree with choice of antibiotic, but dosage was inappropriate per literature 2) Disagree with choice of antibiotics because the spectrum of the antibiotics were overlapped 3) Disagree with choice of antibiotic because the spectrum was not broad enough 4) Disagree with choice of antibiotic because the spectrum was overly broad 5) Disagree with choice of antibiotic because an equally effective drug was available at a lower cost 6) Disagree with need for an antibiotic. Antibiotics were judged unnecessary when the patient had no evidence of infection or indication for prophylaxis. Broad-spectrum antibiotic coverage was considered appropriate if there was no available culture and susceptibility result. If a more effective antibiotic was available based on either culture and susceptibility result of the isolated pathogen or identity of the expected pathogen, the antibiotic given was judged inappropriate. An antibiotic was judged expensive when a substantial difference in cost was not accompanied by a significant therapeutic advantage. 2.4. Statistical analysis Logistic regression (LR) and x2-tests were performed, a P value of B/0.05 was accepted as significant. The difference of inappropriate antibiotic use between surgical and medical wards, and restricted and unrestricted antibiotics were examined using the x2-test. For the analysis of inappropriate use, LR was modelled. Inappropriate use was defined as outcome and gender, age, administration route, antibiotic recommendations
Table 1 Resistance rates of some Gram-negative microorganisms in ANERH in 2000
Cefotaxime Ceftazidime Cefoperazone /sulbactam Ticarcillin /clavulanate Piperacillin /tazobactam Cefepime Imipenem Gentamicin Amikacin Ciprofloxacin
309
Klebsiella spp. (%)
E. coli (%)
Pseudomonas spp. (%)
Acinetobacter spp. (%)
80.0 76.3 59.4 84.8 57.1 56.9 6.9 66.6 45.7 56.6
56.0 49.3 50.0 81.4 25.7 39.5 2.4 58.0 20.0 57.6
93.4 62.6 50.0 76.7 42.6 57.1 31.4 65.2 36.9 46.5
100 96.3 50.0 85.7 82.8 71.9 39.2 88.0 70.3 80.0
5 6 4 4 7 0 0 9 5 2 4 2 0 8 56 0 1 1 0 14 0 0 2 2 1 1 1 0 1 24 0 0 1 0 5 2 1 2 1 5 9 0 0 0 26 0 4 6 0 3 0 0 4 1 3 0 7 0 1 29 0 0 0 0 1 0 6 4 19 2 0 0 2 1 35 0 29 0 0 1 0 4 3 0 0 0 0 0 0 37 UTI, urinary tract infection; LRTI, lower respiratory tract infection.
2 7 1 0 12 2 3 14 8 14 7 11 0 3 84 1 28 1 0 29 0 7 6 7 0 0 3 2 2 86
Surgical prophylaxis Skin and soft tissue No evidence of infection or prophylaxis Table 2 Use of antibiotics by diagnosis
Of the 713 patients hospitalized on the prevalence day, 281 (39.4%) patients received 377 antibiotics; 107 (38%) were women. The mean age was 44.59/22 years. One antibiotic was prescribed for 207 (73.6%) patients, 2 antibiotics for 55 (19.6%) patients, 3 antibiotics for 16 (5.7%) patients and 4 antibiotics for 3 (1.1%) patients. Of 30 different antibiotics, the most frequently prescribed were first generation cephalosporins (19.9%), ampicillin /sulbactam (19.1%), aminoglycosides (11.7%), quinolones (11.1%) and carbapenems (7.2%). Skin and soft tissue infections lead to antibiotic use in 22.3% of patients and urinary tract infections in 9.3% of the patients. Surgical prophylaxis accounted for 9.8% of antibiotic use (Table 2). Fifty-eight (20.6%) patients received antibiotics for treatment of hospital-acquired infections. Most of the antibiotics (76%) were given in parenteral form. The dosages of 34 (9%) antibiotics were lower than those recommended. ID specialists recommended 25% of all antibiotics. The most recommended antibiotics of these were glycopeptides (21%), carbapenems (19%), aminoglycosides (19%) and quinolones (10%). Fifty-one percent of these recommendations were based on susceptibility test results. Glycopeptides were used in 76% of patients with to susceptibility results. Carbapenems were given in 13 (48%) patients according to susceptibility result. Antibiotic use was inappropriate in 35.8% (Table 3). Inappropriate antibiotic use was significantly higher among unrestricted antibiotics than restricted ones (P B/0.001) (Table 4). In multivariable analysis of inappropriate use, age, gender, administration route, ID consultation and culture result were included in the model as independent variables. Age and gender of the patients and administration route were not significant for inappropriate antibiotic use (P /0.05). At the final step ID consultation and a positive culture were included in the model. Antibiotic request without an ID consultation was found to be more inappropriate (OR /14, P B/0.001, CI /0.02 /0.24). Antibiotics ordered empirically were found less appropriate than those ordered with of culture and susceptibility results (OR /4.5, P /0.017, CI /0.06 /0.76). Eighty-six antibiotics were administered to 75 (27%) patients who had no evidence of an infection or indication of prophylaxis. Unnecessary antibiotic use
UTI Abdominal infection
3. Results
Penicillin Cephalosporin 1st generation Cephalosporin 3rd generation Cephalalosporin 4th generation Ampicillin /sulbactam Piperacillin /tazobactam Cephaperazone /sulbactam Aminoglycosides Quinolones Carbapenems Glycopeptides Metronidazole TMP /SMZ Other Total
Septicaemia
by ID consultants and prescription based on susceptibility results were defined as independent variables. The model was constructed by backward selection of independent variables. Software package STATA 7.0 (College station, TX) was used for the analysis.
8 75 14 4 72 4 21 44 43 27 21 24 4 16 377
A.v.c. Erbay et al. / International Journal of Antimicrobial Agents 21 (2003) 308 /312 LRTI Other Total
310
A.v.c. Erbay et al. / International Journal of Antimicrobial Agents 21 (2003) 308 /312 Table 3 Categories of inappropriate antibiotic use
311
Table 5 Appropriateness of antibiotic use in different wards
Categories of inappropriate antibiotic use
n
%
Ward
Unnecessary use (no evidence of an infection or indication 86 63.7 of prophylaxis) Overly broad 15 11.1 Not broad enough 12 8.9 Agree with choice of antibiotic, but dosage was inap12 8.9 propriate Overlap of spectrum ( /1 agents used at the same time) 8 5.9 More expensive than the equivalent 2 1.5 Total 135 100
ICUs Medical Surgical Total
Appropriate use
Inappropriate use
Total
n
%
n
%
n
%
22 77 143 242
68.8 80.2 57.4 64.2
10 19 106 135
31.2 19.8 42.6 35.8
32 96 249 377
100 100 100 100
In our study appropriate antibiotic use was 64.2% and rational use was 95% in restricted antibiotics but 58.2% in unrestricted antibiotics (P B/0.001). Previous studies evaluating antibiotic use in hospitals have reported that 28 /65% of prescriptions can be inappropriate [9,13 /15]. Specific rates of inappropriateness reported in the literature vary widely because of the diversity of the methods used to make such assessment. Although prospective studies are robust in evaluation of antibiotic decision and appropriateness of antibiotic use in hospitals, cross-sectional studies are more feasible for the surveillance allowing antibiotic policy to be assessed. The unnecessary use of antibiotics was the most common reason for inappropriateness in our study. This antibiotic misuse was highest on surgical wards and probably based on the consideration that potential or possible bacterial infection is more hazardous to the patient than the risk from use of antibiotics. Various studies have demonstrated that administration of antibiotics to uninfected patients accounts for 32 /60% of irrational antibiotic use [13,16]. In our study, the doses of 34 (9%) antibiotics were incorrect and this situation might have lead to increased morbidity, prolonged hospital stay and the need for more broad-spectrum and expensive drugs. There were only two cases where an antibiotic was judged inappropriate because of the availability of a less expensive drug, and this was probably the outcome of antibiotic restriction policy at ANERH. The principle aim of antibiotic policies is to bring a change in prescribing which will lead to reduction of resistance, decreased cost and improved quality of antibiotic usage [17]. Approaches that have been taken include educational programmes, development of prescribing guidelines, monitoring of drug resistance pat-
was 30% in surgical wards, 12% in ICU and 8% in medical wards. Ampicillin /sulbactam and first generation cephalosporins were the most frequently unnecessarily used antibiotics (35 and 31%, respectively). Antibiotic orders in surgical wards were found to be significantly more inappropriate than medical wards (P B/0.001) (Table 5). Rational antibiotic use was highest when the results of bacteriological samples were positive. Bacteriological samples had been taken before the antibiotic request in 114 (40.6%) patients. Seventeen percent of the antibiotics were requested because of the susceptibility test result. The most common isolated microorganisms were methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli and Klebsiella pneumoniae (Table 6). Antibiotic prescriptions were switched to another antibiotic in 43 (15%) patients; the main reason was susceptibility test result (44.6%) followed by clinical unresponsiveness to the antibiotic used (29.2%), unnecessary switch (24.6%) and antibiotic side effects (1.5%). In 60% of patients, ID specialists switched the antibiotics.
4. Discussion Antibiotics are the most commonly used drugs in Turkey [13] and only few hospitals have antibiotic restriction policies. Due to the high resistance rates and excessive use of broad-spectrum antibiotics, an antibiotic restriction policy was initiated in ANERH. Table 4 Appropriate and inappropriate use in restricted and unrestricted antibiotics Appropriate use
Restricted antibiotics Unrestricted antibiotics Total
Inappropriate use
Total
n
%
n
%
n
%
58 184 242
95.0 58.2 64.2
3 132 135
5.0 41.8 35.8
61 316 377
100 100 100
312
A.v.c. Erbay et al. / International Journal of Antimicrobial Agents 21 (2003) 308 /312
Table 6 Isolated microorganisms and culture sites Wound
Urine
Blood
Tracheal aspirate
Intraabdominal fluid
Other
Total n
MRSA E. coli K. pneumoniae MSSA P. aeruginosa Acinetobacter spp. Other
11 3 5 6 5 3 3
0 7 4 0 1 0 2
7 1 0 2 0 1 2
0 1 0 0 2 1 0
0 0 1 0 0 1 0
0 0 0 0 0 0 2
18 12 10 8 8 6 9
Total
36
14
13
4
2
2
71
terns, development of restrictive hospital formulary, limitation on reports of sensitivity tests, regulation of interactions between pharmaceutical representatives, and requirement for expert approval before or after prescribing some drugs [9,17 /20]. Education programmes have been successful in facilitating more appropriate antibiotic usage; the critical problem is the re-emergence of misuse without continuous education [1,21]. It was reported that requiring prior approval of an ID specialist for the use of restricted antibiotics seems to be the most effective control method [22]. In our study antibiotic recommendations by ID consultation was found to be significantly appropriate. Since it is impossible to restrict the use of all antibiotics, preparation of local guidelines, interventional studies and encouraging physicians to ask for more ID consultations are other important measures. Surgeons might be a suitable primary target for our interventional studies at ANERH. The panel discussions including different specialities, conferences, and seminars on antimicrobial decision making will be planned. Posters and pamphlets will be disseminated to the residents and specialists. To conclude; a combination of both restriction, continuous education of physicians and elaboration of local guidelines appear to be necessary to improve antibiotic use.
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% 25.4 16.9 14.1 11.3 11.3 8.4 12.6 100
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