Minimal Use of Antibiotics for Acute Respiratory Tract Infections: Validity and Patient Satisfaction

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1 ORIGINAL ARTICLE Minimal Use of Antibiotics for Acute Respiratory Tract Infections: Validity and Patient Satisfaction Keisuke Tomii 1, Yoshihisa Matsumura 2, Kenji Maeda 3, Yuki Kobayashi 4, Yoshihisa Takano 5 and Yoshikazu Tasaka 6 Abstract Background Antibiotics have been overused for acute respiratory tract infections (ARTIs) and the recent guidelines have emphasized limiting their use. Objective To clarify the exact rate of antibiotic use and patient outcomes and satisfaction, under strict adherence to the guideline proposed by the American College of Physicians. Design Prospective cohort observational study. Setting Primary care clinics in Japan. Patients 783 patients diagnosed with ARTIs from October 2004 to April 2005, aged and without any underlying disease. Measurements Scores of symptoms and patient satisfaction at the 5th, 8th and 15th day of their initial visit, when treatment had been initiated according to that strategy. Results In 691 non-influenza patients, comprising 554 (80%) cases of nonspecific upper respiratory tract infection (A), 11 (2%) of acute rhinosinusitis (B), 90 (13%) of acute pharyngitis (C) and 36 (5%) of acute bronchitis (D); the rates of antibiotic use were 5% [0.2%; (A), 9%; (B), 36%; (C), 3%; (D)] initially and 2% [2%; (A), 0%; (B), 1%; (C), 3%; (D)] subsequently. For the remaining 92 influenza patients, no antibiotics were prescribed, though oseltamivir was prescribed in 89 (97%). Within 7 days, more than 90% of all patients felt improved and expressed their satisfaction with the treatment. Furthermore, no patients needed emergency room visits or hospital admission. Limitations Only patients who gave informed consent were enrolled. Conclusions Adhering to the guideline, antibiotic use could be limited to only 5-7% of non-influenza ARTIs-mainly acute pharyngitis-without any problems and with a high degree of patient satisfaction. Key words: antibiotics, primary care, common cold (DOI: /internalmedicine ) Introduction Antibiotics have been overused for colds, upper respiratory tract infections and bronchitis in most countries and the growing resistance to them has been of considerable concern (1). Guidelines and position papers (2-6) have been proposed to restore the situation, and the prescription rates for antibiotics have been declining, but not to a satisfactory level (7). The reason for prescribing antibiotics in general practice seems to be not so much scientific as it is social and cultural (8-10). Patients and families have a poorly informed image of antibiotics (11-14) and they insist on the doctor prescribing them even for acute respiratory infections, most of which are caused by viruses. Non-clinical factors such as geographic location, race, the physician s specialty, health insurance schemes, etc. seem to be associated with antibiotic prescriptions (14) and physicians also often decide to use them with relatively less evident clinical findings such as fatigue, fever, and yellow sputum (15). Furthermore, some general physicians frequently prescribe antibiotics to prevent Department of Pulmonary Medicine, Kobe City General Hospital, Kobe, Matsumura Clinic, Nara, Maeda Clinic of Internal Medicine, Saitama, Kobayashi Clinic, Kobe, Takano Clinic & Health Care, Kumamoto and Tasaka Family Clinic, Hiroshima Received for publication August 23, 2006; Accepted for publication December 1, 2006 Correspondence to Dr. Keisuke Tomii, ktomii@kcgh.gr.jp 267

2 Figure1. Patientflowchart.()Numberofpatientswho wereprescribedantibioticsuntilthedayofevaluation.+patientswhorespondedtothequestionnaireoneachdayof evaluation.-patientswhodidnotrespondtothequestionnaireoneachdayofevaluation.*twoofthesewereinfluenzapatients. secondary bacterial infection, questioning the validity of a strategy that emphasizes a more judicious use of antibiotics. Although some educational trials for patients and physicians have been effective in reducing antibiotics prescriptions (16), showing what exact percentages of patients can really do well without antibiotics would have greater impact. Therefore, we performed a prospective cohort study, tracking patient outcomes and satisfaction, having strictly applied the guideline for judicious use of antibiotics for acute respiratory tract infections (ARTIs) proposed by the American College of Physicians (2-6). Patients and Methods Patients (15-64 years of age), who visited the clinics of 5 general practitioners (GP); Y.K. (Hyogo), Y.T. (Kumamoto), Y.T. (Hiroshima), K.M. (Saitama), and Y.M. (Nara), during the period October 2004 to April 2005, and who were diagnosed as having ARTIs (onset within 7 days) and without underlying diseases, were consecutively enrolled, with a maximum of 200 patients for each GP. First, the patients were classified based on their predominant clinical features as one of 4 types: A) nonspecific upper respiratory tract infection (common cold): having acute respiratory symptoms in the absence of a predominant symptom; B) acute rhinosinusitis: having prominent nasal and sinus symptoms; C) acute pharyngitis: having prominent acute sore throat; and D) acute bronchitis: having prominent acute cough. (2) Thereafter, they were treated according to the principles of the appropriate antibiotic use for ARTIs proposed by the American College of Physician s (ACP) clinical practice guideline, indicating that patients were to be prescribed antibiotics only if they fell into group B) accompanied by facial pain or tenderness, or C) suspected of group A β-hemolytic streptococcus infection (rapid antigen test positive or more than 3 of the Centor criteria; tonsillar exudates, tender anterior cervical lymphadenopathy, absence of cough, and history of fever), hemi-lateral tonsillitis, peritonsillar abscess, or D) unable to exclude pneumonia. Other than these, antibiotics were exceptionally prescribed in cases where the doctor deemed it to be particularly necessity. The antineuraminidase drug oseltamivir was permitted for use in patients also diagnosed as having influenza with antigen detecting kits or clinico-epidemiological prediction. Questionnaires on the patients symptoms: scores of changes in their symptoms after their initial visit (much better, better, no change, worse, much worse) and the presence of residual symptoms (nasal, pharyngeal, bronchial, fever or other) were prospectively answered on the 5th-day by postcard, and on the 8th- and 15th days by telephone or direct interview. The same questionnaire also required patients to indicate scores for their degree of satisfaction with the treatment defined as: very well-satisfied, well-satisfied, neutral, not very satisfied, or very dissatisfied; and whether they had visited other offices or not by the given day. In cases where patients said their symptoms were greatly relieved on the 8 th day, we did not require a further questionnaire on day 15. Postcards for the 5th day s questionnaire were given to the patients in advance at their initial visits and then sent to K. T. at Kobe City General Hospital (KCGH) after they were completed. Care was taken not to disclose any personal information other than an identification number on the card. Questionnaires completed on the 8th and 15th days, together with the patient s enrollment data, were sent in confidence by the 5 GPs to K.T., who stored and analyzed the data without knowledge of the patient s identity. The research protocol was approved by the Institutional Review Board of KCGH and all of the patients enrolled gave written consent to be involved in the study. The 5 GPs involved are all fellows of the Japanese Society of Internal Medicine and 4 of them are fellows of the ACP. Results There was a total enrollment of 783 patients (aged 39 ± 13 years, males 348, females 435), of whom 92 were clinically diagnosed as having influenza. Questionnaires on the 5 th day received 590 (76%) responses, on the 8th day 552 (71%), and on the 15th 313 (40%). The main reason for the marked decline in responses on the 15th day was that we were reluctant to interview all patients after they had fully recovered. There were no responses to any of these 3 questionnaires from 65 (8%) patients (Fig. 1). The percentages of the 4 types of disease among the 691 non-influenza patients were as follows: 554 (80%) cases of non-specific upper respiratory tract infection (A), 11 (2%) of acute rhinosinusitis (B), 90 (13%) of acute pharyngitis (C) and 36 (5%) of acute bronchitis (D) (Table 1). Before their initial visits to the GPs, the maximum temperature and duration of fever for those diagnosed as non-influenza were

3 Figure2. Symptom scoresasevaluatedby(a)non-influenzaand(b)influenzapatients.verticalaxisindicatesnumberofpatientswhoscoredaparticularsymptom changeon the5th,8thand15thdayaftertheirinitialvisit.thenumber forthe15thdayisrathersmalbecausequestionnaireswere notgiventopatientswhohadfulyrecovered. ±0.8 and 2.3 ± 1.5 days, respectively. Antibiotics were initially prescribed in 35 cases (5%): 1 (0.2%) from category (A), 1 (9%) from (B), 32 (36%) from (C) and 1 (3%) from (D), in which exceptional out-of-guideline use was seen in the two cases in (A) and (D), the reason for which was to decrease the patient s anxiety in (A) and to treat predicted Mycoplasma infection from a family member in (D). On subsequent visits, they were prescribed in 14 cases (2%): 12 (2%) of (A), 1 (1%) of (C), and 1 (3%) of (D). Of these 14 cases, 6 (43%) had antibiotics prescribed until 4 days after the initial visits, 5 (36%) until 7 days after, and 3 (21%) Figure3. Residualsymptomsof(a)non-influenzaand(b) influenzapatients.verticalaxisindicatesnumberofresidual symptomsexpresedbypatientson5th,8thand15thdayaftertheirinitialvisit. until 14 days after. Among the patients with initial antibiotics use, the most frequent diagnosis was acute pharyngitis (91%) and among those of subsequent use, nonspecific upper respiratory tract infection (86%). The reasons for subsequent antibiotic use were persistence of symptoms even without validation of bacterial involvement (9/14, 64%), clinical judgment of secondary bacterial bronchitis (2/14, 14%), primary or secondary bacterial sinusitis (2/14, 14%) and secondary bacterial tonsillitis (1/14, 7%). At their initial visit, the prescribed antibiotics comprised penicillins (22/35, 63%), new-macrolides (11/35, 31%), and others (2/35, 6%), while on the subsequent visit they comprised penicillins (6/ 14, 43%), new-macrolides (5/14, 36%), and others (3/14, 21%). No patients needed emergency room visits or admission but 11 (1.6%) visited other offices. Among patients diagnosed as having influenza, those who 269

4 Table1. EnroledPatientswithAcuteRespiratoryTract Infections* Figure4. Patientsatisfactionscoresfortreatmentevaluatedby(a)non-influenzaand(b)influenzapatients.Vertical axisindicatesnumberofpatientswhoevaluatedtheirparticulardegreeofsatisfactiononthe5th,8thand15thdayafter theirinitialvisit.thenumberforthe15thdayisrathersmal becausequestionnaireswerenotgiventopatientswhohad fulyrecovered. were categorized as non-specific upper respiratory tract infection were the most frequent (84%) with those categorized as acute bronchitis, second (13%) (Table 1). The maximum temperature before the initial visit was 38.3 ± 0.6 and the duration of fever was 1.5 ± 1.1 days. All the enrollments with influenza were from February to April 2005, when influenza was at epidemic levels in Japan. Influenza-antigen detecting kits were used for the diagnosis in 29/92 (21%) patients. Oseltamivir was prescribed in 89/92 (97%), and while antibiotics were not prescribed in any cases initially, they were in 2 (2.2%) patients subsequently. No patients needed emergency room visits or admission but 3 (3.3%) visited other offices. The outcome of our treatment under the principles of appropriate antibiotic use was evaluated as shown in Fig. 2. In non-influenza patients, the symptom scores of better and much better were 445 (85%) on the 5th day, 445 (94%) on the 8th day, and 297 (97%) on the 15th day, and in influenza patients, those of better and much better were 100% throughout the period. Cough and phlegm were the most frequent remaining symptoms while rhinorrhea was second for non-influenza, but almost no symptoms remained on the 8th day for cases of influenza treated mostly with oseltamivir (Fig. 3). The non-influenza patients who rated their satisfaction with the treatment as very well-satisfied and well-satisfied were 251/399 (63%) on the 5th day, 345/396 (87%) on the 8th, and 227/239 (95%) on the 15th. Such rates for the influenza patients were 53/71 (75%) on the 5th, 69/71 (97%) on the 8th, and 33/33 (100%) on the 15th day (Fig. 4). Discussion Our study showed that by adhering to the ACP guideline, only about 5% of non-influenza ARTIs, most of which were acute pharyngitis, needed antibiotics initially and that within 7 days most of the symptoms were relieved and about 90% of patients were satisfied with the strategy. For patients with influenza, a strategy of oseltamivir and no antibiotics produced rapid symptom reduction and significant patient satisfaction. In data reported recently (7, 18-20), the antimicrobial prescription rates for ARTIs decreased from the early 1990 s to 2000, but not to an appropriate level. Cantrell et al (18) reported that those in ambulatory care settings might have still accounted for more than 60% in In community-based outpatient practice, Steinman et al (7) showed that 22% of adult patients were still prescribed broad-spectrum antibiotics for the common cold in the period In emergency department visits, Thorpe et al (19) showed that prescribing antibiotics for a narrowly defined subset of ARTIs, where antibiotic therapy is nearly always inappropriate, only 270

5 decreased from 57% to 44% during the period from 1995 to Compared with these data, our rate of initial antibiotic use, 35/691 (5%) for total non-influenza ARTIs and 3/601 (0.5%) for those other than acute pharyngitis, was remarkably low, although their studies were performed several years ago. This means that adhering to the guideline has the power to reduce injudicious antibiotic use for ARTIs. According to the guideline, ARTIs are subdivided into 4 types, but this classification was rather arbitrary and seemed to be accompanied by considerable overlaps. Hueston and colleagues (20) presented the hypothesis that sinusitis, upper respiratory tract infections and acute bronchitis should be considered as the same clinical entity of acute respiratory infection, with primary symptoms related to different anatomic areas rather than as different entities. According to their theory, most ARTIs other than bacterial pharyngitis, such as group A β-hemolytic streptococcus infection, could be regarded as a continuum of one entity not requiring antibiotics. In the present study, we only prescribed antibiotics for cases other than pharyngitis, initially 3/601 (0.5%) and subsequently 13/601 (2.2%), and most of their symptoms were relieved within 7 days. In contrast, we had to prescribe antibiotics for 36% of cases of acute pharyngitis, which should be considered as potentially requiring antibiotics and treated separately. Influenza is a respiratory viral infection associated with respiratory tract symptoms but is clearly different from common colds in some clinical characteristics such as sudden onset, high fever and more generalized symptoms. Antigendetecting kits have been recently used for diagnosing influenza; however, they do not seem to be mandatory when the disease is epidemic. In the present study, influenza patients, including both those diagnosed with kits and those with clinico-epidemiological findings were treated mostly with oseltamivir. As their symptoms were relieved rather promptly and their degree of satisfaction was extremely high, little room was left to consider antibiotics. Moreover, a recent systematic review of antivirals for influenza (21) indicated that oseltamivir decreased the time to alleviation of symptoms (hazard ratio 1.30, ) and prevented lower respiratory tract complications (odd s ratio 0.32, ). Thus, prescribing oseltamivir for influenza seems to have the potential to decrease the number of antibiotic prescriptions; however, for those populations at low risk, this is still controversial, considering the undetermined economical merit (22), the short supply of the drug following the recent worldwide endemic H5N1 strain of avian influenza, and also the potential risk of inducing an oseltamivir-resistant influenza strain (23). Guidelines such those of the ACP describe a theoretical lack of necessity for antibiotics; however, considering the persistently high rates of antibiotic use, such guidelines have not yet been fully accepted either by patients or physicians in the clinical setting. Therefore, it will be important to educate both parties realistically about the policy of reducing antibiotics for ARTIs. Gonzales et al (16) introduced a combination of patient and clinician interventions using educational materials for adults with uncomplicated acute bronchitis, which reduced antibiotics treatment safely. Macfarlane et al (24) produced an information leaflet supported by verbal advice, which reassured patients and shared their uncertainty about prescribing antibiotics and thus reduced antibiotic use in patients with acute bronchitis. Harris et al (25) showed that a combination of patient and provider educational interventions could reduce antibiotics use from 58% to 24% in patients with acute bronchitis and from 14% to 1% in patients with nonspecific upper respiratory tract infections. In the present study, we were able to reduce antibiotics prescriptions to a minimum level and with a high degree of patient satisfaction, perhaps partly thanks to the enthusiastic efforts of the participating GPs in educating their patients. Our data, which indicates the minimum and target rates of antibiotic use for ARTIs, should be both informative and useful for the education of patients and physicians. Some limitations exist in this study. We were unable to perform a randomized control study because of difficulties in setting controls for usual antibiotic use. Therefore, we performed a prospective cohort observational study, which, however, had selection bias by enrolling only patients who could give their consent for the study. Another limitation is that not every patient could be followed at the same interval and 8% of the patients dropped out in total. This study shows the minimum antibiotics use for ARTIs adhering to the guideline. It could be useful in promoting a policy of reducing injudicious antibiotic use for ARTIs. For aged populations and high-risk patients with certain chronic diseases, however, we should not forget that they are excluded from the guideline. Acknowledgments: This study was supported by the Committee of Standard Treatment for the Common Cold organized by the Fellow s Association of the Japanese Society of Internal Medicine (FJSIM). We regret that one of our coauthors, Dr. Yoshikazu Tasaka, passed away unexpectedly on February 11th We all greatly appreciate his dedication to this paper and also his influential career as a model of primary care physician. References 1. Gonzales R, Steiner JF, Sande MA. 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