Systematic Review of Factors Associated with Antibiotic Prescribing for Respiratory Tract Infections

80 Pages·2016·0.79 MB·English

AAC Accepted Manuscript Posted Online 2 May 2016
Antimicrob. Agents Chemother. doi:10.1128/AAC.00209-16
Copyright © 2016, American Society for Microbiology. All Rights Reserved.
1 Systematic Review of Factors Associated with Antibiotic Prescribing for
2 Respiratory Tract Infections
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5 Rachel McKay,a# Allison Mah,b Michael Law,c Kimberlyn McGrail,c o
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6 David M. Patricka,b lo
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8 School of Population and Public Health, University of British Columbia, m

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9 Vancouver Canadaa; Division of Infectious Diseases, University of British tt
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10 Columbia, Vancouver, Canadab; Centre for Health Services and Policy a
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11 Research, School of Population and Public Health, University of British a
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12 Columbiac .o
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15 Running head: Factors Associated with Antibiotic Use m
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18 # Address correspondence to Rachel McKay, [email protected] 8

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20 Abstract Word Count: 250 st
21 Main Body Word Count: 5006
22 Number of Tables: 2
23 Number of Figures: 2
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24 Number of Appendices: 1 (3 tables)
25 Abstract
26 Purpose: Antibiotic use is a modifiable driver of antibiotic resistance. In
27 many circumstances, antibiotic use is overly broad or unnecessary. We D
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28 systematically assessed factors associated with antibiotic prescribing for n
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29 respiratory tract infections (RTI). d
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30 f
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31 Methods: Studies were included if they used used actual (not self-reported
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32 or intended) prescribing data, assessed factors associated with antibiotic :
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33 prescribing for RTIs, and performed multivariable analysis of c
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34 associations. We searched Medline, Embase, and International m
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35 Pharmaceutical Abstracts using keyword and MeSH search terms. Two g
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36 authors reviewed each abstract and independently appraised all included
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37 texts. Data on factors affecting antibiotic prescribing were extracted. c
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38 be
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39 Results: Our searches retrieved a total of 2848 abstracts, with 97 included 3
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40 in full-text review and 28 meeting full inclusion criteria. Comparatively, 1
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41 the diagnosis of acute bronchitis was associated with increased antibiotic y

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42 prescribing (range of adjusted odds ratios [aOR] 1.56-15.9). Features on e
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43 physical exam such as fever, purulent sputum, abnormal respiratory
44 exam, and tonsillar exudate were also associated with higher odds of
45 antibiotic prescribing. Patient desire for an antibiotic was not associated
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46 or modestly associated with prescription (range of aORs 0.61-9.87), in
47 contrast to physician perception of patient desire for antibiotics, which
48 was associated more strongly (range of aORs 2.11-23.3).
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50 Conclusions: Physician’s perception of patient desire for antibiotics was o
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51 strongly associated with antibiotic prescribing. Antimicrobial stewardship lo
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52 programs should continue to expand in the outpatient setting, and d

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53 should emphasize clear and direct communication between patients and m

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54 physicians, as well as signs and symptoms that do, and do not, predict tt
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55 bacterial etiology of upper respiratory tract infections. a
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56 Introduction
57 The rapid and ongoing spread of antimicrobial resistant organisms
58 threatens our ability to successfully treat a growing number of infectious
59 diseases (1, 2). It is well established that antibiotic use is a significant,
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60 and modifiable, driver of antibiotic resistance (3-5), and that antibiotics ow
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61 are often misused (6). In settings where a prescription is required to lo
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62 access antibiotics, the prescriber-patient encounter is a logical target for d

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63 improving appropriate use. m

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65 Despite the importance of the topic, there is no existing systematic a
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66 review to identify drivers of antibiotic prescribing from real prescription as
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67 data. A narrative review of factors influencing antibiotic prescribing o
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68 highlighted the multiple sources of influence affecting a potential o
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69 prescribing encounter, including factors related to the prescribing e
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70 physician (e.g. fear of failure, diagnostic uncertainty, or inadequate m
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71 training), the patient (e.g. a high-risk or vulnerable patient history), and r
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72 the environment (e.g. regulation of pharmaceutical prescribing and 2
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73 dispensing and lack of resources for etiological diagnosis) (7). Another 8

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74 study systematically reviewed reasons for inappropriate antibiotic g
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75 prescriptions, for any indication, from quantitative studies up to 2008; t
76 half of the studies in this review used data based on simulated case
77 scenarios in which the physician was asked how he/she would respond
78 clinically (8). The main focus of that review was attitudes of prescribers;
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79 it found that a desire to fulfill the expectations of the patient/parent and
80 fear of possible complications in the patient were most consistently
81 associated with inappropriate prescribing of antibiotics. The presence of
82 one or more symptoms or signs (e.g. fever, pathological murmur, or
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83 productive cough) was associated with antibiotic prescription in most o
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84 studies assessed. The review also explored characteristics of patients, lo
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85 prescribers, and health care organization in relation to prescribing, but d

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86 the included studies were either too small in number or too m

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87 heterogeneous in approach to offer insights in these areas (8). The tt
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88 authors of this review discuss the limitations of simulated case scenarios a
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89 in understanding prescribing behaviour, and call on further studies a
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90 based on real prescription data. .o
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91 o
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92 Physician visits for respiratory tract infections (RTI) commonly result in e
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93 an antibiotic prescription (9-12), despite the fact that most upper RTIs m
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94 are viral in nature. In these cases, antibiotics provide no benefit, and r
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95 thus guidelines limit their recommended use to certain situations where 2
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96 the etiology is likely bacterial (13-15). Given the common nature of both 8

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97 this condition and potentially inappropriate prescribing practices around g
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98 it, we chose RTIs as the focus for this review. Factors associated with any st
99 antibiotic prescribing for RTI were assessed, with the understanding that
100 a significant proportion of this prescribing is unnecessary and would
101 therefore be considered inappropriate.
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102
103 A comprehensive summary of relevant factors implicated in potentially
104 unnecessary antibiotic use will support physicians to reflect critically on
105 their own practice, and will provide an evidence-based resource for
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106 intervention and policy design. Therefore, we conducted a systematic o
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107 review of factors associated with outpatient antibiotic prescribing for lo
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108 acute respiratory tract infections from the quantitative literature. The d

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109 purpose of this review was two-fold: first, to identify characteristics of m

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110 patients, physicians, and the environment that have been associated tt
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111 with antibiotic use; and second, to describe the strengths of associations a
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112 reported. a
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113 Methods rg
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114 The protocol used for this review is registered with PROSPERO, and can n

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115 be accessed at http://www.crd.york.ac.uk/PROSPERO c
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116 (ID=CRD42014010097). b
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117 3
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118 We restricted our formal review to quantitative studies, as we aimed to 0
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119 focus on the strengths of association reported in retrieved studies. This b
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120 report follows the guidelines in the Preferred Reporting Items for u
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121 Systematic Reviews and Meta-Analyses (PRISMA) statement (16).
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122 1.1 Search strategy
123 Medline, Embase, and International Pharmaceutical Abstracts were
124 searched. Search terms were determined by specifying the broader
125 concepts we sought to assess (“antibiotic”, “outpatient”,
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126 “appropriateness”, “prescribing”, “factors”), and by identifying relevant ow
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127 terms within these concepts. Keywords and MeSH terms were compared lo
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128 from known, relevant studies, as well as similar reviews. In addition, the d

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129 author of a relevant article (17) provided a list of search terms used in m

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130 that review, which served as an additional reference. Our list was then tt
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131 further refined through discussion with a librarian, and consensus a
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132 among the study authors (the final list of search terms is available in the as
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133 supplemental material). o
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134 1.2 Study selection n

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135 Peer-reviewed studies conducted using data from the Organization for c
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136 Economic Co-operation and Development (OECD) countries were eligible b
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137 for consideration. This restriction was used to limit the review to factors 3
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138 that could operate in similar health care system contexts and patient 0
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139 populations. In addition, included studies were required to have (1) used b
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140 actual (not self-reported or intended) prescribing, dispensing, or sales ue
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141 data; (2) investigated the prescription of antibiotics by physicians, i.e. not
142 over-the-counter purchasing; (3) been observational or experimental in
143 design; (4) been written in English language; (5) described factors at one
144 or more of the levels of interest and assessed the association with the
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145 primary outcome of whether or not an antibiotic was prescribed at an
146 individual encounter; and (6) performed multivariable analysis of the
147 associations. These criteria were refined from those presented in the
148 published protocol, based on the initial stages of the review. We omitted
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149 11 studies that included patients with pneumonia, where results were o
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150 not reported separately for the subgroup of patients without pneumonia. lo
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151 d

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152 After performing the full search, titles retrieved from each database were m

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153 combined and duplicates were removed. Two authors (RM and AM) tt
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154 screened each record for potential relevance. The full-texts of these a
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155 studies were then assessed for inclusion eligibility, independently by the a
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156 same two authors. Reference lists of included articles were hand- .o
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157 searched for additional studies. The final search was conducted on o
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158 October 14, 2015. e
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159 1.3 Data extraction and quality assessment b
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160 A customized data extraction form was developed for this study. All 3
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161 studies that met inclusion criteria were then assessed for quality using a 0
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162 form developed for this review, as there is no single recommended tool for b
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163 assessing the quality of observational studies. Our tool was based on the u
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164 SIGN 50 (Scottish Intercollegiate Guidelines Network) for cohort and
165 case-control studies, as recommended by a review of quality assessment
166 tools (18), as well as incorporating elements of the Quality Assessment
167 Tool for Observational Cohort and Cross-Sectional Studies from the
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168 National Institute of Health’s National Heart, Lung, and Blood Institute
169 (19). Two authors (RM and AM) independently performed data
170 abstraction and study appraisal. Abstractions and appraisals were
171 compared for each study, and any discrepancies or disagreements were
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172 resolved by discussion and consensus. Both reviewers extracted all the o
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173 information from each study. There were no major discrepancies between lo
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174 reviewers. d

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175 m

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176 The primary outcome of interest was an antibiotic prescription. Because tt
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177 antibiotic prescribing is a decision made at the level of the prescriber, a
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178 but recorded at the level of the patient, there is a natural clustering of a
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179 patients within prescribers when multiple patients are included per .o
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180 prescriber. We noted whether and how analysts accounted for this o
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181 clustering. e
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182 1.4 Data synthesis b
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183 Adjusted odds ratios (aOR) were extracted for each factor-antibiotic 3
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184 prescription association. Meta-analysis was not pursued, as significant 0
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185 heterogeneity among studies was expected. All factors identified were b
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186 extracted. Selected forest plots are presented in Figure 2. An alpha of u
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187 0.05 was used in all studies for constructing confidence intervals, and
188 was the basis of our interpretation of statistically significant and non-
189 significant findings.
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190 Results
191 2.1 Description of included studies
192 Our initial search identified 3435 records, of which 2848 non-duplicate
193 titles were screened for inclusion (Figure 1). Our initial search included D
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194 non-English articles; however, of the few non-English abstracts retrieved n
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195 and reviewed, none met the criteria for inclusion. Forty-four articles were d
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196 considered relevant. Of these, 16 were determined to be of insufficient f
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197 quality or to have insufficient details to allow further inclusion. The 28
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198 included articles were considered to be of good or high quality (11, 20-46) :
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199 (Table 1). Two studies reported results as risk ratios (34, 37), which c
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200 precluded us from directly comparing them to the odds ratios reported in m
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201 the other studies given that antibiotic prescription is a relatively common rg
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202 occurrence. Consequently, results from these studies are included in the n
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203 tables, but not in the forest plots. c
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204 b
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205 [Insert figure 1 around here] 3
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207 Just over half of the included studies were from the United States (US) b
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208 (n= 15) (11, 20, 21, 24, 26, 28, 30, 31, 33, 38-40, 45-47), with the ue
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209 remainder from Canada (n= 3) (34, 37, 43), The Netherlands (n= 2) (29,
210 35), Germany (n= 2) (23, 42), Italy (n= 1) (27), UK (n=1) (25), Belgium
211 (n=1) (22), and a network of 13 European countries (n=3) (36, 41, 44).
212 Eight of the US studies used the NAMCS (National Ambulatory Medical
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