What are targets for improving antibiotic stewardship for outpatient acute respiratory infections?Among 14 987 outpatients with acute respiratory infections enrolled in this cohort study during influenza seasons, 41% were prescribed antibiotics, 41% of whom had diagnoses for which antibiotics are not indicated, primarily viral upper respiratory tract infections and bronchitis; 29% of patients with influenza confirmed through research testing were prescribed antibiotics. Among patients prescribed antibiotics, 38% with pharyngitis tested negative for group A streptococcus and 38% with sinusitis had symptoms for 3 days or less before the visit, suggesting antibiotic therapy was not required.Eliminating antibiotic treatment of viral upper respiratory tract infections and bronchitis, improving influenza diagnosis and treatment, and reinforcing prescription guidelines for pharyngitis and sinusitis could improve outpatient antibiotic stewardship. Acute respiratory infections (ARIs) are the syndrome for which antibiotics are most commonly prescribed; viruses for which antibiotics are ineffective cause most ARIs.To characterize antibiotic prescribing among outpatients with ARI during influenza season and to identify targets for reducing inappropriate antibiotic prescribing for common ARI diagnoses, including among outpatients with laboratory-confirmed influenza.International Classification of Diseases, Ninth Revision diagnosis codes were collected from medical and pharmacy records, as were group A streptococcal (GAS) testing results in a patient subset.Cohort study enrolling outpatients aged 6 months or older with ARI evaluated at outpatient clinics associated with 5 US Influenza Vaccine Effectiveness Network sites during the 2013-2014 and 2014-2015 influenza seasons. All patients received influenza testing by real-time reverse transcriptase–polymerase chain reaction for research purposes only. Antibiotic prescriptions, medical history, and Visit for ARI, defined by a new cough of 7 days’ duration or less.Antibiotic prescription within 7 days of enrollment. Appropriateness of antibiotic prescribing was based on diagnosis codes, clinical information, and influenza and GAS testing results.Of 14 987 patients with ARI , 6136 (41%) were prescribed an antibiotic. Among these 6136 patients, 2522 (41%) had diagnoses for which antibiotics are not indicated; 2106 (84%) of these patients were diagnosed as having a viral upper respiratory tract infection or bronchitis (acute or not otherwise specified). Among the 3306 patients (22%) not diagnosed as having pneumonia and who had laboratory-confirmed influenza, 945 (29%) were prescribed an antibiotic, accounting for 17% of all antibiotic prescriptions among patients with nonpneumonia ARI. Among 1248 patients with pharyngitis, 1137 (91%) had GAS testing; 440 of the 1248 patients (35%) were prescribed antibiotics, among whom 168 (38%) had negative results on GAS testing. Of 1200 patients with sinusitis and no other indication for antibiotic treatment who received an antibiotic, 454 (38%) had symptoms for 3 days or less prior to the outpatient visit, suggesting acute viral sinusitis not requiring antibiotics.Antibiotic overuse remains widespread in the treatment of outpatient ARIs, including among patients with laboratory-confirmed influenza, although study sites may not be representative of other outpatient settings. Identified targets for improved outpatient antibiotic stewardship include eliminating antibiotic treatment of viral upper respiratory tract infections and bronchitis and improving adherence to prescribing guidelines for pharyngitis and sinusitis. Increased access to sensitive and timely virus diagnostic tests, particularly for influenza, may reduce unnecessary antibiotic use for these syndromes. This cohort study examines patterns and appropriateness of antibiotic prescribing among children and adults with acute respiratory infections visiting outpatient clinics associated with the US Influenza Vaccine Effectiveness Network during influenza season. Inappropriate antibiotic use contributes to the development of antibiotic-resistant organisms, which cause an estimated 2 million illnesses and 23 000 deaths annually in the United States.3 Understanding antibiotic prescribing practices for ARIs in outpatient settings is critical to designing strategies for reducing inappropriate antibiotic use.Acute respiratory infections (ARIs) remain the clinical category for which antibiotics are most commonly prescribed.7 In this study, we include data on illness onset date, laboratory testing for influenza in all patients, and, for many patients, self-reported fever and the results of clinician-ordered group A streptococcal (GAS) testing. We used 3 approaches to assess antibiotic prescribing among outpatients with ARIs during the influenza season. First, we examined antibiotic prescribing by age group, antibiotic type, and diagnosis. Second, because influenza is a frequent cause of ARIs, sensitive point-of-care influenza testing is not widely available,9 and individuals with influenza are often inappropriately prescribed antibiotics,10 we characterized antibiotic prescribing among those with laboratory-confirmed influenza, excluding syndromes for which antibiotics are indicated . Third, we examined appropriateness of antibiotic prescribing for those with pharyngitis, sinusitis, and otitis media (OM), diagnoses that account for nearly one-third of prescribed outpatient antibiotics,2 based on symptom duration, presence of fever, prescription of recommended first-line antibiotics,4 and GAS testing results.Previous studies examining antibiotic overuse have relied on national survey data, and many lack clinical and laboratory testing results.11 The network, which included 57 (2013-2014) and 66 (2014-2015) clinics associated with 5 sites that are geographically diverse academic medical centers and health care organizations, was designed to assess influenza vaccine effectiveness annually; additional data were collected for this secondary analysis. Once sites confirmed local influenza circulation, patients aged 6 months or older with ARI, defined by a new cough of 7 days’ duration or less, were eligible for enrollment. Respiratory swab specimens were obtained and tested for influenza with real-time reverse transcriptase–polymerase chain reaction for research purposes only. Patients could enroll more than once per season more than 14 days apart; we analyzed each patient visit separately. Eligible patients were screened and enrolled if they or their legal guardians provided written or oral informed consent, depending on requirements of local institutional review boards. Study procedures, forms, and consent documents were approved by site institutional review boards.In this cohort study, we used data collected by the US Influenza Vaccine Effectiveness Network during the 2013-2014  and 2014-2015  influenza seasons, as described elsewhere.International Classification of Diseases, Ninth Revision (ICD-9) codes assigned to medical encounters during the year before enrollment. We extracted dates of hospitalizations occurring less than 30 days after enrollment from medical records. Excluding topical antibiotics, we obtained antibiotic and influenza antiviral prescriptions within 7 days of enrollment from pharmacy, insurance, or electronic medical records. Patients were excluded if dates indicated antibiotics were first prescribed during a hospitalization. If more than 1 antibiotic was prescribed, the antibiotic with the earliest prescription date was included.Patient characteristics, including self-reported race and ethnicity selected from options defined by the investigator, and symptom onset date were ascertained by interview. In addition, patients were asked about self-reported fever at 2 sites in 2013-2014 and all sites in 2014-2015. We obtained patients’ history of underlying medical conditions by examining ICD-9 codes assigned to the enrollment visit into 3 tiers based on previously published classifications , influenza, allergy, asthma, and acute bronchitis.2 Because current guidance recommends antibiotic treatment for some patients with chronic obstructive pulmonary disease (COPD) exacerbations,13 adults with a history of COPD or COPD diagnosis code at enrollment were excluded from bronchitis analyses. We excluded patients missing ICD-9 codes or assigned diagnostic codes compatible with nonrespiratory diagnoses for which antibiotics are potentially indicated . If a patient had multiple diagnoses, priority was given to tier 1 diagnoses, then tier 2 diagnoses, then tier 3 diagnoses.We classified the first 4 14 Narrow-spectrum antibiotics included narrow-spectrum penicillins, tetracyclines, first-generation cephalosporins, and sulfonamides. Broad-spectrum antibiotics included macrolides , broad-spectrum penicillins , advanced-generation cephalosporins, quinolones, and lincomycin derivatives (clindamycin). We examined whether clinicians prescribed first-line antibiotics for the most common tier 2 diagnoses, based on national guidelines: penicillin or amoxicillin for pharyngitis, amoxicillin or amoxicillin-clavulanate for sinusitis, and amoxicillin or amoxicillin-clavulanate  for suppurative OM.19We classified antibiotics based on previously established categories.At 1 site, clinicians were provided study real-time reverse transcriptase–polymerase chain reaction results for influenza within 48 hours of enrollment. Results were not available to clinicians at other sites. At 4 sites, we examined data on rapid influenza diagnostic tests or other diagnostic tests ordered the day of enrollment and not performed as part of the study protocol.20 We examined a GAS testing subset comprising patients with a pharyngitis diagnosis with no other diagnosis for which antibiotics may be warranted at 4 sites during the 2014-2015 season for whom we obtained information from medical records on clinician-ordered GAS testing. Rapid antigen detection test results were available at all sites, and some sites performed cultures when rapid antigen detection test results were negative. If a patient had positive results on either the GAS rapid antigen detection test or culture, the patient was considered GAS positive. The proportion of patients in the entire study population with pharyngitis who were prescribed an antibiotic despite a negative result on GAS testing was estimated based on results from the GAS testing subset.For pharyngitis, guidelines recommend antibiotic therapy only for GAS pharyngitis and diagnostic testing if GAS is suspected.18 Among patients with sinusitis and suppurative OM,15 we examined antibiotic prescribing and its relationship to the timing of symptom onset and self-reported fever, when available.For sinusitis, national guidelines recommend antibiotics for adults and children with severe symptoms, defined by a temperature of 39°C or higher, purulent nasal discharge, or facial pain, for at least 3 consecutive days; worsening course after initial improvement; or persistent illness (symptoms lasting ≥10 days).2 test. We used logistic regression to develop 2 models with predictors of antibiotic prescribing. A model examining antibiotic prescribing among those with only tier 3 diagnoses adjusted for sex, site, age group, race, number of chronic conditions, time from symptom onset to presentation for care, and clinical diagnosis. A model that examined antibiotic prescribing among those with laboratory-confirmed influenza adjusted for sex, site, age group, number of chronic medical conditions, time from symptom onset, clinical diagnosis, and presence of fever. Variables with 2-sided P < .20 on univariate analysis were included in multivariable analyses and subjected to model-fitting procedures. A 2-sided P value less than .05 was considered statistically significant. Statistical analyses were conducted using SAS version 9.4 statistical software (SAS Institute Inc).Categorical data were analyzed with a χICD-9 codes, 118 were prescribed an antibiotic while hospitalized, and 483 were diagnosed with a nonrespiratory condition for which antibiotics are potentially indicated. Among the 14 987 patients included, the mean (SD) age was 32 (24) years, 8638 (58%) were women, and 11 892 (80%) were white  had at least 5 codes, less than 1% of which had additional codes indicating tier 1 or tier 2 diagnoses. Results were unchanged when we analyzed all diagnosis codes.During the 2013-2014 and 2014-2015 influenza seasons, we enrolled 15 714 patients. Among these, 727 were excluded: 126 had missing re white . The 14 Among 14 987 patient visits analyzed, 6136 (41%) were associated with an antibiotic prescription, including 3423 (56%) with broad-spectrum antibiotics. Five drugs accounted for 90% of antibiotic prescriptions: azithromycin (37%), amoxicillin (35%), amoxicillin-clavulanate (10%), doxycycline (5%), and levofloxacin (3%) . MacroliInfluenza was confirmed through research testing in 3381 patients (23%), 902 (27%) of whom received a clinical diagnosis code for influenza. Excluding those with a tier 1 diagnosis, among 3306 patients (22%) with laboratory-confirmed influenza, 945 (29%) were prescribed an antibiotic, accounting for 17% of all antibiotic prescriptions among patients with nonpneumonia ARI; 656 (20%) were prescribed an influenza antiviral medication, including 89 prescribed both antibiotic and antiviral medications. Laboratory-confirmed influenza was detected in 72 of 375 patients (16%) diagnosed as having pneumonia, 446 of 2065 patients (18%) with pharyngitis, 129 of 1099 patients (11%) with suppurative OM, and 227 of 1486 patients (13%) with sinusitis; the proportion with laboratory-confirmed influenza among those prescribed antibiotics is shown in P < .01). Azithromycin was the most commonly prescribed antibiotic given to adults who lacked a diagnosis for which antibiotics are indicated; among the 3186 adults aged 50 years and older with no clinical indication for antibiotics (tier 3 diagnoses only), 1183 (37%) received an antibiotic prescription; 688 (58%) of these prescriptions were for azithromycin.Among 6136 patients who received antibiotic prescriptions, 2522 (41%) had only diagnoses for which antibiotics are not indicated (tier 3) . The proP < .001). Both a clinical diagnosis of influenza and laboratory-confirmed influenza through research testing were significantly associated with decreased odds of an antibiotic prescription .Among the 2522 patients with tier 3 diagnoses prescribed an antibiotic, 2106 (84%) were diagnosed as having either a viral URI or bronchitis (acute or not otherwise specified). Among 5553 patients with a viral URI diagnosis, 1376 (25%) received an antibiotic, accounting for 22% of all antibiotic prescriptions . ExcludiThe 3 most frequent diagnoses for which antibiotics are potentially indicated (tier 2 diagnoses) were pharyngitis (diagnosed in 2494 patients [17%]), sinusitis (1707 patients [11%]), and suppurative OM (1212 patients [8%]), which together accounted for 52% of all antibiotics prescribed. Among 3198 persons who received antibiotics for these diagnoses, 2050 (64%) received first-line antibiotics  with a pharyngitis diagnosis who received an antibiotic, 122 (12%) had laboratory-confirmed influenza . Among tAmong 1707 patients assigned a sinusitis diagnosis, 1385 (81%) were prescribed antibiotics, 188 (14%) of whom had laboratory-confirmed influenza . Among tSuppurative OM accounted for 17% of antibiotic prescriptions, including 41% of those in children and 4% in adults. Among 1055 persons with this diagnosis prescribed an antibiotic, 121 (11%) had laboratory-confirmed influenza .Among all 6136 patients with antibiotic prescriptions, we estimated 3303 (54%) likely did not meet clinical criteria or laboratory criteria for GAS pharyngitis for antibiotic treatment. Of these 6136 patients, 2522 (41%) had only clinical diagnoses that do not warrant antibiotics (tier 3 diagnoses only), 454 (7%) had sinusitis that did not meet clinical criteria, and an estimated 327 (5%) had pharyngitis with a negative GAS test result. Among the remaining 2833 patients given antibiotic prescriptions who had a clinical diagnosis for which antibiotic therapy may be indicated , an additional 369 (13%) had influenza virus infection confirmed through research testing and likely did not benefit from antibiotic therapy.Antibiotics were likely prescribed inappropriately to a majority of the nearly 15 000 outpatients in this study who presented during influenza season with symptoms of a broadly defined ARI characterized by cough. Among all patients prescribed antibiotics, 41% lacked a diagnosis code for which antibiotic therapy is potentially indicated. Those with influenza confirmed through research testing accounted for a substantial proportion (17%) of all antibiotics prescribed; fewer than one-third of patients with laboratory-confirmed influenza were given a clinical diagnosis of influenza. Patients with influenza virus infection accounted for a substantial proportion of those given antibiotics for diagnoses for which antibiotics may be appropriate, including pharyngitis (12%), sinusitis (14%), and suppurative OM (11%), although most patients with influenza are unlikely to benefit from antibiotic treatment. In addition, among those patients given diagnoses for which antibiotic therapy may be appropriate, many patients prescribed antibiotics likely did not meet criteria for antibiotic therapy based on clinician-ordered laboratory testing and clinical criteria, including 47% of those with a pharyngitis diagnosis and 38% with a sinusitis diagnosis.7 We used a sensitive clinical definition of ARI and had data including illness onset date, laboratory confirmation of influenza, and, for many patients, self-reported fever and the results of clinician-ordered GAS testing. As noted in previous studies,6 we found that a substantial proportion of antibiotic overuse was driven by prescribing for conditions for which antibiotics were not indicated, including viral URIs and acute bronchitis.19 Our results also suggest antibiotics were frequently overprescribed for patients with 2 common diagnoses for which antibiotics are potentially indicated, pharyngitis and sinusitis, underscoring that these diagnoses are important targets for improving antibiotic use. For pharyngitis, national guidelines recommend antibiotic therapy only for laboratory-confirmed GAS20; in our study, nearly half of patients diagnosed as having pharyngitis who received antibiotics either tested negative for GAS or were not tested. For patients with sinusitis, among those prescribed an antibiotic, 38% had symptoms for 3 days or less and most did not report fever, indicating that many patients likely did not meet clinical criteria for antibiotic treatment as defined by national guidelines.Our study is consistent with previous studies that indicate clinicians overprescribe antibiotics for outpatient ARIs. These studies used national survey data, which lack detailed clinical data, including laboratory testing results.7 Choosing a macrolide when amoxicillin or amoxicillin-clavulanate is the recommended first-line antibiotic is a potential patient safety issue; GAS and Streptococcus pneumoniae infections are more likely to be resistant to macrolides than to amoxicillin or amoxicillin-clavulanate. While all antibiotics have potential risks, macrolides have also been associated with an increased risk of cardiovascular events.21Older adults were more likely than younger adults and children to receive antibiotics without diagnostic documentation of an appropriate indication and were far more likely to receive broad-spectrum antibiotics, particularly macrolides. Azithromycin was prescribed to nearly one-quarter of adults aged 50 years or older with an ARI, regardless of diagnosis, laboratory testing, symptom duration, or medical history, including to 58% of those older adults given a prescription who lacked an indication for antibiotic treatment. Azithromycin also accounted for more than one-quarter of prescriptions among those adults diagnosed as having pharyngitis and sinusitis, even though it is not the first-line agent for either condition. A concerning increase in macrolide use for these conditions has been previously noted in both adults and children.22 As in previous studies,10 we found that patients with influenza confirmed through research testing were more likely to receive an antibiotic than an antiviral medication. In addition, a substantial proportion of patients with diagnoses for which antibiotics may be considered appropriate—pharyngitis, suppurative OM, and sinusitis—actually had influenza virus infection, and depending on the clinical situation, many would likely not benefit from antibiotic treatment. Current widely available point-of-care influenza diagnostic tests have highly variable sensitivity8 and are not recommended for ruling out influenza infection for the purposes of treatment decisions9; clinician-ordered testing was infrequent in this study. Clinicians assigned an influenza diagnosis code to only one-quarter of patients with influenza confirmed through research testing, indicating that influenza virus infections were underdiagnosed. However, among all patients with ARI, those patients to whom clinicians assigned an influenza diagnosis were significantly less likely to receive an antibiotic prescription. The development of sensitive and specific point-of-care testing for influenza may assist clinicians in making treatment decisions for patients with ARI during influenza season and may help to reduce unnecessary antibiotic use for influenza in outpatient settings.23 Inappropriate antibiotic prescribing exposes patients to the risks of unnecessary antibiotics and represents a potential missed opportunity for patients to benefit from influenza antiviral medications.9 Clinicians should be encouraged to consider influenza as a clinical diagnosis during the influenza season, refrain from prescribing antibiotics in situations in which they are not recommended by guidelines, and prescribe influenza antiviral medications when indicated.9This study was conducted during influenza seasons, and we found that 17% of patients with ARI prescribed antibiotics had laboratory-confirmed influenza. Influenza can predispose patients to increased risk of bacterial coinfections. In some instances of influenza infection, antibiotics may be appropriately prescribed if an associated bacterial infection is suspected. However, bacterial coinfection was likely only in a minority of influenza cases.ICD-9 codes to determine whether antibiotics were prescribed appropriately, but these may inaccurately reflect clinical decision making. Medical history information may have been incomplete in some instances, and other factors may have informed prescribing decisions. Our study sites may not be representative of other outpatient settings; some sites are health care organizations that may have institutional prescribing policies or mostly serve insured patients. In addition, sites have been engaged in influenza research for multiple years, which may have influenced clinician awareness of influenza and antibiotic prescribing practices. Of note, the proportion of patients prescribed antibiotics for conditions such as pharyngitis and bronchitis was lower in this study compared with other studies, and assessment of antibiotic overuse may be underestimated.7 We also assumed prescriptions were related to the study visit, but this could not always be verified. We lacked dispensing information for several sites, limiting our ability to know whether clinicians used delayed prescribing strategies in which patients are instructed to fill prescriptions only if symptoms failed to improve. This could have led to an overestimation of antibiotic use. Previous antibiotic treatment of prior infections and allergy history were not available, both of which may have affected antibiotic choice.This study has several limitations. We used up to 4 24 We must strengthen outpatient antibiotic stewardship efforts to eliminate antibiotic treatment for viral URIs and acute bronchitis, which our study indicates would make the largest contribution to decreasing unnecessary antibiotic prescriptions. Increased efforts are needed to support improved adherence to guidelines for antibiotic prescribing for common diagnoses, including more stringent adherence to GAS pharyngitis testing guidelines and clinical criteria for antibiotic treatment of sinusitis, as well as interventions focused on appropriate selection of first-line antibiotics for these conditions if treatment is indicated. In addition, our findings indicate that improved point-of-care influenza diagnostics and increased recognition and appropriate treatment of influenza virus infection may also aid in decreasing unnecessary antibiotic use for ARIs. The Centers for Disease Control and Prevention published “Core Elements of Outpatient Antibiotic Stewardship,”25 which provides guidance to clinicians and facility leadership to implement activities to improve antibiotic use. Improving antibiotic prescribing for ARIs during the influenza season represents an important opportunity to improve the long-term quality of patient care.Our study adds to evidence that misuse of antibiotics, characterized by antibiotic overuse and inappropriate antibiotic selection, is widespread in the treatment of outpatient ARIs. The study indicates a number of potential targets to achieve the goal of the National Action Plan for Combating Antibiotic-Resistant Bacteria of reducing inappropriate outpatient antibiotic use by 50% by 2020.


Inappropriate choices and durations of therapy for urinary tract infections (UTI) are a common and widespread problem. In this qualitative study, we sought to understand why primary care providers (PCPs) choose certain antibiotics or durations of treatment and the sources of information they rely upon to guide antibiotic-prescribing decisions. We conducted semi-structured interviews with 18 PCPs in two family medicine clinics focused on antibiotic-prescribing decisions for UTIs. Our interview guide focused on awareness and familiarity with guidelines (knowledge), acceptance and outcome expectancy (attitudes), and external barriers. We followed a six-phase approach to thematic analysis, finding that many PCPs believe that fluoroquinolones achieve more a rapid and effective control of UTI symptoms than trimethoprim-sulfamethoxazole or nitrofurantoin. Most providers were unfamiliar with fosfomycin as a possible first-line agent for the treatment of acute cystitis. PCPs may be misled by advanced patient age, diabetes, and recurrent UTIs to make inappropriate choices for the treatment of acute cystitis. For support in clinical decision making, few providers relied on guidelines, preferring instead to have decision support embedded in the electronic medical record. Knowing the PCPs’ knowledge gaps and preferred sources of information will guide the development of a primary care-specific antibiotic stewardship intervention for acute cystitis. Antimicrobial resistance is increasingly being recognized as one of the major threats to human health globally . The 201Escherichia coli (E.coli) strain sequence type 131  talking to the patient, and I just click and pop it up.” (AZ) or through a mobile phone app for staying informed about new information on antibiotics, “I use UpToDate. I have the app on my phone, so I am always searching.” (BC). A few providers mentioned publications such as Only two providers mentioned the IDSA guidelines, though most respondents reported varying degrees of familiarity with unspecified guidelines, saying, for example, “I think I am reasonably up-to-date.” (SC), “I guess I would be fairly familiar.” (JQ), and “It’s been about 10 years since I reviewed the guidelines.” (AV). A few providers acknowledged limited recall of the details of any guidelines regarding the treatment of uncomplicated cystitis, as indicated in the following statements: “Not very. There’s very little reason in something as simple as acute cystitis for me to go searching out the guidelines.” (MB), “Try to stay away from Cipro first line. That’s about all I remember.” (DT), and “I have to admit I’m not particularly conversant. I will usually look at UpToDate and just refresh my memory.” (JS).When discussing the extent to which antibiotic resistance is a problem in their own practices, providers had widely differing opinions, ranging from little or no resistance, “I have never noticed resistance within my practice.” (GS), to clear, affirmative responses, “Yes, based on cultures, I have had patients who have had organisms identified that have a pretty concerning resistance profile.” (DS). Some providers expressed uncertainty regarding the extent of antibiotic resistance, for example, “It is so hard for me to predict what’s going to be resistant.” (EJ), while others indicated a need for an antibiogram. One provider stated, “I don’t know if there’s actually resistance in this area or not. It would be nice to get, like, a report to say that.” (AA).In our study PCPs’ antibiotic choices and durations in the case scenario of acute uncomplicated cystitis were generally in line with the guidelines’ recommended first-line therapy. Most providers correctly chose TMP-SMX or nitrofurantoin for the treatment of uncomplicated cystitis in the case scenario. However, ciprofloxacin was often the second antibiotic mentioned when providers responded to the question about the top three most frequently prescribed antibiotics for uncomplicated cystitis. A number of providers chose treatment durations longer than the guideline recommendations. In particular, many were unaware that the current recommended duration of therapy for nitrofurantoin has been reduced to 5 days  comparedWe found that many PCPs believe that fluoroquinolones are more likely to achieve rapid and effective control of UTI symptoms than TMP-SMX or nitrofurantoin. This finding is in line with a previous qualitative study on the effects of knowledge, attitudes, and practices of PCPs on antibiotic selection . Belief In our study, PCPs’ prescribing decisions took into account multiple factors in determining the best course of treatment for patients with acute cystitis such as pregnancy, patients’ past experience with a specific antibiotic, previous antibiotic susceptibilities, frequency of UTI, older age, and presence of diabetes. Some PCPs chose a longer duration of treatment when the patient was older or had diabetes. These results are consistent with our previous observational database study, performed in the same setting, showing that older age and the presence of diabetes were independent, significant predictors of a longer treatment duration for UTIs . Older wAnother condition that triggered uncertainty for choosing the right antibiotic among the PCPs was UTI in pregnancy. Some were concerned about the association between the use of nitrofurantoin and birth defects reported in case-control studies ,29. HoweThe fact that our providers did not seem to be aware of fosfomycin as a first-line recommended antibiotic for uncomplicated UTI was not surprising. Fosfomycin was not prescribed in any visits for UTIs in our previous database study , and it Primary care physicians increasingly have multiple and sometimes conflicting guidelines  for patiAlthough most of the primary care providers were concerned about antibiotic resistance in their practice, some did not consider antibiotic resistance to be a problem in their own practice, citing greater resistance problems in inpatient settings or in non-UTI conditions. Likewise, in a Swedish qualitative study, providers were aware of antibiotic resistance but thought of it as a national problem that does not concern their own practice . Some ofThe main limitation of our study is the relatively small sample size. However, we performed this qualitative study in a preparatory phase of a stewardship intervention and included all PCPs working in two clinics. As with any qualitative study, the results are not meant to be generalizable. In particular, our findings may not be generalizable to public clinics or clinics that are not academically affiliated. Our findings represent an in-depth exploration of the attitudes and beliefs of the study sample. However, findings are transferable as the issues we identified have been seen in other settings ,31,41. WOur findings highlight the necessity of providing point-of-care information for primary care providers from a trusted and easy to access source. This information will help providers to choose the right antibiotic with the right duration, a fundamental aspect of antimicrobial stewardship for UTI.The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of Baylor College of Medicine on 7 February 2019 (H-38265).We selected individual interviews as the data collection strategy most appropriate for our research objectives of exploring individual prescribing decisions. Individual interviews allow for in-depth data collection and minimize the potential influence of group interaction or seniority and supervisory relationships that could have been introduced with focus groups. In addition, individual interviews allowed a much greater flexibility with scheduling, making it more feasible to reach and engage participants. We conducted brief (30 minutes or less), individual, semi-structured interviews with 18 primary care providers (15 family medicine physicians and three physician assistants) in two private, academically affiliated family medicine clinics in a large urban area between late July 2017 and early November 2017. Both clinics utilize Epic Electronic Health Records. The characteristics of our study sample are described in On average, 19,777 patients attend 3248 appointments at these clinics each month. Patients in both clinics are predominantly female (58%) and white (54%). Fluoroquinolones were the most common antibiotic class prescribed (51.6%) for uncomplicated UTI, and 75% of all prescriptions were longer than the recommended duration in these clinics in our previous study in the period of 2011–2014 .The concepts included in our interview guide were based on the Cabana framework for understanding barriers to physician adherence to clinical practice guidelines . AccordiThe interview guide also included questions about clinical and nonclinical factors influencing antibiotic choice and treatment duration, such as patient comorbidities or expected patient compliance. We asked open-ended questions about providers’ experience with the specific antibiotics and their preferred sources of support for clinical decision making. We also asked whether they perceived antibiotic resistance to be a problem in their practices. Before starting the study, we pilot-tested our interview guide with two primary care providers at another institution and adapted the guide as per their suggestions.Primary care providers were recruited by the research team during a weekly clinic meeting and provided an overview of the study. After these meetings, individual follow-up recruitment emails were sent by the research interviewer, a doctoral level social psychologist with substantial experience in conducting qualitative interviews (SN). If providers were interested in participating, the interviewer negotiated a convenient time for the session before or after regularly scheduled patient care responsibilities. At the meeting, the interviewer responded to any additional questions or concerns and obtained consent to participate. All invited providers agreed to participate and received a U.S. $20 gift card for their participation. Each individual participated only once.To protect participant confidentiality, the interviewer asked each participant to select an alias, which we designated by initials during the interview and in the resulting transcripts. The interviews were digitally recorded and transcribed verbatim by professional medical transcriptionists. The interviewer listened to all recordings to verify the accuracy of the transcripts before entering them into NVivo 10 software, a qualitative analysis package  that facilitates the management of qualitative data. Based on a preliminary review of the transcripts and the aims of the study, we determined that the interview questions and subsequent probes provided an appropriate outline for the initial identification of key themes ,45.Two authors (LG and SN) met regularly to read, code, and discuss the transcribed interviews, maintaining a shared consensus on the coding process. We elected to focus on the explicit content of providers’ reported experiences and perspectives . OverallOur qualitative analysis found that many PCPs believe that fluoroquinolones achieve more rapid and effective control of UTI symptoms than trimethoprim-sulfamethoxazole or nitrofurantoin. The majority of the providers were unfamiliar with fosfomycin as a possible treatment option for cystitis, although it is a first-line agent per guidelines. For recurrent UTI, older patients, or those with diabetes, some providers reported that they would go with “a stronger, broad-spectrum antibiotic such as ciprofloxacin” and longer treatment duration. For support in clinical decision making, few providers relied on guidelines, preferring instead to have decision support embedded in the electronic medical record. Understanding primary care providers’ clinical challenges and knowing their preferred sources of information will enable us to develop a primary care-specific antibiotic stewardship intervention for acute cystitis.


Inappropriate and excessive use of surgical antibiotic prophylaxis are associated with the emergence of antibiotic resistance. Antibiotic prophylaxis malpractices are common in obstetrics and gynecology settings and antibiotic stewardship is used to correct such malpractice.To evaluate the impact of antibiotic stewardship interventions on compliance with surgical antibiotic prophylaxis practice in obstetrics and gynecology surgeries.A prospective pre- and post-intervention study was conducted in two tertiary hospitals between May and December 2016. The duration of the each period was 3 months. Antibiotic stewardship interventions including development of a protocol, educational meeting and audit and feedback were implemented. Data were collected using the patient records and analyzed with SPSS version 23.A total of 226 and 238 surgical procedures were included in the pre- and post-intervention periods respectively. Age, length of stay and estimated blood loss were similar between the two groups. However, specialty and surgical procedures varied significantly. There was a significant increase in compliance with timing (from 14.2% to 43.3%) and duration (from 0% to 21.8%) of surgical antibiotic prophylaxis after the interventions. The interventions significantly reduced the prescription of third generation cephalosporin (-8.6%), redundant antibiotic (-19.1%), antibiotic utilization (-3.8 DDD/procedure) and cost of antibiotic prophylaxis (-$4.2/procedure). There was no significant difference in the rate of surgical site infection between the two periods. Post-intervention group , elective surgery  and hospital attended  were significant predictors of compliance with timing while elective surgery  and compliance with timing  were significantly associated with compliance to duration of surgical antibiotic prophylaxis.The interventions improve compliance with surgical antibiotic prophylaxis and reduce antibiotic utilization and cost. However, there is opportunity for further improvement, particularly in non-elective surgical procedures. Surgical Site Infection (SSI) is one of the most common healthcare associated infection in developing countries . In NigeStaphylococcus aureus isolates in Nigeria are detected from surgical wound specimens [Evidence demonstrate that surgical antibiotic prophylaxis; defined as the administration of antibiotic prior to incision with the ultimate goal of preventing infection after surgery, significantly reduce the incidence of SSIs , 9. Howepecimens .Antibiotic stewardship is an antimicrobial resistance containment strategy aim at reducing inappropriate use of antibiotics for empirical, prophylactic and therapeutic purposes –18. The Ethical approval was obtained from Ahmadu Bello University Teaching Hospital Health Research and Ethics Committee (reference number: ABUTH/HREC/T26/2016) and Aminu Kano Teaching Hospital Research Ethics Committee (reference number: AKTH/MAC/SUB/12A/P-3/VI/1735). Furthermore, verbal consent was taken from the participants prior to data collection. High level of confidentiality and anonymity was maintained throughout the study.This was a pre- and post-intervention study conducted in the department of obstetrics and gynecology in two public tertiary hospitals located in Northern Nigeria; Ahmadu Bello University Teaching Hospital (ABUTH), Zaria, and Aminu Kano Teaching Hospital (AKTH), Kano. Sample size was calculated using Pocok’s formula  and the Women who had elective and emergency obstetric and gynecologic surgeries were considered for inclusion. Surgeries with clean, clean-contaminated and contaminated wounds were selected. All adult patients were eligible to participate in the study. Cancer and Human Immunodeficiency Virus (HIV) seropositive patients, who have high risk of infection, and those with existing infection before incision were excluded from the study.The study was conducted in 3 phases: the pre-intervention (baseline), intervention and post intervention phase. The baseline was conducted between May 2016 and July 2016. Antibiotic stewardship interventions  were implemented in August and September 2016 while the post-intervention evaluation was carried out between October 2016 and December 2016.Data were collected using the patients’ medical, anesthesia, nursing and medication records. Information retrieved from the patient records include: dates of admission, surgery and discharge, patient’s age, type of surgery (elective or emergency), surgical procedure performed and estimated blood loss. Information regarding prescribed antibiotic(s) including: name of antibiotic(s), dose(s), time of administration of first dose (either at induction of anesthesia or post-operation) and duration of antibiotic prophylaxis was also documented. Resident doctors inspected patient’s wound during hospital stay and before they were discharged from the hospital. The outcome of wound inspection was also recorded.A bundle of antibiotic stewardship interventions was implemented after the pre-intervention period. The goal of the interventions was to reduce errors associated with surgical antibiotic prophylaxis. The interventions were targeted at changing the behavior of obstetricians and gynecologists regarding surgical antibiotic prophylaxis practice. The interventions include: development and dissemination of departmental protocol for surgical antibiotic prophylaxis; educational meeting with the obstetricians and gynecologists; audit and feedbacks using baseline data and reminder in the form of wall mounted posters. In both hospital, the protocol was developed by a team that comprise of 4–5 consultant obstetricians and gynecologists and a clinical pharmacist. The protocol was presented to the department by the clinical pharmacist before adoption. The protocol states that antibiotic prophylaxis in clean, clean-contaminated and contaminated wounds should be administered within 60 minutes before incision and discontinued within 24 hours after completion of surgery. The protocol recommends intravenous ampicillin-cloxacillin plus intravenous metronidazole  and intravenous amoxicillin-clavulanic acid  as the antibiotics of choice for surgical prophylaxis. The selection of amoxicillin-clavulanic acid in hospital B was due to high incidence of Extended Spectrum Beta-Lactamase (ESBL) infections . The secThe prescribing outcomes evaluated were the compliance with timing and duration of antibiotic prophylaxis. Compliance with timing was defined as administration of an intravenous antibiotic within 60 minutes before incision while compliance with duration of surgical antibiotic prophylaxis was defined as use of a single dose of antibiotic or discontinuation of antibiotic prophylaxis within 24 hours after completion of surgery. High rate of redundancy in surgical antibiotic prophylaxis has been reported in the study settings . TherefoAntibiotic consumption was calculated using the Anatomical Therapeutic Chemical/Defined Daily Dose (ATC/DDD) index (2017) of the World Health Organization (WHO) Collaborating Centre for Drugs Statistics Methodology . DefinedSSI was defined using the Centre for Disease Control and Prevention–National Healthcare Safety Network (CDC-NHNS) criteria . HoweverCost of surgical antibiotic prophylaxis was calculated using the price list of medication obtained from the pharmacy department in each hospital. The unit cost of each dose was multiplied by the total number of doses. The lowest price for generic antibiotics on the price list was used to estimate the costs of antibiotic prophylaxis.Data were entered, coded, cleaned and analyzed using Statistical Package for the Social Sciences (SPSS) version 23. All categorical variables were presented in frequency and percentage while continuous variables were expressed as mean and standard deviation. Pearson Chi Square Test was used to compare patient’s demographic and surgical characteristics between the pre- and post-intervention groups. Continuous variables during the two periods were compared using independent T-test. Compliance with antibiotic selection, timing and duration of antibiotic prophylaxis and rate of SSI during the pre- and post-intervention period were compared using Pearson Chi square and Fisher exact (where appropriate) Tests. Antibiotic utilization and cost of antibiotic prophylaxis in the pre- and post-intervention period were compared using T-test or Mann-Whitney U Test. Logistic regression analysis was used to determine the predictors of compliance with timing and duration of surgical antibiotic prophylaxis. Data was de-identified before analyses and the names of the hospitals were recoded as “Hospital A” and “Hospital B.” P value < 0.05 was considered to be statistically significant in all the inferential statistical analyses.Both hospitals had a team that comprise of Consultants, Senior Registrar, Registrar and House officers who provided obstetrics and gynecology care to the patients. There was an infection control team in each hospital. There were 226 and 238 surgical procedures in the pre- and post-intervention periods respectively. No significant difference in the mean age, length of hospital stay and estimated blood loss was observed between the two periods. However, elective surgeries and gynecology procedures were significantly higher during the post-intervention period. Overall, compliance with timing of surgical antibiotic prophylaxis was increased from 14.2% in the pre-intervention period to 43.3% in the post-intervention period (P < 0.001). Compliance with timing was significantly increased in both hospitals and surgical specialties. No difference in compliance with timing of administration was observed in emergency surgeries after the interventions. Compliance with timing was significantly improved in elective surgeries from 10.6% to 58.9%; P < 0.001 . CompliaPrescription of third generation cephalosporin for surgical antibiotic prophylaxis was reduced from 29.2% in the pre-intervention period to 20.6% in the post-intervention period (P = 0.032). Overall, the rate of redundant antibiotic prescription was reduced by 19.1% . Combination of antibiotic with redundant spectra of activity was eliminated in Hospital A and was reduced significantly in Hospital B  during the post-intervention period.There was a significant decrease in antibiotic utilization after the interventions. The DDD of surgical antibiotic prophylaxis declined from 16.6 ± 3.6 DDD/procedure in the pre-intervention period to 12.8 ± 6.8 DDD/procedure in the post-intervention period (P < 0.001). Antibiotic utilization was reduced from 13.2 ± 4.6 DDD/procedure to 10.6 ± 5.5 DDD/procedure in Hospital A (P = 0.003) and from 18.1 ± 1.6 DDD/procedure to 13.9 DDD/procedure in Hospital B (P < 0.001) see . The meaMultivariate logistic regression analysis shows that antibiotic stewardship interventions increased compliance with timing of surgical antibiotic prophylaxis. Procedures in the post-intervention period were 5.6 times more likely to receive surgical antibiotic prophylaxis within 60 minutes before incision . Elective surgery  and attendance at Hospital A  were also significant predictors of compliance with timing of surgical antibiotic prophylaxis. In addition, elective surgery  and compliance with timing  were significantly associated with compliance with duration of surgical antibiotic prophylaxis .Surveillance during hospitalization revealed that there was no significant difference in the incidence of SSI between the two periods. The rate of SSI in the pre-intervention period was 4% compared to 3.4% in the post-intervention period (P = 0.722).The current study evaluates the impact of antibiotic stewardship interventions on compliance with surgical antibiotic prophylaxis in two hospitals in Nigeria. The outcome shows that development of a protocol, educational meeting coupled with audit and feedback improved compliance with timing of surgical antibiotic prophylaxis. This observation was consistent with studies conducted in South Africa, Egypt and Korea , 37, 38.The current study also found that compliance with duration of surgical antibiotic prophylaxis was significantly increased by 21.8%. Our finding was in consonance with a Chinese study which reported that pharmacist-led educational training for obstetricians coupled with prospective audits and feedbacks significantly increase compliance with duration of surgical antibiotic prophylaxis from 0.0% to 19.3% . Also, aThere was also a significant reduction (22.8%) in antibiotic utilization after the interventions in our study. This decline was attributed to decrease in the rate of redundancy and increase in compliance with duration of surgical antibiotic prophylaxis. Antibiotic stewardship interventions have been associated with 14% - 35% reduction in antibiotic utilization , 30, 42.Our study discovered that increase in compliance with timing did not reduce the rate of SSI neither did reduction in the duration of antibiotic prophylaxis worsen the clinical outcome. The rate of SSI before and after the interventions were similar. However, it is important to note that surveillance of SSI was limited to the period of hospitalization. This limitation could explain the lack of significant difference between the two groups because evidence has shown that about 80% of all SSIs occur after a patient is discharged from the hospital . The outMultivariate logistic regression analysis demonstrated that procedures performed in the post-intervention period were 5.6 times more likely to receive surgical antibiotic prophylaxis within 60 minutes before incision compared to those carried out during the pre-intervention period. This was a confirmation that the improvement in timing could be attributed to the intervention and not confounding factors. In addition, elective surgical procedures and attendance at Hospital A were also significantly associated with compliance with timing and duration of surgical antibiotic prophylaxis. Compliance with timing was found to have a chain effect as it was associated with more than 58.5 times higher likelihood of compliance with duration of surgical antibiotic prophylaxis. Considering the fact that duration of surgical antibiotic prophylaxis was prolonged in all the procedures in the pre-intervention period, it could be argued that the improvement was a result of the interventions implemented.The current study has some limitations including lack of randomization. However, quasi experimental design with a pre- and post-intervention is often used to determine the impact of healthcare interventions. The study was conducted in two tertiary hospitals and this would limit the generalizability of the result. Another limitation of this study was the incomplete surveillance for surgical site infections among the patients. This limits the reliability of the impact of the interventions on clinical outcome. In addition, other factors that affect SSI including: dose, re-dosing, comorbidities  and patients’ characteristics were not reported in the current study. The cost of surgical antibiotic prophylaxis was calculated based on the price of generic antibiotic irrespective of the brand administered. Therefore, the cost of antibiotic prophylaxis presented in the current study was an estimate and not the actual drug cost.Our study demonstrates that antibiotic stewardship interventions significantly improved compliance with timing and duration of surgical antibiotic prophylaxis and reduced redundancy, antibiotic utilization and cost without compromising clinical outcome. However, there is still room for improvement, particularly in emergency surgical procedures. The intervention, elective surgery and hospital attended were significant predictors of compliance with the timing and duration of surgical antibiotic prophylaxis.


In order to explore the drying–wetting cycle test method of concrete under sulfate accelerating erosion, the influence of dry–wet time ratio on concrete sulfate erosion was studied. Under the condition of 7 days for one cycle, five different dry–wet time ratios were designed: 1:3, 1:1, 3:1, 5:1, and 10:1. The basic properties such as compressive strength, splitting tensile strength and dynamic elastic modulus of concrete were tested. Scanning electron microscopy (SEM) was used to analyze the microstructure of concrete before and after erosion. The test results show that under the environment of sulfate drying–wetting cycle erosion, the change of mechanical properties of concrete are divided into three stages: ascending period, fluctuating period and rapid descending period. Concrete is subjected to periodic damage process of initial damage followed by filling compaction, cracking, further filling, and cracking again, in that order. Dry–wet ratio has a significant effect on concrete sulfate attack. Under the same drying–wetting cycle period, as the dry–wet ratio increases, the degree of deterioration of concrete by sulfate attack increases first and then decreases. When the dry–wet ratio is 5:1, the deterioration is the most serious. Sultructure . The addtructure . The exptructure . In the tructure , therebytructure . As a coAt present, there are many studies on the erosion performance of concrete under drying–wetting cycling conditions ,13,14,15Compared with the mechanism of concrete sulfate degradation, the coupling mechanism of sulfate and drying-wetting erosion is not clear and is more complicated, so there is no consensus yet. Many researchers have carried out a lot of research on the macroscopic mechanical properties of concrete after sulfate attack under the self-designed drying–wetting cycle mode. Strength is used as an indicator to evaluate the deterioration of the performance of sulfate-eroded concrete under dry and wet cycles, such as compressive strength and splitting tensile strength. Ganjian et al. found that SF cement (silicon powder content 7% and 10%) has a lower compressive strength loss rate than ordinary concrete, and has better resistance to dry and wet cycles . He et aConsidering the diurnal and semi-diurnal tides, the average infiltration time of the water level in different elevations, and the hydrometeorological data of the saline area in northwest China ,25, fiveA Chinese standard ordinary Portland cement  of PO42.5R produced by a local manufacturer was adopted. Grade I fly ash was from the thermal power plant. Fine aggregate was natural river sand with the maximum size of 4.75 mm, fineness modulus (F.M) of 2.87 and absorption of 1.05%. Coarse aggregate of basalt with a diameter of 5–20 mm was used in this study. The common tap water was used as mixing water. The chemical composition of cement and fly ash is shown in Concrete specimens were prepared in 60 liters compulsory mixer, and all the specimens were prepared from the same batch of concrete with three specimens per set. Cement, fly ash, sand and coarse aggregate were added to the mixer, stirred for one minute, then added with water, and finally mixed and stirred for 2 min. Immediately after mixing, the fresh concrete mixture was placed in molds to prepare the test specimens. After pouring, the molds with fresh concrete composite were placed on a concrete vibrating table for one minute for compaction. The samples were demolded after 24 h and then placed in a standard moist room (T = 20 ± 2 °C and RH > 95%) to be cured for 28 days.2SO4 solution was selected as the corrosion solutions in this study. Five different dry–wet ratios  were designed in the test, as shown in Referring to the standards of ASTM C1012-18a , ASTM C4The test was carried out for 36 drying–wetting cycles during the course of 252 days. The strength, mass, and dynamic elastic modulus of the concrete specimens were measured every 28 days. In order to completely and uniformly etch all the samples, the volume ratio of the solution to all the samples was maintained at about 4:1, and the spacing of each sample was not less than 5 mm, furthermore, it was necessary to ensure that the liquid level exceeded 50 mm of the concrete sample.cM) of each group can be calculated from the average of three samples by Equation (1).m0 and nm are the mass before and after n times of drying wetting cycles.Three specimens with the size of 100 mm × 100 mm × 400 mm were weighed with an electronic balance (resolution of 0.1 g), and the mass of each specimen was recorded once every 28 days’ exposure. The mass change (The measurement of dynamic elastic modulus was conducted according to Chinese standard GB/T 50082-2009 . The insm (kg) is the mass of specimen, L (mm) is the total length, f (Hz) is the fundamental vibration frequency, a (mm) is the length of cross section. The unit for dE is MPa.The side perpendicular to the specimen molding surface was selected as the test surface and the middle point was marked as the measurement point, which avoided visible holes or cracks. The frequency range was selected from 1000 to 3000 Hz. Each specimen should be tested more than twice, and the frequency measurement error of the tests should not exceed 5 Hz. Then the average value of the measured values of the dynamic elastic modulus was taken as the final measurement value. Three specimens per group were taken as the final value of the dynamic elastic modulus of the concrete. The dynamic elastic modulus is calculated by Equation (2).rdE)) can be calculated by Equation (3).E0 and tE are the dynamic elastic modulus before and after t times of drying–wetting cycles.The Relative dynamic elastic modulus , was calculated by Equation (4).P (N) is the peak load, A (mm2) is the pressure area of the specimen. The splitting tensile strength, tsf (MPa), was calculated using Equation (5).P (N) is the peak load, A (mm2) is the fracture surface area of the specimen. The compressive strength and splitting tensile strength change of corroded concrete specimens could be characterized using the relative compressive strength coefficient ccR and the relative tensile strength coefficient csR, which could be calculated by Equations (6) and (7).ccf0 and ccnf are the compressive strength before and after n times of drying wetting cycles; stf0 and stnf are the compressive strength before and after n times of drying wetting cycles.The compressive strength, The microstructure of the concrete was imaged with a scanning electronic microscope (SEM). Using the difference in gray scale of the image, erosive products such as ettringite, gypsum and thernadite could be distinguished. In order to explore the correspondence between microstructural changes and concrete macroscopic properties, a concrete core drilling machine was used to drill a core sample having a diameter of 20 mm and a height of 100 mm at the center of the bearing surface of the concrete specimen, and a thin film having a thickness of 2 mm was cut at a distance of 5 mm from the erosion surface of the cylindrical core sample by using a cutter. The sections were dried in a dry box for 12 h before the observation test. This test used platinum as the spray material, coating thickness was 5–20 nm and the test piece was attached to the copper production with conductive adhesive.It is clearly observed from As is shown in As shown in It can be seen from 2 perhaps due to the active effect of fly ash, which causes an increase in dynamic modulus [During the fluctuating period, the RDEM of dry–wet cycle specimen re-raised to a peak after experiencing a period of decline. This is because the micro-regions inside the concrete cannot withstand the pressure generated by crystal crystallization, resulting in the creation of new micro-cracks, which in turn provide new growth space for the expansive products. In fact, the concrete experienced a cyclical damage process of "steady state—unsteady state—new steady state" at this stage. In addition, the silicon oxide and alumina in fly ash can generate secondary hydration reactions to form C-S-H and C-A-H under the excitation of cement hydration product Ca(OH) modulus ,36.After 140 days, the concrete entered a rapidly descending period. The RDEM of D5W1 specimen has the fastest decline rate, which is 13.7% lower than the initial value at 252 days, while the W specimen is still slowly increasing. Drying has a more serious effect on the deterioration of concretein the later stage of sulfate dry–wet cycle erosion. The reason is that, during the drying process, as the relative humidity inside the concrete gradually decreases, the solution is easily over-saturated. Under the action of supersaturation, the solute particles move toward the nucleus and form an orderly accumulation on the surface, causing the nucleus to grow and form crystals. The crystal grows in a limited space and produces a huge crystallization pressure, which can damage the concrete . In the As with RDEM, after experiencing a period of fluctuation, the mechanical properties of concrete fell rapidly. The rate of deterioration increased first and then decreased as the dry–wet ratio increased. The mechanical properties of D5W1 concrete decreased the fastest, and the compressive strength and splitting tensile strength of 252 days decreased by 24% and 11%, respectively, relative to the initial value. This finding can be explained by that, at the primal phase, a large amount of corrosion products accumulate in the pores inside the concrete to make the concrete dense, but excessive corrosion products cause macroscopic cracks in the specimen, and the concrete crack further expands and connects, becoming a fast passage for aggressive ion transport, which leads to an accelerated deterioration of the mechanical strength of the concrete ,39. More2SO4·10H2O) gradually becomes unstable and begins to change to thenardite (Na2SO4). The thenardite has greater crystallization pressure and produces more serious damage. In many real structures, most concrete members display contamination of soluble salts [le salts . It can As can be seen from In this study, an experimental research on concrete exposed to sulfate solution under different dry–wet ratios was conducted. The mass, dynamic elastic modulus, compressive strength, and splitting tensile strength of concrete were measured, and SEM images of different corrosionages are also recorded. The conclusions are summarized as follows:(1) Under sulfate erosion environments of different dry–wet ratios, the change of mechanical properties of concrete is divided into three periods: ascend period, fluctuate period, and rapid descend period. Under the same dry and wet cycle, as the dry–wet ratio increases, the degree of concrete deterioration increases first and then decreases. When the dry–wet ratio is 5:1, the degree of concrete deterioration is the most serious;(2) The deterioration of concrete during the drying process is a physical reaction process, and the crystallization pressure caused by crystal crystallization and crystal transformation is an important cause of deterioration. The extension of drying time has a greater impact on the later stage of erosion;(3) During the sulfate erosion process, the interior of the concrete undergoes aperiodic damage process of “initial damage—filling compaction—cracking—further filling—cracking again”. The concrete is dense to loose, and the concrete performance of RDEM and strength is initially rising, however after the fluctuating period it drops rapidly;(4) Mass change can better characterize the deterioration of concrete, but the correlation with the change of mechanical properties is weak. The splitting tensile strength is more sensitive than the compressive strength.


IgG4-related disease (IgG4-RD) is a systemic chronic inflammatory disorder that can affect almost every organ. IgG4-RD includes IgG4-related kidney disease (IgG4-RKD), but lesions affecting the kidney alone or first are very rare, and a complete understanding is lacking. Computed tomography (CT) and magnetic resonance imaging (MRI) findings can show the typical characteristics of IgG4-RKD and provide information for accurate and rapid diagnosis.We report a case of a 60-year-old woman who was admitted to our hospital for dizziness and instability while walking, her bilateral eyelids were also slightly swollen. She had no medical history.CT and MRI images of the patient revealed multiple local and diffuse patchy lesions in the bilateral renal parenchyma and mass-like tissue in the bilateral renal pelvis, accompanied by right hydronephrosis. A pathological examination of renal samples showed numerous lymphocyte and plasma cell infiltration. Immunohistochemistry demonstrated approximately 50% of the IgG-positive plasma cells to be IgG4+. The serum IgG level was obviously elevated, with both C3and C4 levels were reduced. The patient was diagnosed with IgG4-RKD.The patient received corticosteroid therapy at another hospital.The bilateral kidney lesions were smaller on follow-up CT images.IgG4-RKD exhibits some characteristic imaging features. Despite the relatively low incidence of IgG4-RKD, it should be included in differential diagnoses when images show multiple lesions in kidneys with mild and delayed enhancement and hypointensity on T2WI in middle-aged to elderly patients IgG4-related kidney disease (IgG4-RKD) was reported for the first time in 2004 as an extra pancreatic feature of autoimmune pancreatitis (AIP). However, lesions affecting the kidney alone or first are very rare. Here, we present a rare case of IgG4-RKD without affected extrarenal organs, providing a better understanding of its computed tomography (CT) and magnetic resonance imaging (MRI) characteristics.IgG4-related disease (IgG4-RD) was first recognized in 2003 by Kamisawa et al.2A 60-year-old woman was admitted to our hospital for dizziness and instability while walking. A physical examination revealed that her bilateral eyelids were slightly swollen and that blood pressure was 148 mmHg/76 mmHg, with no other significant abnormalities. According to laboratory evaluations, her percentages of neutrophilic granulocytes and lymphocytes were 46.00%  and 43.40% , respectively. Indexes of liver function and urinalysis were within normal limits, and urinary cytology was negative. CT images  or sometimes hydronephrosis but seldom lead to hematuria or proteinuria, or cyturia. IgG4-RKD is usually accompanied by involvement of other organs,,11 typically resulting in autoimmune pancreatitis (AIP), and approximately 35% of AIP patients suffer IgG4-RKD. Isolated cases of IgG4-RKD without other organ involvement are very rare. In one study, only 3 (6%) of 48 IgG4-RKD patients had renal lesions alone. IgG4-RD is a recently recognized disease, which that lacks full understanding and might be misdiagnosed in clinical work, particularly in patients with single-organ system involvement including IgG4-RKD. Some studies have suggested that IgG4-RKD shows different types of typical imaging characteristics.–17 The lesions can be divided into 3 types based on their location,16: the renal parenchyma, renal pelvic, and perinephric lesion. The renal parenchymal lesion is the most common subtype and is usually accompanied by TIN, followed by glomerular diseases. Each of the 3 types of lesions could appear alone or sometimes 2 types of lesions might appear together. The renal parenchymal lesions in IgG4-RKD can display 3 imaging patterns: round, wedge-shaped, and diffuse patchy infiltration lesions.,16 In precontrast CT scan, the lesions are usually not clear and reveal mild enhancement in postcontrast and delayed reinforcement.,13,16 The parenchymal lesions are often multifocal. On MRI T2WI images, the parenchymal lesions are hypointense compared with the normal renal parenchyma, and the dynamic enhancement pattern shown on post-T1WI is similar to that on postcontrast CT. Some studies report that the lesions are hyperintense on DWI, and this sequence has higher sensitivity for such lesions.,19 Renal pelvic lesions manifest as diffused wall thickening of the renal pelvis or soft-tissue mass encasing the pelvis, and the lesions exhibit similar intensity (on T2WI images) and enhancement pattern compared with parenchymal lesions.,14,17 Perinephric lesions are rare and appear as a rim-like lesion around the renal capsule, either diffuse or focal.,20 All 3 types of lesions of the kidneys can be unilateral or bilateral. The shape of the involved kidney can enlarge in the early stage and become atrophied over time because of fibrosis. In our case, the right kidney showed slight atrophy, which means that the right kidney was at a late stage of the disease. In IgG4-RKD, hydronephrosis seldom occurs unless accompanied by retroperitoneal fibrosis entrapping ureter, even with pelvic lesions. In our case, the patient had mild right hydronephrosis without retroperitoneal fibrosis. This might be because the pelvic mass in the right kidney was huge.IgG4-RD is a systemic chronic inflammatory disorder. It generally affects middle-aged to elderly patients with a slightly male preponderance and can affect almost any organ, synchronously or metachronously.IgG4-RKD has some characteristic imaging features. Despite the relatively low incidence of IgG4-RKD, it should be included in differential diagnoses when images reveal multiple lesions in kidneys with mild and delayed enhancement and hypointensity on T2WI in middle-aged to elderly patients, especially when coexisting with extrarenal abnormalities.Qian Yang, for providing the patient information; YiHao Yao, for correcting grammatical errors.Resources: Qian Yang.Writing - Original Draft: Shuixia Zhang, Qian Yang.Writing - Review & Editing: Shuixia Zhang.


To conclude our study has provided the first reliable estimates of antibiotic use in the retail sector in India vis-à-vis ESAC-Net countries. In addition, our study could provide a reference point to measure the impact of interventions directed towards reducing antibiotic use.India was the largest consumer of antibiotics in 2010 in the world. Evidence suggests that countries with high per-capita antibiotic consumption have higher rates of antibiotic resistance. To control antibiotic resistance, not only reduction in antibiotic consumption is required, socio-economic factors like access to clean water and sanitation, regulation of private healthcare sector and better governance are equally important. The key objective of this research was to investigate the five year trends in consumption of major antibiotic classes in India and compare them with European Surveillance of Antimicrobial Consumption Network (ESAC-Net) countries. We used Intercontinental Marketing Statistics (IMS) Health (now IQVIA) medicine sales audit data of antibiotic sales in the retail private sector  in India. We then standardized dosage trends and assigned defined daily dose (DDD) to all formulations based on the ATC/DDD index. We expressed our data in standardized matrices of DDD per 1000 inhabitants’ per day (DID) to compare antibiotic use in India with ESAC-Net countries. The antibiotic use was plotted and reported by year and antibiotic class. Our main findings are—per capita antibiotic consumption in the retail sector in India has increased from 13.1 DID in 2008 to 16.0 DID in 2012—an increase of ~22%; use of newer class of antibiotics like carbapenems (J01DH), lincosamides (J01FF), glycopeptides (J01XA), 3 The burden of infectious diseases in India is among one of the highest in the world. The Million Death Study reported that diseases of infectious origin such as pneumonia and diarrhea accounted for 50% (0·67 million of 1·34 million) of all deaths in children aged 1–59 months in India. Van BoeIn India, several studies have reported increasing resistance to antibiotics–9. The rThe key objective of this research was to investigate the trends in consumption of major antibiotic classes in India and compare them with European Surveillance of Antimicrobial Consumption Network (ESAC-Net) countries. The imperative of such an approach stems from the fact that for India to reach an ideal level of antibiotic consumption–benchmark needs to be set and compared to. Additionally, the appropriateness of antibiotic consumption is equally a critical parameter in the narrative around antimicrobial resistance. Given that the European nations have reached a stage of near universal access to medicines and also been a well-regulated market, the approach here is to compare Indian consumption pattern to European standards. Although regulation to control antibiotics use exists in India, the experience in India till now is that most medicines including antibiotics can be bought from retail pharmacies without prescription. This is expected to lead to overuse or inappropriate use of antibiotics. Earlier research had reported an increase in antibiotic consumption in India. However, they reported consumption estimates in standard units (SUs) , which dWe relied on a large, nationally representative dataset for antibiotic sales, assembled by IMS Health (now IQVIA). IMS Health is a for-profit agency that collects information on drug sales, health services and technology involving healthcare industry. This stWe obtained medicine sales audit data of systemic antibiotics grouped according to active substance in the drug, on the basis of Anatomic Therapeutic Chemical (ATC) classification system of the European Pharmaceutical Market Research Association (EphMRA) by IMS Health (now IQVIA). The data was then recoded in accordance with the ATC index (2015) of the World Health Organization Collaborating Centre (WHOCC) for Drug Statistics Methodology. For our study, data on all pharmacological subgroups and chemical subgroups within the group anti-infective was used except antifungal; antibacterial for tuberculosis; and topical antibiotics. We identified 10674 packs of systemic antibacterials, of which 7080 packs were of plain formulations and 3594 packs were of fixed dose combinations (FDCs). DDDs have not been assigned by the WHOCC to a number of formulations marketed in the Indian pharmaceutical market. 66 such packs were identified and excluded from the analysis. Finally, a total of 722 packs were excluded from the analysis due to the problem of missing and ambiguous strengths. This left us with 9886 packs of systemic antibacterials.For this analysis, we used the Defined Daily Dose (DDD), a widely accepted measure for examining drug utilization coined by the WHOCC for Drug Statistics Methodology. The DDD is the assumed average maintenance dose per day for a drug used for its main indication in adults. We assigned defined daily dose to all the formulations under study based on the ATC/DDD index. We observed that for certain fixed dose combinations (FDCs) of antibiotics, DDDs were not available in WHOCC’s ATC/DDD index. For such molecules, we assigned DDD for the antibacterial to the FDC—if the FDC contained single anti-bacterial and sum of the individual DDD of each anti-bacterial to the FDC—if the FDC contained two or more anti-bacterials. The impWe observed that the systemic antibiotic (J01) use increased from 13.1 DID in 2008 to 16.0 DID in 2012, representing 22.1% increase during the study period  in India . FindingA disaggregated trend analysis revealed significant variation in consumption across different antibiotic classes. For example, from 2008 to 2012, cephalosporins (J01D) use increased from 1.7 DID to 2.6 DID and proportional use increased from 12.7% to 16.3%. Similarly, macrolides (J01F) use increased from 1.3 DID to 2.0 DID and proportional use increased from 10.1% to 12.3%. However, utilization of quinolones (J01M) declined from 4.0 DID to 3.7 DID and proportional use declined from 30.7% to 23.4%. A declining trend in proportional use was also observed in aminoglycosides (J01G), sulfonamides (J01E) and tetracyclines (J01A). We also observed that antibiotic use was seasonal in nature with peak consumption during September every year except in year 2009 when it was August .It may be noted that overall utilization of systemic antibiotics grew a little over 22 percent  in India vis-à-vis ESAC-Net countries at the level of the chemical subgroup (ATC 4) for the year 2012. To the best of our knowledge, this study for the first time presents standardized antibiotic consumption estimates for India in comparison to ESAC-Net countries. We adopted ESAC project’s standard methods to arrive at antibiotic consumption estimates for India, expressed in DIDs. The key finding points out that per capita antibiotic consumption in India has increased from 13.1 DID in 2008 to 16.0 DID in 2012—an increase of ~22% and increased utilization of newer class of antibiotics such as carbapenems (J01DH), lincosamides (J01FF), glycopeptides (J01XA), third generation cephalosporins (J01DD) and other antibacterials (J01XX). However, antibiotic consumption rates in India are still low as compared to ESAC-Net countries in the community sector (16.0 DID vs. 21.5 DID).An earlier study on global antibiotic consumption reported that antibiotics consumption in India had increased by 36% between 2000 and 2010. There iThe key strength of our study is usage of standardized ESAC-Net methodology for reporting antibiotic consumption in DDD per 1000 inhabitants per day (DIDs). This has enabled us to show that the average antibiotic consumption in India is still lower than majority of ESAC-Net countries. The defined daily dose (DDD) is a universally accepted measurement unit to express drug utilization and to benchmark countries for their level of drug consumption. Monnet et al. reported that the number of DDDs correctly indicate the number of antimicrobial prescriptions for outpatients at the national level. The obsThe problem of inappropriate antibiotic use get accentuated many folds because of limited access to healthcare and access to medicines in the public health system which foStaphylococcus aureus (MRSA) and extended-spectrum β-lactamase (ESBL) producing Gram-negative bacteria[Another key finding of our study is increasing consumption rates of last resort antibiotics such as carbapenems (J01DH), lincosamides (J01FF), glycopeptides (J01XA), third generation cephalosporins (J01DD) and other antibacterials (including linezolid and daptomycin) (J01XX) which belongs to WHO’s watch and reserve group of antibiotics. Our findings are consistent with results reported by other researchers. Using systemic antibiotic sales data of India, Patricia et al. had also reported that sales of key access antibiotic had risen by 20% in India during 2007 to 2012; whereas sales of fixed dose combinations (FDCs) with watch group or reserve group antibiotics had risen more steeply, by 73% and 174%, respectively. EarlierGovernment of India has initiated a multi-pronged strategy to address the problem of overuse and misuse of antibiotics. For example, Schedule H1 has been implemented by the Central Drugs Standard Control Organization (CDSCO) to prevent over-the-counter (OTC) sales of important antibiotics, such as third and fourth-generation cephalosporins, carbapenems, antituberculosis drugs and newer fluoroquinolones. Under tEvidence from the National Health Accounts for India demonstrated that during 2013–14, an estimated INR 1331 per capita was spent on medicines, out of which households alone incurred INR 1200 per capita, suggesting 90% of all medicines spending in the country is in retail segment. This reOur analysis was based on stockist secondary audits, which represent sales made by the stockists to the retailers and do not capture sales made to the hospitals and doctors. Our study does not account for the utilization of antibiotics in the public sector. We suspect that this may have biased our antibiotic consumption estimates downwards, albeit marginally, as the public sector contribution to the overall drug consumption at national level is less than 10%, in value terms.Our study has provided first reliable estimates of antibiotic use in India vis-à-vis ESAC-Net countries. Interventions directed towards achieving Universal Health Coverage, particularly free access to medicines through public health facilities should be implemented to mitigate demand for antibiotics in the private sector. Since antibiotic use is both prescription and self-medication driven in India, education campaigns and behavior change communication strategies to address overuse and misuse of antibiotics are required. Specific regulation with reference to licensing, sales and prescription of antibiotics are in force, their effectiveness has not been evaluated formally; additional research is required to address this knowledge gap.S1 File(PDF)Click here for additional data file.