{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T18:56:24Z","timestamp":1776192984475,"version":"3.50.1"},"reference-count":31,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T00:00:00Z","timestamp":1698105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacy"],"abstract":"<jats:p>Acute pyelonephritis (APN) is a relatively common community-acquired infection, particularly in women. The early appropriate antibiotic treatment of this potentially life-threatening infection is associated with improved outcomes. The international management guidelines for complicated urinary tract infections and APN recommend using oral antibiotics with &lt;10% resistance among urinary pathogens. However, increasing antibiotic resistance rates among Escherichia coli and other Enterobacterales to fluoroquinolones, trimethoprim-sulfamethoxazole (TMP-SMX), and beta-lactams has left patients without reliable oral antibiotic treatment options for APN. This narrative review proposes using precision medicine concepts to improve empirical antibiotic therapy for APN in ambulatory settings. Whereas resistance rates to a particular antibiotic class may exceed 10% at the population-based level, the predicted antibiotic resistance rates based on patient-specific risk factors fall under 10% in many patients with APN on the individual level. The utilization of clinical tools for the prediction of fluoroquinolones, TMP-SMX, and third-generation cephalosporin resistance improves the ambulatory antibiotic management of APN. It may also reduce the need to switch antibiotic therapy later based on the in vitro antibiotic susceptibility testing results of bacterial isolates in urinary cultures. This approach may mitigate the burden of increasing antibiotic resistance in the community by ensuring that the initial antibiotic prescribed has the highest likelihood of treating APN appropriately.<\/jats:p>","DOI":"10.3390\/pharmacy11060169","type":"journal-article","created":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T06:28:25Z","timestamp":1698128905000},"page":"169","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Application of Precision Medicine Concepts in Ambulatory Antibiotic Management of Acute Pyelonephritis"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8282-4841","authenticated-orcid":false,"given":"Morgan","family":"Pizzuti","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Prisma Health-Midlands, Columbia, SC 29203, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuwei Vivian","family":"Tsai","sequence":"additional","affiliation":[{"name":"The Johns Hopkins Hospital, Baltimore, MD 21287, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6203-6522","authenticated-orcid":false,"given":"Hana R.","family":"Winders","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Prisma Health-Midlands, Columbia, SC 29203, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4409-0963","authenticated-orcid":false,"given":"Paul Brandon","family":"Bookstaver","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Prisma Health-Midlands, Columbia, SC 29203, USA"},{"name":"Department of Clinical Pharmacy and Outcomes Sciences, University of South Carolina College of Pharmacy, Columbia, SC 29208, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6501-492X","authenticated-orcid":false,"given":"Majdi N.","family":"Al-Hasan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Infectious Diseases, Prisma Health-Midlands, Columbia, SC 29203, USA"},{"name":"Department of Internal Medicine, University of South Carolina School of Medicine, Columbia, SC 29209, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1086\/519268","article-title":"Population-Based Epidemiologic Analysis of Acute Pyelonephritis","volume":"45","author":"Czaja","year":"2007","journal-title":"Clin. Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.3201\/eid2209.160148","article-title":"Fluoroquinolone-Resistant and Extended-Spectrum B-Lactamase-Producing Escherichia coli Infections in Patients with Pyelonephritis, United States","volume":"22","author":"Talan","year":"2016","journal-title":"Emerg. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1093\/cid\/ciq257","article-title":"International Clinical Practice Guideline for the Treatment of Acute Uncomplicated Cystitis and Pyelonephritis in Women: A 2010 Update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases","volume":"52","author":"Gupta","year":"2011","journal-title":"Clin. Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/j.ijantimicag.2006.02.009","article-title":"Antibiotic resistance in Escherichia coli outpatient urinary isolates: Final results from the North American Urinary Tract Infection Collaborative Alliance (NAUTICA)","volume":"6","author":"Zhanel","year":"2006","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Critchley, I.A., Cotroneo, N., Pucci, M.J., and Mendes, R. (2019). The burden of antimicrobial resistance among urinary tract isolates of Escherichia coli in the United States in 2017. PLoS ONE, 14.","DOI":"10.1101\/703199"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"74","DOI":"10.2174\/1874285801206010074","article-title":"Fluoroquinolone resistance among gram-negative urinary tract pathogens: Global smart program results, 2009\u20132010","volume":"6","author":"Bouchillon","year":"2012","journal-title":"Open Microbiol. J."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Somorin, Y.M., Weir, N.J.M., Pattison, S.H., Crockard, M.A., Hughes, C.M., Tunney, M.M., and Gilpin, D.F. (2022). Antimicrobial resistance in urinary pathogens and culture-independent detection of trimethoprim resistance in urine from patients with urinary tract infection. BMC Microbiol., 22.","DOI":"10.1186\/s12866-022-02551-9"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1056\/NEJMcp1702758","article-title":"Acute Pyelonephritis in Adults","volume":"378","author":"Johnson","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Dunne, M.W., Puttagunta, S., Aronin, S.I., Brossette, S., Murray, J., and Gupta, V. (2022). Impact of Empirical Antibiotic Therapy on Outcomes of Outpatient Urinary Tract Infection Due to Nonsusceptible Enterobacterales. Microbiol. Spectr., 10.","DOI":"10.1128\/spectrum.02359-21"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1097\/IPC.0000000000000637","article-title":"Minimum Acceptable Susceptibility of Empirical Antibiotic Regimens for Gram-Negative Bloodstream Infections. A Survey of Clinical Pharmacists","volume":"26","author":"Haggard","year":"2018","journal-title":"Infect. Dis. Clin. Pract."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2977","DOI":"10.1128\/JCM.01077-15","article-title":"Challenges in preparation of cumulative antibiogram reports for community hospitals","volume":"53","author":"Moehring","year":"2015","journal-title":"J. Clin. Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1017\/ice.2018.71","article-title":"Feasibility and Value of Developing a Regional Antibiogram for Community Hospitals","volume":"39","author":"Hostler","year":"2018","journal-title":"Infect. Control. Hosp. Epidemiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1093\/jac\/dkn384","article-title":"Stratification of cumulative antibiograms in hospital unit, specimen type, isolate sequence and duration of hospital stay","volume":"62","author":"Kuster","year":"2008","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1086\/505921","article-title":"Comparison of unit-specific and hospital-wide antibiograms: Potential implications for selection of empirical antimicrobial therapy","volume":"27","author":"Binkley","year":"2006","journal-title":"Infect. Control Hosp. Epidemiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.ajic.2013.11.004","article-title":"Development of a urinary-specific antibiogram for gram-negative isolates: Impact of patient risk factors on susceptibility","volume":"42","author":"Rabs","year":"2014","journal-title":"Am. J. Infect. Control"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Marsh, K., Mundy, L., Holter, J., and Johnson, J. (2019). Analysis of Urine-specific Antibiograms from Veterans to Guide Empiric Therapy for Suspected Urinary Tract Infection. Diagn. Microbiol. Infect. Dis., 95.","DOI":"10.1016\/j.diagmicrobio.2019.114874"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"S258","DOI":"10.1093\/ofid\/ofx163.562","article-title":"Evaluating Patient-Specific Antibiograms","volume":"4","author":"Overly","year":"2017","journal-title":"Open Forum Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e02313","DOI":"10.1128\/AAC.02313-16","article-title":"Application of Fluoroquinolone Resistance Score in Management of Complicated Urinary Tract Infections","volume":"61","author":"Shah","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1086\/662379","article-title":"A Clinical Prediction Rule for Fluoroquinolone Resistance in Health-Acquired Gram-Negative Urinary Tract Infection","volume":"32","author":"Rattanaumpawan","year":"2011","journal-title":"Infect. Control Hosp. Epidemiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.jgar.2019.10.023","article-title":"Prediction of trimethoprim\/sulfamethoxazole resistance in community-onset urinary tract infections","volume":"21","author":"DeMarsh","year":"2020","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1093\/jac\/dkg146","article-title":"Prior antimicrobial drug exposure: A risk factor for trimethoprim-sulfamethoxazole-resistant urinary tract infections","volume":"51","author":"Metlay","year":"2003","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1086\/339491","article-title":"Prevalence and Predictors of Trimthoprim-Sulfamethoxazole Resistance among Uropathogenic Escherichia coli Isolates in Michigan","volume":"34","author":"Brown","year":"2002","journal-title":"Clin. Infect. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"ofy357","DOI":"10.1093\/ofid\/ofy357","article-title":"Risk Factors for Community-Acquired Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae Infections\u2014A Retrospective Study of Symptomatic Urinary Tract Infections","volume":"4","author":"Goyal","year":"2019","journal-title":"Open Forum Infect. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1017\/ice.2016.292","article-title":"Clinical Risk Score for Prediction of Extended-Spectrum B-Lactamase-Producing Enterobacteriaceae in Bloodstream Isolates","volume":"38","author":"Augustine","year":"2017","journal-title":"Infect. Control Hosp. Epidemiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1017\/ice.2019.17","article-title":"A methodological comparison of risk scores versus decision trees for predicting drug-resistant infections: A case study using extended-spectrum beta-lactamase (ESBL) bacteremia","volume":"40","author":"Goodman","year":"2019","journal-title":"Infect. Control Hosp. Epidemiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.ajem.2017.06.041","article-title":"Risk factors for early return visits to the emergency department in patients with urinary tract infection","volume":"36","author":"Jorgensen","year":"2018","journal-title":"Am. J. Emerg. Med."},{"key":"ref_27","unstructured":"CLSI (2023). Performance Standards for Antimicrobial Susceptibility Testing, Clinical and Laboratory Standards Institute. [33rd ed.]. CLSI supplement M100."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e026072","DOI":"10.1136\/bmjopen-2018-026072","article-title":"Impact of antimicrobial stewardship managed by clinical pharmacists on antibiotic use and drug resistance in a Chinese hospital, 2010\u20132016: A retrospective observational study","volume":"9","author":"Wang","year":"2019","journal-title":"BMJ Open"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"ofaa513","DOI":"10.1093\/ofid\/ofaa513","article-title":"Antimicrobial Stewardship Practice in the Ambulatory Setting From a National Cohort","volume":"7","author":"Eudy","year":"2020","journal-title":"Open Forum Infect. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1002\/phar.1649","article-title":"A Review of Antibiotic Use in Pregnancy","volume":"35","author":"Bookstaver","year":"2015","journal-title":"Pharmacotherapy"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"(2023). Urinary Tract Infections in Pregnant Individuals. Obstet. Gynecol., 142, 435\u2013445.","DOI":"10.1097\/AOG.0000000000005269"}],"container-title":["Pharmacy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2226-4787\/11\/6\/169\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:10:43Z","timestamp":1760130643000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2226-4787\/11\/6\/169"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,24]]},"references-count":31,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["pharmacy11060169"],"URL":"https:\/\/doi.org\/10.3390\/pharmacy11060169","relation":{},"ISSN":["2226-4787"],"issn-type":[{"value":"2226-4787","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,24]]}}}