Patient-Directed Antimicrobial Duration in Acute Uncomplicated Pyelonephritis

NCT06127160 | Completed Phase 4 FDA Drug

• 1 other identifier: 202303721
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 2

Brief Summary

This pilot study will randomize 40 female patients with acute uncomplicated pyelonephritis to receive standard duration of therapy versus patient-directed antimicrobial duration (PDAD). The primary objectives of this pilot trial are to determine the feasibility and safety of conducting a full-scale multi-center randomized controlled trial.

Conditions

Pyelonephritis Acute

Keywords

cephalexin

Outcome Measures

Primary Outcomes (1)

• Feasibility of completing all clinical trial activities and follow-up

  Percentage of participants that complete all study activities and follow-up through 90 days

  90 days

Secondary Outcomes (6)

• Sustained clinical cure

  30 days

• Sustained microbiological cure

  30 days

• Clinical and microbiological cure rates after the end of treatment

  15-21 days

• Adverse event and side effect event rates

  30 days

• Additional health care visits with the chief complaint of urinary tract infection

  30 days

Study Arms (2)

Standard Duration Treatment

ACTIVE COMPARATOR

Drug: Cephalexin

Patient-directed antimicrobial duration (PDAD)

EXPERIMENTAL

Drug: Cephalexin or placebo

Interventions

Cephalexin DRUG

Cephalexin 1000 mg by mouth 3 times daily for 10 days

Standard Duration Treatment

Cephalexin or placebo DRUG

Cephalexin 1000 mg by mouth 3 times daily for a minimum of 3 days, once participant reports symptom resolution for 24 hours they will switch to placebo for remainder of 10 days of treatment.

Patient-directed antimicrobial duration (PDAD)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Females between 18 and 55 years of age
• Diagnosis of acute uncomplicated pyelonephritis
• Can be discharged home on oral antimicrobial treatment
• Ability to provide written informed consent in English or Spanish

You may not qualify if:

• Took antibiotics in the prior 48 hours
• Insulin-dependent diabetes
• End-stage liver disease
• If the patient reports a penicillin allergy, and is deemed to be high-risk using the penicillin allergy clinical decision rule (PEN-FAST)
• Serious allergy (e.g., angioedema, anaphylaxis) to the study medication or a similarly reported allergy to a cephalosporin
• Known or identified hydronephrosis, obstruction, or abscess identified by emergency department ultrasound
• Presence of a kidney stone
• Pregnancy or lactation
• Renal dysfunction (defined as creatinine clearance of less than 30 mL/min)
• Renal transplantation
• Complicated pyelonephritis (defined anatomical or functional abnormality of the urinary tract that predisposes to infection)
• Need for additional antimicrobial therapy for a coexisting infection
• Human immunodeficiency virus (HIV) infection, with either a recent (in the past 6 months) acquired immune deficiency syndrome-defining condition or a cluster of differentiation-4 (CD-4+) T lymphocyte count \<200/mm\^3

Sponsors & Collaborators

• Brett A Faine: lead
• University of California, Los Angeles: collaborator

Study Sites (2)

Olive View - UCLA Medical Center

Sylmar, California, 91342, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Related Publications (20)

• Foxman B. The epidemiology of urinary tract infection. Nat Rev Urol. 2010 Dec;7(12):653-60. doi: 10.1038/nrurol.2010.190.

  PMID: 21139641 BACKGROUND

• Foxman B. Urinary tract infection syndromes: occurrence, recurrence, bacteriology, risk factors, and disease burden. Infect Dis Clin North Am. 2014 Mar;28(1):1-13. doi: 10.1016/j.idc.2013.09.003. Epub 2013 Dec 8.

  PMID: 24484571 BACKGROUND

• Taylor RA, Moore CL, Cheung KH, Brandt C. Predicting urinary tract infections in the emergency department with machine learning. PLoS One. 2018 Mar 7;13(3):e0194085. doi: 10.1371/journal.pone.0194085. eCollection 2018.

  PMID: 29513742 BACKGROUND

• Hicks LA, Bartoces MG, Roberts RM, Suda KJ, Hunkler RJ, Taylor TH Jr, Schrag SJ. US outpatient antibiotic prescribing variation according to geography, patient population, and provider specialty in 2011. Clin Infect Dis. 2015 May 1;60(9):1308-16. doi: 10.1093/cid/civ076. Epub 2015 Mar 5.

  PMID: 25747410 BACKGROUND

• May L, Cosgrove S, L'Archeveque M, Talan DA, Payne P, Jordan J, Rothman RE. A call to action for antimicrobial stewardship in the emergency department: approaches and strategies. Ann Emerg Med. 2013 Jul;62(1):69-77.e2. doi: 10.1016/j.annemergmed.2012.09.002. Epub 2012 Nov 2.

  PMID: 23122955 BACKGROUND

• Flores-Mireles AL, Walker JN, Caparon M, Hultgren SJ. Urinary tract infections: epidemiology, mechanisms of infection and treatment options. Nat Rev Microbiol. 2015 May;13(5):269-84. doi: 10.1038/nrmicro3432. Epub 2015 Apr 8.

  PMID: 25853778 BACKGROUND

• Gupta K, Hooton TM, Naber KG, Wullt B, Colgan R, Miller LG, Moran GJ, Nicolle LE, Raz R, Schaeffer AJ, Soper DE; Infectious Diseases Society of America; European Society for Microbiology and Infectious Diseases. International clinical practice guidelines 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. Clin Infect Dis. 2011 Mar 1;52(5):e103-20. doi: 10.1093/cid/ciq257.

  PMID: 21292654 BACKGROUND

• Talan DA, Takhar SS, Krishnadasan A, Abrahamian FM, Mower WR, Moran GJ; EMERGEncy ID Net Study Group. Fluoroquinolone-Resistant and Extended-Spectrum beta-Lactamase-Producing Escherichia coli Infections in Patients with Pyelonephritis, United States(1). Emerg Infect Dis. 2016 Sep;22(9):1594-603. doi: 10.3201/eid2209.160148.

  PMID: 27532362 BACKGROUND

• Talan DA, Takhar SS, Krishnadasan A, Mower WR, Pallin DJ, Garg M, Femling J, Rothman RE, Moore JC, Jones AE, Lovecchio F, Jui J, Steele MT, Stubbs AM, Chiang WK, Moran GJ. Emergence of Extended-Spectrum beta-Lactamase Urinary Tract Infections Among Hospitalized Emergency Department Patients in the United States. Ann Emerg Med. 2021 Jan;77(1):32-43. doi: 10.1016/j.annemergmed.2020.08.022. Epub 2020 Oct 31.

  PMID: 33131912 BACKGROUND

• Low M, Neuberger A, Hooton TM, Green MS, Raz R, Balicer RD, Almog R. Association between urinary community-acquired fluoroquinolone-resistant Escherichia coli and neighbourhood antibiotic consumption: a population-based case-control study. Lancet Infect Dis. 2019 Apr;19(4):419-428. doi: 10.1016/S1473-3099(18)30676-5. Epub 2019 Mar 4.

  PMID: 30846277 BACKGROUND

• Brown KA, Khanafer N, Daneman N, Fisman DN. Meta-analysis of antibiotics and the risk of community-associated Clostridium difficile infection. Antimicrob Agents Chemother. 2013 May;57(5):2326-32. doi: 10.1128/AAC.02176-12. Epub 2013 Mar 11.

  PMID: 23478961 BACKGROUND

• McCusker ME, Harris AD, Perencevich E, Roghmann MC. Fluoroquinolone use and Clostridium difficile-associated diarrhea. Emerg Infect Dis. 2003 Jun;9(6):730-3. doi: 10.3201/eid0906.020385.

  PMID: 12781017 BACKGROUND

• Sader HS, Biedenbach DJ, Streit JM, Jones RN. Cefdinir activity against contemporary North American isolates from community-acquired urinary tract infections. Int J Antimicrob Agents. 2005 Jan;25(1):89-92. doi: 10.1016/j.ijantimicag.2004.07.006.

  PMID: 15620832 BACKGROUND

• Mogle BT, Beccari MV, Steele JM, Fazili T, Kufel WD. Clinical considerations for oral beta-lactams as step-down therapy for Enterobacteriaceae bloodstream infections. Expert Opin Pharmacother. 2019 Jun;20(8):903-907. doi: 10.1080/14656566.2019.1594774. Epub 2019 Mar 25. No abstract available.

  PMID: 30908107 BACKGROUND

• Fung-Tomc JC, Huczko E, Stickle T, Minassian B, Kolek B, Denbleyker K, Bonner D, Kessler R. Antibacterial activities of cefprozil compared with those of 13 oral cephems and 3 macrolides. Antimicrob Agents Chemother. 1995 Feb;39(2):533-8. doi: 10.1128/AAC.39.2.533.

  PMID: 7726528 BACKGROUND

• Bonsu BK, Shuler L, Sawicki L, Dorst P, Cohen DM. Susceptibility of recent bacterial isolates to cefdinir and selected antibiotics among children with urinary tract infections. Acad Emerg Med. 2006 Jan;13(1):76-81. doi: 10.1197/j.aem.2005.07.032. Epub 2005 Dec 19.

  PMID: 16365328 BACKGROUND

• MacGregor RR, Graziani AL. Oral administration of antibiotics: a rational alternative to the parenteral route. Clin Infect Dis. 1997 Mar;24(3):457-67. doi: 10.1093/clinids/24.3.457.

  PMID: 9114201 BACKGROUND

• Guay DR. Pharmacodynamics and pharmacokinetics of cefdinir, an oral extended spectrum cephalosporin. Pediatr Infect Dis J. 2000 Dec;19(12 Suppl):S141-6. doi: 10.1097/00006454-200012001-00002.

  PMID: 11144395 BACKGROUND

• Kanan M, Atif S, Mohammed F, Balahmar Y, Adawi Y, AlSaleem R, Farhan A, Alghoribi M, Mohammed S, Alshanbari R, Fahad M, Kallab R, Mohammed R, Alassaf D, Hazza A. A Systematic Review on the Clinical Pharmacokinetics of Cephalexin in Healthy and Diseased Populations. Antibiotics (Basel). 2023 Sep 3;12(9):1402. doi: 10.3390/antibiotics12091402.

  PMID: 37760698 BACKGROUND

• Leigh AP, Nemeth MA, Keyserling CH, Hotary LH, Tack KJ. Cefdinir versus cefaclor in the treatment of uncomplicated urinary tract infection. Clin Ther. 2000 Jul;22(7):818-25. doi: 10.1016/s0149-2918(00)80054-5.

  PMID: 10945508 BACKGROUND

MeSH Terms

Interventions

Cephalexin

Intervention Hierarchy (Ancestors)

Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Associate Professor

Study Record Dates

• First Submitted: October 31, 2023
• First Posted: November 13, 2023
• Study Start: June 4, 2024
• Primary Completion: August 29, 2025
• Study Completion: August 29, 2025
• Last Updated: September 12, 2025

Record last verified: 2025-09

Locations

US (2)