Pooled Antibiotic Susceptibility of Urinary Tract Infections
Margo Lee, Ph.D.
Urinary tract infections (UTIs) are common infections that are caused by bacteria that inhabit the kidneys, bladder, ureter, or urethra.1 These infections effect more than 150 million people globally per year and account for 25% of all infections in the elderly.2,3 Traditionally, they are identified by standard urine culture methodology which grow pathogens on an agar plate. Frequently if there are two or more organisms in the urine, the bacteria may not be able to be fully identified in a standard culture setting and may need to be identified separately.4 Bacteria that grow in culture separately versus together can modify their response to specific antibiotics.5 Standard culture may identify the antibiotic susceptibility of an individual pathogen but will not distinguish a polymicrobial response by multiple bacteria in an infection and as a result, does not provide an accurate prediction of what happens in the body.6
Polymicrobial infections are common in half of positive UTI cases.7 Bacteria from similar or different species (including gram positive and gram negative) in polymicrobial samples interact with each other to collectively change their susceptibility to antibiotics.8,9 These organisms communicate with each other and will often share resistance by transferring plasmid DNA to surrounding bacteria that are sensitive to an antibiotic.10,11 Through these bacterial interactions, pathogens can collectively modify their response in the presence of an antibiotic and increase or decrease antibiotic resistance for their survival. It is essential when determining susceptibility of a polymicrobial infection that these bacteria are examined comprehensively, not individually, to capture all these crucial bacterial interactions.
Pooled Antibiotic Susceptibility Testing (P-ASTTM) is a unique feature of Guidance® UTI that identifies the susceptibility of the comprehensive pool of pathogens in urine. By testing bacterial organisms together instead of each organism individually, P-ASTTM accounts for the essential interactions between bacteria in polymicrobial infections which occur as much as 50% of the time and directly impact susceptibility to antibiotics. P-ASTTM evaluates the collective expression of bacteria in an infection in the body, yielding valuable insight to the response of all the bacteria contained in a patient sample.12
Guidance® UTI is a precision diagnostic tool that evaluates the specimen’s pooled antibiotic susceptibility to 19 commonly prescribed antibiotics for UTI infections. This information helps guide antibiotic selection by identifying antibiotic susceptibility of all the pathogens and their interactions in the infection before treatment begins. By having this knowledge prior to treatment, providers have vital phenotypic guidance to help them with appropriate medication selection, lessen empiric approaches, and support patient antibiotic stewardship.
1 Bono MJ, Leslie SW, Reygaert WC. Urinary Tract Infection. 2022 Jun 15. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan–. PMID: 29261874.
2 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; PMCID: PMC4457377.
3 Cortes-Penfield NW, Trautner BW, Jump RLP. Urinary Tract Infection and Asymptomatic Bacteriuria in Older Adults. Infect Dis Clin North Am. 2017 Dec;31(4):673-688. doi: 10.1016/j.idc.2017.07.002. PMID: 29079155; PMCID: PMC5802407.
4 Wojno KJ, Baunoch D, Luke N, Opel M, Korman H, Kelly C, Jafri SMA, Keating P, Hazelton D, Hindu S, Makhloouf B, Wenzler D, Sabry M, Burks F, Penaranda M, Smith DE, Korman A, Sirls L. Multiplex PCR Based Urinary Tract Infection (UTI) Analysis Compared to Traditional Urine Culture in Identifying Significant Pathogens in Symptomatic Patients. Urology. 2020 Feb;136:119-126. doi: 10.1016/j.urology.2019.10.018. Epub 2019
Nov 9. PMID: 31715272.
5 de Vos MGJ, Zagorski M, McNally A, Bollenbach T. Interaction networks, ecological stability, and collective antibiotic tolerance in polymicrobial infections. Proc Natl Acad Sci U S A. 2017 Oct 3;114(40):10666-10671. doi: 10.1073/pnas.1713372114. Epub 2017 Sep 18. PMID:28923953; PMCID: PMC5635929.
6 Baunoch D, Luke N, Wang D, Vollstedt A, Zhao X, Ko DSC, Huang S, Cacdac P, Sirls LT. Concordance Between Antibiotic Resistance Genes and Susceptibility in Symptomatic Urinary Tract Infections. Infect Drug Resist. 2021 Aug 19;14:3275-3286. doi:10.2147/IDR.S323095. PMID:34447256; PMCID: PMC8382965.
7 Vollstedt, A & Baunoch, D & Wolfe, Alan & Luke, N & Wojno, K & Campbell, Meghan. (2020). Bacterial Interactions as Detected by Pooled Antibiotic Susceptibility Testing (P-AST) in Polymicrobial Urine Specimens. 101. 10.29011/JSU-101.100001.
8 Baunoch D, Luke N, Wang D, Vollstedt A, Zhao X, Ko DSC, Huang S, Cacdac P, Sirls LT. Concordance Between Antibiotic Resistance Genes and Susceptibility in Symptomatic Urinary Tract Infections. Infect Drug Resist. 2021 Aug 19;14:3275-3286. doi:10.2147/IDR.S323095. PMID:34447256; PMCID: PMC8382965.
9 de Vos MGJ, Zagorski M, McNally A, Bollenbach T. Interaction networks, ecological stability, and collective antibiotic tolerance in
polymicrobial infections. Proc Natl Acad Sci U S A. 2017 Oct 3;114(40):10666-10671. doi: 10.1073/pnas.1713372114. Epub 2017 Sep 18. PMID:28923953; PMCID: PMC5635929.
10 Andrup L, Andersen K. A comparison of the kinetics of plasmid transfer in the conjugation systems encoded by the F plasmid from Escherichia coli and plasmid pCF10 from Enterococcus faecalis. Microbiology (Reading). 1999 Aug;145 ( Pt 8):2001-2009. doi:10.1099/13500872-145-8-2001. PMID: 10463166.
11 Cruz MR, Graham CE, Gagliano BC, Lorenz MC, Garsin DA. Enterococcus faecalis inhibits hyphal morphogenesis and virulence of Candida albicans. Infect Immun. 2013 Jan;81(1):189-200. doi: 10.1128/IAI.00914-12. Epub 2012 Oct 31. PMID: 23115035; PMCID: PMC3536143.
12 Baunoch D, Luke N, Wang D, Vollstedt A, Zhao X, Ko DSC, Huang S, Cacdac P, Sirls LT. Concordance Between Antibiotic Resistance Genes and Susceptibility in Symptomatic Urinary Tract Infections. Infect Drug Resist. 2021 Aug 19;14:3275-3286. doi: 10.2147/IDR.S323095. PMID: 34447256; PMCID: PMC8382965.