Antimicrobial resistance in urinary pathogens and culture-independent detection of trimethoprim resistance in urine from patients with urinary tract infection

BMC Microbiology - Tập 22 Số 1 - 2022
Yinka M. Somorin1, Nichola-Jane M. Weir1, S. Pattison2, Martin Crockard3, Carmel Hughes1, Michael Tunney1, D.F. Gilpin1
1School of Pharmacy, Queen’s University Belfast, 97 Lisburn Road, Belfast, Northern Ireland
2Wellcome-Wolfson Institute for Experimental Medicine, Queen’s University Belfast, 97 Lisburn Road,, Belfast, Northern Ireland
3Randox Laboratories Ltd, 55 The Diamond Road, Crumlin, Northern Ireland

Tóm tắt

Abstract Background

Although urinary tract infections (UTIs) are extremely common, isolation of causative uropathogens is not always routinely performed, with antibiotics frequently prescribed empirically. This study determined the susceptibility of urinary isolates from two Health and Social Care Trusts (HSCTs) in Northern Ireland to a range of antibiotics commonly used in the treatment of UTIs. Furthermore, we determined if detection of trimethoprim resistance genes (dfrA) could be used as a potential biomarker for rapid detection of phenotypic trimethoprim resistance in urinary pathogens and from urine without culture.

 Methods

Susceptibility of E. coli and Klebsiella spp. isolates (n = 124) to trimethoprim, amoxicillin, ceftazidime, ciprofloxacin, co-amoxiclav and nitrofurantoin in addition to susceptibility of Proteus mirabilis (n = 61) and Staphylococcus saprophyticus (n = 17) to trimethoprim was determined by ETEST® and interpreted according to EUCAST breakpoints. PCR was used to detect dfrA genes in bacterial isolates (n = 202) and urine samples(n = 94).

 Results

Resistance to trimethoprim was observed in 37/124 (29.8%) E. coli and Klebsiella spp. isolates with an MIC90 > 32 mg/L. DfrA genes were detected in 29/37 (78.4%) trimethoprim-resistant isolates. Detection of dfrA was highly sensitive (93.6%) and specific (91.4%) in predicting phenotypic trimethoprim resistance among E. coli and Klebsiella spp. isolates. The dfrA genes analysed were detected using a culture-independent PCR method in 16/94 (17%) urine samples. Phenotypic trimethoprim resistance was apparent in isolates cultured from 15/16 (94%) dfrA-positive urine samples. There was a significant association (P < 0.0001) between the presence of dfrA and trimethoprim resistance in urine samples containing Gram-negative bacteria (Sensitivity = 75%; Specificity = 96.9%; PPV = 93.8%; NPV = 86.1%).

 Conclusions

This study demonstrates that molecular detection of dfrA genes is a good indicator of trimethoprim resistance without the need for culture and susceptibility testing.

Từ khóa


Tài liệu tham khảo

Pouwels KB, Dolk FCK, Smith DRM, Robotham JV, Smieszek T. Actual versus “ideal” antibiotic prescribing for common conditions in English primary care. J Antimicrob Chemother. 2018;73:19–26.

Dolk FCK, Pouwels KB, Smith DRM, Robotham JV, Smieszek T. Antibiotics in primary care in England: which antibiotics are prescribed and for which conditions? J Antimicrob Chemother. 2018;73:ii2–10.

Devillé WLJM, Yzermans JC, Duijn NP Van, Bezemer D, Windt DAWM Van Der, Bouter LM. The urine dipstick test useful to rule out infections. A meta-analysis of the accuracy. BMC Urol. 2004;4:1–14.

Sundvall PD, Gunnarsson RK. Evaluation of dipstick analysis among elderly residents to detect bacteriuria: a cross-sectional study in 32 nursing homes. BMC Geriatr. 2009;9:32.

Briongos-Figuero LS, Gómez-Traveso T, Bachiller-Luque P, Domínguez-Gil González M, Gómez-Nieto A, Palacios-Martín T, et al. Epidemiology, risk factors and comorbidity for urinary tract infections caused by extended-spectrum beta-lactamase (ESBL)-producing enterobacteria. Int J Clin Pract. 2012;66:891–6.

National Institute for health and care excellence. UTI (lower): antimicrobial prescribing. 2018. https://www.nice.org.uk/guidance/ng109/resources/visual-summary-pdf-6544021069.

Toner L, Papa N, Aliyu SH, Dev H, Lawrentschuk N, Al-Hayek S. Extended-spectrum beta-lactamase-producing Enterobacteriaceae in hospital urinary tract infections: incidence and antibiotic susceptibility profile over 9 years. World J Urol. 2016;34:1031–7.

Farrell DJ, Morrissey I, de Rubeis D, Robbins M, Felmingham D. A UK multicentre study of the antimicrobial susceptibility of bacterial pathogens causing urinary tract infection. J Infect. 2003;46:94–100.

Rosello A, Hayward AC, Hopkins S, Horner C, Ironmonger D, Hawkey PM, et al. Impact of long-term care facility residence on the antibiotic resistance of urinary tract Escherichia coli and Klebsiella. J Antimicrob Chemother. 2017;72:1184–92.

Kahlmeter G. An international survey of the antimicrobial susceptibility of pathogens from uncomplicated urinary tract infections: the ECO.SENS project. J Antimicrob Chemother. 2003;51:69–76.

Lane DJ. 16S/23S rRNA sequencing. In: Stackebrandt E, Goodfellow M, editors. Nucleic acid techniques in bacterial systematic. New York: Wiley; 1991. p. 115–75.

The European committee on antimicrobial susceptibility testing. Breakpoint tables for interpretation of MICs and zone diameters. Version 9.0. 2019. http://www.eucast.org.

Brolund A, Sundqvist M, Kahlmeter G, Grape M. Molecular characterisation of trimethoprim resistance in Escherichia coli and Klebsiella pneumoniae during a two year intervention on trimethoprim use. PLoS One. 2010;5:1–5.

Grape M, Motakefi A, Pavuluri S, Kahlmeter G. Standard and real-time multiplex PCR methods for detection of trimethoprim resistance dfr genes in large collections of bacteria. Clin Microbiol Infect. 2007;13:1112–8.

Raz R, Chazan B, Kennes Y, Colodner R, Rottensterich E, Dan M, et al. Empiric use of trimethoprim-Sulfamethoxazole (TMP-SMX) in the treatment of women with uncomplicated urinary tract infections, in a geographical area with a high prevalence of TMP-SMX–resistant Uropathogens. Clin Infect Dis. 2002;34:1165–9.

Butler CC, Hillier S, Roberts Z, Dunstan F, Howard A, Palmer S. Antibiotic-resistant infections in primary care are symptomatic for longer and increase workload: outcomes for patients with E. coli UTIs. Br J Gen Pract. 2006;56:686–92.

Duffy AM, Hernandez-Santiago V, Orange G, Davey PG, Guthrie B. Trimethoprim prescription and subsequent resistance in childhood urinary infection: multilevel modelling analysis. Br J Gen Pract. 2013;63:238–43.

Public Health England. English surveillance programme for antimicrobial utilisation and resistance (ESPAUR) 2017. London; 2017.

Public Health England. English surveillance programme for antimicrobial utilisation and resistance (ESPAUR) 2018 to 2019. London; 2019.

Health Protection Scotland. Scottish One Health Antimicrobial Use and Antimicrobial Resistance in 2018. Annu Rep. 2019.

Heginbothom M, Howe R. Antibacterial resistance in urinary coliforms Wales 2009–2018. Public Health Wales; 2019.

Nugent C, Patterson L, Sartaj M. Surveillance of antimicrobial use and resistance in Northern Ireland, Annual Report, 2018. Belfast: Public Health Agency: 2019.

Volz C, Ramoni J, Beisken S, Galata V, Keller A, Plum A, et al. Clinical Resistome screening of 1,110 Escherichia coli isolates efficiently recovers diagnostically relevant antibiotic resistance biomarkers and potential novel resistance mechanisms. Front Microbiol. 2019;10:1671.

Michael GB, Butaye P, Cloeckaert A, Schwarz S. Genes and mutations conferring antimicrobial resistance in Salmonella: an update. Microbes Infect. 2006;8:1898–914.

Haslund JMQ, Rosborg Dinesen M, Sternhagen Nielsen AB, Llor C, Bjerrum L. Different recommendations for empiric first-choice antibiotic treatment of uncomplicated urinary tract infections in Europe. Scand J Prim Health Care. 2013;31:235–40.

Kahlmeter G, Poulsen HO. Antimicrobial susceptibility of Escherichia coli from community-acquired urinary tract infections in Europe: the ECO·SENS study revisited. Int J Antimicrob Agents. 2012;39:45–51.

Ny S, Edquist P, Dumpis U, Gröndahl-Yli-Hannuksela K, Hermes J, Kling A-M, et al. Antimicrobial resistance of Escherichia coli isolates from outpatient urinary tract infections in women in six European countries including Russia. J Glob Antimicrob Resist. 2019;17:25–34.

Sanchez GV, Babiker A, Master RN, Luu T, Mathur A, Bordon J. Antibiotic resistance among urinary isolates from female outpatients in the United States in 2003 and 2012. Antimicrob Agents Chemother. 2016;60:2680–3.

Fasugba O, Das A, Mnatzaganian G, Mitchell BG, Collignon P, Gardner A. Incidence of single-drug resistant, multidrug-resistant and extensively drug-resistant Escherichia coli urinary tract infections: an Australian laboratory-based retrospective study. J Glob Antimicrob Resist. 2019;16:254–9.

Koningstein M, Van Der Bij AK, De Kraker MEA, Monen JC, Muilwijk J, De Greeff SC, et al. Recommendations for the empirical treatment of complicated urinary tract infections using surveillance data on antimicrobial resistance in the Netherlands. PLoS One. 2014;9:e86634.

Magyar A, Köves B, Nagy K, Dobák A, Arthanareeswaran VKA, Bálint P, et al. Spectrum and antibiotic resistance of uropathogens between 2004 and 2015 in a tertiary care hospital in Hungary. J Med Microbiol. 2017;66:788–97.

Public health England PHE. English surveillance Programme for antimicrobial utilisation and resistance (ESPAUR) 2018. London; 2018.

De Sousa VS, Da-Silva APS, Sorenson L, Paschoal RP, Rabello RF, Campana EH, et al. Staphylococcus saprophyticus recovered from humans, food, and recreational waters in Rio de Janeiro, Brazil. Int J Microbiol. 2017;2017:4287547.

Coelho C, de Lencastre H, Aires-de-Sousa M. Frequent occurrence of trimethoprim-sulfamethoxazole hetero-resistant Staphylococcus aureus isolates in different African countries. Eur J Clin Microbiol Infect Dis. 2017;36:1243–52.

Thông tin
Thông tin xuất bản

BMC Microbiology

Tập 22 Số 1

Thông tin tác giả