The high incidence of urinary tract infection (UTI) among women and children, in combination with a lack of antibiotic efficacy with regard to pathogen eradication and recurrence prevention, as well as the negative side effects associated with antibiotics, has led researchers to explore the role of non-steroidal anti-inflammatory drugs as a primary management strategy. The aim of this study was to determine whether ibuprofen (IBU) or one of its major metabolites, 2-carboxyibuprofen (CIBU), could affect the growth and adhesion of the two most common uropathogens, Escherichia coli and Enterococcus faecalis. The bacterial growth and adhesion to the urothelial cells of E. coli UTI89 and E. faecalis 1131 in the presence of physiologically relevant concentrations of IBU and CIBU were assessed. The effect of IBU on bacterial adhesion to urothelial cells was also assessed following exposure to trimethoprim/sulfamethoxazole (TMP/SMX) and nitrofurantoin. Bacterial growth was not affected by IBU. Further, only at high levels of IBU not regularly found in the bladder was there a significant increase in E. faecalis 1131 attachment at growth inhibitory concentrations of TMP/SMX. There was no effect on the attachment of E. faecalis or E. coli to urothelial cells in the presence of nitrofurantoin. These studies indicate that the beneficial effects of IBU for UTI management are likely mediated through its anti-inflammatory properties rather than direct interactions with uropathogens in the bladder.
GuptaK,
HootonTM,
NaberKG,
WulltB,
ColganR et al. 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 Dis2011; 52:e103–e120 [View Article]
DaiB,
LiuY,
JiaJ,
MeiC.
Long-term antibiotics for the prevention of recurrent urinary tract infection in children: a systematic review and meta-analysis. Arch Dis Child2010; 95:499–508 [View Article]
GágyorI,
Hummers-PradierE,
KochenMM,
SchmiemannG,
WegscheiderK et al. Immediate versus conditional treatment of uncomplicated urinary tract infection - a randomized-controlled comparative effectiveness study in general practices. BMC Infect Dis2012; 12:146–152 [View Article]
BleidornJ,
Hummers-PradierE,
SchiemannG,
WieseB,
GágyorI.
Recurrent urinary tract infections and complications after symptomatic versus antibiotic treatment: follow-up of a randomised controlled trial. Ger Med Sci2016; 14:Doc01
HannanTJ,
RobertsPL,
RiehlTE,
van der PostS,
BinkleyJM et al. Inhibition of cyclooxygenase-2 prevents chronic and recurrent cystitis. EBioMedicine2014; 1:46–57 [View Article]
LaudyAE,
MrowkaA,
KrajewskaJ,
TyskiS.
The influence of efflux pump inhibitors on the activity of non-antibiotic NSAIDs against Gram-negative rods. PLoS One2016; 11:e0147131 [View Article]
GłówkaFK,
KaraźniewiczM.
High performance capillary electrophoresis method for determination of ibuprofen enantiomers in human serum and urine. Anal Chim Acta2005; 540:95–102 [View Article]
JiaW,
LiG,
WangW.
Prevalence and antimicrobial resistance of Enterococcus species: a hospital-based study in China. Int J Environ Res Public Health2014; 11:3424–3442 [View Article]
MobleyHLT,
GreenDM,
TrifillisAL,
JohnsonDE,
ChippendaleGR et al. Pyelonephritogenic Escherichia coli and killing of cultured human renal proxiaml tubular epithelial cells: role of hemolysin in some strains. Infect Immun1990; 58:1281–1289
McGroartyJA,
LeeV,
BruceAW,
ReidG.
Modulation of adhesion of uropathogenic Enterococcus faecalis to human epithelial cells in vitro by Lactobacillus species. Microb Ecol Health Dis1992; 5:309–314 [View Article]
MillsapK,
ReidG,
Van der MeiHC,
BusscherHJ.
Displacement of Enterococcus faecalis from hydrophobic and hydrophilic substrata by Lactobacillus and Streptococcus spp. as studied in a parallel plate flow chamber. Appl Environ Microb1994; 60:1867–1874
HuttV,
KlingmannI,
PabstGU,
SalamaZ,
NiederM et al. Studies of the pharacokinetics and bioavailability of a new trimethoprim/sulfamethoxazole preparation in healthy volunteers. Arzneimittelforschung1988; 38:1347–1350
MagieraS,
GülmezŞ.
Ultrasound-assisted emulsification microextraction combined with ultra-high performance liquid chromatography-tandem mass spectrometry for the analysis of ibuprofen and its metabolites in human urine. J Pharm Biomed Anal2014; 92:193–202 [View Article]
García-VázquezA,
BorrullF,
CalullM,
AguilarC.
Single-drop microextraction combined in-line with capillary electrophoresis for the determination of nonsteroidal anti-inflammatory drugs in urine samples. Electrophoresis2016; 37:274–281 [View Article]
Gallardo-MorenoAM,
van der MeiHC,
BusscherHJ,
González-MartínML,
BruqueJM et al. Adhesion of Enterococcus faecalis 1131 grown under subinhibitory concentrations of ampicillin and vancomycin to a hydrophilic and a hydrophobic substratum. FEMS Microbiol Lett2001; 203:75–79 [View Article]
MartinsM,
DastidarSG,
FanningS,
KristiansenJE,
MolnarJ et al. Potential role of non-antibiotics (helper compounds) in the treatment of multidrug-resistant Gram-negative infections: mechanisms for their direct and indirect activities. Int J Antimicrob Ag2008; 31:198–208 [View Article]