Antimicrobial Prophylaxis for Recurrent Urinary Tract Infections in Premenopausal and Postmenopausal Women: A Retrospective Observational Study from an Outpatient Clinic in a Tertiary University Hospital
Abstract
1. Introduction
1.1. Epidemiology and Definition
1.2. Predisposing Factors
1.3. Causative Agents
1.4. Antimicrobial Prophylaxis
- Continuous low-dose prophylaxis—consists of administration of 1/4 or 1/2 of the therapeutic dose of antibiotics once a day before bedtime.
- Postcoital prophylaxis—consists of administering a single dose of an antibiotic selected based on previous urine cultures within two hours after sexual intercourse.
- Self-diagnosis and self-treatment—appropriate in patients with good compliance.
2. Results
2.1. Eligible Patients and Characteristics of the Index UTI Episode
2.2. General Prophylactic Strategies in Peri-/Postmenopausal and Premenopausal Women
2.3. Relative Efficacy of Nitrofurantoin-Based vs. Other Antibiotic-Based Prophylaxis
2.4. Tolerability of the Continuous Antibiotic Prophylaxis
3. Discussion
3.1. Antibiotic Prophylaxis Strategies and Their Application
3.2. Relapse Rates and Causative Agents
3.3. Comparative Efficacy of Nitrofurantoin in Prophylaxis
3.4. Tolerability of Antibiotic Prophylaxis
3.5. Recommendations According to Our Clinical Practice
- Urine Culture Isolate
- (a)
- Sensitivity of the isolated bacteria to antibiotics that can be used in prophylaxis: If the causative agent is sensitive only to broad-spectrum antibiotics, the necessity of antimicrobial prophylaxis should be reassessed. If the potential for side effects outweighs the benefit to the patient, it may be better to treat each episode individually.
- (b)
- Occurrence of different isolates in urine cultures: This refers to the (in)feasibility of using a single antimicrobial drug for prophylaxis. If antimicrobial prophylaxis is ineffective against all isolates appearing in repeated urine cultures in rUTIs, there is a high likelihood of recurrence caused by a uropathogen not covered by the prophylactic antibiotic. Although antimicrobial prophylaxis is usually based on the most recent positive urine culture, when selecting an antimicrobial agent for patients with multiple different isolates in their urine cultures, it is ideal to choose an antibiotic that is effective against all isolates.
- Choice of Antibiotic
- 3.
- Patient Characteristics
- (a)
- Age: Verify whether the antibiotic intended for prophylactic use is associated with a higher risk of side effects in older adults, e.g., nitrofurantoin (refer to “Beers criteria for inappropriate medication use in older patients” [49]). For women of childbearing age, select antibiotics that are safe during pregnancy.
- (b)
- Chronic illnesses and ongoing treatment: Consider possible interactions between the patient’s current therapy and the antibiotic intended for prophylaxis.
- (c)
- Renal and liver function: Especially in older patients, check serum creatinine, creatinine clearance, and liver enzymes before starting prophylaxis. Some antibiotics have usage restrictions in cases of renal or hepatic insufficiency (e.g., nitrofurantoin), and antibiotics themselves may worsen pre-existing kidney or liver damage.
- (d)
- Antibiotic allergies
- 4.
- Possible Complications/Side Effects of Antibiotics
- 5.
- Expectations
- 6.
- Predisposing Factors
- Clinical Evaluation—assessment of how well the patient tolerates antimicrobial prophylaxis, presence or absence of UTI symptoms, and documentation of side effects.
- Laboratory Tests
- (a)
- Urinalysis and urine culture (collected without interrupting prophylaxis)—urinalysis should not indicate inflammation, and the culture is preferably sterile.
- (b)
- Complete blood count—monitor for anemia, leukopenia and neutropenia (with nitrofurantoin), and eosinophilia (possible with all antibiotics).
- (c)
- Serum creatinine—should be within reference range for certain antibiotics (e.g., nitrofurantoin).
- (d)
- Liver function tests—abnormal results may be due to antibiotic use.
- Reassessment of the need for continued prophylaxis or a shift to a different prophylactic strategy (e.g., postcoital prophylaxis, self-treatment, or non-antimicrobial prophylaxis), depending on the patient’s clinical status and preferences.
4. Materials and Methods
4.1. Patients
4.2. Data Sources and Management
4.3. Data Analysis
5. Conclusions and Limitations
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Geerlings, S.E. Clinical presentations and epidemiology of urinary tract infections. In Urinary Tract. Infections: Molecular Pathogenesis and Clinical Management; WILEY: Hoboken, NJ, USA, 2017; Volume 15, pp. 27–40. [Google Scholar]
- Gupta, K.; Trautner, B.W. Diagnosis and management of recurrent urinary tract infections in non-pregnant women. BMJ 2013, 346, f3140. [Google Scholar] [CrossRef]
- Foxman, B. Epidemiology of urinary tract infections: Incidence, morbidity, and economic costs. Am. J. Med. 2002, 113, 5–13. [Google Scholar] [CrossRef]
- Bonkat, G.; Bartoletti, R.; Bruyere, F.; Cai, T.; Geerlings, S.E.; Köves, B.; Kranz, J.; Schubert, S.; Pilatz, A.; Veeratterapillay, R.; et al. EAU Guidelines on Urological Infections. 2025. Available online: https://uroweb.org/guidelines/urological-infections (accessed on 20 June 2025).
- Anger, J.T.; Lee, U.; Ackerman, A.L.; Chou, R.; Chughtai, B.; Clemens, J.Q.; Hickling, D.; Kapoor, A.; Kenton, K.S.; Kaufman, M.R.; et al. Recurrent uncomplicated urinary tract infections in women: AUA/CUA/SUFU guideline. J. Urol. 2019, 202, 282–289. [Google Scholar] [CrossRef]
- Foxman, B.; Somsel, P.; Tallman, P.; Gillespie, B.; Raz, R.; Colodner, R.; Kandula, D.; Sobel, J.D. Urinary tract infection among women aged 40 to 65: Behavioral and sexual risk factors. J. Clin. Epidemiol. 2001, 54, 710–718. [Google Scholar] [CrossRef] [PubMed]
- Hooton, T.M. Recurrent urinary tract infection in women. Int. J. Antimicrob. Agents 2001, 17, 259–268. [Google Scholar] [CrossRef]
- Hooton, T.M.; Scholes, D.; Hughes, J.P.; Winter, C.; Roberts, P.L.; Stapleton, A.E.; Stergachis, A.; Stamm, W.E. A prospective study of risk factors for symptomatic urinary tract infection in young women. N. Engl. J. Med. 1996, 335, 468–474. [Google Scholar] [CrossRef]
- Scholes, D.; Hooton, T.M.; Roberts, P.L.; Stapleton, A.E.; Gupta, K.; Stamm, W.E. Risk factors for recurrent urinary tract infection in young women. J. Infect. Dis. 2000, 182, 1177–1182. [Google Scholar] [CrossRef] [PubMed]
- Fihn, S.D.; Boyko, E.J.; Normand, E.H.; Chen, C.-L.; Grafton, J.R.; Hunt, M.; Yarbro, P.; Scholes, D.; Stergachis, A. Association between use of spermicide coated condoms and Escherichia coli urinary tract infection in young women. Am. J. Epidemiol. 1996, 144, 512–520. [Google Scholar] [CrossRef]
- Fihn, S.D.; Boyko, E.J.; Chen, C.L.; Normand, E.H.; Yarbro, P.; Scholes, D. Use of spermicide coated condoms and other risk factors for urinary tract infection caused by Staphylococcus saprophyticus. Arch. Intern. Med. 1998, 158, 281. [Google Scholar] [CrossRef]
- Raz, R.; Gennesin, Y.; Wasser, J.; Stoler, Z.; Rosenfeld, S.; Rottensterich, E.; Stamm, W.E. Recurrent urinary tract infections in postmenopausal women. Clin. Infect. Dis. 2000, 30, 152–156. [Google Scholar] [CrossRef] [PubMed]
- Aydin, A.; Ahmed, K.; Zaman, I.; Khan, M.S.; Dasgupta, P. Recurrent urinary tract infections in women. Int. Urogynecol. J. 2015, 26, 795–804. [Google Scholar] [CrossRef]
- Pfau, A.; Sacks, T. The bacterial flora of the vaginal vestibule, urethra and vagina in premenopausal women with recurrent urinary tract infections. J. Urol. 1981, 126, 630–634. [Google Scholar] [CrossRef] [PubMed]
- Ejrnæs, K. Bacterial characteristics of importance for recurrent urinary tract infections caused by Escherichia coli. Dan. Med. Bull. 2011, 58, B4187. [Google Scholar] [PubMed]
- Luo, Y.; Ma, Y.; Zhao, Q.; Wang, L.; Guo, L.; Ye, L.; Zhang, Y.; Yang, J. Similarity and divergence of phylogenies, antimicrobial susceptibilities, and virulence factor profiles of Escherichia coli isolates causing recurrent urinary tract infections that persist or result from reinfection. J. Clin. Microbiol. 2012, 50, 4002–4007. [Google Scholar] [CrossRef]
- Foxman, B.; Gillespie, B.; Koopman, J.; Zhang, L.; Palin, K.; Tallman, P.; Marsh, J.V.; Spear, S.; Sobel, J.D.; Marty, M.J.; et al. Risk factors for second urinary tract infection among college women. Am. J. Epidemiol. 2000, 151, 1194–1205. [Google Scholar] [CrossRef]
- Ikähelmo, R.; Siitonen, A.; Heiskanen, T.; Kärkkäinen, U.; Kuosmanen, P.; Lipponen, P.; Mäkelä, P.H.; Helena, P.; Makela, P.H. Recurrence of urinary tract infection in a primary care setting: Analysis of a 1 year follow up of 179 women. Clin. Infect. Dis. 1996, 22, 91–99. [Google Scholar] [CrossRef]
- Schmiemann, G.; Kranz, J.; Mandraka, F.; Schubert, S.; Wagenlehner, F.; Gágyor, I. The diagnosis, treatment, and prevention of recurrent urinary tract infection. Dtsch. Ärzteblatt Int. 2024, 121, 373–382. [Google Scholar] [CrossRef]
- Ellis, A.K.; Verma, S. Quality of life in women with urinary tract infections: Is benign disease a misnomer? J. Am. Board Fam. Pract. 2000, 13, 392–397. [Google Scholar] [CrossRef] [PubMed]
- Naber, K.G.; Tirán-Saucedo, J.; Wagenlehner, F.M.E.; RECAP group. The psychological burden of recurrent urinary tract infections. Eur. Urol. Suppl. 2014, 13, 26–30. [Google Scholar] [CrossRef]
- Ennis, S.S.; Guo, H.; Raman, L.; Tambyah, P.A.; Chen, S.L.; Tiong, H.Y. Premenopausal women with recurrent urinary tract infections have lower quality of life. Int. J. Urol. 2018, 25, 684–689. [Google Scholar] [CrossRef] [PubMed]
- Chung, S.; Huang, C.; Lin, H.; Kao, L.; Nalliah, S.; Fong, J.H.; Thor, A.Y.; Lim, O. The use of chemotherapeutic agents as prophylaxis for recurrent urinary tract infection in healthy nonpregnant women: A network meta-analysis. Indian J. Urol. 2019, 35, 147–155. [Google Scholar] [CrossRef]
- Ahmed, H.; Davies, F.; Francis, N.; Farewell, D.; Butler, C.; Paranjothy, S. Long term antibiotics for prevention of recurrent urinary tract infection in older adults: Systematic review and meta-analysis of randomised trials. BMJ Open 2017, 7, e015233. [Google Scholar] [CrossRef]
- Price, J.R.; Guran, L.A.; Gregory, W.T.; McDonagh, M. S Nitrofurantoin vs other prophylactic agents in reducing recurrent urinary tract infections in adult women: A systematic review and meta-analysis. Am. J. Obstet. Gynecol. 2016, 215, 548–560. [Google Scholar] [CrossRef] [PubMed]
- European Society of Clinical Microbiology and Infectious Diseases (ESCMID). ESCMID Guidelines [Internet]. Available online: https://www.escmid.org/guidelines_publications/escmid_guidelines/ (accessed on 22 June 2025).
- Gupta, K.; Hooton, T.M.; Naber, K.G.; Wullt, B.; Colgan, R.; Miller, L.G.; Moran, G.J.; Nicolle, L.E.; Raz, R.; Schaeffer, A.J.; 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. Dis. 2011, 52, e103–e120. [Google Scholar] [CrossRef] [PubMed]
- National Institute for Health and Care Excellence (NICE). Urinary Tract Infection (UTI): Diagnosis and Management [Internet]. Available online: https://www.nice.org.uk/guidance/cg54 (accessed on 25 June 2025).
- Deutsche Gesellschaft für Urologie (DGU). Official Website [Internet]. Available online: https://www.dgu.de/ (accessed on 25 June 2025).
- Ari, M.M.; Dashtbin, S.; Ghasemi, F.; Shahroodian, S.; Kiani, P.; Bafandeh, E.; Darbandi, T.; Ghanavati, R.; Darbandi, A. Nitrofurantoin: Properties and potential in treatment of urinary tract infection: A narrative review. Front Cell Infect Microbiol. 2023, 13, 1148603. [Google Scholar] [CrossRef]
- Munoz Davila, M.J. Role of old antibiotics in the era of antibiotic resistance: Highlighted nitrofurantoin for the treatment of lower urinary tract infections. Antibiotics 2014, 3, 39–48. [Google Scholar] [CrossRef]
- Dijkmans, A.C.; Zacarías, N.V.O.; Burggraaf, J.; Mouton, J.W.; Wilms, E.B.; Van Nieuwkoop, C.; Touw, D.J.; Stevens, J.; Kamerling, I.M.C. Fosfomycin: Pharmacological, clinical and future perspectives. Antibiotics 2017, 6, 24. [Google Scholar] [CrossRef]
- Raz, R. Fosfomycin: An old–new antibiotic. Clin. Microbiol. Infect. 2012, 18, 4–7. [Google Scholar] [CrossRef]
- Zhanel, G.G.; Parkinson, K.; Higgins, S.; Denisuik, A.; Adam, H.; Pitout, J.; Noreddin, A.; Karlowsky, J.A. Pharmacodynamic activity of fosfomycin simulating urinary concentrations achieved after a single 3-g oral dose versus Escherichia coli using an in vitro model. Diagn. Microbiol. Infect. Dis. 2017, 88, 271–275. [Google Scholar] [CrossRef] [PubMed]
- Costantini, E.; Zucchi, A.; Salvini, E.; Cicalese, A.; Marzi, V.L.; Filocamo, M.T.; Bini, V.; Lazzeri, M. Prulifloxacin vs fosfomycin for prophylaxis in female patients with recurrent UTIs: A non-inferiority trial. Int. Urogynecology J. 2014, 25, 1173–1178. [Google Scholar] [CrossRef]
- Rudenko, N.; Dorofeyev, A. Prevention of recurrent lower urinary tract infections by long term administration of fosfomycin trometamol: A double blind, randomized, parallel group, placebo controlled study. Arzneimittelforschung 2005, 55, 420–427. [Google Scholar]
- Alghoraibi, H.; Asidan, A.; Aljawaied, R.; Almukhayzim, R.; Alsaydan, A.; Alamer, E.; Baharoon, W.; Masuadi, E.; Al Shukairi, A.; Layqah, L.; et al. Recurrent Urinary Tract Infection in Adult Patients, Risk Factors, and Efficacy of Low Dose Prophylactic Antibiotics Therapy. J. Epidemiol. Glob. Health 2023, 13, 200–211. [Google Scholar] [CrossRef]
- Goedken, A.M.; Foster, K.Y.; Ernst, E.J. Urinary Tract Infection Frequency and Prescription Prophylaxis in Females and Males with Recurrent Urinary Tract Infection. Pathogens 2023, 12, 170. [Google Scholar] [CrossRef] [PubMed]
- Jent, P.; Berger, J.; Kuhn, A.; Trautner, B.W.; Atkinson, A.; Marschall, J. Antibiotics for Preventing Recurrent Urinary Tract Infection: Systematic Review and Meta-analysis. Open Forum Infect. Dis. 2022, 9, ofac327. [Google Scholar] [CrossRef] [PubMed]
- Shafrir, A.; Oster, Y.; Shauly-Aharonov, M.; Strahilevitz, J. Real-Life Comparison of Fosfomycin to Nitrofurantoin for the Treatment of Uncomplicated Lower Urinary Tract Infection in Women. Biomedicines 2023, 11, 1019. [Google Scholar] [CrossRef] [PubMed]
- Taich, L.; Zhao, H.; Cordero, C.; Anger, J.T. New paradigms in the management of recurrent urinary tract infections. Curr. Opin. Urol. 2020, 30, 833–837. [Google Scholar] [CrossRef]
- Finley, C.R.; Falk, J.; Korownyk, C.S. Antibiotic prophylaxis for urinary tract infection. Can. Fam. Physician 2022, 68, 896. [Google Scholar] [CrossRef]
- Saatchi, A.; Yoo, J.W.; Marra, F. Outpatient prescribing and prophylactic antibiotic use for recurrent urinary tract infections in British Columbia, Canada. Can. Urol. Assoc. J. 2021, 15, 397–404. [Google Scholar] [CrossRef] [PubMed]
- Huttner, A.; Verhaegh, E.M.; Harbarth, S.; Muller, A.E.; Theuretzbacher, U.; Mouton, J.W. Nitrofurantoin revisited: A systematic review and meta-analysis of controlled trials. J. Antimicrob. Chemother. 2015, 70, 2456–2464. [Google Scholar] [CrossRef]
- Sharma, S.; Verma, P.K.; Rawat, V.; Varshney, U.; Singh, R.K. Fosfomycin versus Nitrofurantoin for the Treatment of Lower UTI in Outpatients. Lab. Physicians 2021, 13, 118–122. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Datta, R.; Juthani-Mehta, M. Nitrofurantoin vs Fosfomycin: Rendering a Verdict in a Trial of Acute Uncomplicated Cystitis. JAMA 2018, 319, 1771–1772. [Google Scholar] [CrossRef]
- Konwar, M.; Gogtay, N.J.; Ravi, R.; Thatte, U.M.; Bose, D. Evaluation of efficacy and safety of fosfomycin versus nitrofurantoin for the treatment of uncomplicated lower urinary tract infection (UTI) in women—A systematic review and meta-analysis. J. Chemother. 2022, 34, 139–148. [Google Scholar] [CrossRef]
- Koh, S.W.C.; Ng, T.S.M.; Loh, V.W.K.; Goh, J.C.; Low, S.H.; Tan, W.Z.; Wong, H.C.; Durai, P.; Sun, L.J.; Young, D.; et al. Antibiotic treatment failure of uncomplicated urinary tract infections in primary care. Antimicrob. Resist. Infect. Control. 2023, 12, 73. [Google Scholar] [CrossRef] [PubMed]
- Croke, L. Beers Criteria for inappropriate medication use in older patients: An update from the AGS. Am. Fam. Physician 2020, 101, 56–57. [Google Scholar] [PubMed]
- de los Angeles Resa, M.; Zubizarreta, J.R. Direct stable weight adjustment in non-experimental studies with multivalued treatments: Analysis of the effect of an earthquake on post-traumatic stress. J. R. Stat. Soc. Ser. A Stat. Soc. 2020, 183, 1387–1410. [Google Scholar] [CrossRef]
- Greifer, N. WeightIt: Weighting for Covariate Balance in Observational Studies. Version 1.5.0. 2025. Available online: https://ngreifer.github.io/WeightIt/ (accessed on 25 September 2025).
- Ho, D.; Imai, K.; King, G.; Stuart, E.A. MatchIt: Nonparametric preprocessing for parametric causal inference. J. Stat. Softw. 2011, 42, 1–28. [Google Scholar] [CrossRef]
- VanderWeele, T.J.; Ding, P. Sensitivity analysis in observational research: Introducing the E-value. Ann. Intern. Med. 2017, 167, 268–274. [Google Scholar] [CrossRef]
All | Continuous Only | Continuous + Non-atb | Continuous + Intermittent | |
---|---|---|---|---|
N | 630 | 476 | 97 | 57 |
Age (years) | 68 ± 9 (45–89) | 68 ± 9 (45–89) | 67 ± 10 (45–87) | 64 ± 10 (48–88) |
Urine incontinence | 220 (34.9) | 182 (38.2) | 22 (22.7) | 16 (28.1) |
Bladder diverticulosis | 9 (1.4) | 9 (1.9) | 0 | 0 |
Urine retention | 25 (4.0) | 21 (4.4) | 3 (3.1) | 1 (1.7) |
Self-catheterization | 7 (1.1) | 5 (1.1) | 1 (1.0) | 1 (1.7) |
Urogenital prolapse | 25 (4.0) | 20 (4.2) | 2 (2.1) | 3 (5.3) |
Diabetes mellitus | 84 (13.3) | 69 (14.5) | 12 (12.4) | 3 (5.3) |
Urolithiasis | 45 (7.1) | 34 (7.1) | 10 (10.3) | 1 (1.7) |
Hydronephrosis | 8 (1.3) | 7 (1.5) | 1 (1.0) | 0 |
Chronic kidney disease | 18 (2.9) | 13 (2.7) | 3 (3.1) | 2 (3.5) |
Bladder prosthesis | 2 (0.3) | 2 (0.4) | 0 | 0 |
Cystocele | 66 (10.5) | 56 (11.8) | 5 (5.2) | 5 (8.8) |
Rectocele | 13 (2.1) | 13 (2.7) | 0 | 0 |
Urogenital surgery | 4 (0.6) | 3 (0.6) | 1 (1.0) | 0 |
Total risk factors | 1 (0–4) | 1 (0–2) | 0 (0–2) | 0 (0–2) |
0 | 265 (42.1) | 181 (38.0) | 50 (51.6) | 34 (59.7) |
1 | 233 (37.0) | 183 (38.5) | 35 (36.1) | 15 (26.3) |
≥2 | 132 (20.9) | 112 (23.5) | 12 (12.4) | 8 (14.0) |
Prophylaxis (months) | 6 (0.25–36.0) | 6 (0.25–36.0) | 6 (0.5–18) | 6 (0.5–36) |
Total patient-months | 4011 | 3057.5 | 569.5 | 384 |
Relapse | 222 (35.2) | 166 (34.9) | 41 (42.3) | 15 (26.3) |
Relapse rate/100 p-m | 5.54 (4.88–6.28) | 5.43 (4.68–6.30) | 7.20 (5.58–9.28) | 3.91 (2.34–6.52) |
Agents in relapse | ||||
E. coli | 132/222 (60.0) | 97/166 (58.4) | 26/41 (63.4) | 9/15 (60.0) |
K. pneumoniae | 27/222 (12.3) | 20/166 (12.0) | 4/41 (9.8) | 3/15 (13.3) |
E. faecalis | 15/222 (6.8) | 10/166 (6.0) | 3/41 (7.3) | 2/15 (13.3) |
P. mirabilis | 12/222 (5.5) | 10/166 (6.0) | 1/41 (2.4) | 1/15 (6.7) |
E. coli ESBL | 8/222 (3.6) | 8/166 (4.8) | 0/41 | 0/15 |
P. aeruginosa | 5/222 (2.3) | 4/166 (2.4) | 1/41 (2.4) | 0/15 |
E. cloacae | 3/222 (1.4) | 2/166 (1.2) | 1/41 (2.4) | 0/15 |
K. aerogenes | 3/222 (1.4) | 3/166 (1.8) | 0/41 | 0/15 |
K. pneumoniae ESBL | 3/222 (1.4) | 2/166 (1.2) | 1/41 (2.4) | 0/15 |
C. freundii | 2/222 (0.9) | 2/166 (1.2) | 0/41 | 0/15 |
C. koseri | 2/222 (0.9) | 1/166 (0.6) | 1/41 (2.4) | 0/15 |
K. oxytoca | 2/222 (0.9) | 1/166 (0.6) | 1/41 (2.4) | 0/15 |
M. morganii | 2/222 (0.9) | 2/166 (1.2) | 0/41 | 0/15 |
Acinetobacter spp. | 1/222 (0.45) | 1/166 (0.6) | 0/41 | 0/15 |
Citrobacter spp. | 1/222 (0.45) | 1/166 (0.6) | 1 (2.4) | 0/15 |
K. oxytoca ESBL | 1/222 (0.45) | 1/166 (0.6) | 0/41 | 0/15 |
S. marcenscens | 1/222 (0.45) | 0/166 | 1/41 (2.4) | 0/15 |
Unknown | 0/222 | 2/166 (1.2) | 0/41 | 0/15 |
All | Continuous Only | Continuous + Non-atb | Continuous + Intermittent | |
---|---|---|---|---|
N | 238 | 104 | 21 | 113 |
Age (years) | 34 ± 8 (18–51) | 36 ± 8 (18–51) | 38 ± 7 (24–49) | 32 ± 8 (18–47) |
Urine incontinence | 7 (2.9) | 2 (1.9) | 3 (14.3) | 2 (1.8) |
Bladder diverticulosis | 0 | 0 | 0 | 0 |
Urine retention | 7 (2.9) | 5 (4.8) | 1 (4.8) | 1 (0.9) |
Self-catheterization | 3 (1.3) | 3 (2.9) | 0 | 0 |
Urogenital prolapse | 1 (0.4) | 1 (1.0) | 0 | 0 |
Diabetes mellitus | 1 (0.4) | 1 (1.0) | 0 | 0 |
Urolithiasis | 5 (2.1) | 4 (3.8) | 0 | 1 (0.9) |
Hydronephrosis | 1 (0.4) | 1 | 0 | 0 |
Chronic kidney disease | 0 | 0 | 0 | 0 |
Bladder prosthesis | 1 (0.4) | 1 (1.0) | 0 | 0 |
Cystocele | 2 (0.8) | 2 (1.9) | 0 | 0 |
Rectocele | 0 | 0 | 0 | 0 |
Urogenital surgery | 0 | 0 | 0 | 0 |
Pregnancy | 10 (4.2) | 10 (9.6) | 0 | 0 |
Total risk factors | 0 (0–2) | 0 (0–2) | 0 (0–1) | 0 (0–1) |
0 | 208 (87.4) | 82 (78.9) | 17 (81.0) | 109 (96.5) |
1 | 23 (9.7) | 15 (14.4) | 4 (19.0) | 4 (3.5) |
≥2 | 7 (2.9) | 7 (6.7) | 0 | 0 |
Prophylaxis (months) | 6 (0.5–36) | 5 (0.5–24) | 6 (2–36) | 6 (1–18) |
Total patient-months | 1337 | 555 | 180 | 602 |
Relapse | 42 (17.6) | 22 (21.1) | 6 (28.6) | 14 (12.4) |
Relapse rate/100 p-m | 3.14 (2.34–4.21) | 3.96 (2.59–6.07) | 3.33 (1.74–6.38) | 2.33 (1.40–3.871) |
Agents in relapse | ||||
E. coli | 26/42 (61.9) | 10/22 (45.5) | 5/6 | 11/14 (78.6) |
K. pneumoniae | 3/42 (7.1) | 3/22 (13.6) | 0/6 | 0/14 |
E. faecalis | 4/42 (9.5) | 3/22 (13.6) | 1/6 | 0/14 |
P. mirabilis | 2/42 (4.8) | 1/22 (4.6) | 0/6 | 1/14 (7.1) |
P. aeruginosa | 1/42 (2.4) | 1/22 (4.6) | 0/6 | 0/14 |
C. koseri | 1/42 (2.4) | 0/22 | 0/6 | 1/14 (7.1) |
K. oxytoca | 1/42 (2.4) | 0/22 | 0/6 | 1/14 (7.1) |
BHS-B | 2/42 (4.8) | 2/22 (9.1) | 0/6 | 0/14 |
E. faecium | 1/42 (2.4) | 1/22 (4.6) | 0/6 | 0/14 |
S. saprophyticus | 1/42 (2.4) | 1/22 (4.6) | 0/6 | 0/14 |
Postmenopausal Women | Premenopausal Women | |||
---|---|---|---|---|
Nitrofurantoin | Fosfomycin or Other | Nitrofurantoin | Fosfomycin or Other | |
N | 425 | 111 (91 + 20) | 185 | 26 (16 + 10) |
Age (years) | 67 ± 9 (45–88) | 71 ± 10 (49–89) | 34 ± 8 (18–51) | 36 ± 7 (23–48) |
Causative index agents | ||||
E. coli | 379 (89.2) | 99 (89.2) | 168 (90.8) | 24 (92.3) |
E. faecalis | 25 (5.9) | 9 (8.1) | 14 (7.6) | 2 (7.7) |
E. coli ESBL | 21 (4.9) | 3 (2.7) | 3 (1.6) | 0 |
Total risk factors | 1 (0–4) | 1 (0–4) | 0 (0–2) | 0 (0–3) |
0 | 193 (45.4) | 39 (35.1) | 166 (89.7) | 18 (69.2) |
1 | 152 (35.8) | 46 (41.4) | 15 (8.2) | 6 (23.1) |
≥2 | 80 (18.8) | 26 (23.4) | 4 (2.2) | 2 (7.7) |
Only continuous therapy | 384 (90.3) | 100 (90.1) | 86 (46.5) | 20 (76.9) |
Continuous + intermittent | 41 (9.7) | 11 (9.9) | 99 (53.5) | 6 (23.1) |
Additional non-antibiotic | 81 8 (19.1) | 27 (24.3) | 80 (43.2) | 5 (19.1) |
Prophylaxis (months) | 6 (0.5–36.0) | 4 (1.0–19.0) | 6 (0.5–36.0) | 4 (1.0–12.0) |
Total patient-months | 3010.25 | 561.50 | 1100.5 | 113 |
Relapse | 131 (30.8) | 56 (51.4) | 29 (15.7) | 6 (23.1) |
Relapse rate/100 p-m | 4.35 (3.69–5.14) | 10.2 (8.12–12.7) | 2.36 (1.86–3.73) | 5.31 (2.39–11.8) |
Agents in relapse | ||||
E. coli | 85/131 (65.4) | 28/56(50.0) | 17/29 (58.6) | 4/6 |
K. pneumoniae | 13/131 (10.0) | 10/56 (17.9) | 2/29 (6.9) | 0/6 |
P. mirabilis | 9/131 (6.9) | 1/56 (1.8) | 2/29 (6.9) | 0/6 |
E. faecalis | 8/131 (6.2) | 6/56 (10.7) | 2/29 (6.9) | 1/6 |
P. aeruginosa | 3/131 (2.3) | 0/56 | 1/29 (3.4) | 0/6 |
K. aerogenes | 3/131 (2.3) | 0/56 | 0/29 | 0/6 |
E. coli ESBL | 2/131 (1.5) | 5/56 (8.9) | 0/29 | 0/6 |
K. oxytoca | 0/131 | 2/56 (3.6) | 1/29 (3.4) | 0/6 |
K. oxytoca ESBL | 0/131 | 1/56 (1.8) | 0/29 | 0/6 |
K. pneumoniae ESBL | 1/131 (0.8) | 1/56 (1.8) | 0/29 | 0/6 |
E. cloacae | 1/131 (0.8) | 1/56 (1.8) | 0/29 | 0/6 |
Acinetobacter spp. | 1/131 (0.8) | 0/56 | 0/29 | 0/6 |
Citrobacter spp. | 0/131 | 1/56 (1.8) | 0/29 | 0/6 |
C. freundii | 1/131 (0.8) | 0/56 | 0/29 | 0/6 |
C. koseri | 1/131 (0.8) | 0/56 | 0/29 | 1/6 |
M. morganii | 1/131 (0.8) | 0/56 | 0/29 | 0/6 |
S. marcescens | 1/131 (0.8) | 0/56 | 0/29 | 0/6 |
BHS-B | 0/131 | 0/56 | 2/29 (6.9) | 0/6 |
E. faecium | 0/131 | 0/56 | 1/29 (3.4) | 0/6 |
S. saprophyticus | 0/131 | 0/56 | 1/29 (3.4) | 0/6 |
Postmenopausal Women 1 | Premenopausal Women 2 | |||||
---|---|---|---|---|---|---|
Nitrofurantoin | Fosfomycin or Other | d | Nitrofurantoin | Fosfomycin or Other | d | |
N | 425 | 111 | --- | 169 matched | 26 matched | --- |
Used for weighting/matching | ||||||
Age (years) | 67 ± 9 | 68 ± 10 | 0.075 | 33 ± 8 | 36 ± 9 | --- |
Causative index agents | ||||||
E. coli | 89.2 | 89.2 | 0.000 | 94.9 | 94.9 | 0.000 |
E. faecalis | 5.2 | 5.2 | 0.000 | 5.1 | 5.1 | 0.000 |
E. coli ESBL | 5.6 | 5.6 | 0.000 | 0.0 | 0.0 | 0.000 |
Number of risk factors | ||||||
0 | 43.2 | 43.2 | 0.000 | 91.3 | 91.3 | 0.000 |
1 | 36.9 | 36.9 | 0.000 | 5.6 | 5.6 | 0.000 |
≥2 | 19.8 | 19.8 | 0.000 | 3.1 | 3.1 | 0.000 |
Only continuous therapy | 90.3 | 90.3 | 0.000 | 49.7 | 49.7 | 0.000 |
Continuous + intermittent | 9.7 | 9.7 | 0.000 | 50.3 | 50.3 | 0.000 |
Additional non-antibiotic | 20.1 | 20.1 | 0.000 | 40.0 | 40.0 | 0.000 |
Outcomes | ||||||
Relapse rate/100 p-m | 4.59 (2.93–7.20) | 9.70 (5.91–15.2) | --- | 2.54 (1.71–3.78) | 7.25 (1.81–29.1) | --- |
Rate ratio (nitrofurantoin vs. fosfomycin/other) | 0.47 (0.34–0.67) | --- | 0.35 (0.08–1.46) | --- |
All Women | Postmenopausal | Premenopausal | |
---|---|---|---|
N | 868 | 630 | 238 |
Gastrointestinal adverse events | 26 (3.0) | 6 (0.9) | 20 (8.4) |
General (e.g., “malaise, fatigue, feeling unwell”) | 16 (1.8) | 4 (0.6) | 12 (5.0) |
Hepatological (liver enzyme increases) | 14 (1.6) | 2 (0.3) | 12 (5.0) |
Hematological (e.g., blood cell counts alterations) | 12 (1.4) | 5 (0.8) | 7 (2.8) |
Hypersensitivity reactions (e.g., skin rashes) | 10 (1.2) | 4 (0.6) | 6 (2.5) |
Neurological (e.g., dizziness, headache) | 7 (0.8) | 2 (0.3) | 5 (2.1) |
Pulmonary (e.g., cough) | 5 (0.6) | 3 (0.5) | 3 (1.3) |
C. difficile diarrhea | 2 (0.2) | 2 (0.3) | 0 |
Vulvovaginal candidiasis | 2 (0.2) | 0 | 2 (0.8) |
Other | 4 (0.5) | 0 | 4 (1.7) |
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Skuhala, T.; Rimac, M.; Trkulja, V.; Zidovec-Lepej, S. Antimicrobial Prophylaxis for Recurrent Urinary Tract Infections in Premenopausal and Postmenopausal Women: A Retrospective Observational Study from an Outpatient Clinic in a Tertiary University Hospital. Antibiotics 2025, 14, 998. https://doi.org/10.3390/antibiotics14100998
Skuhala T, Rimac M, Trkulja V, Zidovec-Lepej S. Antimicrobial Prophylaxis for Recurrent Urinary Tract Infections in Premenopausal and Postmenopausal Women: A Retrospective Observational Study from an Outpatient Clinic in a Tertiary University Hospital. Antibiotics. 2025; 14(10):998. https://doi.org/10.3390/antibiotics14100998
Chicago/Turabian StyleSkuhala, Tomislava, Marin Rimac, Vladimir Trkulja, and Snjezana Zidovec-Lepej. 2025. "Antimicrobial Prophylaxis for Recurrent Urinary Tract Infections in Premenopausal and Postmenopausal Women: A Retrospective Observational Study from an Outpatient Clinic in a Tertiary University Hospital" Antibiotics 14, no. 10: 998. https://doi.org/10.3390/antibiotics14100998
APA StyleSkuhala, T., Rimac, M., Trkulja, V., & Zidovec-Lepej, S. (2025). Antimicrobial Prophylaxis for Recurrent Urinary Tract Infections in Premenopausal and Postmenopausal Women: A Retrospective Observational Study from an Outpatient Clinic in a Tertiary University Hospital. Antibiotics, 14(10), 998. https://doi.org/10.3390/antibiotics14100998