Appendix 1
Systematic review inclusion/exclusion criteria
Population: women aged >18 years with signs and symptoms of uncomplicated UTI
Interventions: fosfomycin, trimethoprim, nitrofurantoin, pivmecillinam (those recommended for treatment of uncomplicated UTI by Public Health England).
Outcomes: UTI resolution, persistence, pyelonephritis development and health-related quality of life (HRQoL)
Exclusion criteria: no clinical response measure, study not in English, studys specifically of older people patients who were pregnant or had a catheter
Search strategy
Randomised controlled trial (RCT) and systematic review study search strategies
Database: Ovid MEDLINE® In-Process & Other Non-Indexed Citations, Ovid MEDLINE® Daily, Ovid MEDLINE®, and Ovid OLDMEDLINE® <1946 to Present>
Search strategy:
   Population terms (1–6)

  1. exp Urinary Tract Infections/

  2. urinary tract infection$.ab,ti.

  3. uti.ab,ti.

  4. acute cystitis.ab,ti.

  5. Cystitis/

  6. 1 or 2 or 3 or 4 or 5

    Intervention terms (7–14)

  7. Fosfomycin/

  8. fosfomycin.ab,ti.

  9. phosphonomycin.ab,ti.

  10. phosphomycin.ab,ti.

  11. monuril.ab,ti.

  12. monurol.ab,ti.

  13. 2N81MY12TE.rn.

  14. 7 or 8 or 9 or 10 or 11 or 12 or 13

    Population and intervention terms combined (15)

  15. 6 and 14

    Comparator terms (16–47)

  16. Nitrofurantoin/

  17. nitrofurantoin.ab,ti.

  18. furadoine.ab,ti.

  19. furantoin.ab,ti.

  20. macrodantin.ab,ti.

  21. furadonine.ab,ti.

  22. furadantine.ab,ti.

  23. furadantin.ab,ti.

  24. macrobid.ab,ti.

  25. 927AH8112L.rn.

  26. Trimethoprim/

  27. trimethoprim.ab,ti.

  28. proloprim.ab,ti.

  29. trimpex.ab,ti.

  30. monotrim.ab,ti.

  31. triprim.ab,ti.

  32. tmi.ab,ti.

  33. tmp.ab,ti.

  34. AN164J8Y0X.rn.

  35. Amdinocillin Pivoxil/

  36. pivmecillinam.ab,ti.

  37. amdinocillin.ab,ti.

  38. selexid.ab,ti.

  39. pivamdinocillin.ab,ti.

  40. fl 1039.ab,ti.

  41. fl-1039.ab,ti.

  42. fl1039.ab,ti.

  43. mecillinam.ab,ti.

  44. penomax.ab,ti.

  45. coactabs.ab,ti.

  46. 1WAM1OQ30B.rn.

  47. or/16-46

    Population and comparator terms combined (48)

  48. 6 and 47

    Population and intervention OR population and comparator (49)

  49. 15 or 48

    Excluded comparator (50–54)

  50. Trimethoprim-Sulfamethoxazole Combination/

  51. Sulfamethoxazole.ab,ti.

  52. sulphamethoxazole.ab,ti.

  53. 50 or 51 or 52

  54. 49 not 53

    Search filter to identify RCTs (92–106)

  55. randomized controlled trial.pt.

  56. controlled clinical trial.pt.

  57. randomized controlled trials/

  58. random allocation/

  59. double blind method/

  60. single blind method/

  61. clinical trial.pt.

  62. exp Clinical Trial/

  63. (clin$ adj25 trial$).ti,ab.

  64. ((singl$ or doubl$ or trebl$ or tripl$) adj25 (blind$ or mask$)).ti,ab.

  65. placebos/

  66. placebos.ti,ab.

  67. random.ti,ab.

  68. research design/

  69. or/92-105

    (Population and Intervention OR population and comparator) AND RCT filter (107)

  70. 54 and 106

Search results
The searches identified 978 citations, of which 958 were excluded by title or abstract. Twenty full papers were reviewed. Seven were excluded due to having no clinical outcome measure. Of the remaining 13 RCTs, 11 formed a connected network of evidence and were used in the network meta analysis (NMA). A total of 3983 participants were randomised across the trials, with the mean age across the trials ranging from 21 to 48 years.
Evidence synthesis
Evidence on clinical cure rates for the different regimens was synthesised by NMA using a random (treatment) effects model, with a logit link function to allow for heterogeneity in treatment effects between studies. All analyses were implemented in WinBUGS. 35 Results of the NMA are reported in terms of the odds ratios and 95% credible intervals relative to fosfomycin 3 g, which was used as the reference intervention. Absolute estimates of clinical cure rates were estimated for each intervention by projecting the estimates of treatment effect (log OR) from the NMA onto the fosfomycin 3 g clinical cure rates.