{"id":28957,"date":"2025-09-26T04:02:00","date_gmt":"2025-09-25T20:02:00","guid":{"rendered":"https:\/\/csccm.org.cn\/?p=28957"},"modified":"2025-09-26T05:41:16","modified_gmt":"2025-09-25T21:41:16","slug":"lancet-infect-dis%e5%8f%91%e8%a1%a8%e8%ae%ba%e6%96%87%ef%bc%9a%e6%b3%8c%e5%b0%bf%e7%b3%bb%e6%84%9f%e6%9f%93%e5%8f%91%e7%83%ad%e6%82%a3%e5%84%bf%e4%b8%aa%e4%bd%93%e5%8c%96%e4%b8%8e%e6%a0%87%e5%87%861","status":"publish","type":"post","link":"https:\/\/csccm.org.cn\/?p=28957","title":{"rendered":"[Lancet Infect Dis\u53d1\u8868\u8bba\u6587]\uff1a\u6ccc\u5c3f\u7cfb\u611f\u67d3\u53d1\u70ed\u60a3\u513f\u4e2a\u4f53\u5316\u4e0e\u6807\u51c610\u5929\u6297\u751f\u7d20\u6cbb\u7597\u7684\u6548\u679c\u4e0e\u5b89\u5168\u6027"},"content":{"rendered":"\n

Efficacy and safety of individualised versus standard 10-day antibiotic treatment in children with febrile urinary tract infection (INDI-UTI): a pragmatic, open-label, multicentre, randomised, controlled, non-inferiority trial in Denmark<\/h1>\n\n\n\n

Naqash Javaid\u00a0Sethi,\u00a0Emma Louise Malchau\u00a0Carlsen,\u00a0Abdullah\u00a0Tabassum, et al<\/h3>\n\n\n\n

Lancet Infect Dis 2025; 25: 925-935<\/h3>\n\n\n\n

Summary<\/h2>\n\n\n\n

Background<\/h3>\n\n\n\n

The optimal antibiotic duration for febrile urinary tract infection (UTI) in children remains uncertain. We aimed to assess whether individualised treatment was non-inferior to standard 10-day treatment in terms of recurrent UTI and superior in reducing overall antibiotic exposure.<\/p>\n\n\n\n

Methods<\/h3>\n\n\n\n

INDI-UTI was a pragmatic, open-label, multicentre, randomised, controlled, non-inferiority trial conducted at eight Danish hospitals. Children aged 3 months to 12 years who were febrile (\u226538\u00b0C), within 24 h of treatment start, and with significant growth of uropathogenic bacteria were randomly assigned (1:1) using a web-based module with randomly permuted blocks to individualised or standard 10-day treatment. Main exclusion criteria included known urinary tract abnormalities, complicated medical history, bacteraemia, and elevated serum creatinine. The individualised group stopped treatment 3 days after adequate clinical improvement (ie, absence of fever, flank pain, and dysuria), with a minimum treatment duration of 4 days. The primary outcomes were recurrent UTI within 28 days after treatment cessation (non-inferiority margin 7\u00b75 percentage points) and total antibiotic days within 28 days of treatment initiation (superiority assessment). No sample size calculation was performed for the assessment of total antibiotic days. Safety was assessed in all included patients. Main analyses were done in the intention-to-treat population. This study is registered with ClinicalTrials.gov<\/a>, NCT05301023.<\/p>\n\n\n\n

Findings<\/h3>\n\n\n\n

Between March 28, 2022, and March 3, 2024, 694 patients were assessed for eligibility and 408 patients were randomly assigned to individualised (n=205; median antibiotic duration 5\u00b73 days [IQR 4\u00b78 to 6\u00b75]) or standard 10-day treatment (n=203; 10\u00b70 days [10\u00b70 to 10\u00b70]). Median age was 1\u00b75 years (IQR 0\u00b77 to 5\u00b74), and there were 326 (80%) female and 82 (20%) male participants. Recurrent UTI within 28 days occurred in 23 (11%) of 205 patients in the individualised group and 12 (6%) of 203 patients in the standard 10-day group (difference 5\u00b73 percentage points, one-sided 97\u00b75% CI \u2013\u221e to 11\u00b71, pnon_inferiority<\/em><\/sub>=0\u00b724). Total antibiotic days within 28 days were 6\u00b70 (IQR 5\u00b73 to 7\u00b75) in the individualised group and 10\u00b70 (10\u00b70 to 10\u00b70) in the standard 10-day group (median difference \u20134\u00b70 days [97\u00b75% CI \u20134\u00b75 to \u20133\u00b77], p<0\u00b70001). The incidence rate of antibiotic-related adverse events within 28 days was 6\u00b78 per 100 patient-days in the individualised group and 11\u00b71 per 100 patient-days in the standard 10-day group (rate ratio 0\u00b761 [95% CI 0\u00b747 to 0\u00b780], p=0\u00b70003). Serious adverse events occurred in 17 (8%) of 205 patients in the individualised group and 15 (7%) of 203 patients in the standard 10-day group (difference 0\u00b79 percentage points [95% CI \u20134\u00b76 to 6\u00b75], p=0\u00b779).<\/p>\n\n\n\n

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Table 1. Baseline characteristics of the intention-to-treat population<\/p>\n\n\n\n

<\/td><\/td>Individualised group (n=205)<\/strong><\/th>Standard 10-day group (n=203)<\/strong><\/th><\/tr><\/thead>
Age, years<\/td>1\u00b76 (0\u00b76\u20135\u00b74)<\/td>1\u00b74 (0\u00b77\u20135\u00b75)<\/td><\/tr>
Age 3\u201323 months<\/td>112 (55%)<\/td>117 (58%)<\/td><\/tr>
Age 2\u20135 years<\/td>54 (26%)<\/td>37 (18%)<\/td><\/tr>
Age 6\u201312 years<\/td>39 (19%)<\/td>49 (24%)<\/td><\/tr>
Female sex<\/td>166 (81%)<\/td>160 (79%)<\/td><\/tr>
Male sex<\/td>39 (19%)<\/td>43 (21%)<\/td><\/tr>
Previous UTI<\/td>31 (15%)<\/td>28 (14%)<\/td><\/tr>
Previous febrile UTI<\/td>22 (11%)<\/td>18 (9%)<\/td><\/tr>
Febrile UTI in the past year<\/td>15 (7%)<\/td>8 (4%)<\/td><\/tr>
Constipation<\/td>25 (12%)<\/td>26 (13%)<\/td><\/tr>
Temperature, \u00b0C<\/td>39\u00b75 (39\u00b70\u201340\u00b70)<\/td>39\u00b75 (38\u00b79\u201340\u00b70)<\/td><\/tr>
Fever duration before treatment initiation, h<\/td>72 (30\u2013118)<\/td>60 (24\u2013104)<\/td><\/tr>
Clinical symptoms<\/td><\/tr>
<\/td>Any clinical symptom<\/td>183 (89%)<\/td>177 (87%)<\/td><\/tr>
<\/td>Reduced food intake<\/td>150 (73%)<\/td>145 (71%)<\/td><\/tr>
<\/td>Stomach pain<\/td>77 (38%)<\/td>65 (32%)<\/td><\/tr>
<\/td>Nausea<\/td>74 (36%)<\/td>70 (34%)<\/td><\/tr>
<\/td>Vomiting<\/td>70 (34%)<\/td>65 (32%)<\/td><\/tr>
<\/td>Dysuria<\/td>58 (28%)<\/td>58 (29%)<\/td><\/tr>
<\/td>Flank pain<\/td>36 (18%)<\/td>26 (13%)<\/td><\/tr>
<\/td>Pollakisuria<\/td>19 (9%)<\/td>21 (10%)<\/td><\/tr>
<\/td>Increased regurgitation<\/td>9 (4%)<\/td>10 (5%)<\/td><\/tr>
<\/td>Haematuria<\/td>3 (1%)<\/td>11 (5%)<\/td><\/tr>
Urine collection method<\/td><\/tr>
<\/td>Midstream collection<\/td>148 (72%)<\/td>138 (69%)<\/td><\/tr>
<\/td>Catheterisation<\/td>49 (24%)<\/td>56 (28%)<\/td><\/tr>
<\/td>Bladder puncture<\/td>8 (4%)<\/td>9 (4%)<\/td><\/tr>
Urine dipstick result<\/td><\/tr>
<\/td>Leucocyturia<\/td>188 (92%)<\/td>186 (92%)<\/td><\/tr>
<\/td>Nitrite<\/td>85 (42%)<\/td>76 (37%)<\/td><\/tr>
<\/td>Leucocyturia or nitrite<\/td>196 (96%)<\/td>191 (94%)<\/td><\/tr>
C-reactive protein*<\/a><\/td>73 (25\u2013130)<\/td>73 (30\u2013120)<\/td><\/tr>
Uropathogenic bacteria<\/td><\/tr>
<\/td>Escherichia coli<\/em><\/td>192 (94%)<\/td>183 (90%)<\/td><\/tr>
<\/td>Non-Escherichia coli<\/em>\u2020<\/sup><\/a><\/td>13 (6%)<\/td>20 (10%)<\/td><\/tr>
Restrictive microbiological criteria\u2021<\/sup><\/a><\/td>192 (94%)<\/td>180 (89%)<\/td><\/tr>
Abnormal urine dipstick and restrictive microbiological criteria<\/td>187 (91%)<\/td>172 (85%)<\/td><\/tr><\/tbody><\/table>
Data are median (IQR) or n (%). CFU=colony-forming unit. UTI=urinary tract infection.*
Data on C-reactive protein was missing for nine patients in the individualised group and eight in the standard 10-day group.\u2020
Non-Escherichia coli<\/em>\u00a0pathogens in the individualised group included\u00a0Klebsiella pneumoniae<\/em>(n=2),\u00a0Klebsiella oxytoca<\/em>\u00a0(n=2),\u00a0Enterococcus faecalis<\/em>\u00a0(n=2),\u00a0Staphylococcus saprophyticus<\/em>\u00a0(n=2),\u00a0Aerococcus urinae<\/em>\u00a0(n=1),\u00a0Proteus mirabilis<\/em>\u00a0(n=1),\u00a0Staphylococcus aureus<\/em>\u00a0(n=1),\u00a0Proteus vulgaris<\/em>(n=1), and\u00a0Raoultella planticola<\/em>\u00a0(n=1). In the standard 10-day group, non-Escherichia coli<\/em>pathogens included\u00a0Klebsiella pneumoniae<\/em>\u00a0(n=7),\u00a0Klebsiella oxytoc a<\/em>\u00a0(n=3),\u00a0Aerococcus urinae<\/em>(n=3),\u00a0Enterococcus faecalis<\/em>\u00a0(n=1),\u00a0Staphylococcus saprophyticus<\/em>\u00a0(n=1),\u00a0Proteus mirabilis<\/em>\u00a0(n=1),\u00a0Staphylococcus aureus<\/em>\u00a0(n=1),\u00a0Citrobacter koseri<\/em>\u00a0(n=1),\u00a0Pseudomonas aureginosa<\/em>\u00a0(n=1), and\u00a0Streptococcus agalactiae<\/em>\u00a0(n=1).\u2021
Excluding patients with 103<\/sup>\u00a0CFU per mL using catheterisation and 104<\/sup>\u00a0CFU per mL in two cultures using midstream collection.<\/figcaption><\/figure>\n\n\n\n

Table 2. Characteristics of the baseline antibiotic treatment in the intention-to-treat population<\/p>\n\n\n\n

<\/td><\/td>Individualised group (n=205)<\/strong><\/th>Standard 10-day group (n=203)<\/strong><\/th><\/tr><\/thead>
Amoxicillin\u2013clavulanic acid1<\/sup><\/a><\/td>141 (69%)<\/td>140 (69%)<\/td><\/tr>
<\/td>Empirical treatment<\/td>132\/141 (94%)<\/td>135\/140 (96%)<\/td><\/tr>
<\/td>Resistance<\/td>9\/132 (7%)<\/td>8\/135 (6%)<\/td><\/tr>
Mecillinam1<\/sup><\/a><\/td>28 (14%)<\/td>34 (17%)<\/td><\/tr>
<\/td>Empirical treatment<\/td>27\/28 (96%)<\/td>30\/34 (88%)<\/td><\/tr>
<\/td>Resistance<\/td>1\/27 (4%)<\/td>2\/30 (7%)<\/td><\/tr>
Gentamicin and ampicillin*<\/a><\/td>22 (11%)<\/td>17 (8%)<\/td><\/tr>
<\/td>Empirical treatment<\/td>22\/22 (100%)<\/td>17\/17 (100%)<\/td><\/tr>
<\/td>Resistance<\/td>0<\/td>0<\/td><\/tr>
Amoxicillin1<\/sup><\/a><\/td>12 (6%)<\/td>9 (4%)<\/td><\/tr>
<\/td>Empirical treatment<\/td>6\/12 (50%)<\/td>7\/9 (78%)<\/td><\/tr>
<\/td>Resistance<\/td>3\/6 (50%)<\/td>3\/7 (43%)<\/td><\/tr>
Other antibiotics\u2020<\/sup><\/a><\/td>2 (1%)<\/td>3 (1%)<\/td><\/tr>
<\/td>Empirical treatment<\/td>2\/2 (100%)<\/td>1\/3 (33%)<\/td><\/tr>
<\/td>Resistance<\/td>1\/2 (50%)<\/td>0<\/td><\/tr><\/tbody><\/table>
Data are n (%) or n\/N (%). Amoxicillin\u2013clavulanic acid (oral): 50 mg amoxicillin plus 12\u00b75 mg clavulanic acid per kg per day in three doses; mecillinam (oral): 20\u201340 mg per kg per day in three doses; gentamicin and ampicillin (intravenous): gentamicin 5 mg per kg once daily and ampicillin 100 mg per kg per day in three doses; and amoxicillin (oral): 50 mg per kg per day in three doses.*
39 patients received intravenous antibiotics empirically with combined gentamicin and ampicillin due to the following reasons: unstable appearance at treatment initiation (n=14), stable appearance but markedly increased C-reactive protein (median C-reactive protein 195 [IQR 123\u2013257]) at treatment initiation (n=10), not tolerating oral antibiotics (n=6), no specific reason (n=5), and elevated serum creatinine at treatment initiation (n=4).\u2020
In the individualised group, one patient was treated with oral trimethoprim (8 mg per kg per day in two doses) and one with oral sulfamethizol (50 mg per kg per day in three doses); in the standard 10-day group, one patient was treated with oral trimethoprim, one with oral dicloxacillin (50 mg per kg per day in three doses), and one, who was not empirically treated, with intravenous cefuroxime (60 mg per kg per day in three doses) due to the growth of a multiresistant pathogen with no suitable oral treatment option.<\/figcaption><\/figure>\n\n\n\n

Table 3. Outcome results for the intention-to-treat population<\/p>\n\n\n\n

<\/td>Individualised group (n=205)<\/strong><\/th>Standard 10-day group (n=203)<\/strong><\/th>Group difference<\/strong><\/th>p<\/strong>non-inferiority<\/sub><\/th>p<\/strong>superiority<\/sub><\/th><\/tr><\/thead>
Primary outcomes<\/strong><\/td><\/tr>
Recurrent UTI within 28 days<\/td>23 (11%)<\/td>12 (6%)<\/td>5\u00b73 (\u2212\u221e to 11\u00b71)*<\/a><\/td>0\u00b724<\/td>NA<\/td><\/tr>
Antibiotic days within 28 days<\/td>6\u00b70 (5\u00b73-7\u00b75)<\/td>10\u00b70 (10\u00b70\u201310\u00b70)<\/td>\u22124\u00b70 (\u22124\u00b75 to \u22123\u00b77)\u2020<\/sup><\/a><\/td>NA<\/td><0\u00b70001<\/td><\/tr>
Secondary outcomes<\/strong><\/td><\/tr>
Recurrent UTI within 100 days<\/td>33 (16%)<\/td>29 (14%)<\/td>1\u00b78 (\u2212\u221e to 9\u00b70)*<\/a><\/td>0\u00b7012<\/td>NA<\/td><\/tr>
Absence incidence rate within 28 days\u2021<\/sup><\/a><\/td>348\/1720 (20\u00b72)<\/td>442\/1858 (23\u00b78)<\/td>0\u00b784 (0\u00b766 to 1\u00b708)\u00a7<\/sup><\/a><\/td>NA<\/td>0\u00b718<\/td><\/tr>
Exploratory outcomes<\/strong><\/td><\/tr>
Hospital contacts during treatment for the baseline infection<\/td>76 (37%)<\/td>31 (15%)<\/td>21\u00b78 (13\u00b70 to 30\u00b72)\u00b6<\/sup><\/a><\/td>NA<\/td><0\u00b70001<\/td><\/tr>
Hospital contacts for UTI symptoms within 28 days<\/td>50 (24%)<\/td>28 (14%)<\/td>10\u00b76 (2\u00b73 to 18\u00b73)\u00b6<\/sup><\/a><\/td>NA<\/td>0\u00b70066<\/td><\/tr>
Resistant recurrent infection within 100 days\u2016<\/sup><\/a><\/td>3 (2%)<\/td>5 (3%)<\/td>\u22121\u00b70 (\u22124\u00b74 to 2\u00b71)\u00b6<\/sup><\/a><\/td>NA<\/td>0\u00b751<\/td><\/tr><\/tbody><\/table>
Data are n (%), median (IQR), or event days per patient-days at risk (incidence rate per 100 patient-days at risk), unless otherwise specified. The statistical hypotheses for recurrent UTI within 28 and 100 days were tested for non-inferiority, whereas the remaining hypotheses were tested for superiority. Accordingly, pnon-inferiority<\/sub>was assessed for non-inferiority hypotheses and psuperiority<\/sub>\u00a0for superiority hypotheses. UTI=urinary tract infection. NA=not applicable.*
Risk difference (one-sided 97\u00b75% CI).\u2020
Difference in median antibiotic days in 28 days (two-sided 97\u00b75% CI).\u2021
98 (71%) of 138 patients attending school or daycare in the individualised group and 101 (70%) of 144 patients attending school or daycare in the standard 10-day group had available data; accordingly, 126 (67 in the individualised group and 59 in the standard 10-day group) patients not attending school or daycare were removed from the analysis and 83 (40 in the individualised group and 43 in the standard 10-day group) patients were lost to follow-up.\u00a7
Incidence rate ratio (95% CI).\u00b6
Risk difference (95% CI).\u2016
Two (1%) of 205 patients in the individualised group and two (1%) of 203 patients in the standard 10-day group had a resistant recurrent infection within 28 days.<\/figcaption><\/figure>\n\n\n\n

Table 4. Adverse events in the safety population<\/p>\n\n\n\n

Empty Cell<\/td>Individualised group<\/strong><\/th>Standard 10-day group<\/strong><\/th>Group difference<\/strong><\/th>p<\/strong>superiority<\/sub><\/th><\/tr><\/thead>
Antibiotic-related adverse event within 28 days<\/strong>*<\/a><\/td><\/tr>
Number of patients<\/td>173<\/td>168<\/td>..<\/td>..<\/td><\/tr>
Any adverse event<\/td>102 (59%)<\/td>109 (65%)<\/td>\u22125\u00b79 (\u221216\u00b73 to 4\u00b75)\u2020<\/sup><\/a><\/td>0\u00b727<\/td><\/tr>
Loss of appetite or nausea<\/td>65 (38%)<\/td>72 (43%)<\/td>..<\/td>..<\/td><\/tr>
Diarrhoea<\/td>55 (32%)<\/td>61 (36%)<\/td>..<\/td>..<\/td><\/tr>
Abdominal pain<\/td>46 (27%)<\/td>40 (24%)<\/td>..<\/td>..<\/td><\/tr>
Vomiting<\/td>27 (16%)<\/td>32 (19%)<\/td>..<\/td>..<\/td><\/tr>
Adverse event incidence rate<\/td>329\/4844 (6\u00b78)<\/td>523\/4704 (11\u00b71)<\/td>0\u00b761 (0\u00b747 to 0\u00b780)\u2021<\/sup><\/a><\/td>0\u00b70003<\/td><\/tr>
Serious adverse events within 100 days<\/strong><\/td><\/tr>
Number of patients<\/td>205<\/td>203<\/td><\/td><\/td><\/tr>
Any serious adverse event<\/td>17 (8%)<\/td>15 (7%)<\/td>0\u00b79 (\u22124\u00b76 to 6\u00b75)\u2020<\/sup><\/a><\/td>0\u00b779<\/td><\/tr>
All-cause hospitalisation<\/td>17 (8%)<\/td>15 (7%)<\/td>..<\/td>..<\/td><\/tr>
Bacteraemia<\/td>2 (1%)<\/td>0<\/td>..<\/td>..<\/td><\/tr><\/tbody><\/table>
Data are n, n (%), or event days per patient-days at risk (incidence rate per 100 patient-days at risk). Some cells are empty because we did not plan to estimate group differences for specific types of antibiotic-related adverse events or serious adverse events.*
173 (84%) of 205 patients in the individualised group and 168 (83%) of 203 patients in the standard 10-day group had available data; accordingly, 67 patients (32 in the individualised group and 35 in the standard 10-day group) were lost to follow-up.\u2020
Risk difference (95% CI).\u2021
Incidence rate ratio (95% CI).<\/figcaption><\/figure>\n\n\n\n

Interpretation<\/h3>\n\n\n\n

Children with febrile UTI assigned to individualised treatment duration had an increased risk of recurrent UTI (by 5\u00b73 percentage points) but reduced antibiotic use and fewer adverse event days within 28 days compared with those assigned to standard 10-day treatment. These findings highlight the potential of individualised treatment strategies to reduce antibiotic exposure and associated harms in most children with febrile UTI, supporting antimicrobial stewardship goals. Further research is needed to identify those requiring 10-day treatment to avoid compromising care for most children with febrile UTI who respond well to shorter durations.<\/p>\n\n\n\n

Funding<\/h3>\n\n\n\n

Copenhagen University Hospital Rigshospitalet Research Fund, Innovation Fund Denmark, and Greater Copenhagen Health Science Partners.<\/p>\n","protected":false},"excerpt":{"rendered":"

Efficacy and safety of individualised versus standard 1 […]<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":[],"categories":[32,23],"tags":[],"_links":{"self":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/28957"}],"collection":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=28957"}],"version-history":[{"count":1,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/28957\/revisions"}],"predecessor-version":[{"id":28958,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/28957\/revisions\/28958"}],"wp:attachment":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=28957"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=28957"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=28957"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}