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Antibiotic Prophylaxis in Infants with Grade III, IV, or V Vesicoureteral Reflux
William Morello1, Esra Baskin1, Augustina Jankauskiene1
1From the Pediatric Nephrology, Dialysis, and Transplant Unit (W.M., G.P., J.S., G.M.) and the Pediatric Urology Unit (D.G.M.), Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, and the Department of Clinical Sciences and Community Health, University of Milan (G.M.), Milan, the Department of General and Specialized Surgery for Women and Children, Università degli Studi della Campania "Luigi Vanvitelli," Naples (A.L.M., S.G., P.M.), the Institute for Maternal and Child Health-IRCCS Burlo Garofolo (M.P., E. Barbi) and the Department of Medical, Surgical, and Health Sciences, University of Trieste (E. Barbi), Trieste, Pediatric Nephrology and Dialysis, Pediatric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna (C.L.S., A.P.), the Nephrology and Dialysis Unit, Meyer Children's Hospital, Florence (F.B., M.M.), Pediatria C, Ospedale Donna Bambino, Verona (M.B.), the Pediatric Nephrology and Rheumatology Unit, Azienda Ospedaliera Universitaria Gaetano Martino, University of Messina, Messina (R.C.), the Nuclear Medicine Unit, Circolo Hospital and Macchi Foundation, Azienda Socio Sanitaria Territoriale Sette Laghi, Varese (D.D.P.), the Nuclear Medicine Unit, Department of Medicine, University Hospital of Padua (P.Z.), and the Pediatric Nephrology, Dialysis, and Transplantation Unit, Department of Women's and Children's Health, University of Padua (I.A.), Padua - all in Italy; the Department of Pediatric Nephrology, Başkent University Faculty of Medicine (E. Baskin, K.G.), and the Department of Pediatric Nephrology, Ankara University School of Medicine (F.Y., Z.B.O.), Ankara, the Department of Pediatric Nephrology and Pediatric Rheumatology, Pamukkale University School of Medicine, Denizli (S.Y.), and the Department of Pediatric Nephrology, Istanbul University-Cerrahpaşa, Cerrahpaşa School of Medicine, Istanbul (S.C.) - all in Turkey; the Pediatric Center, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius (A.J., D.R.), and the Department of Radiology, Medical Academy, Lithuanian University of Health Sciences Kauno Klinikos, Kaunas (D.V.) - both in Lithuania; the Department of Pediatrics, Nephrology, and Hypertension, Medical University of Gdansk, Gdansk (A.Z., A.K.), the Department of Pediatrics and Nephrology, Medical University of Warsaw, Warsaw (G.K., A.S.), the Department of Pediatric Nephrology and Hypertension, Chair of Pediatrics, Pediatric Institute, Jagiellonian University Medical College, Krakow (D.D.), the Department of Pediatrics, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, Katowice (M.S.), the Department of Pediatrics and Nephrology, Medical University of Bialystok, Bialystok (K.T.-J.), and the Department of Pediatrics, Immunology, and Nephrology, Polish Mother's Memorial Hospital Research Institute, Lodz (M.T.) - all in Poland; the Department of Pediatric Nephrology, University Hospitals Leuven (D.M., S.D.R.), and PKD Research Group, Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine, KU Leuven (D.M.), Leuven, and the Division of Nephrology, Department of Pediatrics, University Hospital Center of Liège, Liège (J.L.) - all in Belgium; the Department of Pediatric Nephrology, University Hospital Vall d'Hebron, and Universidad Autónoma de Barcelona, Hospital Vall d'Hebron (G.A.), and Pediatric Nephrology, Hospital General de Granollers, Universitat Internacional de Catalunya (M.C.), Barcelona, and Hospital General Universitario Santa Lucía, Cartagena (J.E.C.S.) - all in Spain; the University of Cologne, Faculty of Medicine and University Hospital Cologne, Children's and Adolescents' Hospital, Cologne (L.T.W.), and the Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, Heidelberg University Hospital, Heidelberg (O.M., F.S.) - both in Germany; and the Division of Pediatric Nephrology, Centro Materno Infantil do Norte, Centro Hospitalar Universitário do Porto, Porto, Portugal (A.C.A.).
Insights
Continuous antibiotic prophylaxis significantly reduced first urinary tract infections (UTIs) in infants with severe vesicoureteral reflux. However, it also increased antibiotic resistance and non-E. coli infections.
Area of Science:
- Pediatric Nephrology
- Infectious Diseases
- Clinical Trials
Background:
- Efficacy of continuous antibiotic prophylaxis for preventing urinary tract infections (UTIs) in infants with high-grade vesicoureteral reflux (VUR) remains debated.
- Infants with grade III, IV, or V VUR are at risk for recurrent UTIs and potential kidney damage.
Purpose of the Study:
- To evaluate the effectiveness of continuous antibiotic prophylaxis in preventing first UTIs in infants with grade III-V VUR.
- To assess secondary outcomes including new kidney scarring and renal function (GFR).
Main Methods:
- A randomized, open-label trial involving 292 infants (1-5 months old) with grade III-V VUR and no prior UTIs.
- Participants were assigned to receive continuous antibiotic prophylaxis or no treatment for 24 months.
- Primary outcome: occurrence of the first UTI; secondary outcomes: kidney scarring and GFR at 24 months.
Main Results:
- A first UTI occurred in 21.2% of the prophylaxis group versus 35.6% of the untreated group (HR 0.55; P=0.008).
- No significant differences were observed in new kidney scarring or estimated GFR between groups.
- Increased occurrence of non-E. coli organisms and antibiotic resistance was noted in the prophylaxis group.
Conclusions:
- Continuous antibiotic prophylaxis offers a significant, albeit small, benefit in preventing initial UTIs in infants with high-grade VUR.
- The prophylaxis strategy led to an increased prevalence of antibiotic resistance and non-E. coli pathogens.
- Careful consideration of risks and benefits is warranted when prescribing prophylaxis for this population.
Background:
The efficacy of continuous antibiotic prophylaxis in preventing urinary tract infection (UTI) in infants with grade III, IV, or V vesicoureteral reflux is controversial.
Methods:
In this investigator-initiated, randomized, open-label trial performed in 39 European centers, we randomly assigned infants 1 to 5 months of age with grade III, IV, or V vesicoureteral reflux and no previous UTIs to receive continuous antibiotic prophylaxis (prophylaxis group) or no treatment (untreated group) for 24 months. The primary outcome was the occurrence of the first UTI during the trial period. Secondary outcomes included new kidney scarring and the estimated glomerular filtration rate (GFR) at 24 months.
Results:
A total of 292 participants underwent randomization (146 per group). Approximately 75% of the participants were male; the median age was 3 months, and 235 participants (80.5%) had grade IV or V vesicoureteral reflux. In the intention-to-treat analysis, a first UTI occurred in 31 participants (21.2%) in the prophylaxis group and in 52 participants (35.6%) in the untreated group (hazard ratio, 0.55; 95% confidence interval [CI], 0.35 to 0.86; P = 0.008); the number needed to treat for 2 years to prevent one UTI was 7 children (95% CI, 4 to 29). Among untreated participants, 64.4% had no UTI during the trial. The incidence of new kidney scars and the estimated GFR at 24 months did not differ substantially between the two groups. Pseudomonas species, other non-Escherichia coli organisms, and antibiotic resistance were more common in UTI isolates obtained from participants in the prophylaxis group than in isolates obtained from those in the untreated group. Serious adverse events were similar in the two groups.
Conclusions:
In infants with grade III, IV, or V vesicoureteral reflux and no previous UTIs, continuous antibiotic prophylaxis provided a small but significant benefit in preventing a first UTI despite an increased occurrence of non-E. coli organisms and antibiotic resistance. (Funded by the Italian Ministry of Health and others; PREDICT ClinicalTrials.gov number, NCT02021006; EudraCT number, 2013-000309-21.).
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