While working in an urgent care, a mother and her 5-year-old daughter come in. The mother explains that her daughter is crying with urination and her daughter has said that her urine smells “funny.” The daughter also has a low-grade fever and does admit to some burning when she urinates. The urinalysis has elevated leukocyte esterase and nitrites so you diagnose the patient with a urinary tract infection. The mother asks how long does her child need to be on the antibiotics for.

Search Question:

For children with urinary tract infections, does a shorter course of antibiotics lead to a similar resolution of symptoms and lowered reinfection rates after resolution compared to a longer course of antibiotics?

Question Type: What kind of question is this?

☐Prevalence                             ☐Screening                  ☐Diagnosis

☒Prognosis                              ☐Treatment                 ☒Harms

Assuming that the highest level of evidence to answer your question will be meta-analysis or systematic review, what other types of study might you include if these are not available (or if there is a much more current study of another type)? Please explain your choices.

– If meta-analysis or systematic review are not available, randomized controlled clinical trials will also offer great supporting evidence as they are carefully planned experiments, reduce the potential for bias, and allow for comparison between intervention and control groups.

– Cohort studies could also be used since they allow to follow the patients who have already received a particular treatment forward over time. This is not as reliable as randomized controlled clinical trials since patients might differ in ways other than in the variable that is being observed.

PICO search terms:

P	I	C	O
Children with urinary tract infections	Shorter course of antibiotics	Longer course of antibiotics	Shorter resolution in symptoms
Children with UTIs			Lowered reinfection rates after resolution
Urinary tract infections

Search tools and strategy used:

Please indicate what data bases/tools you used, provide a list of the terms you searched together in each tool, and how many articles were returned using those terms and filters.
Explain how you narrow your choices to the few selected articles.

Results found:

TRIP Database

• Children with urinary tract infections AND Shorter course of antibiotics – 35
• Children with urinary tract infections AND Shorter course of antibiotics AND Longer course of antibiotics – 16

PubMed

• Children with urinary tract infections AND Shorter course of antibiotics (last 10 years) – 16
• Children with urinary tract infections AND Shorter course of antibiotics AND Longer course of antibiotics (last 10 years) – 9

Google Scholar

• Children with urinary tract infections AND Shorter course of antibiotics AND Longer course of antibiotics – 46,300
• Children with urinary tract infections AND Shorter course of antibiotics AND Longer course of antibiotics (last 10 years) – 19,100

The articles I chose were a mixture of systematic review, meta-analysis, randomized clinical trials, and retrospective cohort study that dealt with my topic. Unfortunately, there were not too many articles that dealt with antibiotics duration for the pediatric population, so I needed to dig deeper with the search engines that I had. Fortunately, I found articles that were very recent (2022-2024) which I was very thankful for. Many articles I found were unfortunately taken from overseas which were very specific to this PICO, but I was looking for articles that were more situated in the United States.

Identify at least 4 articles (or other appropriate reputable sources) that answer your specific question with the highest available level of evidence (you will probably need to look at more than 4 articles to get the 4 most focused and highest-level articles to address your question). Please make sure that they are Medline indexed.

Citation: Vinicius M, Rezende L, Luiza Mendes Fonseca, et al. Shorter versus longer-course of antibiotic therapy for urinary tract infections in pediatric population: an updated meta-analysis. European Journal of Pediatrics. 2024;183(5):2037-2047. doi:https://doi.org/10.1007/s00431-024-05512-8

Type of article: Systematic Review and Meta-analysis

Abstract   Urinary tract infections (UTI) affect between 3% to 7.5% of the febrile pediatric population each year, being one of the most common bacterial infections in pediatrics. Nevertheless, there is no consensus in the medical literature regarding the duration of per oral (p.o.) antibiotic therapy for UTI among these patients. Therefore, our meta-analysis aims to assess the most effective therapy length in this scenario. PubMed, Cochrane, and Embase were searched for randomized controlled trials (RCTs) comparing short (≤ 5 days) with long-course (≥ 7 days) per os (p.o.) antibiotic therapy for children with UTI. Statistical analysis was performed using R Studio version 4.2.1, heterogeneity was assessed with I2 statistics, and the risk of bias was evaluated using the RoB-2 tool. Risk Ratios (RR) with p < 0.05 were considered statistically significant. Seventeen studies involving 1666 pediatric patients were included. Of these, 890 patients (53.4%) were randomized to receive short-course therapy. Patients undergoing short-course therapy showed higher treatment failure rates (RR 1.61; 95% CI 1.15–2.27; p = 0.006). Furthermore, there were no statistically significant differences between groups regarding reinfection (RR 0.73; 95% CI 0.47–1.13; p = 0156) and relapse rates (RR 1.47; 95% CI 0.8–2.71; p = 0.270). Conclusion: In summary, our results suggest that long-course p.o. antibiotic therapy is associated with a lower rate of treatment failure when compared to short-course p.o. antibiotic therapy. There was no statistical difference between both courses regarding reinfection and relapse rates within 15 months.

Key Points: – This systematic review and meta-analysis included 17 studies from the PubMed, Cochrane Central Register of Controlled Trials, and Embase databases – There were 1,666 pediatric patients (ages 0-18) total who were given PO antibiotics – The mean age among the patients ranged from 4.2 – 7.8 years old – 890 patients received the shorter course of antibiotics (≤ 5 days) – 776 patients received the longer course of antibiotics (≥ 7 days) – There were 87 cases of treatment failure (9.8%) in the group that was given the shorter course of antibiotics, and there were 40 cases of treatment failure (5.4%) in the group that was given the longer course of antibiotics. This is a significant high failure rate for the shorter antibiotic course group – There was not a significant difference between both group arms in both reinfection rates and relapse rates

Why I chose it: This article was my only systematic review and meta-analysis, so it was on the top of my list. It was also published in March of this year, so I think it is very topical and relevant to my PICO. I was surprised to learn that a shorter course of antibiotics was more detrimental to the pediatric population than a longer course of antibiotics. A shorter course of antibiotics for an adult with a urinary tract infection is just as efficacious as a longer course. I was happy to see that the division of patients between both treatment arms were almost identical and that the article answered both outcomes I was looking for.

Citation: Samar Hikmat, Jolie Lawrence, Amanda Gwee; Short Intravenous Antibiotic Courses for Urinary Infections in Young Infants: A Systematic Review. Pediatrics February 2022; 149 (2): e2021052466. 10.1542/peds.2021-052466

Type of article: Systematic review

Abstract Context: Urinary tract infections (UTIs) are common in young infants, yet there is no guidance on the optimal duration of intravenous (IV) treatment. Objective: To determine if shorter IV antibiotic courses (≤7 days) are appropriate for managing UTIs in infants aged ≤90 days. Methods: PubMed, the Cochrane Library, Medline, and Embase (February 2021) were used as data sources. Included studies reported original data for infants aged ≤90 days with UTIs, studied short IV antibiotic durations (≤7 days), and described at least 1 treatment outcome. The Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline was followed. Studies were screened by 2 investigators, and bias was assessed by using the Newcastle-Ottawa Scale and the Revised Cochrane Risk-of-Bias Tool. Results: Eighteen studies with 16,615 young infants were included. The largest 2 studies on bacteremic UTI found no difference in the rates of 30-day recurrence between those treated with ≤7 vs >7 days of IV antibiotics. For nonbacteremic UTI, there was no significant difference in the adjusted 30-day recurrence between those receiving ≤3 vs >3 days of IV antibiotics in the largest 2 studies identified. Three studies of infants aged ≥30 days used oral antibiotics alone and reported good outcomes, although only 85 infants were ≤90 days old. Conclusions: Shorter IV antibiotic courses of ≤7 days and ≤3 days with early switch to oral antibiotics should be considered in infants aged ≤90 days with bacteremic and nonbacteremic UTI, respectively, after excluding meningitis. Further studies of treatment with oral antibiotics alone are needed in this age group.

Key Points: – This systematic review included 16 randomized controlled trials and 2 retrospective studies (for a total of 18 studies) that included 16,615 pediatric patients that were under three months old – In four studies, 468 infants were treated for bacteremic UTIs with 267 patients in the treatment arm that received IV antibiotics for under 7 days, and the other treatment arm with 207 patients who received IV antibiotics for longer than 7 days. There were no statistically significant differences with either treatment arm in regards to UTI resolution or 30-day UTI recurrence – The remaining fourteen studies included 15,816 infants who had non-bacteremic UTIs. Half of the participants were given oral antibiotics for under three days and the other half were given oral antibiotics for over three days. There were no statistically significant differences with either treatment arm in regards to UTI resolution or 30-day UTI recurrence

Why I chose it: This article had the most participants for pediatric patients who had UTIs (over 16,000 patients). Unlike the last article, this article said that giving a shorter course of antibiotics (whether it was IV or oral antibiotics) was just as efficacious in resolving the patients UTI versus giving a much longer course. This article also included giving IV antibiotics which helped more bacteremic UTI patients

Citation: Zaoutis T, Shaikh N, Fisher BT, et al. Short-Course Therapy for Urinary Tract Infections in Children: The SCOUT Randomized Clinical Trial. JAMA Pediatr. 2023;177(8):782–789. doi:10.1001/jamapediatrics.2023.1979

Type of article: Randomized Clinical Trial

Abstract Importance: There is a paucity of pediatric-specific comparative data to guide duration of therapy recommendations in children with urinary tract infection (UTI). Objective: To compare the efficacy of standard-course and short-course therapy for children with UTI. Design, Setting, Participants: The Short Course Therapy for Urinary Tract Infections (SCOUT) randomized clinical noninferiority trial took place at outpatient clinics and emergency departments at 2 children’s hospitals from May 2012, through, August 2019. Data were analyzed from January 2020, through, February 2023. Participants included children aged 2 months to 10 years with UTI exhibiting clinical improvement after 5 days of antimicrobials. Intervention: Another 5 days of antimicrobials (standard-course therapy) or 5 days of placebo (short-course therapy). Main Outcome Measures: The primary outcome, treatment failure, was defined as symptomatic UTI at or before the first follow-up visit (day 11 to 14). Secondary outcomes included UTI after the first follow-up visit, asymptomatic bacteriuria, positive urine culture, and gastrointestinal colonization with resistant organisms. Results: Analysis for the primary outcome included 664 randomized children (639 female [96%]; median age, 4 years). Among children evaluable for the primary outcome, 2 of 328 assigned to standard-course (0.6%) and 14 of 336 assigned to short-course (4.2%) had a treatment failure (absolute difference of 3.6% with upper bound 95% CI of 5.5.%). Children receiving short-course therapy were more likely to have asymptomatic bacteriuria or a positive urine culture at or by the first follow-up visit. There were no differences between groups in rates of UTI after the first follow-up visit, incidence of adverse events, or incidence of gastrointestinal colonization with resistant organisms. Conclusions and Relevance: In this randomized clinical trial, children assigned to standard-course therapy had lower rates of treatment failure than children assigned to short-course therapy. However, the low failure rate of short-course therapy suggests that it could be considered as a reasonable option for children exhibiting clinical improvement after 5 days of antimicrobial treatment.

Key Points: – This randomized control trial had 664 children that were assigned either a short course of oral antibiotics (5 days) or a standard course of oral antibiotics (10 days) – This was a multicenter, randomized, double-blind, placebo-controlled, noninferiority clinical trial took place in the Children’s Hospital of Philadelphia and the UPMC Children’s Hospital of Pittsburgh – Six hundred and thirty-nine (96%) of the pediatric patients were female – The patients who received the standard course of antibiotic therapy were associated with lower rates of treatment failure as compared to the patients who got the shorter course of therapy (0.6% vs. 4.2%) – There were no statistical differences between either treatment group regarding reinfection rates after UTI resolution (which was looked at 2 weeks after resolution)

Why I chose it: I chose this article because I wanted to include a randomized control trial from actual American cities to see how pediatric patients dealt with different courses of antibiotic therapies. This article mirrored the first one that concluded a longer (or a more standardized) course of antibiotics was more clinically effective than a shorter course was. I was also pleased to see that, just as mentioned with the other articles, there was no statistical difference in reinfection rates two weeks after resolution

Citation: Zu’bi F, Pokarowski M, Al-Kutbi R, et al. A Comparison of Short Versus Long Course Intravenous Antibiotics When Treating Urinary Tract Infection in Infants <60 Days of Age. Clinical Pediatrics. 2023;62(10):1201-1208. doi:10.1177/00099228231154364

Type of article: Retrospective Cohort Study

Abstract Urinary tract infections (UTIs) are a common reason for hospitalization in infants younger than 60 days, and the optimal approach to intravenous (IV) antibiotic therapy upon UTI diagnosis in this cohort is unknown. We determined whether there was an association between IV antibiotic therapy duration (long [>3 days] vs short [≤3 days]) and treatment failure via a retrospective review of infants with confirmed UTIs receiving IV antibiotics at a tertiary referral center. A total of 403 infants were included; 39% were treated with ampicillin and cefotaxime, and 34% with ampicillin and gentamycin or tobramycin. The median IV antibiotic duration was 5 (interquartile range: 3-10) days, and 5% of patients experienced treatment failure. The treatment failure rate was similar in both short- and long-course IV antibiotic groups (P > .05), and there was no significant association between treatment duration and failure. We conclude that treatment failure for infants hospitalized with UTI is uncommon and not associated with IV antibiotic duration.

Key Points: – This retrospective cohort study had 403 pediatric patients who were under the age of 60 days – 236 patients (59% of the cohort) received the longer course of antibiotics (> 3 days) – 167 patients (41% of the cohort) received the shorter course of antibiotics (< 3 days) – Close to 75% of the cohort were male patients – Median age of the patients was 21 days old – There was no significant association between administering a shorter course or longer course of antibiotics regarding treatment failure – There were also no significant differences in readmission rates between either treatment arm

Why I chose it: I chose this article because it mimics the conclusion that the second article had where a shorter course of antibiotics was just as helpful in resolving a UTI as a longer course was. I also enjoying reading about the reasons why a shorter course of antibiotics had more potential benefits to it (including shorter hospital stays, lowered medical costs, and reduced nosocomial infections/adverse events). I was also very interested in seeing that more males had UTIs in this patient group set, as opposed to the other groups that had mostly females.

What is the clinical “bottom line” derived from these articles in answer to your question?

Urinary tract infections (UTIs) affect close to 10% of the pediatric population, but unfortunately there is not a clear consensus on whether a shorter course or longer course of antibiotics is more efficacious in resolving the symptoms quickly and avoiding readmission for the same pathology. Shorter courses of antibiotics may lead to treatment failures such as urosepsis, renal scarring, and chronic kidney disease. Longer antibiotic regimens may lead to increased risks of hospital acquired infections and adverse events, and leads to increased hospital stays and inflated costs. The articles I chose were split down the middle between recommending a longer course of antibiotics and shorter course. If asked, I would recommend a longer course of antibiotics (5-7 days) to avoid any treatment failures that might come with a shorter 3-day course and I would not advise a longer course (like 10 days), to stave off any possible nosocomial infections and to hopefully reduce hospital adjacent costs.