Published online February 1, 2007
PEDIATRICS Vol. 119 No. 2 February 2007, pp. e325-e329 (doi:10.1542/peds.2006-1134)
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ARTICLE

Repeat Urine Cultures in Children Who Are Admitted With Urinary Tract Infections

Nicolas M. Oreskovic, MDa,b and Eduardo U. Sembrano, MDb

a Departments of Internal Medicine
b Pediatrics, Mount Sinai Hospital, New York, New York


    ABSTRACT
 TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
OBJECTIVE. Urinary tract infections are a common cause of hospitalization in the pediatric population. Hospitalization for urinary tract infections in children usually involves intravenous antibiotics, invasive methods of obtaining sterile urine specimens, and imaging studies to assess the anatomy of the urinary system. The objective of this study was to determine the frequency of positive repeat urine cultures that are obtained after 2 days of antibiotics among pediatric inpatients who are admitted with diagnosed or suspected infections of the urinary tract.

METHODS. A retrospective survey was conducted of all pediatric patients (≤18 years of age) who were admitted to Elmhurst Hospital in Queens, New York, with a suspected or diagnosed urinary infection from December 1998 through December 2004. Results of repeat urine cultures that were obtained after 2 days of antibiotics were abstracted from a computerized medical charts database. Nominal data analysis was used to establish the frequency of positive repeat urine cultures.

RESULTS. A total of 328 (54.8%) of 599 eligible admissions met inclusion criteria. Of these 328 admissions, only 1 (0.3%) repeat urine culture was positive after 2 days of antimicrobial therapy.

CONCLUSIONS. Positive repeat urine cultures after 2 days of antibiotics are exceedingly rare. Elimination of mandatory "proof-of-bacteriologic-cure" benchmarks before hospital discharge is supported by this study.


Key Words: pediatrics • urinary tract infections • practice guideline

Abbreviations: UTI—urinary tract infection • AAP—American Academy of Pediatrics • CFU—colony-forming unit(s)

Infections of the urinary tract are relatively common in children, accounting for a significant number of pediatric hospital admissions.1,2 Urinary tract infections (UTIs) are an important cause of acute morbidity in children and may result in long-term sequelae, including renal scarring and hypertension.35 Treatment with antibiotics is directed at eradicating the acute infection. Various imaging studies, including renal ultrasound, voiding cystourethrography, and radionuclide cystourethrography, commonly are undertaken after resolution of the acute infection to stratify risk in children further. Prophylactic antimicrobial agents usually are prescribed until the imaging studies are obtained. Children with anatomic abnormalities of the urinary tract, including hydronephrosis, posterior urethral valves, vesicoureteral reflux, and ureteropelvic obstruction, are thought to be predisposed to recurrent UTIs. These recurrent UTIs are thought to put children at higher risk for long-term renal damage, such as renal scarring, reduced renal function, and eventual hypertension in adulthood. Although recent literature suggests that the rate of long-term sequelae and the need for imaging studies may be lower than previously thought,6,7 children with anatomic defects often are placed on prophylactic antibiotics or undergo corrective surgery.

Successful treatment of an acute UTI aims at eradicating the infective organism from the urinary tract, with the ultimate goal of decreasing the likelihood of pyelonephritis and long-term kidney damage. Although not recommended by the American Academy of Pediatrics (AAP) in their 1999 practice parameters on UTIs in children, many practicing pediatricians routinely obtain a repeat urine culture after 2 days of antimicrobial therapy to verify a "proof of bacteriologic cure."8 Obtaining a routine repeat culture can prolong length of hospital stay, increase costs, and be a source of discomfort to the patient. A repeat urine culture may be appropriate in certain circumstances, however, including infants or young children who do not have the expected clinical response after 48 hours of antimicrobial therapy.

The primary aim of this study was to quantify the frequency of positive repeat urine cultures after 2 days of antibiotics in an inpatient setting. Our hypothesis was that treatment failure, as defined by the percentage of positive repeat cultures, would be low, suggesting that proof-of-bacteriologic-cure cultures do not change patient treatment, potentially are harmful to the patient, and are a waste of medical resources.


    METHODS
 TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Study Design
This study was a retrospective chart review using data from Elmhurst Hospital, which is a public, teaching hospital in Queens, New York. All inpatients who are younger than 21 years at Elmhurst Hospital are admitted to the pediatrics service. It is routine practice in the department of pediatrics at Elmhurst Hospital to obtain a repeat urine culture after 2 days of antimicrobial therapy in all children who are admitted and treated for UTIs. This study was approved by the hospital review boards of Elmhurst Hospital, Mount Sinai Hospital (New York, NY), and the New York City Health and Hospitals Corporation.

Eligible Patients
All children who were younger than 18 years and admitted to the pediatrics service at Elmhurst Hospital with a suspected or diagnosed infection of the urinary tract were eligible for inclusion. A suspected or diagnosed UTI was defined as an admission diagnosis of (1) UTI, (2) presumed UTI, (3) rule-out UTI, (4) pyelonephritis, (5) rule-out pyelonephritis, (6) urosepsis, or (7) rule-out urosepsis. When multiple diagnoses were listed for hospitalization, inclusion of any of these urinary diagnoses was considered sufficient for eligibility. Inclusion criteria required a urine culture on the day of admission, as well as a repeat urine culture 2 to 3 days later. The aim was to evaluate cultures that were taken after the patient had received 2 full days of antimicrobial therapy. Cultures that are obtained late in the evening often are not entered into the computer system until the next morning at Elmhurst Hospital. To account for these cultures, we extended inclusion criteria to repeat urine cultures that were documented on day 2 or 3 after admission (not including the day of admission). Inclusion criteria further required that a culture that was obtained from a voided specimen grow >100000 colony-forming units (CFU)/mL of a single pathogen. Specimens that were obtained by in-and-out urethral catheterization were considered significant when they grew at least 10000 CFU/mL of a single pathogen. This was meant to reflect medical practice at Elmhurst Hospital, where catheterized urine cultures in children with at least 10000 CFU/mL of a single colony are treated with antibiotics. Finally, growth of any number of bacteria on a urine culture that was obtained by suprapubic aspiration was considered significant and met inclusion criteria.

Patients were excluded when the repeat urine culture was obtained too early (on day 1 after hospitalization) or too late (>3 days after hospitalization). Patients were excluded also when their original urine culture was negative, when they did not have a repeat urine culture, when they had multiple colonies growing on a culture, when they had a culture without quantitative analysis of CFUs, or when they had multiple conflicting cultures or data that made objective data analysis impossible.

Data Analysis
All children who met inclusion criteria were identified as having 1 of 2 possible outcomes: positive repeat urine culture or negative repeat urine culture. Because data analysis was performed on nominal values, we established the percentage of repeat urine cultures that were positive, effectively representing treatment failure. Data analysis was performed using SAS 9.1 (SAS Institute, Cary, NC).


    RESULTS
 TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
We identified 599 pediatric admissions to Elmhurst Hospital between December 1998 and December 2004 that were eligible for inclusion. Of these 599 admissions, 328 (54.8%) met inclusion criteria. Of the 328 admissions that met inclusion criteria, 45.4% were female. The most common single admission diagnosis among eligible patients (33.2%) was UTI, followed by pyelonephritis (20.1%) and urosepsis (1.8%). Forty-seven (14.3%) admissions were combined urinary diagnoses (eg, UTI versus rule-out pyelonephritis), and 100 (30.5%) were combined diagnoses of urinary pathology with unrelated medical problems (eg, UTI and pneumonia). Of the 271 admissions that were excluded, 205 had a negative urine culture on the day of admission; 31 had cultures that grew multiple organisms; 20 were missing a repeat culture; 7 had repeat cultures that were obtained past day 3; 2 had repeat urine cultures that were obtained on the first day after admission; 3 had cultures that did not report quantitative analysis of CFUs; and 3 had multiple conflicting points of data, including multiple urine cultures that were taken before admission, making it unable to distinguish the onset and timing of treatment.

Of the 328 admissions that met inclusion criteria, only 1 (0.3%) patient had a positive repeat urine culture after 2 days of intravenous antibiotics (95% confidence interval: 0%–1.7%). This 1 treatment failure was a 7-month-old male patient who was admitted with a diagnosis of UTI and bronchiolitis. Because of a recorded drug allergy to amoxicillin, the child was started on trimethoprim-sulfamethoxazole for his UTI. Routine urine cultures were obtained on admission and on the morning of the third hospital day. Admission urine culture grew >100000 CFU/mL Escherichia coli that was resistant to trimethoprim-sulfamethoxazole. The organism identity and drug sensitivities of the admission urine culture, however, did not become available until after the repeat urine culture was obtained on the third hospital day. The patient's antibiotic regimen was changed to cefaclor, a second-generation cephalosporin, to which the organism was known to be sensitive. The patient remained afebrile throughout the entire admission, and a urine dip analysis before discharge was negative for nitrate and leukocyte esterase. The patient was discharged from the hospital on hospital day 3. A follow-up urine culture that was obtained 2 days after changing the patient's antibiotic was negative. Renal ultrasound and voiding cystourethrography that were performed after discharge were both unremarkable.


    DISCUSSION
 TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
The 1999 AAP practice parameters for UTIs states that routine reculturing of the urine for proof of bacteriologic cure in children who are aged 2 months to 2 years and are otherwise responding well to therapy is not necessary. The strength of evidence behind this recommendation was considered to be "good."8

Many recent studies have validated this recommendation. A medical chart review study by Bachur9 analyzed 288 children who were ≤2 years and admitted to a pediatric service with a discharge diagnosis of UTI or pyelonephritis during 65 consecutive months. In the study, repeat urine cultures were obtained in 93% of the patients, and all repeat cultures were negative. Although 20 patients in this study did not have repeat urine cultures drawn, all of these patients defervesced in <48 hours of antibiotic treatment. The lack of universal repeat urine cultures potentially could represent a sampling error. Given that all 20 patients had a favorable clinical response, however, this seems unlikely. In addition, it is worth noting that the primary aim of the study was to describe fever patterns in children who were treated for UTIs, not to assess the rate of positive repeat urine cultures.

In a study by Currie et al,10 all children who were 18 years and younger and admitted to a children's hospital in Wisconsin with a discharge diagnosis of UTI or pyelonephritis were reviewed, looking specifically at repeat urine cultures and fever curves. Of the 364 identified patients with UTIs, 291 had follow-up cultures, and none was positive.

Whereas the study by Bachur9 is limited by the young age of its participants (≤2 years), the study by Currie et al10 complements this nicely by including all children who were younger than 18 years. The 2 studies together give a more complete picture of UTIs among children. Our study adds to this body of evidence and once again illustrates that repeat cultures are unnecessary. This study provides a vital addition to the current literature in this field by encompassing the largest number of patients to date in a single study that attempted to objectify the value of repeat urine cultures. In addition, unlike the studies by Bachur and Currie et al, we did not exclude any patients on the basis of known anatomic defects or medical disease.

Antibiotic resistance has become more prevalent among urinary tract pathogens. Emerging resistance to ampicillin and amoxicillin has made these agents less effective as primary antimicrobial agents for UTIs.8 Increasing resistance among urinary pathogens, especially E coli, to trimethoprim-sulfamethoxazole also has become a global reality.1113 The 1 treatment failure in our study was in a patient who was placed on trimethoprim-sulfamethoxazole for a suspected UTI because of a documented allergic reaction to amoxicillin. The patient later was found to have a strain of E coli that was resistant to trimethoprim-sulfamethoxazole that was present in his urine. The lesson from this patient is simple: pediatricians should be aware of the rising resistance of urinary pathogens to commonly prescribed antibiotics, as well as the profile of antibiotic resistance within their community.

Repeat urine cultures are uncomfortable for the patient and time-consuming for the practitioner. Infants and young children are too young and not sufficiently coordinated to give sterile voided urine samples by the midstream, clean-catch technique. Consequently, many urine specimens for culture in pediatrics are obtained via suprapubic aspiration or urethral catheterization. These procedures require physician experience and expertise. In addition, there is a very real but difficult-to-quantify discomfort to children who undergo invasive procedures.

The financial costs of repeating a urine culture may be deduced more easily. Although not often at the forefront of medical decision-making, the financial impact to a hospital and families often is substantial. At Elmhurst Hospital, the combined cost to the institution for materials that are used to obtain a urine culture is less than $1.00. The laboratory fees for a negative urine culture, including culture plates and technician fees, cost the institution approximately $4.50 per specimen. More poignant, however, the billed charge to the patient's family for a 1-night stay on the pediatric service at Elmhurst Hospital is $2940.00. This cost includes all basic hospital charges, including food, antibiotics, and cultures. Often, a child shows signs of clinical improvement (absence of fever, decreasing serum leukocyte count, absence of nitrate or leukocyte esterase on urine dip) but remains in hospital overnight until the results of the repeat urine culture become available the next day. Elmhurst Hospital averaged 65 pediatric hospitalizations per year from 1999 through 2004 for urinary tract–related infections. Clearly, the potential economic savings from a policy change regarding proof of bacteriologic cure are not insignificant.

There are several limitations to our study. First and foremost, this study was purely retrospective and observational. In addition, this study analyzed all pediatric patients, not simply children who were aged 2 months to 2 years, the age group for which the AAP practice parameters are intended. We opted to include all ages in this study because we believed that it would represent best the entire spectrum of pediatric UTIs in a community hospital, and our aim was to affect change in hospital policy. Another potential limitation was our inclusion criteria of colony counts of at least 10000 CFU/mL on catheterized specimens. As explained, this was done to reflect hospital practice. If anything, this broad definition of a positive culture would increase the likelihood of capturing treatment failures, opening the criteria for a positive culture to be lower than the ≥50000 CFU/mL definition that commonly is cited in the literature.14 Another important limitation of this study is the hospital setting from which the data were collected. The pediatric patient population in this study represents a healthy cohort of children, who, in large part, are without major medical problems. Similar results may not be applicable to hospitals that care for children with chronic complex medical problems or hospitals that are known to have a high degree of resistant organisms among its patient population. It is worth mentioning, however, that we did not exclude from this study children with known medical problems that might predispose one to a complicated UTI (eg, neurogenic bladder, spina bifida, hydronephrosis). Even with the inclusion of all such patients, our low yield of treatment failure was consistent with past studies. The almost complete absence of any treatment failures among all children who were admitted during 5 years with any urinary-related diagnosis makes the practice of routinely repeating urine cultures seem wasteful and unfounded.

It now has been shown by several retrospective studies that requiring repeat cultures before discharge is not only unhelpful but also may be harmful, both physically and financially.9,10 Nevertheless, despite the AAP recommendations and several studies that have reported a low, if not absent, rate of treatment failure in repeat urine cultures, routine reculturing of urine remains a controversial issue. Many pediatricians and some establishments continue a policy of mandatory follow-up urine culture regardless of the patient's clinical status. Short of a prospective, randomized, controlled study, a study design that is unlikely to happen in the near future, this body of evidence ought to be sufficient to suggest that there is little to gain from repeat urine cultures.


    CONCLUSIONS
 TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
After 2 days of antibiotics, the overwhelming majority of community-acquired, uncomplicated UTIs respond adequately to treatment. Obtaining a proof-of-bacteriologic-cure urine culture is not supported by the findings in this retrospective study.


    FOOTNOTES
 
Accepted Sep 14, 2006.

Address correspondence to Nicolas Oreskovic, MD, Mount Sinai Hospital, 1 Gustave L. Levy Place, Box 1110, New York, NY 10029. E-mail: nicolas.oreskovic{at}gmail.com

The authors have indicated they have no financial relationships relevant to this article to disclose.


    REFERENCES
 TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 

  1. Freedman A. Urologic diseases in North America project: trends in resource utilization for urinary tract infections in children. J Urol. 2005;173 :949 –954[CrossRef][ISI][Medline]
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  3. Jodal U. The natural history of bacteriuria in childhood. Infect Dis Clin North Am. 1987;1 :713 –729[Medline]
  4. Jacobson SH, Eklof O, Erikson CG, Lins LE, Tidgren B, Winberg J. Development of hypertension and uremia after pyelonephritis in childhood: 27 year follow up. BMJ. 1989;299 :703 –706[ISI][Medline]
  5. Jacobson SH, Eklof O, Lins LE, Wikstad I, Winberg J. Long-term prognosis of post-infectious renal scarring in relation to radiologic findings in childhood: a 27 year follow-up. Pediatr Nephrol. 1992;6 :19 –24[CrossRef][ISI][Medline]
  6. Hoberman A, Charron M, Hickey RW, Baskin M, Kearney DH, Wald ER. Imaging studies after a first febrile urinary tract infection in young children. N Engl J Med. 2003;348 :195 –202[Abstract/Free Full Text]
  7. Garin EH, Olavarria F, Nieto VG, Valenciano B, Campos A, Young L. Clinical significance of primary vesicoureteral reflux and urinary antibiotic prophylaxis after acute pyelonephritis: a multicenter, randomized, controlled study. Pediatrics. 2006;117 :626 –632[Abstract/Free Full Text]
  8. American Academy of Pediatrics, Committee on Quality Improvement, Subcommittee on Urinary Tract Infection. Practice parameter: the diagnosis, treatment, and evaluation of the initial urinary tract infection in febrile infants and young children [published corrections appear in Pediatrics. 1999;103:1052; Pediatrics. 1999;104:118; and Pediatrics. 2000;105:141]. Pediatrics. 1999;103 :843 –852[Abstract/Free Full Text]
  9. Bachur R. Nonresponders: prolonged fever among infants with urinary tract infections. Pediatrics. 2000;105 (5). Available at: www.pediatrics.org/cgi/content/full/105/5/e59
  10. Currie ML, Mitz L, Raasch CS, Greenbaum LA. Follow-up urine cultures and fever in children with urinary tract infection. Arch Pediatr Adolesc Med. 2003;157 :1237 –1240[Abstract/Free Full Text]
  11. Manges AR, Natarajan P, Solberg OD, Dietrich PS, Riley LW. The changing prevalence of drug-resistant Escherichia coli clonal groups in a community: evidence for community outbreaks of urinary tract infections. Epidemiol Infect. 2005;000 :1 –7
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PEDIATRICS (ISSN 1098-4275). ©2007 by the American Academy of Pediatrics




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