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1.  Actinobaculum schaalii, a Common Uropathogen in Elderly Patients, Denmark 
Emerging Infectious Diseases  2010;16(1):76-80.
This organism is identified more often by PCR than by cultivation.
Actinobaculum schaalii can cause urinary tract infections and septicemia but is difficult to identify by cultivation. To obtain a fast diagnosis and identify A. schaalii, we developed a TaqMan real-time quantitative PCR. Routine urine samples were obtained from 177 hospitalized patients and 75 outpatients in Viborg County, Denmark, in 2008–2009. The PCR detected A. schaalii in 22% of samples from patients >60 years of age. This assay showed that A. schaalii is more common than implied by routine cultivation. In 90% of PCR-positive urine samples, other common uropathogens were identified. This finding suggests that A. schaalii is a common, undetected, bacterial pathogen. Our results suggest that A. schaalii may be a more common pathogen than previously thought, especially in patients with unexplained chronic urinary tract infections, who are often treated with trimethoprim or ciprofloxacin, to which A. schaalii is resistant.
PMCID: PMC2874361  PMID: 20031046
Actinobaculum schaalii; real-time PCR; uropathogen; urinary tract infections; bacteria; research
2.  Actinobaculum schaalii - invasive pathogen or innocent bystander? A retrospective observational study 
BMC Infectious Diseases  2011;11:289.
Actinobaculum schaalii is a Gram-positive, facultative anaerobic coccoid rod, classified as a new genus in 1997. It grows slowly and therefore is easily overgrown by other pathogens, which are often found concomitantly. Since 1999, Actinobaculum schaalii is routinely investigated at our hospital, whenever its presence is suspected due to the detection of minute grey colonies on blood agar plates and negative reactions for catalase. The objective of this study was to determine the clinical significance of Actinobaculum schaalii, identified in our microbiology laboratory over the last 11 years.
All consecutive isolates with Actinobaculum schaalii were obtained from the computerized database of the clinical microbiology laboratory and patients whose cultures from any body site yielded this pathogen were analyzed. Observation of tiny colonies of Gram-positive, catalase-negative coccoid rods triggered molecular identification based on 16S rRNA gene sequencing.
40 isolates were obtained from 27 patients during the last 11 years. The patient's median age was 81 (19-101) years, 25 (92.6%) had underlying diseases and 12 (44.4%) had a genitourinary tract pathology. Actinobaculum schaalii was isolated in 12 urine cultures, 21 blood cultures, and 7 deep tissue biopsies. Twenty-five (62.5%) specimens were monobacterial, the remaining 15 (37.5%) were polybacterial 7/7 deep tissue samples (three bloodcultures and five urine cultures). Recovery from urine was interpreted as colonization in 5 (18.6%) cases (41.6% of all urine samples). Six (22.2%) suffered from urinary tract infections, six (22.2%) from abscesses (skin, intraabdominal, genitourinary tract, and surgical site infections) and 10 (37.0%) from bacteremia.
In this largest case series so far, detection of Actinobaculum schaalii was associated with an infection - primarily sepsis and abscesses - in 81.5% of our patients. Since this pathogen is frequently part of polymicrobial cultures (42.5%) it is often overlooked or considered a contaminant. Detection of Actinobaculum schaalii in clinical isolates mainly reflects infection indicating that this Gram-positive rod is not an innocent bystander.
PMCID: PMC3252262  PMID: 22029906
3.  Ten Cases of Actinobaculum schaalii Infection: Clinical Relevance, Bacterial Identification, and Antibiotic Susceptibility 
Journal of Clinical Microbiology  2005;43(10):5305-5308.
Nine of 10 strains of Actinobaculum schaalii caused urinary tract infections in predisposed individuals. Identification included 16S rRNA gene sequence analysis and use of the API Coryne and Rapid ID32A test systems. A. schaalii is easily overlooked due to its slow growth in ambient air and its resemblance to the normal bacterial flora on skin and mucosa.
PMCID: PMC1248514  PMID: 16208004
4.  Urosepsis with Actinobaculum schaalii and Aerococcus urinae 
Journal of Clinical Microbiology  2006;44(2):652-654.
Actinobaculum was isolated from urine only after prolonged incubation in 5% CO2 after discrepancy between urine Gram stain and initial culture results was observed. Additional patients were diagnosed using this method. The prevalence of Actinobaculum species in urinary tract infections is underestimated since it is not isolated by routine urine culture procedures.
PMCID: PMC1392690  PMID: 16455938
5.  Complete Genome Sequence of Actinobaculum schaalii Strain CCUG 27420 
Genome Announcements  2014;2(5):e00880-14.
Complete genome sequencing of the emerging uropathogen Actinobaculum schaalii indicates that an important mechanism of its virulence is attachment pili, which allow the organism to adhere to the surface of animal cells, greatly enhancing the ability of this organism to colonize the urinary tract.
PMCID: PMC4155593  PMID: 25189588
6.  Actinobaculum schaalii: identification with MALDI-TOF 
Actinobaculum schaalii is an emerging uropathogen. So far, its identification has been performed with 16S rRNA gene sequencing or PCR. The diagnosis has often been delayed due to fastidious growth and identification problems. Eleven clinical isolates of A. schaalii from bloodstream infections that were initially identified with 16S rRNA sequencing analysis were recovered and later identified with matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF). We present a review of bacteriological data of these patients, an algorithm for fast laboratory work-up and advocate the use of sensitized culture of urine to allow better recovery of A. schaalii in susceptible patients.
PMCID: PMC4184588  PMID: 25356339
Actinobaculum schaalii infection; bacteriological diagnostics; emerging infections; Gram-positive rod; urinary tract infection
7.  Actinobaculum schaalii: An Emerging Uropathogen? 
Case Reports in Urology  2012;2012:468516.
A. schaalii is a rare uropathogen. We report urosepsis with Actinobaculum schaalii detected serendipitously in blood and urine culture in a 79-year-old with urinary tract obstruction. This paper illuminates the flaws in our current system in detecting A. schaalii and raises awareness among clinicians and laboratory teams.
PMCID: PMC3350018  PMID: 22606634
8.  Actinobaculum schaalii Causing Fournier's Gangrene▿ 
Journal of Clinical Microbiology  2011;49(6):2369-2371.
Actinobaculum schaalii, which belongs to the group of Gram-positive rods, is difficult to culture. Using molecular genetics, Actinobaculum schaalii could be identified as a causing microorganism in a case of Fournier's gangrene.
PMCID: PMC3122759  PMID: 21508151
9.  Urinary Tract Infection in Boys Less Than Five Years of Age: A General Pediatric Perspective 
To examine the pattern of urinary tract infection (UTI) in boys < 5 years admitted to general pediatric wards and to identify the approach to imaging investigations.
During the period from January 2002 through December 2002, 34 boys < 5 years of age were admitted to Farwania Hospital with UTI. Age at diagnosis, presenting features, urinalysis, pathogens, acute phase reactants and imaging procedures were reviewed for these patients.
All 34 patients in this study were less than one year. Fever was the most common presenting feature and was seen in 70.6% of patients. Pyuria was found in 77% , positive leukocyte esterase (LE) test in 85.7% and positive nitrite test in 45.7% of patients. Significant leukocytosis was found in 39.3%, high C-reactive protein (CRP) in 46.8% and high erythrocyte sedimentation rate (ESR) in 50% of children. Escherichia coli (E.coli) were the most common pathogen affecting 77.1% patients. Radiological investigations were recommended as follows: ultrasound scan (US) for all patients (94.2% did the test, 46.8% had normal scans and 43.7% had dilatation of pelvicalyceal system); Early-scheduled 99mTc dimercaptosuccinic scan (DMSA) was done in seven patients. Five or 71% had evidence of acute pyelonephritis; Late-scheduled DMSA was recommended for 25 patients. Only 52% did the test and out of those 46% had evidence of chronic involvement of the kidney(s); Micturating cystourethrogram (MCUG) was advised for 32 patients. 43.8% failed to carry out the procedure. Vesicoureteric reflux (VUR) was found in 38.8% of those who performed the test.
Unexplained fever in young boys should suggest UTI. Absence of fever does not exclude UTI, if other suggestive features exist particularly in the very young. UTI is commonly suggested by findings on urinalysis, on the other hand, negative urinalysis should not exclude the infection. Empiric antibiotics should cover gram-negative bacilli. Innovative strategies to ensure compliance to radiological investigations are needed.
PMCID: PMC2678846  PMID: 19430582
dimercaptosuccinic (DMSA); Farwania hospital; micturating cystourethrogram (MCUG); urinalysis; 2002
10.  Urinary Tract Infections in Older Women 
JAMA  2014;311(8):844-854.
Asymptomatic bacteriuria and symptomatic urinary tract infections (UTIs) in older women are commonly encountered in outpatient practice.
To review management of asymptomatic bacteriuria and symptomatic UTI and review prevention of recurrent UTIs in older community-dwelling women.
A search of Ovid (Medline, PsycINFO, Embase) for English-language human studies conducted among adults aged 65 years and older and published in peer-reviewed journals from 1946 to November 20, 2013.
The clinical spectrum of UTIs ranges from asymptomatic bacteriuria, to symptomatic and recurrent UTIs, to sepsis associated with UTI requiring hospitalization. Recent evidence helps differentiate asymptomatic bacteriuria from symptomatic UTI. Asymptomatic bacteriuria is transient in older women, often resolves without any treatment, and is not associated with morbidity or mortality. The diagnosis of symptomatic UTI is made when a patient has both clinical features and laboratory evidence of a urinary infection. Absent other causes, patients presenting with any 2 of the following meet the clinical diagnostic criteria for symptomatic UTI: fever, worsened urinary urgency or frequency, acute dysuria, suprapubic tenderness, or costovertebral angle pain or tenderness. A positive urine culture (≥105 CFU/mL) with no more than 2 uropathogens and pyuria confirms the diagnosis of UTI. Risk factors for recurrent symptomatic UTI include diabetes, functional disability, recent sexual intercourse, prior history of urogynecologic surgery, urinary retention, and urinary incontinence. Testing for UTI is easily performed in the clinic using dipstick tests. When there is a low pretest probability of UTI, a negative dipstick result for leukocyte esterase and nitrites excludes infection. Antibiotics are selected by identifying the uropathogen, knowing local resistance rates, and considering adverse effect profiles. Chronic suppressive antibiotics for 6 to 12 months and vaginal estrogen therapy effectively reduce symptomatic UTI episodes and should be considered in patients with recurrent UTIs.
Establishing a diagnosis of symptomatic UTI in older women requires careful clinical evaluation with possible laboratory assessment using urinalysis and urine culture. Asymptomatic bacteriuria should be differentiated from symptomatic UTI. Asymptomatic bacteriuria in older women should not be treated.
PMCID: PMC4194886  PMID: 24570248
11.  Isolation of Actinobaculum schaalii and Actinobaculum urinale from a Patient with Chronic Renal Failure 
Journal of Clinical Microbiology  2005;43(7):3567-3569.
We report on the isolation of two species of Actinobaculum from blood culture of a patient with chronic renal failure. The two isolates were distinct with regard to their morphological and biochemical characteristics. Subsequent 16S rRNA gene sequencing classified the two species as Actinobaculum schaalii and A. urinale.
PMCID: PMC1169164  PMID: 16000509
12.  Bacterial susceptibility to oral antibiotics in community acquired urinary tract infection 
Archives of Disease in Childhood  2003;88(3):215-218.
Background: The most common oral antibiotics used in the treatment of urinary tract infection (UTI) are sulphonamides and cephalosporins, but emerging resistance is not unusual.
Aims: To assess the change in susceptibility of urinary pathogens to oral antibiotics during the past decade in children with community acquired UTI.
Methods: The study sample included two groups of children with a first community acquired UTI: 142 children enrolled in 1991 and 124 enrolled in 1999. UTI was diagnosed by properly collected urine specimen (suprapubic aspiration, transurethral catheterisation, or midstream specimen in circumcised males) in symptomatic patients. Antimicrobial susceptibility of the isolates was compared between the two groups.
Results: The pathogens recovered in the two groups were similar: in 1991—E coli 86%, Klebsiella 6%, others 8%; in 1999—E coli 82%, Klebsiella 13%, and others 5%. A slight but generalised decrease in bacterial susceptibility to common antibiotics in the two groups was shown: ampicillin 35% versus 30%; cephalexin 82% versus 63% (p < 0.001); nitrofurantoin 93% versus 92%. The only exception was co-trimoxazole, 60% versus 69%. Overall resistance to antibiotics in 1999 was as follows: ampicillin 70%, cephalexin 37%, co-trimoxazole 31%, amoxicillin-clavulanate 24%, nitrofurantoin 8%, cefuroxime-axetil 5%, nalidixic acid 3%.
Conclusions: This study shows a slight but generalised decrease in bacterial susceptibility to common oral antibiotics in the past decade in our population. Empirical initial treatment with co-trimoxazole or cephalexin is inadequate in approximately one third of UTI cases. A larger number of pathogens may be empirically treated with amoxicillin-clavulanate (24% resistance); 95% of organisms are susceptible to cefuroxime-axetil.
PMCID: PMC1719471  PMID: 12598381
13.  Urinary tract infections in infants and children: Diagnosis and management 
Paediatrics & Child Health  2014;19(6):315-319.
Recent studies have resulted in major changes in the management of urinary tract infections (UTIs) in children. The present statement focuses on the diagnosis and management of infants and children >2 months of age with an acute UTI and no known underlying urinary tract pathology or risk factors for a neurogenic bladder. UTI should be ruled out in preverbal children with unexplained fever and in older children with symptoms suggestive of UTI (dysuria, urinary frequency, hematuria, abdominal pain, back pain or new daytime incontinence). A midstream urine sample should be collected for urinalysis and culture in toilet-trained children; others should have urine collected by catheter or by suprapubic aspirate. UTI is unlikely if the urinalysis is completely normal. A bagged urine sample may be used for urinalysis but should not be used for urine culture. Antibiotic treatment for seven to 10 days is recommended for febrile UTI. Oral antibiotics may be offered as initial treatment when the child is not seriously ill and is likely to receive and tolerate every dose. Children <2 years of age should be investigated after their first febrile UTI with a renal/bladder ultrasound to identify any significant renal abnormalities. A voiding cystourethrogram is not required for children with a first UTI unless the renal/bladder ultrasound reveals findings suggestive of vesicoureteral reflux, selected renal anomalies or obstructive uropathy.
PMCID: PMC4173959  PMID: 25332662
Bacteremia; Cefixime; Cystitis; Gentamicin; Pyelonephritis; Pyuria; Sepsis; UTI; VUR
14.  Urinary tract infection in children 
Clinical Evidence  2010;2010:0306.
Up to 11.3% of girls and 3.6% of boys will have had a urinary tract infection (UTI) by the age of 16 years, and recurrence of infection is common. Vesicoureteric reflux is identified in up to 40% of children being investigated for a first UTI, and is a risk factor for, but weak predictor of, renal parenchymal defects.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatment of acute urinary tract infection in children? What are the effects of interventions to prevent recurrence? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
We found 25 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics (short initial intravenous antibiotics, long initial intravenous antibiotics, initial oral antibiotics, single-dose or single-day courses of oral antibiotics, short courses of oral antibiotics, long courses of oral antibiotics, immediate empirical antibiotics, delayed antibiotics, prolonged delay of antibiotics, prophylactic antibiotics); immunotherapy; surgical correction of minor functional abnormalities; and surgical correction of moderate to severe vesicoureteric reflux.
Key Points
Up to 11.3% of girls and 3.6% of boys will have had a UTI by the age of 16 years, and recurrence of infection is common. Vesicoureteric reflux is identified in up to 40% of children being investigated for a first UTI, and it is a risk factor for, but weak predictor of, renal scarring.Renal parenchymal defects occur in 5% to 15% of children within 1 to 2 years of their first presentation with UTI, and it is associated with increased risks of progressive renal damage. The risk of parenchymal defects probably diminishes over time.
There is consensus that antibiotics are beneficial in children with UTI compared with no treatment, although few studies have been done to confirm this. Shorter courses (2–4 days) of initial intravenous antibiotics seem as effective as longer courses (7–14 days) at curing infections, preventing recurrence of infection, and preventing renal parenchymal defects in children with acute pyelonephritis. Oral antibiotics may be as effective as intravenous antibiotics at treating UTI (including pyelonephritis) and preventing complications. Single doses or single-day courses of oral antibiotics may be less effective than longer courses of oral antibiotics at treating UTI in children. Shorter courses (2–4 days) of oral antibiotics seem as effective as longer courses at treating UTI in children without acute pyelonephritis or known renal tract abnormalities and may be associated with fewer adverse effects.We don't know whether immediate empirical antibiotic treatment is more effective at preventing renal parenchymal defects compared with treatment after a delay of 24 hours.Immediate treatment may reduce the risk of renal parenchymal defects compared with treatment delayed for over 4 days.
Prophylactic antibiotics probably don’t reduce the risk of recurrent UTI, and can cause adverse effects. Immunotherapy, used in addition to prophylactic antibiotics, may reduce recurrence of UTI, but studies so far have been small.
Surgical correction of moderate to severe vesicoureteric reflux may be no more effective than medical management in preventing UTI recurrence or complications and increases morbidity associated with surgery. Children with minor functional anomalies do not seem to develop renal parenchymal defects, and so may not benefit from surgery for minor functional anomalies.
PMCID: PMC2907613  PMID: 21733199
To determine if urinary symptoms or urinary tract infections (UTI) were associated with sexually transmitted infections (STI) and which history, clinical, and laboratory findings could distinguish these infections in symptomatic women.
A cross sectional sample of 296 sexually-active females aged 14–22 attending a hospital-based teen health center or emergency department were recruited. Genitourinary symptoms, medical and sexual history, and urinalysis results were recorded. STI was defined as a vaginal swab positive for Trichomonas vaginalis or urine nucleic acid amplification test positive for Neisseria gonorrheae or Chlamydia trachomatis. A urine culture with >10,000 colonies of a single pathogen was considered a positive UTI.
In the full sample, prevalence of UTI and STI were 17% and 33%, respectively. Neither urinary symptoms nor UTI was significantly associated with STI. Further analyses are reported for the 154 (51%) with urinary symptoms: Positive urine leukocytes, >1 partner in the last 3 months and history of STI predicted STI. Urinalysis results identified four groups: (1)Normal urinalysis – 67% had no infection; (2)Positive nitrites or protein – 55% had UTI; (3)Positive leukocytes or blood – 62% had STI; and (4)Both nitrites/protein and leukocytes/blood positive – 28% had STI and 65% had UTI. Those without a documented UTI were more likely to have trichomoniasis than those with a UTI, and 65% of those with sterile pyuria had STI, mainly trichomoniasis or gonorrhea.
Adolescent females with urinary symptoms should be tested for both UTI and STIs. Urinalysis results may be helpful to direct initial therapy.
PMCID: PMC1976261  PMID: 17448399
16.  Detection of Intracellular Bacterial Communities in Human Urinary Tract Infection 
PLoS Medicine  2007;4(12):e329.
Urinary tract infections (UTIs) are one of the most common bacterial infections and are predominantly caused by uropathogenic Escherichia coli (UPEC). While UTIs are typically considered extracellular infections, it has been recently demonstrated that UPEC bind to, invade, and replicate within the murine bladder urothelium to form intracellular bacterial communities (IBCs). These IBCs dissociate and bacteria flux out of bladder facet cells, some with filamentous morphology, and ultimately establish quiescent intracellular reservoirs that can seed recurrent infection. This IBC pathogenic cycle has not yet been investigated in humans. In this study we sought to determine whether evidence of an IBC pathway could be found in urine specimens from women with acute UTI.
Methods and Findings
We collected midstream, clean-catch urine specimens from 80 young healthy women with acute uncomplicated cystitis and 20 asymptomatic women with a history of UTI. Investigators were blinded to culture results and clinical history. Samples were analyzed by light microscopy, immunofluorescence, and electron microscopy for evidence of exfoliated IBCs and filamentous bacteria. Evidence of IBCs was found in 14 of 80 (18%) urines from women with UTI. Filamentous bacteria were found in 33 of 80 (41%) urines from women with UTI. None of the 20 urines from the asymptomatic comparative group showed evidence of IBCs or filaments. Filamentous bacteria were present in all 14 of the urines with IBCs compared to 19 (29%) of 66 samples with no evidence of IBCs (p < 0.001). Of 65 urines from patients with E. coli infections, 14 (22%) had evidence of IBCs and 29 (45%) had filamentous bacteria, while none of the gram-positive infections had IBCs or filamentous bacteria.
The presence of exfoliated IBCs and filamentous bacteria in the urines of women with acute cystitis suggests that the IBC pathogenic pathway characterized in the murine model may occur in humans. The findings support the occurrence of an intracellular bacterial niche in some women with cystitis that may have important implications for UTI recurrence and treatment.
Analyzing urine specimens from women with bladder infections, Scott Hultgren and colleagues find evidence for intracellular bacterial communities, which have been associated with recurrent urinary tract infections in mice.
Editors' Summary
Every year, nearly 10 million people in the United States—mainly women—consult their doctors because of a urinary tract infection (UTI). UTIs occur when bacteria living in the gut—usually Escherichia coli—get transferred to the opening of the urethra (the tube through which urine leaves the body), as may occur during sexual intercourse. From here, the bacteria can move into the bladder (the muscular sac that stores urine until it is excreted) where they can multiply and cause cystitis (inflammation of the bladder). If cystitis is untreated, the bacteria can move further up the urinary tract and infect the kidneys (which make urine). Symptoms of UTIs include pain when urinating, frequent and intense urges to urinate, and cloudy urine. UTIs are diagnosed by looking for bacteria and white blood cells (that fight infection) in the urine; the usual treatment is a short course of antibiotics.
Why Was This Study Done?
Half the women who get a UTI will have another attack within a year, often caused by the same bacterial strain. It is generally thought that these strains persist in the gut and reinfect the urinary tract, but recent animal studies suggest an additional explanation. In mice, E. coli strains that cause UTIs can invade the cells lining the bladder. Here, they replicate and form so-called intracellular bacterial communities (IBCs). Many of the infected cells fall off the bladder's surface into the urine, but IBCs also release bacteria, many of which have a long, slender filamentous appearance (E. coli usually have a simple rod-like shape). Immune system cells normally kill bacteria in the urine but cannot deal with filamentous bacteria. In mice, these bacteria can then reinfect the lining of the bladder and establish long-lasting intracellular reservoirs of bacteria that are protected from antibiotics and probably from the host immune system. If this IBC cycle occurs in people, it might explain why some UTIs recur and might suggest ways to manage these recurrences. In this study, therefore, the researchers have investigated whether there is an IBC cycle in women.
What Did the Researchers Do and Find?
The researchers collected urine from 80 young women with cystitis and from 20 women with no symptoms who had had cystitis previously. They identified the type of bacteria in each sample and looked for IBCs and filamentous bacteria using light microscopy, electron microscopy, and a technique called immunofluorescence. None of the women without cystitis had IBCs or filamentous bacteria in their urine, but IBCs were found in nearly 1 in 5, and filamentous bacteria were in nearly half, of urine samples from the women with cystitis. All the urine samples that contained IBCs also contained filamentous bacteria. All of the women with IBCs and most of them with filamentous bacteria had E coli infections. Finally, the women with IBCs and filamentous bacteria in their urine had higher bacterial counts in their urine and had symptoms of cystitis for slightly longer than those without.
What Do These Findings Mean?
These findings suggest that the IBC cycle identified in mice occurs in at least some women with UTIs and may be associated with infections caused by E. coli. Because only one urine sample was collected from each woman, the cycle may be more common than these findings suggest. That is, in some cases the sample may have been taken at a time when there were no IBCs or filamentous bacteria in the urine. Also, because samples were taken at only one point in time, this study does not show whether intracellular bacteria persist and contribute to recurrent UTIs in women, as they appear to do in mice. To provide more information about the IBC cycle in people and its clinical relevance, additional studies are needed to examine whether there are any associations between the presence of IBCs and filamentous bacteria and treatment responses and recurrence, and to examine what is actually happening in the bladder during UTI. Until such studies are done, the clinical implications of the current findings remain uncertain. However, one possibility is that the presence of IBCs and filamentous bacteria in urine might identify people who would benefit from longer treatment with antibiotics or treatment with antibiotics that kill bacteria inside human cells.
Additional Information.
Please access these Web sites via the online version of this summary at
The MedlinePlus encyclopedia contains pages on urinary tract infection, on cystitis, and on recurrent cystitis (in English and Spanish)
Information is available from the UK National Health Service Direct health encyclopedia on urinary tract infections and on cystitis
The US National Kidney and Urologic Diseases Information Clearinghouse provides information on urinary tract infections (in English and Spanish)
Information is available from the American Urological Association on urinary tract infections in adults
PMCID: PMC2140087  PMID: 18092884
17.  Diversity of Group B Streptococcus Serotypes Causing Urinary Tract Infection in Adults▿  
Journal of Clinical Microbiology  2009;47(7):2055-2060.
Serotypes of group B streptococcus (GBS) that cause urinary tract infection (UTI) are poorly characterized. We conducted a prospective study of GBS UTI in adults to define the clinical and microbiological characteristics of these infections, including which serotypes cause disease. Patients who had GBS cultured from urine over a 1-year period were grouped according to symptoms, bacteriuria, and urinalysis. Demographic data were obtained by reviewing medical records. Isolates were serotyped by latex agglutination and multiplex PCR-reverse line blotting (mPCR/RLB). Antibiotic susceptibilities were determined by disc diffusion. GBS was cultured from 387/34,367 consecutive urine samples (1.1%): 62 patients had bacteriuria of >107 CFU/liter and at least one UTI symptom; of these patients, 31 had urinary leukocyte esterase and pyuria (others not tested), 50 (81%) had symptoms consistent with cystitis, and 12 (19%) had symptoms of pyelonephritis. Compared with controls (who had GBS isolated without symptoms), a prior history of UTI was an independent risk factor for disease. Increased age was also significantly associated with acute infection. Serotyping results were consistent between latex agglutination and mPCR/RLB for 331/387 (85.5%) isolates; 22 (5.7%) and 7 (1.8%) isolates were nontypeable with antisera and by mPCR/RLB, respectively; and 45/56 (80.4%) isolates with discrepant results were typed by mPCR/RLB as belonging to serotype V. Serotypes V, Ia, and III caused the most UTIs; serotypes II, Ib, and IV were less common. Nontypeable GBS was not associated with UTI. Erythromycin (39.5%) and clindamycin (26.4%) resistance was common. We conclude that a more diverse spectrum of GBS serotypes causes UTI than previously recognized, with the exception of nontypeable GBS.
PMCID: PMC2708523  PMID: 19439533
18.  Use of Urine Testing in Outpatients Treated for Urinary Tract Infection 
Pediatrics  2013;132(3):437-444.
To characterize urine test use in ambulatory, antibiotic-treated pediatric urinary tract infection (UTI).
We studied children <18 years who had an outpatient UTI and a temporally associated antibiotic prescription from 2002 through 2007 by using a large claims database, Innovus i3. We evaluated urine-testing trends and performed multivariable logistic regression to assess for factors associated with urine culture use.
Of 40 603 treated UTI episodes in 28 678 children, urinalysis was performed in 76%, and urine culture in 57%; 32% of children <2 years had no urinalysis or culture performed for an antibiotic-treated UTI episode. Urine culture use decreased during the study period from 60% to 54% (P < .001). We observed variation in urine culture use with age (<2 years: odds ratio [OR] 1.0, 95% confidence interval [CI] 0.9–1.1; 2–5 years: OR 1.3, 95% CI 1.2–1.4; 6–12 years: OR 1.3, 95% CI 1.2–1.4, compared with 13–17 years); gender (boys: OR 0.8, 95% CI 0.8–0.9); and specialty (pediatrics: OR 2.6, 95% CI 2.5–2.8; emergency medicine, OR 1.2, 95% CI 1.1–1.3; urology: OR 0.5, 95% CI 0.4–0.6, compared with family/internal medicine). Recent antibiotic exposure (OR 1.1, 95% CI 1.1–1.2) and empirical broad-spectrum prescription (OR 1.2, 95% CI 1.1–1.2) were associated with urine culture use, whereas previous UTI and urologic anomalies were not.
Providers often do not obtain urine tests when prescribing antibiotics for outpatient pediatric UTI. Variation in urine culture use was observed based on age, gender, and physician specialty. Additional research is necessary to determine the implications of empirical antibiotic prescription for pediatric UTI without confirmatory urine testing.
PMCID: PMC3876750  PMID: 23918886
urinary tract infection; urinalysis; urine culture; antibiotic prescription; pediatric
19.  Study of Aetiology and Anti-biogram of Uropathogens in Children-A Retrospective Analysis 
Objectives: Urinary Tract Infections (UTIs) are the most common serious bacterial infections which are seen during infancy. The aim of the present study was to evaluate aetiology, and antimicrobial resistance patterns among infants and children who approached our hospital for treatment of UTIs.
Methods: In this observational study which was carried out from 2007 to 2010, 1575 urine samples which were collected from children with suspected UTIs were studied. Demographic characteristics, aetiological agents and antimicrobial resistance were evaluated.
Results: UTIs were more common in the 0-1 year age group, among males. Among females, UTIs were commonly seen after 2 years of life. The most common isolated pathogen was Escherichia coli spp (45.12%), followed by Klebsiella spp (18.17%) and Enterococcus spp (9.23%). Isolated pathogens were highly resistant to ampicillin, co-trimoxazole, and norfloxacin (82%–98%) and highly sensitive to gentamicin (83%),amikacin (76.5%), and nitrofurantoin (71.5%).
Conclusion: The most common pathogen which caused UTIs in children was E. coli spp.
The isolated pathogens were highly resistant to commonly used antibiotics, ampicillin and co-trimoxazole, while they were highly sensitive to gentamicin, amikacin and nitrofurantoin. So, these antibiotics may be used as alternative drug therapies for the treatment of UTIs.
PMCID: PMC3939551  PMID: 24596714
Urinary tract infection; Antibiotic resistance; Sensitivity; Escherichia coli
20.  The diagnosis of urinary tract infections in young children (DUTY): protocol for a diagnostic and prospective observational study to derive and validate a clinical algorithm for the diagnosis of UTI in children presenting to primary care with an acute illness 
BMC Infectious Diseases  2012;12:158.
Urinary tract infection (UTI) is common in children, and may cause serious illness and recurrent symptoms. However, obtaining a urine sample from young children in primary care is challenging and not feasible for large numbers. Evidence regarding the predictive value of symptoms, signs and urinalysis for UTI in young children is urgently needed to help primary care clinicians better identify children who should be investigated for UTI. This paper describes the protocol for the Diagnosis of Urinary Tract infection in Young children (DUTY) study. The overall study aim is to derive and validate a cost-effective clinical algorithm for the diagnosis of UTI in children presenting to primary care acutely unwell.
DUTY is a multicentre, diagnostic and prospective observational study aiming to recruit at least 7,000 children aged before their fifth birthday, being assessed in primary care for any acute, non-traumatic, illness of ≤ 28 days duration. Urine samples will be obtained from eligible consented children, and data collected on medical history and presenting symptoms and signs. Urine samples will be dipstick tested in general practice and sent for microbiological analysis. All children with culture positive urines and a random sample of children with urine culture results in other, non-positive categories will be followed up to record symptom duration and healthcare resource use. A diagnostic algorithm will be constructed and validated and an economic evaluation conducted.
The primary outcome will be a validated diagnostic algorithm using a reference standard of a pure/predominant growth of at least >103, but usually >105 CFU/mL of one, but no more than two uropathogens.
We will use logistic regression to identify the clinical predictors (i.e. demographic, medical history, presenting signs and symptoms and urine dipstick analysis results) most strongly associated with a positive urine culture result. We will then use economic evaluation to compare the cost effectiveness of the candidate prediction rules.
This study will provide novel, clinically important information on the diagnostic features of childhood UTI and the cost effectiveness of a validated prediction rule, to help primary care clinicians improve the efficiency of their diagnostic strategy for UTI in young children.
PMCID: PMC3575241  PMID: 22812651
Urinary Tract Infection; Children; Primary care; Point-of-care-test; Dipstick test; Near-patient testing; Diagnosis; Economic models
21.  Prospective Cohort Study of Microbial and Inflammatory Events Immediately Preceding Escherichia coli Recurrent Urinary Tract Infection in Women 
The Journal of infectious diseases  2009;200(4):528-536.
A prospective cohort study was conducted to characterize the temporal sequence of microbial and inflammatory events immediately preceding Escherichia coli recurrent urinary tract infection (rUTI).
Women with acute cystitis and a history of UTI within the previous year self-collected periurethral and urine samples daily and recorded measurements of urine leukocyte esterase, symptoms, and sexual intercourse daily for 3 months. rUTI strains were characterized by pulsed-field gel electrophoresis and genomic virulence profiling. Urinary cytokine levels were measured.
There were 38 E. coli rUTIs in 29 of 104 women. The prevalence of periurethral rUTI strain carriage increased from 46% to 90% during the 14 days immediately preceding rUTI, with similar increases in same-strain bacteriuria (from 7% to 69%), leukocyte esterase (from 31% to 64%), and symptoms (from 3% to 43%), most notably 2–3 days before rUTI (P < .05 for all comparisons). Intercourse with periurethral carriage of the rUTI strain also increased before rUTI (P = .008). Recurrent UTIs preceded by bacteriuria, pyuria, and symptoms were caused by strains less likely to have P fimbriae than other rUTI strains (P = .002).
Among women with frequent rUTIs, the prevalences of periurethral rUTI strain carriage, bacteriuria, pyuria, and intercourse dramatically increase over the days preceding rUTI. A better understanding of the pathogenesis of rUTI will lead to better prevention strategies.
PMCID: PMC3674869  PMID: 19586416
22.  Urinary ATP and visualization of intracellular bacteria: a superior diagnostic marker for recurrent UTI in renal transplant recipients? 
SpringerPlus  2014;3:200.
Renal transplant recipients (RTR) are highly susceptible to urinary tract infections (UTIs) with over 50% of patients having at least one UTI within the first year. Yet it is generally acknowledged that there is considerable insensitivity and inaccuracy in routine urinalysis when screening for UTIs. Thus a large number of transplant patients with genuine urine infections may go undiagnosed and develop chronic recalcitrant infections, which can be associated with graft loss and morbidity. Given a recent study demonstrating ATP is released by urothelial cells in response to bacteria exposure, possibly acting at metabotropic P2Y receptors mediating a proinflammatory response, we have investigated alternative, and possibly more appropriate, urinalysis techniques in a cohort of RTRs.
Mid-stream urine (MSU) samples were collected from 53 outpatient RTRs. Conventional leukocyte esterase and nitrite dipstick tests, and microscopic pyuria counts (in 1 μl), ATP concentration measurements, and identification of intracellular bacteria in shed urothelial cells, were performed on fresh unspun samples and compared to ‘gold-standard’ bacterial culture results.
Of the 53 RTRs, 22% were deemed to have a UTI by ‘gold-standard’ conventional bacteria culture, whereas 87%, 8% and 4% showed evidence of UTIs according to leukocyte esterase dipstick, nitrite dipstick, and a combination of both dipsticks, respectively. Intracellular bacteria were visualized in shed urothelial cells of 44% of RTRs, however only 1 of the 23 RTRs (44%) was deemed to have a UTI by conventional bacteria culture. A significant association of the ‘gold-standard’ test with urinary ATP concentration combined with visualization of intracellular bacteria in shed urothelial cells was determined using the Fisher’s exact test.
It is apparent that standard bedside tests for UTIs give variable results and that seemingly quiescent bacteria in urothelial cells are very common in RTRs and may represent a focus of subclinical infection. Furthermore, our results suggest urinary ATP concentration combined with detection of intracellular bacteria in shed urinary epithelial cells may be a sensitive means by which to detect ‘occult’ infection in RTRs.
PMCID: PMC4022969  PMID: 24839587
Intracellular bacteria; IBC; Pyuria; Urinary ATP; Bladder; Acridine orange stain
Objective: This study was designed to determine the frequency and causative agent(s) of urinary tract infections (UTIs) in individuals with symptoms of urinary tract infections in Enugu State of Southeast Nigeria, and to determine the antibiotic susceptibility pattern of microbial agents isolated from urine culture.
Methods: The study involved 211 individuals (149 females and 62 males) clinically suspected for UTI. Urine samples were collected by the mid-stream ‘clean catch’ method and tested using standard procedures. Antibiotic susceptibility of the isolated pathogens was tested using the Kirby-Bauer technique according to the Clinical and Laboratory Standards Institute (CLSI) guidelines.
Results: Microscopy of centrifuged urine samples showed 16 patients had pyuria while 54 had pus cells. Calcium oxalate crystals were found in 14 samples. Urinalysis performed with urine samples showed 17 had protein; seven were nitrite positive and three had moderate to high glucose concentration. Fifty-four urine samples (36.2%) from females and 12 (19.4%) from males showed significant growth upon culture. Gram stain and biochemical tests identified nine different organisms with Escherichia coli as the most common isolated species. Forty three randomly selected strains were further tested for their susceptibility against a panel of antibiotics. Thirty isolates (81.08%) were resistant to four or more antibiotics with the highest resistance shown by E. coli (76.67%). All the Gram- negative isolates were resistant to Ampicilox, Cefuroxime and Amoxicillin.
Conclusion: Urinary tract infections were found more in females in the area under study. As found in other studies, E. coli was the most predominant isolate, although other organisms seem to be on the increase.
PMCID: PMC4085832  PMID: 24553609
Urinary tract infection; Pathogen; Southeast Nigeria; Etiology; Antibiotic susceptibility
24.  Frequency and antimicrobial resistance patterns of bacteria implicated in community urinary tract infections: a ten-year surveillance study (2000–2009) 
Urinary tract infection (UTI) is one of the most common infectious diseases at the community level. In order to assess the adequacy of the empirical therapy, the prevalence and the resistance pattern of the main bacteria responsible for UTI in the community (in Aveiro, Portugal) was evaluated throughout a ten-year period.
In this retrospective study, all urine samples from patients of the District of Aveiro, in ambulatory regime, collected at the Clinical Analysis Laboratory Avelab during the period 2000–2009 were analysed. Samples with more than 105 CFU/mL bacteria were considered positive and, for these samples, the bacteria were identified and the profile of antibiotic susceptibility was characterized.
From the 155597 samples analysed, 18797 (12.1%) were positive for bacterial infection. UTI was more frequent in women (78.5%) and its incidence varied with age, affecting more the elderly patients (38.6%). Although E. coli was, as usual, the most common pathogen implicated in UTI, it were observed differences related to the other bacteria more implicated in UTI relatively to previous studies. The bacteria implicated in the UTI varied with the sex of the patient, being P. aeruginosa a more important cause of infection in men than in women. The incidence of the main bacteria changed over the study period (P. aeruginosa, Klebsiella spp and Providencia spp increased and Enterobacter spp decreased). Although E. coli was responsible for more than an half of UTI, its resistance to antibiotics was low when compared with other pathogens implicated in UTI, showing also the lowest percentage of multidrug resistant (MDR) isolates (17%). Bacteria isolated from females were less resistant than those isolated from males and this difference increased with the patient age.
The differences in sex and age must be taken into account at the moment of empirical prescription of antimicrobials. From the recommended antimicrobials by the European Association of Urology guidelines, the first line drugs (pivmecillinam and nitrofurantoin) and the alternative antibiotic amoxicillin-clavulanic acid (AMX-CLA) are appropriate to treat community-acquired UTI, but the fluoroquinolones should not be suitable to treat male infections and the trimethoprim-sulfamethoxazole (SXT) shall not be used in the treatment of UTI at this level.
PMCID: PMC3556060  PMID: 23327474
Community-acquired urinary tract infection; Uropathogens; Antibiotics; Antimicrobial resistance; Multidrug resistance
25.  Short compared with standard duration of antibiotic treatment for urinary tract infection: a systematic review of randomised controlled trials 
Archives of Disease in Childhood  2002;87(2):118-123.
Aims: To compare the effectiveness of short course (2–4 days) with standard duration oral antibiotic treatment (7–14 days) for urinary tract infection (UTI).
Methods: Meta-analysis of randomised controlled trials using a random effects model. Ten trials were eligible, involving 652 children with lower tract UTI recruited from outpatient or emergency departments. Main outcome measures were UTI at the end of treatment, UTI during follow up (recurrent UTI), and urinary pathogens resistant to the treating antibiotic.
Results: There was no significant difference in the frequency of positive urine cultures between the short (2–4 days) and standard duration therapy (7–14 days) for UTI in children at 0–7 days after treatment (eight studies: RR 1.06; 95% CI 0.64 to 1.76) and at 10 days to 15 months after treatment (10 studies: RR 1.01; 95% CI 0.77 to 1.33). There was no significant difference between short and standard duration therapy in the development of resistant organisms in UTI at the end of treatment (one study: RR 0.57, 95% CI 0.32 to 1.01) or in recurrent UTI (three studies: RR 0.39, 95% CI 0.12 to 1.29).
Conclusion: A 2–4 day course of oral antibiotics is as effective as 7–14 days in eradicating lower tract UTI in children.
PMCID: PMC1719177  PMID: 12138060

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