A Case of Sulfhemoglobinemia Secondary to a Urinary Tract Infection.

Sulfhemoglobinemia (SulfHb) is a rare dyshemoglobinemia that can present with cyanosis in the absence of respiratory distress. It has been reported secondary to drug ingestion and chronic constipation. We present a case of SulfHb in an adolescent female with spina bifida and neurogenic bladder in the setting of an Escherichia coli urinary tract infection. An arterial blood gas differentiated a dyshemoglobinemia from other causes of hypoxemia. The resolution was achieved with antibiotics and red cell transfusion. Here we review the pathophysiology of SulfHb and contribute a unique case report to the limited body of literature on this topic.

Diagnosis of Urinary Tract Infection in the Neuropathic Bladder: Changing the Paradigm to Include the Microbiome.

Bacteriuria, a non-specific term that refers to the presence of bacteria in the urine, is common in people with neuropathic bladders. However, accurately determining when bacteriuria represents a urinary tract infection (UTI) as opposed to asymptomatic bacteriuria is difficult. There is currently no widely accepted definition of what constitutes a UTI in people with neuropathic bladders. As a result, there is significant variation in care, which likely leads to unnecessary use of antibiotics for bacteriuria. To improve the clinical management of people with neuropathic bladders, it is important to be able to accurately diagnose and treat UTIs. In this article, we review the difficulties associated with accurately diagnosing UTIs and then review proposed definitions. Finally, we discuss the emerging literature of the urinary microbiome and how this may assist in accurately diagnosing UTIs in people with neuropathic bladders.

Infecciones urinarias en niños con vejiga neurogénica y los patrones de resistencia a los uropatógenos más frecuentes / Urinary tract infections in children with neurogenic bladder and resistance patterns of most frequent urological pathogens

Las infecciones del tracto urinario (ITU) en niños con vejiga neurogénica, pueden producir alteraciones tanto morfológicas como funcionales, y desencadenan una respuesta inmune que no siempre es evidente. Las ITU son una de las principales causas de morbilidad y mortalidad. Resulta de suma importancia un correcto diagnóstico de las mismas, para un buen tratamiento y así evitar las complicaciones y secuelas que puedan ocasionar. El objeto del trabajo fue analizar la prevalencia y la etiología de las ITU en pacientes con vejiga neurogénica, y su patrón de resistencia. En un estudio descriptivo, retrospectivo se incluyeron 46 muestras de orina para cultivo de niños de 1 a 18 años, de ambos sexos, con vejiga neurogénica, que fueron procesadas en un laboratorio de microbiología. De 46 urocultivos, 19 correspondieron a varones (19/46) 41% y 27 a niñas (27/46) 59%, los niños tenían una edad promedio de 11(2. De estos 21 resultaron positivos (21/46) 46%, aislando en mayor proporción E. coli. La frecuencia de ITU en niños con vejiga neurogénica fue de 21/46, 46%, siendo el porcentaje en este tipo de pacientes mucho más elevado que en niños que no presentan dicha anomalía. Los uropatógenos aislados con mayor frecuencia fueron E coli y K pneumoniae. El uso de sondas y pañales, así como la mala higiene predisponen a estas infecciones. En este estudio se vio buena sensibilidad a la nitrofurantoina y cefixima(AU)

The ability of prior urinary cultures results to predict future culture results in neurogenic bladder patients.

AIMS: To determine if previous urinary cultures can predict the organism and susceptibility of subsequent urinary cultures in patients with neurogenic bladder dysfunction. METHODS: We retrospectively identified a sample of neurogenic bladder patients from a tertiary care urology clinic (July 2015-July 2016). We reviewed the patient chart, and then used the electronic laboratory record to identify all urine cultures done in the 2 years prior. We identified sequential culture pairs and determined the concordance of the initial culture organism to the subsequent one and similarly the concordance of the initial culture's antibiotic resistance status to the subsequent culture's one. RESULTS: We identified 146 people with neurogenic bladder (mostly due to spinal cord injury [n = 61], multiple sclerosis [n = 26], or spina bifida [n = 25]). These individuals used primarily intermittent catheterization (n = 69, 47%) spontaneous voiding (n = 59, 40%), or indwelling foley catheter (n = 31, 21%). During the previous 2-years, 81 participants had at least two positive urine cultures and a total of 479 cultures could be examined for organism/susceptibility concordance. There was 56% concordance of bacterial species between subsequent urine cultures, and this decreased significantly with increasing time between cultures (P = 0.02). Antibiotic susceptibility concordance was high for ciprofloxacin (77%), nitrofurantoin (79%), and trimethoprim-sulfamethoxazole (75%), with no significant change with increasing time between cultures (P > 0.90). CONCLUSIONS: Previous positive urine cultures can provide valuable information regarding future organism and antibiotic susceptibility in individuals with neurogenic bladder. The practise of reviewing the previous urine culture when selecting empiric therapy is likely an effective practise in this population.

Uropathogens and Pyuria in Children With Neurogenic Bladders.

: media-1vid110.1542/5727212324001PEDS-VA_2017-3006Video Abstract BACKGROUND: A recent study revealed that specific uropathogens are associated with lower odds of pyuria in a general pediatrics population. Children with neurogenic bladders who require clean intermittent catheterization (CIC) frequently have pyuria. Our objective with this study was to determine if an association exists between pyuria and type of uropathogen in CIC-dependent children. METHODS: We obtained urinalysis and urine culture results from electronic medical records from January 2008 through December 2014 for patients ≤18 years of age with neurogenic bladders managed at a single institution. Cultures without concurrent urinalyses were excluded from analysis, as were cultures that yielded no growth, fungal growth, or growth of unidentified mixed organisms. We used logistic regression to determine the association of pyuria and leukocyte esterase with specific uropathogens. RESULTS: We included 2420 cultures in this analysis. The growth of Enterococcus on urine culture was associated with lower odds of both pyuria and leukocyte esterase. In contrast, the growth of more than 100 000 colony-forming units per milliliter of Proteus mirabilis was associated with increased odds of both pyuria and leukocyte esterase, and the growth of Pseudomonas aeruginosa was associated with increased odds of leukocyte esterase but not pyuria. Certain etiologies of neurogenic bladder, such as bladder exstrophy and cloacal malformations, were also associated with increased odds of pyuria compared with neurogenic bladder due to myelomeningocele. CONCLUSIONS: In children with neurogenic bladders who require CIC, Enterococcus may grow in urine culture without pyuria or positive leukocyte esterase. Accordingly, urine cultures should be obtained in symptomatic children, regardless of urinalysis results.

[Original strategy for prevention of recurrent symptomatic urinary tract infections in patients with neurogenic bladder: Bacterial interference, state of the art]. / Stratégie préventive originale des infections urinaires symptomatiques chez les patients porteurs d'une vessie neurologique : l'interférence bactérienne, état de l'art.

PURPOSE: Urinary tract infection (UTI) is the most common complication in patients with neurogenic bladder. The long-term use of antibiotic drugs induces an increase in antimicrobial resistance and adverse drug reactions. Bacterial interference is a new concept to prevent recurrent UTI which consists in a bladder colonization with low virulence bacteria. We performed a literature review on this emerging therapy. MATERIALS AND METHODS: Literature review of bacterial interference to prevent symptomatic urinary tract infection in neurological population. RESULTS: Seven prospectives study including 3 randomized, double-blind and placebo controlled trial were analyzed. The neurological population was spinal cord injured in most cases. The bladder colonization was performed with 2 non-pathogen strains of Escherichia coli: HU 2117 and 83972. At 1 month, 38 to 83% of patients were colonized. Mean duration of colonization was 48.5 days to 12.3 months. All studies showed that colonization might reduce the number of urinary tract infections and is safe with absence of serious side effects. CONCLUSION: Bacterial interference is a promising alternative therapy for the prevention of recurrent symptomatic urinary tract infections in neurogenic patients. This therapy should have developments for a daily use practice and for a long-term efficacy.

Pasteurella aerogenes as an Asymptomatic Bacteriuria Agent.

'Asymptomatic bacteriuria' (ASB) is isolation of a specified quantitative count of bacteria in an appropriately collected urine specimen obtained from a person without symptoms or signs referable to urinary infection. Catheterized specimens are less likely to be contaminated compared with voided specimens; therefore, positive cultures of catheterized specimens are more likely to reflect true bladder bacteriuria even with low colony counts. The common pathogens for ASB are Escherichia coli, Klebsiella and Streptococcus spp. Pasteurella spp. was not previously reported as an ASB agent. ASB is important for pregnant women, children, individuals with obstructive uropathy, chronic renal failure and neutropenia, before the urologic procedures and after renal transplantation. Treatment of ASB is required for above situations. We report an 11-year-old-girl with neurogenic bladder who made clean intermittent catheterization and had Pasteurella aerogenes as an ASB agent.

Chronic infection of a Brindley sacral nerve root stimulator.

The Finetech-Brindley sacral anterior root stimulator (SARS) is implanted for the treatment of bladder dysfunction following spinal cord injury (SCI) and has been successful in improving micturition in many patients with SCI. This case describes a 62-year-old man who presented with a chronic Staphylococcus aureus infection of a Brindley SARS 26 years after implantation following a T5 American Spinal Injury Association A spinal cord injury (T5 ASIA A SCI). He presented with chronic sacral osteomyelitis with a history of periodic implant erosion through the skin. Following a series of interventions, definitive management involved removal of the intradural electrodes and epidural and intradural phlegmon, ligation of the thecal sac and flap reconstruction. In the case of delayed infection of a Brindley SARS, removal of the entire system should be considered, especially if extension of the infection to the intradural compartment is suspected.

Redefining Healthy Urine: A Cross-Sectional Exploratory Metagenomic Study of People With and Without Bladder Dysfunction.

PURPOSE: We used the PathoScope platform to perform species level analyses of publicly available, 16S rRNA pyrosequenced, asymptomatic urine data to determine relationships between microbiomes, and clinical and functional phenotypes. MATERIALS AND METHODS: We reanalyzed previously reported, cross-sectionally acquired urine samples from 47 asymptomatic subjects, including 23 controls and 24 subjects with neuropathic bladder. Urine was originally collected by the usual method of bladder drainage and analyzed by urinalysis, culture and pyrosequencing. Urinalysis and culture values were stratified as leukocyte esterase (0, or 1 or greater), nitrite (positive or negative), pyuria (fewer than 5, or 5 or greater white blood cells per high power field), cloudy urine (positive or negative) and urine culture bacterial growth (less than 50,000, or 50,000 or greater cfu/ml). PathoScope was used for next generation sequencing alignment, bacterial classification and microbial diversity characterization. RESULTS: Subjects with neuropathic bladder were significantly more likely to have positive leukocyte esterase and pyuria, cloudy urine and bacterial growth. Of 47 samples 23 showed bacterial growth on culture and in all samples bacteria were identified by pyrosequencing. Nonneuropathic bladder urine microbiomes included greater proportions of Lactobacillus crispatus in females and Staphylococcus haemolyticus in males. The Lactobacillus community differed significantly among females depending on bladder function. Irrespective of gender the subjects with neuropathic bladder had greater proportions of Enterococcus faecalis, Proteus mirabilis and Klebsiella pneumonia. In 4 subjects with neuropathic bladder Actinobaculum sp. was detected by sequencing and by PathoScope but not by cultivation and in all cases it was associated with pyuria. CONCLUSIONS: Using PathoScope plus 16S pyrosequencing we were able to identify unique, phenotype dependent, species level microbes. Novel findings included absent L. crispatus in the urine of females with neuropathic bladder and the presence of Actinobaculum only in subjects with neuropathic bladder.

[Evaluation of the adhesive characteristics of uropathogenic escherichia coli strains in patients with spinal cord injuries].

The adhesion characteristics of 9 clinical E.coli strains, isolated from the urine of 9 patients with spinal cord injuries in late period were evaluated. Patient age was 21 to 54 years. Neurogenic urination disordes observed in patients were the result of a spinal injury in the cervical (5 patients), thoracic (2 patients) and thoracolumbar (2 patients) spine. The duration of disease ranged from 2 to 12 years. Despite primarily a low adhesion activity of tested strains, the formation of biofilm occurs on the surfaces having both hydrophobic (polystyrene) and hydrophilic (cover glass) properties. After 24 h, according to the photometric evaluation, 7 of 9 strains had weak, 1 - medium, and 1 - high ability to form biofilms. After 48 hours, only 4 strains had low ability to form biofilms, of whom 2 had an increase ability compared to the previous period of observation. Other strains possess the medium ability to form biofilm. When quantifying the ability of bacteria to form biofilms on the surface of the cover glass, it was revealed that a large fraction of the area of the field of view was accounted for microcolonies with size 10 microm2 at 24 hours, and microcolony with size from 100 to 1000 microm2 at 48 h. There were number of significant correlations between parameters studied. After 24 h, the correlation coefficient between the optical density (OD630) and the number, OD630 and proportion of microcolonies with size 10 to 10000 microm2 varied from 0.79 to 0.9. After 48 hours, there was a direct correlation between the OD630 and the number (r = 0.73, P = 0.025), OD630 and proportion (r = 0.81, P = 0.009) of microcolonies with size 1,000 to 10,000 mkm2.

Persistent neurogenic bladder dysfunction due to infantile botulism.

We present a child, 5 months of age, diagnosed with infantile botulism, showing the signs of neurogenic bladder dysfunction. The patient presented with progressive muscle weakness, hypotonia, suckling and swallowing problems and absent peripheral reflexes at clinical examination. Botulinum neurotoxin type A was detected in her serum, confirming the diagnosis. Starting at day 6, the girl presented with a urinary retention initially necessitating free bladder drainage and subsequently intermittent catheterisation. After 6 weeks in intensive care, the patient recovered but the bladder underactivity persisted. Four months following recovery, a urodynamic evaluation was performed, showing a near normal detrusor activity and normal bladder emptying, and the catheterisation was ceased. At 6 months, the girl was diagnosed with a urinary tract infection and bladder emptying problems, which persisted, and clean intermittent catheterisation was started. The final urodynamic evaluation, a year and a half after her initial presentation, revealed a normal detrusor activity and an adequate bladder emptying.

Integrated next-generation sequencing of 16S rDNA and metaproteomics differentiate the healthy urine microbiome from asymptomatic bacteriuria in neuropathic bladder associated with spinal cord injury.

BACKGROUND: Clinical dogma is that healthy urine is sterile and the presence of bacteria with an inflammatory response is indicative of urinary tract infection (UTI). Asymptomatic bacteriuria (ABU) represents the state in which bacteria are present but the inflammatory response is negligible. Differentiating ABU from UTI is diagnostically challenging, but critical because overtreatment of ABU can perpetuate antimicrobial resistance while undertreatment of UTI can result in increased morbidity and mortality. In this study, we describe key characteristics of the healthy and ABU urine microbiomes utilizing 16S rRNA gene (16S rDNA) sequencing and metaproteomics, with the future goal of utilizing this information to personalize the treatment of UTI based on key individual characteristics. METHODS: A cross-sectional study of 26 healthy controls and 27 healthy subjects at risk for ABU due to spinal cord injury-related neuropathic bladder (NB) was conducted. Of the 27 subjects with NB, 8 voided normally, 8 utilized intermittent catheterization, and 11 utilized indwelling Foley urethral catheterization for bladder drainage. Urine was obtained by clean catch in voiders, or directly from the catheter in subjects utilizing catheters. Urinalysis, urine culture and 16S rDNA sequencing were performed on all samples, with metaproteomic analysis performed on a subsample. RESULTS: A total of 589454 quality-filtered 16S rDNA sequence reads were processed through a NextGen 16S rDNA analysis pipeline. Urine microbiomes differ by normal bladder function vs. NB, gender, type of bladder catheter utilized, and duration of NB. The top ten bacterial taxa showing the most relative abundance and change among samples were Lactobacillales, Enterobacteriales, Actinomycetales, Bacillales, Clostridiales, Bacteroidales, Burkholderiales, Pseudomonadales, Bifidobacteriales and Coriobacteriales. Metaproteomics confirmed the 16S rDNA results, and functional human protein-pathogen interactions were noted in subjects where host defenses were initiated. CONCLUSIONS: Counter to clinical belief, healthy urine is not sterile. The healthy urine microbiome is characterized by a preponderance of Lactobacillales in women and Corynebacterium in men. The presence and duration of NB and method of urinary catheterization alter the healthy urine microbiome. An integrated approach of 16S rDNA sequencing with metaproteomics improves our understanding of healthy urine and facilitates a more personalized approach to prevention and treatment of infection.

The encrustation and blockage of long-term indwelling bladder catheters: a way forward in prevention and control.

OBJECTIVES: To review the literature showing that understanding how Foley catheters become encrusted and blocked by crystalline bacterial biofilms has led to strategies for the control of this complication in the care of patients undergoing long-term indwelling bladder catheterization. METHODS: A comprehensive PubMed search of the literature published between 1980 and December 2009 was made for relevant articles using the Medical Subject Heading terms 'biofilms', 'urinary catheterization', 'catheter-associated urinary tract infection' and 'urolithiasis'. Papers on catheter-associated urinary tract infections and bacterial biofilms collected during 40 years of working in the field were also reviewed. RESULTS: There is strong experimental and epidemiological evidence that infection by Proteus mirabilis is the main cause of the crystalline biofilms that encrust and block Foley catheters. The ability of P. mirabilis to generate alkaline urine and to colonize all available types of indwelling catheters allows it to take up stable residence in the catheterized tract in bladder stones and cause recurrent catheter blockage. CONCLUSION: The elimination of P. mirabilis by antibiotic therapy as soon as it appears in the catheterized urinary tract could improve the quality of life for many patients and reduce the current expenditure of resources when managing the complications of catheter encrustation and blockage. For patients who are already chronic blockers and stone formers, antibiotic treatment is unlikely to be effective owing to the resistance of cells in the crystalline biofilms. Strategies such as increasing fluid intake with citrated drinks could control the problem until bladder stone removal can be organized.

Bladder dysfunction in spinal tuberculosis: clinical, urodynamic and MRI study.

STUDY DESIGN: An observational study. OBJECTIVE: We report clinical, MRI and urodynamic findings in spinal tuberculosis. SETTING: Tertiary care teaching hospital. METHOD: Patients with spinal tuberculosis having micturition disturbances or high postvoidal residual (PVR) urine were subjected to clinical evaluation, urodynamic and spinal MRI. Urinary symptoms were scored as per the American Urological Association Symptom (AUAS) Index. The outcome was defined at 12 months into complete, partial and poor. RESULTS: Of 30 spinal tuberculosis patients, 15 had micturition disturbance and included urinary retention in 4, stress incontinence in 2, hesitancy in 6, urgency in 11 and urge incontinence in 9 patients. Thirteen patients had paraparesis and one had quadriparesis. Spinal MRI revealed granuloma in 2, dorsal vertebral involvement in 12 and cervical and lumbar vertebral involvement in 1 patient each. On urodynamic study, detrusor hyperreflexia (DH) with high-pressure voiding was present in six, detrusor areflexia (DA) in four, normal study in one and increased PVR urine in the remaining patients. AUAS score improved on follow-up. DA changed to DH with high-pressure voiding in one patient. The 15 patients without micturition disturbance had no horizontal sensory level, milder or no weakness and only 2 had spinal cord signal changes. Patients with micturition disturbances had poorer functional recovery at 1 year compared to those without micturition disturbances. CONCLUSION: Bladder symptoms were present in 50% of the admitted patients with spinal tuberculosis and related to severity of paraplegia, horizontal sensory level, cord signal abnormality and poorer outcome compared to those without spinal tuberculosis. Urodynamic study helped in categorization and management.

[Pneumococcal meningitis in children--9 1/2-year-experience at Szent László Hospital, Budapest, Hungary]. / Pneumococcus-meningitis gyermekkorban--kilenc és fél év tapasztalata a Szent László kórházban.

BACKGROUND AND OBJECTIVE: No recent publications are available about pneumococcal meningitis in Hungarian children. The aim of this study was to collect data of epidemiological, clinical and prognostic features of pneumococcal meningitis in children treated at Szent László Hospital, Budapest, Hungary. METHODS: We conducted a retrospective review of medical charts and follow-up records of patients aged 1 to 18 years admitted to our Pediatric and Pediatric Intensive Care Units due to pneumococcal meningitis between 1st Jan 1998 and 30th Jun 2007. RESULTS: 31 children with 34 cases of pneumococcal meningitis were admitted to our hospital in the study period. Two children developed recurrent illness. The mean age was 6 years, 26% were under 1 year of age. The mean duration of hospital stay was 21 days, 97% required intensive care. Frequent clinical symptoms were fever (100%), nuchal rigidity and vomiting (78%), altered mental status (71%), Kernig's and Brudzinski's signs (58%) and seizures (41%). Otitis media, sinusitis, mastoiditis were present in 44%, 58%, 41%, respectively. Subdural effusion, parenchymal cerebral lesion and sinus thrombosis were documented in 5, 3 and 2 cases, respectively. One third of the patients received ceftriaxon, two thirds were administered ceftriaxon and vancomycin. Adjunctive therapy with dexamethasone was given to 91% of the children. 70% of patients required mechanical ventilation. 9 patients (25%) required endoscopic sinus surgery. In 13 cases (38%) mastoidectomy, in 5 children (15%) neurosurgery was performed. The case fatality rate was 23.5%. 8 (23.5%) patients had mild or moderate, 1 child (3%) developed severe neurological sequelae. CONCLUSION: Pneumococcal meningitis in children remains a source of substantial morbidity and mortality in childhood. The long hospital stay, the frequent need for intensive care and severe neurologic sequelae emphasize the importance of early diagnosis, early treatment and prevention with pneumococcal conjugate vaccines.

Coating urinary catheters with an avirulent strain of Escherichia coli as a means to establish asymptomatic colonization.

We investigated whether insertion of urinary catheters that had been coated with Escherichia coli HU2117 could establish bladder colonization with this nonvirulent organism. Ten of 12 subjects were successfully colonized for 14 days or more. The rate of symptomatic UTI during colonization was 0.15 per 100 patient-days.

Candida glabrata fungemia in a diabetic patient with neurogenic bladder: successful treatment with micafungin.

A 69-year-old man was transferred to our hospital because of fever and acute renal failure. 5 weeks prior to admission, he was admitted to another hospital and treated with several antibiotics including vancomycin, but fever did not subside and renal dysfunction showed rapid progression. On admission, laboratory findings revealed pyuria, inflammatory changes, acute renal failure, and disseminated intravascular coagulation (DIC). Computed tomography showed left ureteral stone and hydronephrosis. Gallium scintigraphy showed avid uptake in the left kidney. Serum concentration of vancomycin was 57.4 micro/ml. Candida glabrata was isolated from blood, sputum and urine. Under the diagnosis of fungemia and left pyelonephritis, he was treated with micafungin (150 mg/day), gabexate mesilate and insertion of a double-ended pigtail catheter. The above treatment produced regression of systemic inflammation, DIC and acute renal failure. At the last follow-up 3 weeks after discharge, ureteroscopy showed that the ureter stone had already passed but a soft white-yellowish bezoar was detected in the ureter. In this case, neurogenic bladder, poorly controlled diabetes, and long-term antibiotic treatment probably enhanced the development of C. glabrata infection. Antifungal treatment with micafungin is useful in patients with non-albicans Candida infection.