Antimicrobial resistance and recurrent bacterial urinary tract infections in hospitalized patients following kidney transplantation: A single-center experience.

PURPOSE: The burden of urinary tract infections (UTIs) and risk factors for developing infections with multidrug resistant organisms (MDROs) post-kidney transplantation (KT) are poorly understood. METHODS: Single-center retrospective cohort study (January 2015-December 2017) evaluating first and recurrent episodes of bacteriuria and subsequent analysis of episodes caused by MDROs up to 6 months post-KT. Donor and recipient variables were reviewed. RESULTS: A total of 743 adults underwent single KT during the study period, and 106 patients were hospitalized with bacteriuria. 45% were asymptomatic in their first episode. 73.6% had a single episode, and 26.4% had 2 or more episodes. A total of 28 patients had recurrent episodes; 64.3% had an MDRO on the first episode and 78.6% on the second episode. Escherichia coli was the most common organism isolated, 88.5% were resistant to trimethoprim-sulfamethoxazole (TMP-SMX), 9.3% were extended-spectrum beta-lactamase (ESBL) producers, and 38.1% were MDROs. Body mass index ≥30 was significantly associated with the presence of MDROs in both univariate and multivariate analyses (RR 1.37, 95% CI 1.01-1.88; OR 3.26, CI 1.29-8.25). A total of 12 donors had bacteremia or bacteriuria and 6 (50%) with E coli. A total of 10 KT recipients received antibiotic prophylaxis to prevent donor-derived infections. CONCLUSIONS: Our results suggest that a significant proportion of patients develop recurrent bacteriuria post-transplantation; of those, more than half caused by MDROs. There is a possible association between obesity and MDROs in KT recipients that merits further investigation. With the global crisis in antimicrobial resistance, innovative strategies are needed to prevent and treat UTIs in KT patients.

The resonance® metallic ureteral stent in the treatment of malignant ureteral obstruction: a prospective observational study.

BACKGROUND: To study the outcomes and experiences of using metallic stents in treating patients with malignant ureteral obstruction (MUO), we examined the effects of metallic ureteral stenting using the Cook Resonance® stent in the treatment of MUO. METHODS: All patients who had a Resonance metallic stent inserted between April 2015 and March 2018 at one of multiple facilities were prospectively observed with a 1-year follow-up. The primary outcome was the patency rate of the metallic ureteral stent. The secondary outcomes included the complications (e.g., infection and fever). RESULTS: Although stent insertion was attempted in 50 patients, the stent could not be inserted as a ureteral stent in three patients due to severe ureteral stricture, and one ureteral cancer patient was excluded from the analysis. The remaining 46 patients' median age was 67 years (range 28-85 years) (16 males, 30 females). Twenty-four patients died during the study; their median survival time was 226 days. The median follow-up period for the censored patients was 355 days (range 16-372 days), and just seven patients were still alive without Resonance failure > 1 year later. The women's IPSS scores tended to be lower than those of the men. Regarding the OABSS score, although the women's total score tended to be low, the difference between the men's and women's scores was nonsignificant. The bacteria detected from urine culture after stent insertion were more gram-positive than gram-negative. CONCLUSION: Metallic ureteric stenting using the Resonance stent is safe and effective for treating MUO. Subjective symptoms were relatively less in the female patients.

Widespread antimicrobial resistance among bacterial infections in a Rwandan referral hospital.

BACKGROUND: Resistance among bacterial infections is increasingly well-documented in high-income countries; however, relatively little is known about bacterial antimicrobial resistance in low-income countries, where the burden of infections is high. METHODS: We prospectively screened all adult inpatients at a referral hospital in Rwanda for suspected infection for seven months. Blood, urine, wound and sputum samples were cultured and tested for antibiotic susceptibility. We examined factors associated with resistance and compared hospital outcomes for participants with and without resistant isolates. RESULTS: We screened 19,178 patient-days, and enrolled 647 unique participants with suspected infection. We obtained 942 culture specimens, of which 357 were culture-positive specimens. Of these positive specimens, 155 (43.4%) were wound, 83 (23.2%) urine, 64 (17.9%) blood, and 55 (15.4%) sputum. Gram-negative bacteria comprised 323 (88.7%) of all isolates. Of 241 Gram-negative isolates tested for ceftriaxone, 183 (75.9%) were resistant. Of 92 Gram-negative isolates tested for the extended spectrum beta-lactamase (ESBL) positive phenotype, 66 (71.7%) were ESBL positive phenotype. Transfer from another facility, recent surgery or antibiotic exposure, and hospital-acquired infection were each associated with resistance. Mortality was 19.6% for all enrolled participants. CONCLUSIONS: This is the first published prospective hospital-wide antibiogram of multiple specimen types from East Africa with ESBL testing. Our study suggests that low-resource settings with limited and inconsistent access to the full range of antibiotic classes may bear the highest burden of resistant infections. Hospital-acquired infections and recent antibiotic exposure are associated with a high proportion of resistant infections. Efforts to slow the development of resistance and supply effective antibiotics are urgently needed.

Host and Bacterial Markers that Differ in Children with Cystitis and Pyelonephritis.

OBJECTIVE: To determine whether treatment for urinary tract infections in children could be individualized using biomarkers for acute pyelonephritis. STUDY DESIGN: We enrolled 61 children with febrile urinary tract infections, collected blood and urine samples, and performed a renal scan within 2 weeks of diagnosis to identify those with pyelonephritis. Renal scans were interpreted centrally by 2 experts. We measured inflammatory proteins in blood and urine using LUMINEX or an enzyme-linked immunosorbent assay. We evaluated serum RNA expression using RNA sequencing in a subset of children. Finally, for children with Escherichia coli isolated from urine cultures, we performed a polymerase chain reaction for 4 previously identified virulence genes. RESULTS: Urinary markers that best differentiated pyelonephritis from cystitis included chemokine (C-X-C motif) ligand (CXCL)1, CXCL9, CXCL12, C-C motif chemokine ligand 2, INF γ, and IL-15. Serum procalcitonin was the best serum marker for pyelonephritis. Genes in the interferon-γ pathway were upregulated in serum of children with pyelonephritis. The presence of E coli virulence genes did not correlate with pyelonephritis. CONCLUSIONS: Immune response to pyelonephritis and cystitis differs quantitatively and qualitatively; this may be useful in differentiating these 2 conditions.

What can we learn by examining variations in the use of urine culture in the management of acute cystitis? A retrospective cohort study with linked administrative data in British Columbia, Canada, 2005-2011.

INTRODUCTION: Urinary tract infections (UTI) are common community-based bacterial infections. Empiric antibiotic recommendations are guided by local resistance rates. Previous research suggests that cultures are overused for uncomplicated cystitis, but practice patterns have not been described in detail. Variations in culturing have implications for the interpretation of antibiotic resistance rates. METHODS: We used a retrospective cohort study to analyze variations in urine culturing among physicians, controlling for patient and physician characteristics. We identified all outpatient physician visits among adults and children for cystitis in British Columbia between 2005 and 2011 using administrative data and linked these to laboratory data on urine cultures. Using hierarchical generalized linear mixed models we explored variations in urine culture submissions for cystitis (ICD code 595) and the associations with patient and physician characteristics, stratified by patient sex. RESULTS: Urine cultures were associated with 16% of visits for cystitis among females and 9% among males, and 59% of visits overall were associated with antibiotic treatment. Older patients, patients with a recent antibiotic prescription, and long term care residents were significantly less likely to have a culture associated with a cystitis visit, whether male or female. Female physicians and physicians with 16-35 years' experience were more likely to culture, while international medical graduates were less likely-particularly for female visits. Notably, there was substantial unexplained variation among physicians after controlling for physician characteristics: we found a 24-fold variation in the odds of culturing a female UTI between physicians who were otherwise similar. CONCLUSION: Individual physicians show substantial variation in their propensity to submit cultures for cystitis visits. Reducing such variation and encouraging appropriate levels of culturing would support effective antibiotic use.

An Evaluation of the Automated Cobas u 701 Microscopy Analyzer for the Routine Screening of Urine to Identify Negative Samples.

BACKGROUND: Urinalysis based on microbiological culture and manual microscopy requires expertise and is labor intensive. Automated screening could save time and improve patient management in clinical settings. METHODS: We evaluated the fully automated cobas u 701 analyzer for identifying infection-negative urine samples using 2,046 anonymized samples from a routine pathology laboratory. Samples containing ≥ 40 white blood cells (WBC)/µL and/or ≥ 100 bacteria/µL were considered positive. For microbiological cultures: pure growth of ≥ 108 colony-forming units (cfu)/L was considered significant; > 107 cfu/L was considered significant for pregnant women, children < 12 years, immune-compromised/critical care patients or patients with > 100 WBC/µL. RESULTS: The cobas u 701 analyzer identified 1,346 positive samples, giving a 65.7% culture rate. Sensitivity and negative predictive value were high (> 99%). Most replicates were within two standard deviations of the original measurement. CONCLUSIONS: The cobas u 701 analyzer is an effective screening tool for routine urinalysis and demonstrates rapid turnaround times, thus benefiting patients and clinicians.

Urinary neutrophil gelatinase-associated lipocalin for diagnosis of spontaneous bacterial peritonitis.

Cirrhotic patients with ascites are at high risk of developing spontaneous bacterial peritonitis (SBP). After exclusion of patients with acute kidney injury (AKI) or other infections, urinary neutrophil gelatinase-associated lipocalin (NGAL) levels were compared between two matched groups of Egyptian cirrhotic patients with ascites, mostly secondary to hepatitis C infection (98%). Group 1 had SBP (n = 41) and group 2 did not (n = 45). By univariate analysis, urinary-NGAL, high total bilirubin, serum creatinine, international normalised ratio and the Model of End-Stage Liver Disease (MELD) score and low platelet count were all significantly correlated with the presence of SBP, but only urinary-NGAL could independently predict development of SBP (P = 0.001). Urinary-NGAL at a cut-off value of 1225 pg/mL, showed a sensitivity of 95% and a specificity of 76%, and is therefore a most useful tool.

[Urinary tract infections in children]. / Harnwegsinfekte bei Kindern.

Urinary tract infections (UTI) are the most common bacterial infections in children. The symptoms are not very specific and range from abdominal pain, poor feeding to nocturnal urinary incontinence. The technique of collecting urine plays an important role for securing the diagnosis. The best way to obtain urine in non-toilet-trained children is catheterization or suprapubic bladder aspiration. In toilet-trained children midstream urine is an acceptable alternative after cleaning the foreskin or labia. In the case of an infection a prompt empirical antibiotic therapy is necessary to reduce the risk of parenchymal scarring of the kidneys. There are different approaches to diagnose vesicoureteral reflux in different countries. The commonly used standard approach in Germany is voiding cystourethrography. In the case of reflux dimercaptosuccinic acid (DMSA) scintigraphy should be performed additionally to exclude renal scarring (bottom-up approach).

Validity of Neutrophil Gelatinase Associated Lipocaline as a Biomarker for Diagnosis of Children with Acute Pyelonephritis.

PURPOSE: Novel biomarkers have been investigated for various renal disorders, including urinary tract infection (UTI). The aim of this study was to assess whether urine neutrophil gelatinase associated lipocaline (NGAL), could represent a reliable biomarker for diagnosis and treatment of children with acute pyelonephritis (APN). MATERIALS AND METHODS: A total of 37 children (32 females, 5 males) with APN were included in this prospective study. Urine NGAL was measured before and 5-7 days after antibiotic treatment in the UTI group, using ELISA kit and compared with 26 (8 females, 18 males) control group children admitted for other bacterial infections. RESULTS: Mean age of the UTI group was 39 ± 28 months, compared to 43.6 ± 31.5 months for the control group with no statistically significant difference. Median urine NGAL level was significantly higher in patients with APN than the other subjects [0.48 (interquartile range (IQR): 0.15-0.72) vs. 0.065 (0.01-0.24), P = .001], and decreased significantly after antibiotic treatment (P = .002). Using a cutoff of 0.20 ng/mL, sensitivity and specificity of urine NGAL were 76% and 77% for prediction of APN, respectively. The area under the ROC curve (AUC) for urine NGAL was 0.75 (CI= 0.61-0.88), suggesting urine NGAL as a relatively good predictive biomarker of APN. CONCLUSION: Urine NGAL is a good biomarker for diagnosis and treatment monitoring of APN in children. .

Elevated urinary levels of carcinogenic N-nitrosamines in patients with urinary tract infections measured by isotope dilution online SPE LC-MS/MS.

N-nitrosamines (NAms) are well-documented for their carcinogenic potential. Human exposure to NAms may arise from the daily environment and endogenous formation via the reaction of secondary amines with nitrites or from bacteria infection. We describe the use of isotope dilution online solid-phase extraction (SPE) LC-MS/MS to quantify nine NAms in human urine. This method was validated and further applied to healthy subjects and patients with urinary tract infection (UTI). N-nitrosodimethylamine (NDMA), N-nitrosomethylethylamine (NMEA), N-nitrosopyrrolidine (NPYR) and N-nitrosomorpholine (NMOR) were analyzed with an APCI source, while N-nitrosodiethylamine (NDEA), N-nitrosopiperidine (NPIP), N-nitrosodi-n-propylamine (NDPA), N-nitrosodibutylamine (NDBA) and N-nitrosodiphenylamine (NDPhA) were quantified with an ESI source, due to their effect on the sensitivity and chromatography. NDMA was the most abundant N-nitrosamine, while NDPhA was firstly identified in human. UTI patients had three to twelve-fold higher concentrations for NDMA, NPIP, NDEA, NMOR and NDBA in urine than healthy subjects, and the NAms were significantly decreased after antibiotics treatment. NDMA concentrations were also significantly correlated with the pH value, leukocyte esterase activity or nitrite in urines of UTI patients. Our findings by online SPE LC-MS/MS method evidenced that UTI patients experienced various NAms exposures, especially the potent carcinogen NDMA, which was likely induced by bacteria infection.

Epidemiology and resistance pattern of bacterial isolates among cancer patients in a Tertiary Care Oncology Centre in North India.

OBJECTIVES: To examine the epidemiology of microbiologically documented bacterial infection and the resistance pattern, among cancer patients undergoing treatment at RGCIRC, Delhi. DESIGN AND SETTING: Retrospective observational study in which culture reports obtained over 1 year in 2013, were analyzed. RESULTS: 13329 cultures were obtained over 1 year in 2013 and were analyzed. 23.6 % samples showed positive culture with majority being gram negative isolates (67.9 %). E. coli was the commonest gram negative isolate (49.4%) followed by klebsella (29.7%) and Staph. aureus was the commonest gram positive isolate. There was high incidence of ESBL in blood and urine (87.2% & 88.5%) and BLBLI were also high (78% & 83.9%). Carbapenem resistance was comparatively low (10%) and colistin sensitivity was quiet high (> 95%). CONCLUSIONS: Prevalence of MRSA and VRE in our institute is very less, whereas prevalence of ESBLs and BLBLI isolates amongst gram negative infections is around 80%. Gram negative isolates had poor sensitivity to cephalosporins and fluoroquinolones.

Diagnostic accuracy of urinary prostate protein glycosylation profiling in prostatitis diagnosis.

INTRODUCTION: Although prostatitis is a common male urinary tract infection, clinical diagnosis of prostatitis is difficult. The developmental mechanism of prostatitis is not yet unraveled which led to the elaboration of various biomarkers. As changes in asparagine-linked-(N-)-glycosylation were observed between healthy volunteers (HV), patients with benign prostate hyperplasia and prostate cancer patients, a difference could exist in biochemical parameters and urinary N-glycosylation between HV and prostatitis patients. We therefore investigated if prostatic protein glycosylation could improve the diagnosis of prostatitis. MATERIALS AND METHODS: Differences in serum and urine biochemical markers and in total urine N-glycosylation profile of prostatic proteins were determined between HV (N=66) and prostatitis patients (N=36). Additionally, diagnostic accuracy of significant biochemical markers and changes in N-glycosylation was assessed. RESULTS: Urinary white blood cell (WBC) count enabled discrimination of HV from prostatitis patients (P<0.001). Urinary bacteria count allowed for discriminating prostatitis patients from HV (P<0.001). Total amount of biantennary structures (urinary 2A/MA marker) was significantly lower in prostatitis patients compared to HV (P<0.001). Combining the urinary 2A/MA marker and urinary WBC count resulted in an AUC of 0.79, 95% confidence interval (CI)=(0.70-0.89) which was significantly better than urinary WBC count (AUC=0.70, 95% CI=[0.59-0.82], P=0.042) as isolated test. CONCLUSIONS: We have demonstrated the diagnostic value of urinary N-glycosylation profiling, which shows great potential as biomarker for prostatitis. Further research is required to unravel the developmental course of prostatic inflammation.

An AKI biomarker lipocalin 2 in the blood derives from the kidney in renal injury but from neutrophils in normal and infected conditions.

BACKGROUND: Lipocalin 2 (LCN2 or neutrophil gelatinase-associated lipocalin) is a secretory protein discovered from neutrophils, which accumulates in the blood and urine during acute kidney injury (AKI) and in the blood by bacterial infection. Little is known about the tissue source and molecular forms of this protein under normal and pathophysiologic conditions. METHODS: By sandwich ELISA, serum and urinary LCN2 levels were measured in 36 patients with hematologic malignancies who transiently became neutropenic by stem cell transplantation (SCT). To evaluate contribution of neutrophil-derived LCN2 in the physiologic blood LCN2 concentrations, we examined CCAAT/enhancer-binding protein ε (C/EBPε) knockout mice, which lack mature neutrophils. RESULTS: In patients without AKI and bacterial infection, at 1 week after SCT, the median blood neutrophil counts became zero and serum LCN2 levels were decreased by 76 ± 6 % (p < 0.01), but urinary LCN2 levels were not altered. During neutropenic conditions, bacterial infection caused only a modest rise of serum LCN2 but AKI produced a marked rise of serum and urinary LCN2 levels. Serum LCN2 concentrations in C/EBPε knockout mice were reduced by 66 ± 11 % compared to wild-type mice (p < 0.05). Blood LCN2 existed predominantly in high molecular weight forms (>100 kDa), while urinary LCN2 was mainly in low molecular weight forms. CONCLUSION: Our findings suggest that neutrophils are the major source of circulating LCN2 in normal and infected conditions, whereas blood and urinary LCN2 mainly derive from the kidney during AKI, and that the molecular forms and regulation of blood and urinary LCN2 are clearly distinct.

A multiplex biomarker approach for the diagnosis of transitional cell carcinoma from canine urine.

Transitional cell carcinoma (TCC), the most common cancer of the urinary bladder in dogs, is usually diagnosed at an advanced disease stage with limited response to chemotherapy. Commercial screening tests lack specificity and current diagnostic procedures are invasive. A proof of concept pilot project for analyzing the canine urinary proteome as a noninvasive diagnostic tool for TCC identification was conducted. Urine was collected from 12 dogs in three cohorts (healthy, urinary tract infection, TCC) and analyzed using liquid chromatography tandem mass spectrometry. The presence of four proteins (macrophage capping protein, peroxiredoxin 5, heterogeneous nuclear ribonucleoproteins A2/B, and apolipoprotein A1) was confirmed via immunoblot. Of the total 379 proteins identified, 96 were unique to the TCC group. A statistical model, designed to evaluate the accuracy of this multiplex biomarker approach for diagnosis of TCC, predicted the presence of disease with 90% accuracy.

Urinary neutrophil gelatinase-associated lipocalin predicts kidney outcome and death in patients with cirrhosis and bacterial infections.

BACKGROUND & AIMS: Infections in cirrhosis are frequently complicated by kidney dysfunction that entails a poor prognosis. Urinary biomarkers may be of potential clinical usefulness in this setting. We aimed at assessing the value of urinary neutrophil gelatinase-associated lipocalin (uNGAL), a biomarker overexpressed in kidney tubules during kidney injury, in predicting clinical outcomes in cirrhosis with infections. METHODS: One-hundred and thirty-two consecutive patients hospitalized with infections were evaluated prospectively. Acute kidney injury (AKI) was defined according to AKIN criteria. uNGAL was measured at infection diagnosis and at days 3 and 7 (ELISA, Bioporto, DK). RESULTS: Patients with AKI (n=65) had significantly higher levels of uNGAL compared to patients without AKI (203 ± 390 vs. 79 ± 126 µg/g creatinine, p<0.001). Moreover, uNGAL levels were significantly higher in patients who developed persistent AKI (n=40), compared to those with transient AKI (n=25) (281 ± 477 vs. 85 ± 79 µg/g creatinine, p<0.001). Among patients with persistent AKI, uNGAL was able to discriminate type-1 HRS from other causes of AKI (59 ± 46 vs. 429 ± 572 µg/g creatinine, respectively; p<0.001). Moreover, the time course of uNGAL was markedly different between the two groups. Interestingly, baseline uNGAL levels also predicted the development of a second infection during hospitalization. Overall, 3-month mortality was 34%. Independent predictive factors of 3-month mortality were MELD score, serum sodium, and uNGAL levels at diagnosis, but not presence or stage of AKI. CONCLUSIONS: In patients with cirrhosis and infections, measurement of urinary NGAL at infection diagnosis is useful in predicting important clinical outcomes, specifically persistency and type of AKI, development of a second infection, and 3-month mortality.

Recognizing purple bag syndrome at first look.

Purple urine bag syndrome is a clinical entity first described in 1978. Its typical discoloration is worrying for clinicians. In the past, these patients sometimes reached the emergency unit only because of this exceptional worrying urinary sign and underwent invasive diagnostic examinations including cystoscopy, without any abnormal finding. It is now clear that this astonishing phenomenon of double discoloration of the urine, appearing purple in the bag and dark blue in the test tube, results from the formation of 2 different pigments (indirubin and indigo) in very alkaline urines due to enzymes produced by gram-negative bacteria, such as indoxyl phosphatase/sulfatase, which can convert urinary metabolites of dietary tryptophan. Practicing physicians should identify purple urine bag syndrome as a usually benign medical condition diagnosed in asymptomatic patients, which only requires treatment of bacteriuria with antibiotics, prevention of constipation, substitution of catheter and acidification of the urine. After these measures, urine typically returns to its normal color.

UF-1000i flow cytometry is an effective screening method for urine specimens.

This study was undertaken to evaluate the UF-1000i™ (UF) flow cytometer to count urine constituents including bacteria. The objective was to screen urine samples and determine what white blood cell (WBC) and/or bacteria screening criteria would minimize the number of specimens cultured yet ensuring that all true positives were cultured. UF screening and culture on CHROMagar™ Orientation (CO) medium were performed on 2496 specimens. Various combinations of WBC/bacterial counts were assessed as screening criteria and correlated with significant growth on CO medium. A bacterial count of ≥20 from UF gave an overall screening sensitivity of 92.6%, allowing 35% of specimens to be screened out and not cultured. The sensitivity was 99.2% and 85.0% for Gram-negative and Gram-positive organisms, respectively, using the same bacterial count. Our study indicated that UF was a simple, rapid, and reliable method for urine screening when the bacterial count of ≥20 was used as the sole screening criterion.

Contributory factors to postoperative spinal fusion complications for children with myelomeningocele.

STUDY DESIGN: This is a retrospective review of all children with myelomeningocele (MMC) who were undergoing surgery for scoliosis at our institution. OBJECTIVE: Our aim was to investigate possible correlations between poor nutritional indexes and/or positive urinary cultures before surgery to perioperative infection risk. SUMMARY OF BACKGROUND DATA: Patients who have scoliosis secondary to MMC have been shown to have a high rate of infectious complications. Many children with MMC have been found to have asymptomatic urinary tact infections due to their neurogenic bladder. There is little literature on risk factors for and ways to prevent postoperative infections for these patients. METHODS: We reviewed a comprehensive database for the outcome for spinal fusion surgeries of 59 patients with MMC treated at our institution over the past 45 years. Perioperative infections were correlated to preoperative nutritional status (measured by patient hematocrit [Hct]) and presence of active infection using Fisher Exact Probability Test. RESULTS: A total of 84 different spinal fusion operations for 59 patients were recorded. Patients presenting with poor preoperative nutrition (Hct