Sensitivity of point-of-care testing C reactive protein and procalcitonin to diagnose urinary tract infections in Dutch nursing homes: PROGRESS study protocol.

INTRODUCTION: Suspected urinary tract infection (UTI) ranks among the most common reasons for antibiotic use in nursing homes. However, diagnosing UTI in this setting is challenging because UTI often presents with non-specific symptomatology. Moreover asymptomatic bacteriuria is common in elderly, which complicates attribution of causality to detection of bacteria in urine. These diagnostic challenges contribute to overuse of antibiotics and emergence of antimicrobial resistance in nursing homes. Given the diagnostic challenges, there is a need for point-of-care (POC) diagnostic tests to support clinical rules for diagnosing UTI. Procalcitonin (PCT) and C reactive protein (CRP) are inflammatory blood markers that have been proven useful to support diagnosis and monitoring of (bacterial) respiratory tract infections and sepsis. While limited studies suggest their usefulness in supporting UTI diagnosis, their utility has not been studied in elderly populations for this purpose. METHODS AND ANALYSIS: In a 24-month matched prospective study, 'PROGRESS' will assess and compare the sensitivity of rapid POC measurements of blood CRP and PCT levels to support clinical rules for diagnosing UTI in nursing home residents. The primary outcome measure is sensitivity of the POC tests to identify patients with true UTI based on the predefined definition, as derived from receiver operating curves. ETHICS AND DISSEMINATION: This study will be conducted in accordance with Good Clinical Practice guidelines and the principles of the Declaration of Helsinki. The study protocol is approved by the Medical Ethical Committee of Amsterdam UMC location VUmc with reference number 2017.350 and National Central Committee on Research involving Human Subjects with reference number NL62067.029.17. TRIAL REGISTRATION NUMBER: NTR6467.

Antimicrobial prophylaxis for transurethral resection of bladder tumor: A retrospective comparison of preoperative single-dose administration of piperacillin and tazobactam/piperacillin.

We aimed to clarify prophylactic antimicrobial effects of single-dose piperacillin (PIPC) for perioperative infections in the transurethral resection of bladder tumor (TURBT) in comparison with those of single-dose tazobactam/piperacillin (TAZ/PIPC) through a retrospective analysis. We analyzed data from 192 TURBT patients treated with single-dose (4 g) intravenous PIPC (P group) between April 2015 and April 2017. For comparison, we analyzed data from 50 TURBT patients treated with single-dose (4.5 g) intravenous TAZ/PIPC (T/P group) between June 2013 and April 2014. We compared the perioperative incidences of fever (≥38 °C) and bacteriuria in the two groups. The number of febrile patients was four (2.1%) in the P group and one (2.0%) in the T/P group, without significant difference (p = 0.970). Among these febrile patients, urine and blood samples of two patients in the P group tested positive for bacterial cultures of Citrobacter koseri and Enterococcus faecalis, respectively. None of the patients in the T/P group tested positive for urine culture, postoperatively. However, 22 patients (18.2%) in the P group tested positive for urine culture, and Staphylococcus epidermidis (six patients), E. faecalis (three patients), Escherichia coli (three patients), Streptococcus agalactiae (two patients), Staphylococcus aureus (two patients), and C. koseri (one patient) were isolated. There was no significant difference in the incidence of bacteriuria in these two groups (p = 0.055). Based on these results, single-dose PIPC administration for the prevention of perioperative infections in TURBT was as effective as TAZ/PIPC.

What is the role of catheter antibiotic prophylaxis for patients undergoing joint arthroplasty?

BACKGROUND: Antimicrobial prophylaxis at the time of urinary catheter insertion and removal is commonly administered in patients undergoing joint arthroplasty, despite the lack of evidence to support this practice. The rationale is the theoretical risk of prosthetic joint infection arising from bacterial seeding from the urinary tract at the time of catheterization. In an era of antimicrobial stewardship, further assessment is warranted. METHODS: This study aimed to investigate the incidence of catheter-associated (CA) bacteriuria and bacteraemia in patients undergoing total joint arthroplasty and to assess the antimicrobial susceptibility of any isolated microorganisms. This prospective observational study undertaken over a 6-month period (May to October 2014) included 99 patients undergoing elective primary hip and knee arthroplasty at St Vincent's Hospital, Melbourne. Urine specimens were collected at insertion and removal of urinary catheters along with blood cultures upon urinary catheter removal. RESULTS: Overall 98% of the cohort received catheter antimicrobial prophylaxis for urinary catheter insertion and removal; the majority of patients received gentamicin (94%). Bacteriuria on catheter insertion had an incidence of 4.4%. The incidence of CA bacteriuria was 1.3%. All cultured organisms were sensitive to commonly used antibiotics including cephazolin. There were no cases of bacteraemia with urinary catheter removal. Increasing age, American Society of Anesthesiologists status and female gender were associated with the development of bacteriuria. CONCLUSION: The incidence of CA bacteriuria and bacteraemia with antimicrobial prophylaxis is low. This study provokes discussion about the requirement of catheter prophylaxis in this surgical context and the utility of preoperative urine screening.

Diagnostic methods to determine microbiology of postpartum endometritis in South Asia: laboratory methods protocol used in the Postpartum Sepsis Study: a prospective cohort study.

BACKGROUND: The South Asian region has the second highest risk of maternal death in the world. To prevent maternal deaths due to sepsis and to decrease the maternal mortality ratio as per the World Health Organization Millenium Development Goals, a better understanding of the etiology of endometritis and related sepsis is required. We describe microbiological laboratory methods used in the maternal Postpartum Sepsis Study, which was conducted in Bangladesh and Pakistan, two populous countries in South Asia. METHODS/DESIGN: Postpartum maternal fever in the community was evaluated by a physician and blood and urine were collected for routine analysis and culture. If endometritis was suspected, an endometrial brush sample was collected in the hospital for aerobic and anaerobic culture and molecular detection of bacterial etiologic agents (previously identified and/or plausible). DISCUSSION: The results emanating from this study will provide microbiologic evidence of the etiology and susceptibility pattern of agents recovered from patients with postpartum fever in South Asia, data critical for the development of evidence-based algorithms for management of postpartum fever in the region.

Antigenic specificity and expression of a natural idiotope on human pentameric and hexameric IgM polymers.

Natural antibodies (NAbs) are present in circulation even before the exposure to antigen and they exert various biological functions. They are polyreactive and mainly represented by immunoglobulin M (IgM), which is the first antibody produced in an ongoing immune response to infection and/or immunization. IgM is always secreted as a polymer with predominant pentameric structure, although other polymeric forms such as hexamer can be also formed. The biological functions of hexameric IgM are still not known and it is proposed that its existence as a NAb could be deleterious. However, the nature of IgM hexamers has not been investigated yet. In this paper, we have tested the expression of natural idiotope and antigenic specificities of pentameric and hexameric IgM polymers originating from sera of patients with Waldenström's macroglobulinemia, as well as patients suffering from recurrent urinary bacterial infections. We demonstrate that although pentameric IgM polymers can exist as natural and immune antibodies, IgM hexamers are exclusively immune and do not exist as NAbs.

Asymptomatic bacteriuria in elderly humans is associated with increased levels of circulating TNF receptors and elevated numbers of neutrophils.

Low-grade inflammatory activity is strongly associated with age-associated diseases such as atherosclerosis, dementia, type-2 diabetes, sarcopenia, and osteoporosis and predicts mortality risk in elderly populations. The aim of the current study was to investigate if asymptomatic bacteriuria in elderly humans was associated with inflammation. Midstream clean-catch urine culture was collected from consecutive, elderly patients at admission to a department of internal medicine due to functional disability. Forty patients (age 70-91 years) were selected and included in the current study; 20 subjects had positive urine culture and 20 sex- and age-matched subjects had negative urine culture. Inclusion criteria were temperature below 37.8 degrees C, no clinical signs of infection and no current antibiotic treatment. Patients with asymptomatic bacteriuria had significantly increased levels of circulating tumor necrosis factor receptors (sTNFR-I) and a higher number of neutrophils in the blood compared to the group without bacteriuria. Thus, the present study provides some support for the hypothesis that asymptomatic urinary infections are associated with low-grade immune activity in frail, elderly humans.

Association of Lewis blood group phenotypes with urinary tract infection in children.

Many blood group antigens, genetically controlled carbohydrate molecules, are found on the surface of uroepithelial cells and may affect bacterial adherence and increase the frequency of urinary tract infection (UTI) in adults. Sixty-two children aged 2 weeks to 17 years (mean, 2.3 years) who were hospitalized with fever in association with UTIs caused by Escherichia coli had complete (n = 50) or partial (n = 12) erythrocyte antigen typing to determine the role of erythrocyte antigens and phenotypes in UTI in children; 62 healthy children undergoing nonurologic elective surgery, matched 1 to 1 for age, sex, and race to the patient group, formed the control group. In univariate tests, patients and control subjects did not differ in ABO, Rh, P, Kell, Duffy, MNSs, and Kidd systems by the McNemar test of symmetry (p > 0.05). The frequency of the Lewis (Le) (a-b-) phenotype was higher (16/50 vs 5/50; p = 0.0076) and the frequency of the Le(a + b +) phenotype was lower (8/50 vs 16/50; p = 0.0455) in the patient population than in the control subjects. A stepwise logistic regression model to predict UTI with the explanatory variables A, B, O, M, N, S, s, Pl, Lea, and Leb showed that only the Lea and Leb antigens entered the model with p < 0.1. The Le(a-b-) phenotype was associated with UTI in this pediatric population. The relative risk of UTI in children with the Le(a-b-) phenotype was 3.2 (95% confidence interval, 1.3 to 7.9). Specific blood group phenotypes in pediatric populations may provide a means to identify children at risk of having UTI.

Comparison of urine and serum concentrations of interleukin-6 in women with acute pyelonephritis or asymptomatic bacteriuria.

The mucosal and systemic interleukin-6 (IL-6) response to urinary tract infection was analyzed in women with acute pyelonephritis or asymptomatic bacteriuria. Urine and serum samples were obtained at diagnosis and after treatment. IL-6 activity was elevated in urine samples from most bacteriuric women, regardless of the severity of infection. Urinary levels greater than 20 units/mL occurred in 25 of 29 women with acute pyelonephritis and in 36 of 42 women with asymptomatic bacteriuria. Elevated serum IL-6 levels were found mainly in patients with acute pyelonephritis: Levels greater than 20 units/mL occurred in 14 of 28 women with acute pyelonephritis compared with 0 of 28 women with asymptomatic bacteriuria. These results suggest that bacteriuria is accompanied by elevated urinary IL-6 levels and that this IL-6 is locally produced. The spread of IL-6 to the circulation in patients with acute pyelonephritis may contribute to the elevation of fever and C-reactive protein characteristic of the disease.

Blood group non-secretors have an increased inflammatory response to urinary tract infection.

The aim of this study was to assess the possible relationship between secretor state and the inflammatory response to urinary tract infection (UTI). Girls with recurrent UTI were prospectively studied. They included 61 secretor and 23 non-secretor individuals with 604 episodes of recurrent UTI. The response to each UTI episode was measured as the levels of C-reactive protein, erythrocyte sedimentation rate and the body temperature as well as renal concentrating capacity and pyuria. The levels of C-reactive protein, erythrocyte sedimentation rate and the body temperature were significantly higher in non-secretors than in secretors (p less than 0.04). As a consequence, non-secretors had an increased probability of being assigned a diagnosis of acute pyelonephritis rather than asymptomatic bacteriuria (p less than 0.05). The higher inflammatory response in non-secretors was independent of the Gal alpha 1-4Gal beta adhesin expression of the infecting Escherichia coli strains. The increased inflammatory response to UTI in non-secretors might explain the accumulation of these individuals among patients with renal scarring.

Six year follow up of infants with bacteriuria on screening.

OBJECTIVE: To determine the value of screening for bacteriuria in infants with special emphasis on the natural course of untreated asymptomatic bacteriuria, renal growth, and renal damage. DESIGN: Prospective six year follow up of infants with bacteriuria on screening in an unselected infant population. SETTING: Paediatric outpatient clinic. PATIENTS: 50 Infants (14 girls, 36 boys) with bacteriuria on screening verified by suprapubic aspiration from an unselected population of 3581 infants in a defined area of Gothenburg. INTERVENTIONS: Children with asymptomatic bacteriuria and normal findings on initial urography were untreated, although other infections were treated. MAIN OUTCOME MEASURES: Culture of urine and determination of C reactive protein concentration every six weeks for the first six months after diagnosis, every three months from six months to two years, and every six months between two and three years; thereafter yearly urine culture. Evaluation of renal concentrating capacity with a desmopressin test; radiological examination, including first and follow up urography and micturition cystourethrography without antibiotic cover; and measurement of renal parenchymal thickness and renal surface area. RESULTS: Of the original 50 infants, 37 (12 girls, 25 boys) were followed up for at least six years. Two infants developed pyelonephritis within two weeks after bacteriuria was diagnosed; the others remained free of symptoms. 45 Infants were untreated; the bacteriuria cleared spontaneously in 36 and in response to antibiotics given for infections in the respiratory tract in eight. Recurrences of bacteriuria were observed in 10 of the 50 children, of whom one had pyelonephritis. No child had more than one recurrence. At follow up urography in 36 of the 50 children (9 girls, 27 boys) after a median of 32 months no child had developed renal damage. First samples tested for renal concentrating capacity showed significantly higher values than those from a reference population (mean SD score 0.50, 95% confidence interval 0.21 to 0.79; p less than 0.001), but the last samples showed no significant difference (mean SD score 0.08, -0.24 to 0.40; p greater than 0.05). CONCLUSIONS: Mass screening for bacteriuria in infancy results primarily in detection of innocent bacteriuric episodes and is not recommended.

Bacteriuria asitomatica en el embarazo / Asymptomatic bacteriuria in pregnancy

Se analiza la epidemiologia, diagnostico, manejo y pronostico de la Bacteriuria Asintomatica en las pacientes que asistieron a control prenatal en el Instituto Materno Infantil de Bogota y Clinica Hospital Fray Bartolome de las Casas, desde el 1 de mayo de 1987 hasta el 30 de abril de 1988. La frecuencia de Bacteriuria Asintomatica en la mujer embarazada fue del 3%. El 80% de las pacientes estaban entre los 20 y 35 anos. El 60% eran multiparas; la totalidad de raza blanca y mestiza y el 97% de nivel socioeconomico bajo y medio. El 33% tenian factores de riesgo como anemia, preeclampsia, enfermedad renal cronica y flujo gential. En el 64% se hizo el diagnostico en el primero y segundo trimestre, siendo el E. Coli el genero mas frecuente (73%) y el tratamiento se hizo de acuerdo con el antibiograma, teniendo en cuenta las drogas que se pueden utilizar durante el embarazo, con una persistencia del 4% y una recidiva del 4.1% y ninguna paciente presento pielonefritis. La morbilidad materna fue del 26%. Amenaza del parto pretermino, preeclampsia y RPM. La morbilidad perinatal fue del 23%: pretermino y retardo del crecimiento intrauterino.

Relationships between human blood groups, bacterial pathogens, and urinary tract infections.

Blood groups of 137 patients with acute pyelonephritis and chronic upper tract infection, cystitis, and asymptomatic bacteriuria were compared with those of a normal uninfected control population. In addition, the identified uropathogens were categorized according to the patient's blood group. There was a significant association between the diagnosis of chronic upper tract infection and blood group B as compared with controls (p = less than 0.05, chi 2). Analysis of the bacterial isolates showed that more patients with blood group B had infections with Pseudomonas sp., Klebsiella pneumoniae, and Proteus sp. than was expected; and fewer patients with blood group A had infections with Pseudomonas than predicted (p = less than 0.05, chi 2). There was an increased number of patients in blood group AB with infections caused by Escherichia coli and Klebsiella pneumoniae. These results suggest that an individual's blood group may be a significant factor in the host-response to bacterial invasion and influence the development of infection with certain gram-negative bacilli.

Use of nitroblue tetrazolium (NBT) test in the differentiation between pyelonephritis and cystitis.

NBT tests were performed on blood from 37 patients with urinary tract infections caused by coliform bacteria. The level of infections was evaluated by the clinical signs, ESR, renal concentrating capacity and titre of antibodies against the strains of E. coli isolated in their urine. Elevated proportions of NBT-positive neutrophils were found in 11 of 14 patients with pyelonephritis and in 3 of 23 patients with cystitis or asymptomatic bacteriuria (ABU). The total number of NBT-positive neutrophils was 1000 or more per mm3 blood in 11 of 13 patients considered to have pyelonephritis, while it was 800 or less in all the patients investigated, evaluated as having cystitis or asymptomatic bacteriuria. The NBT test is recommended as an adjunct in the level diagnosis or urinary tract infections in children. The utility of the test in smouldering pyelonephritis is presently being investigated.