Tract Infections In People Research Articles

Population incidence and associated mortality of urinary tract infection in people living with dementia

OBJECTIVESUrinary tract infections (UTIs) frequently cause hospitalisation and death in people living with dementia (PLWD). We examine UTI incidence and associated mortality among PLWD relative to matched controls and people with diabetes and investigate whether delayed or withheld treatment further impacts mortality. METHODSData were extracted for n=2,449,814 people aged ≥ 50 in Wales from 2000-2021, with groups matched by age, sex, and multimorbidity. Poisson regression was used to estimate incidences of UTI and mortality. Cox regression was used to study the effects of treatment timing. RESULTSUTIs in dementia (HR=2.18, 95%CI [1.88-2.53], p<.0) and diabetes (1.21[1.01-1.45], p=.035) were associated with high mortality, with the highest risk in individuals with diabetes and dementia (both) (2.83[2.40-3.34], p<.0) compared to matched individuals with neither dementia nor diabetes. 5.4% of untreated PLWD died within 60 days of GP diagnosis—increasing to 5.9% in PLWD with diabetes. CONCLUSIONSIncidences of UTI and associated mortality are high in PLWD, especially in those with diabetes and dementia. Delayed treatment for UTI is further associated with high mortality.

Nirsevimab: A Review.

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in people of all ages and is the leading cause of hospitalization among infants in the United States. The year 2023 was exciting for RSV prevention. The Food and Drug Administration (FDA) approved 3 new tools for preventing severe lower respiratory tract RSV infections in infants, young children, and elderly persons. In May 2023, the FDA approved 2 vaccines, RSVpreF3 (Arexvy™, GSK) and RSVpreF (Abrysvo™, Pfizer), for adults ages 60 years or older to be given as a single-dose intramuscular injection. July 2023 brought the approval of the first long-acting monoclonal antibody nirsevimab (Beyfortus™, Sanofi and AstraZeneca) for the prevention of RSV disease in infants and young children. Then in August, the FDA approved a vaccine (Abrysvo™, Pfizer) to be given to pregnant women to protect their newborns through passive immunity. This article focuses on nirsevemab that has been recommended by the Advisory Committee on Immunization Practices (ACIP) and American Academy of Pediatrics (AAP) to be administered for all infants <8 months of age and for children 8 to 19 months of age who are at increased risk for severe RSV disease.

A simple and successful solution to issues relating to urinary tract infections in people with MS

The coronavirus pandemic prompted one of the authors to develop a simple yet innovative solution to detecting urinary tract infections in people with multiple sclerosis, in order to improve their wellbeing and reduce hospital admissions. The initiative has been longer lasting, wider reaching and has had better outcomes than expected. The authors discuss the initiative, how and why it was developed, patient outcomes and limitations.

Secondary messenger signalling influences Pseudomonas aeruginosa adaptation to sinus and lung environments.

Pseudomonas aeruginosa is a cause of chronic respiratory tract infections in people with cystic fibrosis (CF), non-CF bronchiectasis, and chronic obstructive pulmonary disease. Prolonged infection allows the accumulation of mutations and horizontal gene transfer, increasing the likelihood of adaptive phenotypic traits. Adaptation is proposed to arise first in bacterial populations colonizing upper airway environments. Here, we model this process using an experimental evolution approach. Pseudomonas aeruginosa PAO1, which is not airway adapted, was serially passaged, separately, in media chemically reflective of upper or lower airway environments. To explore whether the CF environment selects for unique traits, we separately passaged PAO1 in airway-mimicking media with or without CF-specific factors. Our findings demonstrated that all airway environments-sinus and lungs, under CF and non-CF conditions-selected for loss of twitching motility, increased resistance to multiple antibiotic classes, and a hyper-biofilm phenotype. These traits conferred increased airway colonization potential in an in vivo model. CF-like conditions exerted stronger selective pressures, leading to emergence of more pronounced phenotypes. Loss of twitching was associated with mutations in type IV pili genes. Type IV pili mediate surface attachment, twitching, and induction of cAMP signalling. We additionally identified multiple evolutionary routes to increased biofilm formation involving regulation of cyclic-di-GMP signalling. These included the loss of function mutations in bifA and dipA phosphodiesterase genes and activating mutations in the siaA phosphatase. These data highlight that airway environments select for traits associated with sessile lifestyles and suggest upper airway niches support emergence of phenotypes that promote establishment of lung infection.

Molecular typing and epidemiology profiles of human adenovirus infection among children with severe acute respiratory infection in Huzhou, China.

Human adenoviruses (HAdVs) are prevalent worldwide and are a common cause of respiratory tract infection in people of all ages. However, little is known about HAdV infection among children with severe acute respiratory infection (SARI). The present study retrospectively analysed the molecular typing and epidemiological characteristics of HAdV-positive samples from children with SARI from January 2017 to December 2021 in Huzhou. The results showed that 89 (8·27%) of 1078 SARI paediatric patients were positive for HAdVs. Children <5 years of age accounted for 87·64% of the positive cases. The peak seasons for HAdV infection were the first quarter and the fourth quarter. In addition, HAdV-B and HAdV-C were circulating among paediatric patients with SARI, of which the B3 genotype (n = 30, 51·72%) was the most prevalent and was detected every year, indicating that B3 is the main epidemic strain in the Huzhou area, followed by C1 (n = 9, 15·52%), C2 (n = 7, 12·07%) and B7 (n = 5, 8·62%). These findings provide a benchmark for future epidemiology and prevention strategies for HAdVs.

490 Evaluation of the BioFire FilmArray Pneumonia Panel Plus for diagnosis of lower respiratory tract infections in people with cystic fibrosis who have undergone lung transplantation

490 Evaluation of the BioFire FilmArray Pneumonia Panel Plus for diagnosis of lower respiratory tract infections in people with cystic fibrosis who have undergone lung transplantation

A Real-world Data Analysis of Intermittent Catheterization, Showing the Impact of Prelubricated Versus Hydrophilic Catheter Use on the Occurrence of Symptoms Suggestive of Urinary Tract Infections

BackgroundSystematic reviews have highlighted the lack of evidence on choosing the type of intermittent urinary catheter (IUC) with regard to the occurrence of urinary tract infections (UTIs). ObjectiveTo describe the incidence and frequency of symptoms suggestive of UTIs (ssUTIs) for prelubricated versus hydrophilic IUCs. Design, setting, and participantsAn observational study of a patient database compiled by UK general practitioners was conducted. Outcome measurements and statistical analysisThe primary outcome measures were the proportion of patients with at least one ssUTI (prescription of a nonspecific antibiotic with a UTI-related diagnosis, or prescription of a UTI-specific antibiotic) and the mean number of ssUTIs per affected patient in the 12 mo following the index IUC prescription. Comparable prelubricated (“PRELUBE”) and hydrophilic (“HYDRO”) catheter groups were obtained with 1:1 propensity score matching (PSM). Results and limitationsA total of 5296 patients were included (prelubricated: n = 458; hydrophilic: n = 4838). After PSM, the two groups had similar proportions of patients with ssUTIs at baseline. The proportion of patients with ssUTIs during exposure was similar in the PRELUBE (36.9%) and HYDRO groups (41.5%; p = 0.155). However, among patients having used the same type of catheter throughout the exposure period, the proportion with ssUTIs was significantly lower in the PRELUBE group (44.6%, vs 55.0% for HYDRO; p = 0.015), as was the number of ssUTIs per patient (1.3 vs 1.8; p = 0.036). ConclusionsWhen choosing a coated IUC, physicians and patients should not rule out PRELUBE IUCs for safety reasons alone. Patient summaryUsing real-world data compiled by UK general practitioners, we described the incidence and frequency of symptoms suggestive of urinary tract infection in people who were using various types of intermittent urinary catheters. When the same type of prelubricated catheter was used throughout the study period, the incidence of these symptoms was lower than for hydrophilic catheters.

A Semi-Supervised Machine Learning Model for Risk Analysis of Urinary Tract Infections in People with Dementia

Background: Urinary Tract Infections (UTIs) are common conditions in the elderly population and one of the key causes of hospital admissions in people with dementia. One of the key challenges in dealing with UTIs is that the condition often remains undiagnosed until it advances and shows severe symptoms which can lead to hospitalisation. Method: This study presents a new system for detecting UTI in people with dementia. The system relies on low-cost in-home sensory monitoring combined with a novel machine learning algorithm. Environmental and physiological monitoring devices provide continuous data collection from homes, and the proposed machine learning model is trained to extract and identify the risk of UTIs. In conditions such as UTI, collecting sufficient training data to train machine learning models is a challenging task. The limited access to labelled data and examples creates the risk that learning models can become overfitted or biased. We propose a semi-supervised learning model to process a large unlabelled data set in combination with a smaller labelled dataset. We use an unsupervised learning technique which trains a model by extracting the underlying features from a set of unlabelled data and use the probabilistic neural network to estimate the density distribution. We use the unsupervised model for feature extraction and use these features from the smaller dataset to train a supervised classifier. The proposed approach is tested in real-world application and within a healthcare monitoring system with 110 participants. Finding: The proposed system can record the environmental and clinical data in an integrated framework. This provides information for the proposed machine learning model to identify the risks of UTIs by processing the patterns and changes in vital signs and activity patterns. The evaluation results show that the proposed model can detect the risk of UITs with an F1-score of 84%, which outperforms the baseline methods by 10% on average. Interpretation: The proposed model uses continuous environmental monitoring data and vital signs to detect early symptoms and the risk of UTIs. This is a first study using deep learning and semi-supervised models to analyse in-home sensory data in remote healthcare monitoring scenarios. The model provides a new approach to analyse and interpret continuous observation and measurement data for dementia care. Funding: The UK Dementia Research Institute, Medical Research Council (MRC), Alzheimer's Society and Alzheimer's Research UK. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The study protocol for this work has been reviewed and approved by the South East Coast Surrey NHS Research Ethics Committee and all the research has been performed in accordance with relevant guidelines and regulations. We obtained informed consent from all the study participants.

Canagliflozin and Risk of Genital Infections and Urinary Tract Infections in People with Diabetes Mellitus and Kidney Disease in the CREDENCE Trial

Canagliflozin and Risk of Genital Infections and Urinary Tract Infections in People with Diabetes Mellitus and Kidney Disease in the CREDENCE Trial

Immunotherapy to reduce frequency of urinary tract infections in people with neurogenic bladder dysfunction; a pilot randomised, placebo-controlled trial

Objective: To establish the feasibility of a randomized, placebo-controlled trial to investigate the effect of a specific immunotherapy bacterial lysate OM-89 (Uro-Vaxom®) in reducing the frequency of urinary tract infections in people with neurogenic bladder dysfunction. Design: A parallel-group, double-blind, randomized, placebo-controlled trial. Setting: Patients at home, recruited through out-patient contact, social media and patient support groups. Subjects: People with a spinal cord injury, multiple sclerosis, transverse myelitis or cauda equina syndrome who had suffered three or more clinically diagnosed urinary tract infections treated with antibiotics over the preceding 12 months. Interventions: All participants took one capsule of oral OM-89 immunotherapy (6 mg) or matching Placebo (randomisation ratio 1:1), once daily in the morning for 3 months. Main measures: The primary outcome was occurrence of a symptomatic urinary tract infection treated with an antibiotic, assessed at 3 and 6 months. Feasibility measures included recruitment, retention and practical difficulties. Results: Of 115 patients screened, 49 were recruited, one withdrew before randomization, and 23 were allocated to the control group receiving matching placebo. Six participants, all in the control group, discontinued the intervention; all participants provided full data at both follow-up times. Over 6 months, 18/25 active group patients had 55 infections, and 18/23 control group patients had 47 infections. Most research and clinical procedures were practical, and acceptable to participants. Conclusion: It is feasible to undertake a larger trial. We recommend broader inclusion criteria to increase eligibility and generalizability.

Use of antibiotics and asthma medication for acute lower respiratory tract infections in people with and without asthma: retrospective cohort study

BackgroundAntibiotics are overused in patients with acute lower respiratory tract infections (ALRTIs), but less is known about their use in patients with asthma, or the use of asthma medication for ALRTI in patients without asthma. Our aim was to describe the frequency, variation and drivers in antibiotic and asthma medication prescribing for ALRTI in adults with and without asthma in primary care.MethodsA retrospective cohort analysis of patients aged ≥12 years, diagnosed with an ALRTI in primary care in 2014–15 was conducted using data from the Clinical Practice Research Datalink. Current asthma status, asthma medication and oral antibiotic use within 3 days of ALRTI infection was determined. Treatment frequency was calculated by asthma status. Mixed-effect regression models were used to explore between-practice variation and treatment determinants.ResultsThere were 127,976 ALRTIs reported among 110,418 patients during the study period, of whom 17,952 (16%) had asthma. Respectively, 81 and 79% of patients with and without asthma received antibiotics, and 41 and 15% asthma medication. There were significant differences in between-practice prescribing for all treatments, with greatest differences seen for oral steroids (odds ratio (OR) 18; 95% CI 7–82 and OR = 94; 33–363, with and without asthma) and asthma medication only (OR 7; 4–18 and OR = 17; 10–33, with and without asthma).Independent predictors of antibiotic prescribing among patients with asthma included fewer previous ALRTI presentations (≥2 vs. 0 previous ALRTI: OR = 0.25; 0.16–0.39), higher practice (OR = 1.47; 1.35–1.60 per SD) and prior antibiotic prescribing (3+ vs. 1 prescriptions OR = 1.28; 1.04–1.57) and concurrent asthma medication (OR = 1.44; 1.32–1.57). Independent predictors of asthma medication in patients without asthma included higher prior asthma medication prescribing (≥7 vs. 0 prescriptions OR = 2.31; 1.83–2.91) and concurrent antibiotic prescribing (OR = 3.59; 3.22–4.01).ConclusionFindings from the study indicate that antibiotics are over-used for ALRTI, irrespective of asthma status, and asthma medication is over-used in patients without asthma, with between-practice variation suggesting considerable clinical uncertainty. Further research is urgently needed to clarify the role of these medications for ALRTI.

Pellino-1 Regulates Immune Responses to Haemophilus influenzae in Models of Inflammatory Lung Disease.

Non-typeable Haemophilus influenzae (NTHi) is a frequent cause of lower respiratory tract infection in people with chronic obstructive pulmonary disease (COPD). Pellino proteins are a family of E3 ubiquitin ligases that are critical regulators of TLR signaling and inflammation. The aim of this study was to identify a role for Pellino-1 in airway defense against NTHi in the context of COPD. Pellino-1 is rapidly upregulated by LPS and NTHi in monocyte-derived macrophages (MDMs) isolated from individuals with COPD and healthy control subjects, in a TLR4 dependent manner. C57BL/6 Peli1−/− and wild-type (WT) mice were subjected to acute (single LPS challenge) or chronic (repeated LPS and elastase challenge) airway inflammation followed by NTHi infection. Both WT and Peli1−/− mice develop airway inflammation in acute and chronic airway inflammation models. Peli1−/− animals recruit significantly more neutrophils to the airway following NTHi infection which is associated with an increase in the neutrophil chemokine, KC, in bronchoalveolar lavage fluid as well as enhanced clearance of NTHi from the lung. These data suggest that therapeutic inhibition of Pellino-1 may augment immune responses in the airway and enhance bacterial clearance in individuals with COPD.

Cefiderocol in context

New antibiotics reaching clinical development are scarce, although bacterial plasmids encoding antibiotic resistance genes seem to be everywhere. 1 Madec JY Haenni M Ponsin C et al. Sequence type 48 Escherichia coli carrying the blaCTX-M-1 IncI1/ST3 plasmid in drinking water in France. Antimicrob Agents Chemother. 2016; 60: 6430-6432 Crossref PubMed Scopus (28) Google Scholar Thus, the first clinical trial of cefiderocol, a siderophore cephalosporin active against multidrug-resistant Gram-negative pathogens, 2 Kohira N West J Ito A et al. In vitro antimicrobial activity of a siderophore cephalosporin, S-649266, against Enterobacteriaceae clinical isolates, including carbapenem-resistant strains. Antimicrob Agents Chemother. 2016; 60: 729-734 Crossref PubMed Scopus (172) Google Scholar reported by Simon Portsmouth and colleagues in The Lancet Infectious Diseases, 3 Portsmouth S van Veenhuyzen D Echols R et al. Cefiderocol versus imipenem-cilastatin for the treatment of complicated urinary tract infections caused by Gram-negative uropathogens: a phase 2, randomised, double-blind, non-inferiority trial. Lancet Infect Diseases. 2018; (published online Oct 25.)http://dx.doi.org/10.1016/S1473-3099(18)30554-1 Summary Full Text Full Text PDF PubMed Scopus (198) Google Scholar represents an eagerly-awaited development in the field. The definitive mechanism of action of cefiderocol is not novel; once inside the bacterial cell, it interrupts the synthesis of peptidoglycan, a key component of the bacterial cell wall. What is novel is its manner of getting inside to do the job—no easy task in the era of increasing efflux pump overproduction and porin mutations. Cefiderocol versus imipenem-cilastatin for the treatment of complicated urinary tract infections caused by Gram-negative uropathogens: a phase 2, randomised, double-blind, non-inferiority trialIntravenous infusion of cefiderocol (2 g) three times daily was non-inferior compared with imipenem-cilastatin (1 g each) for the treatment of complicated urinary tract infection in people with multidrug-resistant Gram-negative infections. The results of this study will provide the basis for submission of a New Drug Application to the US Food and Drug Administration. Clinical trials of hospital-acquired pneumonia and carbapenem-resistant infections are ongoing. Full-Text PDF Cefiderocol for treatment of complicated urinary tract infections – Author's replyThe enormous efforts of investigators and trial participants in the premarket development of cefiderocol should be neither disregarded nor underestimated: thanks to their work,1 this drug might soon be accessible to patients who might benefit from it. Nonetheless, a drug tested on only a few hundred people and for a few narrow indications will always require additional, postmarket development. As I have stated,2 because we, the public, have demanded an accelerated path to approval, novel antibiotics are now entering the market on the basis of very thin clinical experience. Full-Text PDF Cefiderocol for treatment of complicated urinary tract infectionsWe were pleased to read the generally positive Comment1 regarding our Article,2 published in The Lancet Infectious Diseases. However, we would like to respond to some of the points raised. Full-Text PDF

Cefiderocol versus imipenem-cilastatin for the treatment of complicated urinary tract infections caused by Gram-negative uropathogens: a phase 2, randomised, double-blind, non-inferiority trial

Carbapenem-resistant Gram-negative bacteria represent the highest priority for addressing global antibiotic resistance. Cefiderocol (S-649266), a new siderophore cephalosporin, has broad activity against Enterobacteriaceae and non-fermenting bacteria, such as Pseudomonas aeruginosa and Acinetobacter baumannii, including carbapenem-resistant strains. We assessed the efficacy and safety of cefiderocol versus imipenem-cilastatin for the treatment of complicated urinary tract infection in patients at risk of multidrug-resistant Gram-negative infections. We did a phase 2, multicentre, double-blind, parallel-group non-inferiority trial at 67 hospitals in 15 countries. Adults (≥18 years) admitted to hospital with a clinical diagnosis of complicated urinary tract infection with or without pyelonephritis or those with acute uncomplicated pyelonephritis were randomly assigned (2:1) by an interactive web or voice response system to receive 1 h intravenous infusions of cefiderocol (2 g) or imipenem-cilastatin (1 g each) three times daily, every 8 h for 7-14 days. Patients were excluded if they had a baseline urine culture with more than two uropathogens, a fungal urinary tract infection, or pathogens known to be carbapenem resistant. The primary endpoint was the composite of clinical and microbiological outcomes at test of cure (ie, 7 days after treatment cessation), which was used to establish non-inferiority (15% and 20% margins) of cefiderocol versus imipenem-cilastatin. The primary efficacy analysis was done on a modified intention-to-treat population, which included all randomly assigned individuals who received at least one dose of study drug and had a qualifying Gram-negative uropathogen (≥1 × 105 colony-forming units [CFU]/mL). Safety was assessed in all randomly assigned individuals who received at least one dose of study drug, according to the treatment they received. This study is registered with ClinicalTrials.gov, number NCT02321800. Between Feb 5, 2015, and Aug 16, 2016, 452 patients were randomly assigned to cefiderocol (n=303) or imipenem-cilastatin (n=149), of whom 448 patients (n=300 in the cefiderocol group; n=148 in the imipenem-cilastatin group) received treatment. 371 patients (n=252 patients in the cefiderocol group; n=119 patients in the imipenem-cilastatin group) had qualifying Gram-negative uropathogen (≥1 × 105 CFU/mL) and were included in the primary efficacy analysis. At test of cure, the primary efficacy endpoint was achieved by 183 (73%) of 252 patients in the cefiderocol group and 65 (55%) of 119 patients in the imipenem-cilastatin group, with an adjusted treatment difference of 18·58% (95% CI 8·23-28·92; p=0·0004), establishing the non-inferiority of cefiderocol. Cefiderocol was well tolerated. Adverse events occurred in 122 (41%) of 300 patients in the cefiderocol group and 76 (51%) of 148 patients in the imipenem-cilastatin group, with gastrointestinal disorders (ie, diarrhoea, constipation, nausea, vomiting, and abdominal pain) the most common adverse events for both treatment groups (35 [12%] patients in the cefiderocol group and 27 [18%] patients in the imipenem-cilastatin group). Intravenous infusion of cefiderocol (2 g) three times daily was non-inferior compared with imipenem-cilastatin (1 g each) for the treatment of complicated urinary tract infection in people with multidrug-resistant Gram-negative infections. The results of this study will provide the basis for submission of a New Drug Application to the US Food and Drug Administration. Clinical trials of hospital-acquired pneumonia and carbapenem-resistant infections are ongoing. Shionogi & Co Ltd, Shionogi Inc.

Probiotics for preventing urinary tract infection in people with neuropathic bladder.

Neuropathic or neurogenic bladder describes a process of dysfunctional voiding as the result of injury in the brain, spinal cord or nerves innervating the bladder. People with neuropathic bladder, such as from spinal cord injury (SCI), are at significant risk of morbidity from urinary tract infections (UTI). Effective methods to prevent UTI in people with SCI have been sought for many years. Probiotics (micro-organisms that exert beneficial health effects in the host) have been recommended for bacterial interference of the urological tract to reduce colonisation by uropathogen and to manage the dual problems of infection and antibiotic resistance. This review looked at the benefits and harms of probiotics in preventing symptomatic UTI in people with neuropathic bladder compared with placebo, no therapy, or non-antibiotic prophylaxis (cranberry juice, methenamine hippurate, topical oestrogen). We searched the Cochrane Kidney and Transplant Specialised Register up to 10 March 2017 through contact with the Information Specialist using search terms relevant to this review. Studies in the Specialised Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov. All randomised controlled trials (RCTs), quasi-RCTs and cross-over RCTs looking at the use of probiotics for the prophylaxis of UTI in people with neuropathic bladders was considered for inclusion. Men, women and children of all ages with neuropathic bladders from neurological injury such as suprapontine, supra sacral and sacral aetiologies was included. All bladder management types, including reflex voiding, time voiding, indwelling and intermittent catheterization were eligible for this review.Studies comparing probiotics to placebo, no treatment or other non-antibiotic prophylaxis was included. Studies comparing probiotics with antibiotics or in combination with antibiotics were excluded. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) or standardised mean difference (SMD) and 95% CI were planned for continuous outcomes. This review includes a total of three studies (one cross-over and two parallel RCTs) which involved 110 participants. All three studies looked at intravesical instillation of a low virulent Escherichia coli (E. coli) strain in reducing the risk of symptomatic UTI in participants with neuropathic bladder, predominantly from SCI. Two studies used the E. coli 83972 strain and one study used the E. coli HU2117 strain.We did not find any RCTs involving other probiotics or other routes of administration for preventing UTI in people with neuropathic bladder.There was consistency in definition of symptomatic UTI in all three studies. Symptoms that all studies considered were relevant to diagnose UTI were adequately defined. All three studies defined microbiological diagnosis of symptomatic UTI.Asymptomatic bacteriuria was not considered an outcome measure in any of the included studies; however it was defined in two studies to establish successful inoculation.It is uncertain if the risk of symptomatic UTI is reduced with bladder inoculation using E. coli because the certainty of the evidence is very low (3 studies, 110 participants: RR 0.32, 95% CI 0.08 to 1.19; I2 = 82%).Two studies reported adverse events. One study reported one episode of autonomic dysreflexia. One study reported three symptomatic UTI occurring in two patients, and two studies mentioned the absence of septicaemia and pyelonephritis. Intravesical instillation was reported as "generally safe". One study reported high attrition rates in participants due to the need to adhere to strict instillation protocols.The overall quality of the studies was poor. All three studies had high risk of attrition bias due to failure of an intention-to-treat analysis which undermines the randomisation process and weakened the results of the studies. All three studies also had high risk of reporting bias. In this review, there were no studies identified addressing oral probiotics in preventing UTI in people with neuropathic bladder. It is uncertain if the risk of symptomatic UTI is reduced in people with neuropathic bladders via intravesical instillation of non-pathogenic E. coli as data were derived from small studies with high risk of bias.Although very minimal levels of harm was reported with this procedure, due to variable success rates, the need for strict adherence to instillation protocols together with high attrition rates in these studies, it is doubtful bladder instillation will be a widely accepted intervention in its current form.It is recommended that further appropriately powered RCTs with more robust methodological reporting be carried out.

Recommending Oral Probiotics to Reduce Winter Antibiotic Prescriptions in People With Asthma: A Pragmatic Randomized Controlled Trial.

Evidence from studies mainly in children has shown that orally administered probiotics may prevent respiratory tract infections and associated antibiotic use. We evaluated whether advice to take daily probiotics can reduce antibiotic prescribing for winter respiratory tract infections in people with asthma. We conducted a randomized controlled, parallel-group pragmatic study for participants aged 5 years and older with asthma in a UK primary care setting. The intervention was a postal leaflet with advice to take daily probiotics from October 2013 to March 2014, compared with a standard winter advice leaflet. Primary outcome was the proportion of participants prescribed antibiotics for respiratory tract infections. There were 1,302 participants randomly assigned to a control group (n = 650) or intervention group (n = 652). There was no significant difference in the primary outcome measure, with 27.7% receiving antibiotics in the intervention group and 26.9% receiving antibiotics in the control group (odds ratio = 1.04; 95% CI, 0.82-1.34). Uptake of probiotics was low, but outcomes were similar in those who accessed probiotics (adjusted odds ratio = 1.08; 95% CI, 0.69-1.69, compared with controls). We also found no evidence of an effect on respiratory tract infections or asthma exacerbations. In this pragmatic community-based trial in people with asthma, we found no evidence that advising use of winter probiotics reduces antibiotic prescribing.

The etiology of lower respiratory tract infections in people with diabetes.

Patients with diabetes mellitus (DM) are likely to develop many types of infections, which affect the transport of glucose into tissues. Diabetes increases the susceptibility to different kinds of respiratory infections, is often identified as an independent risk factor for developing lower respiratory tract infections. Pulmonary infections caused by Mycobacterium tuberculosis, Staphylococcus aureus, gram-negative bacteria and fungi may occur with an increased frequency, whereas infections due to Streptococcus pneumonia or influenza virus may be associated with increased morbidity and mortality. During lung infection, there are changes in the local and ciliary epithelial lining. Increased susceptibility to pneumococcal infection by people with diabetes is the result of reduced defense capability of antibodies to protein antigens. The relationship between diabetes and pulmonary tuberculosis is well known, and the incidence of tuberculosis in diabetic individuals is 4-5 times greater than among the non-diabetic population. It is thought that malfunction of monocytes in patients with diabetes may contribute to the increased susceptibility to tuberculosis and/or a worse prognosis. Hospitalization of patients with diabetes due to influenza virus or flu-like infections is up to 6 times more likely to occur compared to healthy individuals, also diabetic patients are more likely to be hospitalized due to infection complications. Immunization with influenza and anti-pneumococcal vaccines is recommended to reduce hospitalizations, deaths, and medical expenses. Diabetes, especially the uncontrolled one, predisposes to fungal infection, the most common candidiasis and mucormycosis.

Comparative genome analysis of Mycoplasma pneumoniae

BackgroundMycoplasma pneumoniae is a common pathogen that causes upper and lower respiratory tract infections in people of all ages, responsible for up to 40 % of community-acquired pneumonias. It also causes a wide array of extrapulmonary infections and autoimmune phenomena. Phylogenetic studies of the organism have been generally restricted to specific genes or regions of the genome, because whole genome sequencing has been completed for only 4 strains. To better understand the physiology and pathogenicity of this important human pathogen, we performed comparative genomic analysis of 15 strains of M. pneumoniae that were isolated between the 1940s to 2009 from respiratory specimens and cerebrospinal fluid originating from the USA, China and England.ResultsIllumina MiSeq whole genome sequencing was performed on the 15 strains and all genome sequences were completed. Results from the comparative genomic analysis indicate that although about 1500 SNP and indel variants exist between type1 and type 2 strains, there is an overall high degree of sequence similarity among the strains (>99 % identical to each other). Within the two subtypes, conservation of most genes, including the CARDS toxin gene and arginine deiminase genes, was observed. The major variation occurs in the P1 and ORF6 genes associated with the adhesin complex. Multiple hsdS genes (encodes S subunit of type I restriction enzyme) with variable tandem repeat copy numbers were found in all 15 genomes.ConclusionsThese data indicate that despite conclusions drawn from 16S rRNA sequences suggesting rapid evolution, the M. pneumoniae genome is extraordinarily stable over time and geographic distance across the globe with a striking lack of evidence of horizontal gene transfer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1801-0) contains supplementary material, which is available to authorized users.

Differential roles of RND efflux pumps in antimicrobial drug resistance of sessile and planktonic Burkholderia cenocepacia cells.

Burkholderia cenocepacia is notorious for causing respiratory tract infections in people with cystic fibrosis. Infections with this organism are particularly difficult to treat due to its high level of intrinsic resistance to most antibiotics. Multidrug resistance in B. cenocepacia can be ascribed to different mechanisms, including the activity of efflux pumps and biofilm formation. In the present study, the effects of deletion of the 16 operons encoding resistance-nodulation-cell division (RND)-type efflux pumps in B. cenocepacia strain J2315 were investigated by determining the MICs of various antibiotics and by investigating the antibiofilm effect of these antibiotics. Finally, the expression levels of selected RND genes in treated and untreated cultures were investigated using reverse transcriptase quantitative PCR (RT-qPCR). Our data indicate that the RND-3 and RND-4 efflux pumps are important for resistance to various antimicrobial drugs (including tobramycin and ciprofloxacin) in planktonic B. cenocepacia J2315 populations, while the RND-3, RND-8, and RND-9 efflux systems protect biofilm-grown cells against tobramycin. The RND-8 and RND-9 efflux pumps are not involved in ciprofloxacin resistance. Results from the RT-qPCR experiments on the wild-type strain B. cenocepacia J2315 suggest that there is little regulation at the level of mRNA expression for these efflux pumps under the conditions tested.

Vaccines for preventing influenza in people with cystic fibrosis

Viral respiratory tract infections in people with cystic fibrosis have a deteriorating effect on their lung function and disease progression. Annual influenza vaccination is therefore commonly recommended for people with cystic fibrosis. To assess the effectiveness of influenza vaccination for people with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises of references identified from comprehensive electronic database searches and handsearching of relevant journals and abstract books of conference proceedings. We also contacted the companies which market the influenza vaccines used in the trials to obtain further information about randomised controlled trials.Date of the most recent search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Cystic Fibrosis Trials Register: 08 July 2013. All randomised and quasi-randomised trials (published or unpublished) comparing any influenza vaccine with a placebo or with another type of influenza vaccine. Two authors independently assessed study quality and extracted data. Additional information was obtained by contacting the investigators when it was indicated. Four studies enrolling a total of 179 participants with cystic fibrosis (143 (80%) were children aged 1 to 16 years) were included in this review. There was no study comparing a vaccine to a placebo or a whole virus vaccine to a subunit or split virus vaccine. Two studies compared an intranasal applied live vaccine to an intramuscular inactivated vaccine and the other two studies compared a split virus to a subunit vaccine and a virosome to a subunit vaccine (all intramuscular). The incidence of all reported adverse events was high depending on the type of influenza vaccine. The total adverse event rate ranged from 48 out of 201 participants (24%) for the intranasal live vaccine to 13 out of 30 participants (43%) for the split virus vaccine. With the limitation of a statistical low power there was no significant difference between the study vaccinations. None of the events were severe. All study influenza vaccinations generated a satisfactory serological antibody response. No study reported other clinically important benefits. There is currently no evidence from randomised studies that influenza vaccine given to people with cystic fibrosis is of benefit to them. There remains a need for a well-constructed clinical study, that assesses the effectiveness of influenza vaccination on important clinical outcome measures.