Bronchiolitis

INTRODUCTION: Bronchiolitis is the most common lower respiratory tract infection in infants, occurring in a seasonal pattern, with highest incidence in the winter in temperate climates and in the rainy season in warmer countries. Bronchiolitis is a common reason for attendance at and admission to hospital.

METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of prophylactic interventions for bronchiolitis in high-risk children? What are the effects of measures to prevent transmission of bronchiolitis in hospital? What are the effects of treatments for children with bronchiolitis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

RESULTS: We found 59 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.

CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics, bronchodilators (oral, inhaled salbutamol, inhaled adrenaline [epinephrine], hypertonic saline), chest physiotherapy, continuous positive airway pressure, corticosteroids, fluid management, heliox, montelukast, nasal decongestants, nursing interventions (cohort segregation, hand washing, gowns, masks, gloves, and goggles), oxygen, respiratory syncytial virus immunoglobulins, pooled immunoglobulins, or palivizumab (monoclonal antibody), ribavirin, or surfactants.

Intravaginal immunization using the recombinant HIV-1 clade-C trimeric envelope glycoprotein CN54gp140 formulated within lyophilized solid dosage forms

Vaccine-mediated prevention of primary HIV-1 infection at the heterosexual mucosal portal of entry may be facilitated by highly optimised formulations or drug delivery devices for intravaginal (i.vag) immunization. Previously we described hydroxyethylcellulose (HEC)-based rheologically structured gel vehicles (RSVs) for vaginal immunization of an HIV-1 vaccine candidate, a soluble recombinant trimeric HIV-1 clade-C envelope glycoprotein designated CN54gp140. Here we investigated the efficacy of lyophilized solid dosage formulations (LSDFs) for prolonging antigen stability and as i.vag delivery modalities. LSDFs were designed and developed that upon i.vag administration they would reconstitute with the imbibing of vaginal fluid to mucoadhesive, site-retentive semi-solids. Mice were immunized with lyophilized equivalents of (i) RSVs, (ii) modified versions of the RSVs more suited to lyophilization (sodium carboxymethyl cellulose (NaCMC)-based gels) and (iii) Carbopol® gel, all containing CN54gp140. NaCMC-based LSDFs provided significantly enhanced antigen stability compared to aqueous-based RSVs. Rheological analysis indicated the NaCMC-based LSDFs would offer enhanced vaginal retention in woman compared to more conventional vaginal gel formulations. All LSDFs were well tolerated in the mouse model. Following i.vag administration, all LSDFs boosted systemic CN54gp140-specific antibody responses in sub-cutaneously primed mice. Induction of CN54gp140-specific antibody responses in the female genital tract was evident. Of all the LSDFs the fastest releasing which was lyophilized Carbopol® gel elicited immune responses comparable to buffer instillation of antigen suggesting that rather than slower sustained release, initial high burst release from the LSDFs may suffice. The boosting of specific immune responses upon i.vag administration indicates that LSDFs are viable mucosal vaccine delivery modalities promoting antigen stability and facilitating intimate exposure of CN54gp140 to the mucosal-associated lymphoid tissue of the female genital tract.

Antimicrobial prescribing in Nursing Homes in Northern Ireland: Results of Two Point-Prevalence Surveys

BACKGROUND: In 2005, the European Commission recommended that all member states should establish or strengthen surveillance systems for monitoring the use of antimicrobial agents. There is no evidence in the literature of any surveillance studies having been specifically conducted in nursing homes (NHs) in Northern Ireland (NI).

OBJECTIVE: The aim of this study was to determine the prevalence of antimicrobial prescribing and its relationship with certain factors (e.g. indwelling urinary catheterization, urinary incontinence, disorientation, etc.) in NH residents in NI.

METHODS: This project was carried out in NI as part of a wider European study under the protocols of the European Surveillance of Antimicrobial Consumption group. Two point-prevalence surveys (PPSs) were conducted in 30 NHs in April and November 2009. Data were obtained from nursing notes, medication administration records and staff in relation to antimicrobial prescribing, facility and resident characteristics and were analysed descriptively.

RESULTS: The point prevalence of antimicrobial prescribing was 13.2% in April 2009 and 10.7% in November 2009, with a 10-fold difference existing between the NHs with the highest and lowest antimicrobial prescribing prevalence during both PPSs. The same NH had the highest rate of antimicrobial prescribing during both April (30.6%) and November (26.0%). The group of antimicrobials most commonly prescribed was the penicillins (April 28.6%, November 27.5%) whilst the most prevalent individual antimicrobial prescribed was trimethoprim (April 21.3%, November 24.3%). The majority of antimicrobials were prescribed for the purpose of preventing urinary tract infections (UTIs) in both April (37.8%) and in November (46.7%), with 5% of all participating residents being prescribed an antimicrobial for this reason. Some (20%) antimicrobials were prescribed at inappropriate doses, particularly those which were used for the purpose of preventing UTIs. Indwelling urinary catheterization and wounds were significant risk factors for antimicrobial use in April [odds ratio {OR} (95% CI) 2.0 (1.1, 3.5) and 1.8 (1.1, 3.0), respectively] but not in November 2009 [OR (95% CI) 1.6 (0.8, 3.2) and 1.2 (0.7, 2.2), respectively]. Other resident factors, e.g. disorientation, immobility and incontinence, were not associated with antimicrobial use. Furthermore, none of the NH characteristics investigated (e.g. number of beds, hospitalization episodes, number of general practitioners, etc.) were found to be associated with antimicrobial use in either April or November 2009.

CONCLUSIONS: This study has identified a high overall rate of antimicrobial use in NHs in NI, with variability evident both within and between homes. More research is needed to understand which factors influence antimicrobial use and to determine the appropriateness of antimicrobial prescribing in this population in general and more specifically in the management of recurrent UTIs.

Early target cells of measles virus after aerosol infection of non-human primates

Measles virus (MV) is highly infectious, and has long been thought to enter the host by infecting epithelial cells of the respiratory tract. However, epithelial cells do not express signaling lymphocyte activation molecule (CD150), which is the high-affinity cellular receptor for wild-type MV strains. We have generated a new recombinant MV strain expressing enhanced green fluorescent protein (EGFP), based on a wild-type genotype B3 virus isolate from Khartoum, Sudan (KS). Cynomolgus macaques were infected with a high dose of rMV(KS)EGFP by aerosol inhalation to ensure that the virus could reach the full range of potential target cells throughout the entire respiratory tract. Animals were euthanized 2, 3, 4 or 5 days post-infection (d.p.i., n?=?3 per time point) and infected (EGFP(+)) cells were identified at all four time points, albeit at low levels 2 and 3 d.p.i. At these earliest time points, MV-infected cells were exclusively detected in the lungs by fluorescence microscopy, histopathology and/or virus isolation from broncho-alveolar lavage cells. On 2 d.p.i., EGFP(+) cells were phenotypically typed as large mononuclear cells present in the alveolar lumen or lining the alveolar epithelium. One to two days later, larger clusters of MV-infected cells were detected in bronchus-associated lymphoid tissue (BALT) and in the tracheo-bronchial lymph nodes. From 4 d.p.i. onward, MV-infected cells were detected in peripheral blood and various lymphoid tissues. In spite of the possibility for the aerosolized virus to infect cells and lymphoid tissues of the upper respiratory tract, MV-infected cells were not detected in either the tonsils or the adenoids until after onset of viremia. These data strongly suggest that in our model MV entered the host at the alveolar level by infecting macrophages or dendritic cells, which traffic the virus to BALT or regional lymph nodes, resulting in local amplification and subsequent systemic dissemination by viremia.

In vivo tropism of attenuated and pathogenic measles virus expressing green fluorescent protein in macaques

The global increase in measles vaccination has resulted in a significant reduction of measles mortality. The standard route of administration for the live-attenuated measles virus (MV) vaccine is subcutaneous injection, although alternative needle-free routes, including aerosol delivery, are under investigation. In vitro, attenuated MV has a much wider tropism than clinical isolates, as it can use both CD46 and CD150 as cellular receptors. To compare the in vivo tropism of attenuated and pathogenic MV, we infected cynomolgus macaques with pathogenic or attenuated recombinant MV expressing enhanced green fluorescent protein (GFP) (strains IC323 and Edmonston, respectively) via the intratracheal or aerosol route. Surprisingly, viral loads and cellular tropism in the lungs were similar for the two viruses regardless of the route of administration, and CD11c-positive cells were identified as the major target population. However, only the pathogenic MV caused significant viremia, which resulted in massive virus replication in B and T lymphocytes in lymphoid tissues and viral dissemination to the skin and the submucosa of respiratory epithelia. Attenuated MV was rarely detected in lymphoid tissues, and when it was, only in isolated infected cells. Following aerosol inhalation, attenuated MV was detected at early time points in the upper respiratory tract, suggesting local virus replication. This contrasts with pathogenic MV, which invaded the upper respiratory tract only after the onset of viremia. This study shows that despite in vitro differences, attenuated and pathogenic MV show highly similar in vivo tropism in the lungs. However, systemic spread of attenuated MV is restricted.

Antimicrobial prescribing in residential homes.

Objectives: Research in residential homes has been limited to date and the extent of systemic and topical antimicrobial prescribing is largely unknown. The aim of this study was to investigate antimicrobial prescribing in residential homes in Northern Ireland (NI).

Methods: Point prevalence studies (PPSs) were completed in November 2010 (PPS1) and April 2011 (PPS2) in 30 residential homes. Data were obtained from care plans, medication administration records and staff in relation to antimicrobial prescribing and facility and resident characteristics, and analysed descriptively.

Results: The point prevalence of systemic antimicrobial prescribing was 9.4% in PPS1 and 9.2% in PPS2 (range 0.0%–33.3% during both PPSs). Trimethoprim was the most commonly prescribed systemic antimicrobial and the main indication was the prevention of urinary tract infections. Almost 25% of systemic antimicrobials were prescribed at inappropriate doses. The point prevalence of topical antimicrobial prescribing was 6.4% (range 0.0%–22.2%) in PPS1 and 5.9% (range 0.0%–21.1%) in PPS2. The most commonly prescribed topical antimicrobials were chloramphenicol eye preparations in PPS1 and fusidic acid skin preparations in PPS2; treatment with these topical antimicrobials was generally prolonged. More than 25% of all systemic and 55% of all topical antimicrobials were initiated following telephone consultations as opposed to face-to-face consultations.

Conclusions: The prevalence of systemic antimicrobial prescribing in residential homes in NI is relatively high compared with care homes (particularly nursing homes) in other countries. Systemic and topical antimicrobial prescribing is not always appropriate in terms of the doses prescribed and the duration of use. It is apparent that current strategies employed in NI are insuf?cient to ensure prudent antimicrobial prescribing within this environment.

Electrical methods of controlling bacterial adhesion and biofilm on device surfaces.

This review will summarize the significant body of research within the field of electrical methods of controlling the growth of microorganisms. We examine the progress from early work using current to kill bacteria in static fluids to more realistic treatment scenarios such as flow-through systems designed to imitate the human urinary tract. Additionally, the electrical enhancement of biocide and antibiotic efficacy will be examined alongside recent innovations including the biological applications of acoustic energy systems to prevent bacterial surface adherence. Particular attention will be paid to the electrical engineering aspects of previous work, such as electrode composition, quantitative electrical parameters and the conductive medium used. Scrutiny of published systems from an electrical engineering perspective will help to facilitate improved understanding of the methods, devices and mechanisms that have been effective in controlling bacteria, as well as providing insights and strategies to improve the performance of such systems and develop the next generation of antimicrobial bioelectric materials.

COMPARISON OF THE GROWTH INHIBITORY AND BACTERIOCIDAL EFFECTS OF TAUROLIDINE AND TAURULTAM ON A CLINICAL ISOLATE OF ESCHERICHIA-COLI

To investigate the mode of action of Taurolin, an antimicrobial preparation, the growth inhibitory and bacteriocidal effects of taurolidine and taurultam solutions on Escherichia coli isolated from a diagnosed urinary tract infection were examined at 37-degrees-C. The inhibitory effects of taurolidine solutions were observed to be greater than those of taurultam solutions at comparative concentrations; however, the presence of sublethal concentrations of formaldehyde (methylene glycol) associated with taurolidine was sufficient to account for this. The bacteriocidal activity of taurolidine (2.0% w/v) was greater than that of taurultam (4.5% w/v). Both compounds produced biphasic death rates with dissimilar initial slopes, suggested to be due to the presence of formaldehyde in taurolidine solutions. These observations indicate that the growth inhibitory and bacteriocidal effects of Taurolin solutions are primarily due to taurultam, however, the presence of sublethal concentrations of formaldehyde is significant in the expression of this activity.

Crossing the eukaryote-prokaryote divide:A ubiquitin homolog in the human commensal bacterium Bacteroides fragilis

The resident microbiota of the human gastrointestinal (GI) tract is comprised of ~2,000 bacterial species, the majority of which are anaerobes. Colonization of the GI tract is important for normal development of the immune system and provides a reservoir of catabolic enzymes that degrade ingested plant polysaccharides. Bacteroides fragilis is an important member of the microbiota because it contributes to T helper cell development, but is also the most frequently isolated Gram-negative anaerobe from clinical infections. During the annotation of the B. fragilis genome sequence, we identified a gene predicted to encode a homolog of the eukaryotic protein modifier, ubiquitin. Previously, ubiquitin had only been found in eukaryotes, indicating the bacterial acquisition as a potential inter-kingdom horizontal gene transfer event. Here we discuss the possible roles of B. fragilis ubiquitin and the implications for health and disease. © 2012 Landes Bioscience

Chronic cough in children: bronchoalveolar lavage findings

Isolated chronic cough in childhood is a common complaint. Although the symptom cough is included in the definition of clildhood asthma, there is debate as to whether the majoritv of these children have asthma. The authors studied children with isolated chronic cough looking for evidence of airway inflammation typical of asthma, with increased numbers of airway eosinophils as assessed from bronchoalveolar lavage (BAL).

The investigations were carried out on 23 children (median age: 6.7 yrs; range: 1.7-12.75 yrs), attending the Royal Belfast Hospital for Sick Children for elective surgery, who also had a chronic unexplained cough. Written informed consent was obtained from the parent(s) and a nonbronchoscopic BAL was performed. BAL samples were analysed for total and differential white cell counts and also for the inflammatory mediators, eosinophil cationic protein (ECP) and histamine. Results were compared with a group of normal nonatopic children and also a group of atopic asthmatic children, who had been recruited for other studies on airway inflammation.

There was a small but statistically significant increase in BAL percentage eosinophils in the children with chronic cough compared with nonasthmatic controls (0.28% versus 0.10%, p=0.03). However, the children with cough had lower percentage eosinophils than the atopic asthmatic controls (0.28% versus 0.66%, p=0.01). Three out of 23 children with chronic cough had BAL eosinophils greater than the normal upper 95% reference interval in BAL. There was a small but statistically significant increase in percentage neutrophils in the children with cough compared with the nonasthmatic controls (5.85% versus 3.21%, p=0.03). Four out of the 23 children had BAL neutrophils greater than the normal upper 95% reference interval in BAL.

The authors conclude that only a minority of children with chronic unexplained cough have asthmatic-type airway inflammation. It is speculated that the increased percentage neutrophils in bronchoalveolar lavage from children with cough could relate to underlying persistent airways infection.

Gross anatomy of the muscle systems of Fasciola hepatica as visualized by phalloidin-fluorescence and confocal microscopy

Neuropeptides, biogenic amines and acetylcholine are expressed abundantly within the nervous systems of parasitic flatworms, and are particularly evident in the innervation of the musculature. Such associations have implicated the nervous system in locomotion, host attachment and reproductive co-ordination. Information on the muscle systems of parasitic flatworms is generally sparse, in particular those muscles associated with the reproductive system, intestinal tract and attachment apparatus. Also, the use of sectioned material has left description of the 3-dimensional organization of the musculature largely unrecorded. Using fluorescein isothiocyanate (FITC)-labelled phalloidin as a site-specific probe for filamentous actin, applied to whole-mount preparations of adult Fasciola hepatica and examined by confocal scanning laser microscopy, the present work reports on the organization of the major muscle systems in this trematode parasite. A highly regular array of outer circular, intermediate longitudinal and inner diagonal fibres distinguishes the body wall musculature, which is also involved in the development of both ventral and oral suckers. Circular fibres dominate the duct walls of the male and female reproductive systems, whereas the muscles of the intestinal tract have a somewhat diffuse arrangement of fibres. An understanding of the structural complexity of the muscle systems of parasitic flatworms is considered as fundamental to the interpretation of results from physiological experiments.

Vitamin D, calcium and dairy intake, and risk of oesophageal adenocarcinoma and its precursor conditions

Evidence is accumulating that vitamin D may be protective against carcinogenesis, although exceptions have been observed for some digestive tract neoplasms. The aim of the present study was to explore the association between dietary vitamin D and related nutrients and the risk of oesophageal adenocarcinoma and its precursor conditions, Barrett's oesophagus and reflux oesophagitis. In an all-Ireland case-control study conducted between March 2002 and July 2005, 218 oesophageal adenocarcinoma patients, 212 Barrett's oesophagus patients, 208 reflux oesophagitis patients and 252 population-based controls completed a 101-item FFQ, and provided lifestyle and demographic information. Multiple logistic regression analysis was applied to examine the association between dietary intake and disease risk. Oesophageal adenocarcinoma risk was significantly greater for individuals with the highest compared with the lowest tertile of vitamin D intake (OR 1·99, 95 % CI 1·03, 3·86; P for trend = 0·02). The direct association could not be attributed to a particular vitamin D food source. Vitamin D intake was unrelated to Barrett's oesophagus and reflux oesophagitis risk. No significant associations were observed for Ca or dairy intake and oesophageal adenocarcinoma, Barrett's oesophagus or reflux oesophagitis development. High vitamin D intake may increase oesophageal adenocarcinoma risk but is not related to reflux oesophagitis and Barrett's oesophagus. Ca and dairy product intake did not influence the development of these oesophageal lesions. These findings suggest that there may be population subgroups at an increased risk of oesophageal adenocarcinoma if advice to improve vitamin D intake from foods is implemented. Limited work has been conducted in this area, and further research is required.

An expression vector containing a rhamnose-inducible promoter provides tightly regulated gene expression in Burkholderia cenocepacia

Infection of the respiratory tract caused by Burkholderia cepacia complex poses a serious risk for cystic fibrosis (CF) patients due to the high morbidity and mortality associated with the chronic infection and the lack of efficacious antimicrobial treatments. A detailed understanding of the pathogenicity of B. cepacia complex infections is hampered in part by the limited availability of genetic tools and the inherent resistance of these isolates to the most common antibiotics used for genetic selection. In this study, we report the construction of an expression vector which uses the rhamnose-regulated P(rhaB) promoter of Escherichia coli. The functionality of the vector was assessed by expressing the enhanced green fluorescent protein (eGFP) gene (e-gfp) and determining the levels of fluorescence emission. These experiments demonstrated that P(rhaB) is responsive to low concentrations of rhamnose and it can be effectively repressed with 0.2% glucose. We also demonstrate that the tight regulation of gene expression by P(rhaB) promoter allows us to extend the capabilities of this vector to the identification of essential genes.

Use of adhesion counts to help predict symptomatic infection and the ability of fluoroquinolones to penetrate bacterial biofilms on the bladder cells of spinal cord injured patients

There were three objectives to the present study: (1) compare the bladder infection rate and extent of biofilm formation for seven untreated spinal cord injured (SCI) patients and seven given prophylactic co-trimoxazole, (2) identify a level of bacterial adhesion to bladder cells which could be used to help predict symptomatic infection, and (3) determine from in vivo and in vitro studies whether fluoroquinolones were effective at penetrating bacterial biofilms. The results showed that the infection rate had not changed with the introduction of prophylaxis. However, the uropathogenic population had altered subsequent to the introduction of prophylaxis with E. coli being replaced by E. faecalis as the most common cause of infection. In 63% of the specimens from asymptomatic patients, the bacterial counts per cell were <20, while 81% of specimens from patients with at least one sign and one symptom of urinary tract infection (UTI) had > 20 adherent bacteria per bladder cell. Therefore, it is proposed that counts of > 20 bacteria adherent to sediment transitional epithelial bladder cells may be predictive of symptomatic UTI. Clinical data showed that fluoroquinolone therapy reduced the adhesion counts to <20 per cell in 63% of cases, while trimethoprim-sulfamethoxazole only did so in 44%. Further in vitro testing showed that ciprofloxacin (0.1, 0.5 and 1.0 micrograms/ml) partially or completely eradicated adherent biofilms from 92% of spinal cord injured patients' bladder cells, while ofloxacin did so in 71% cases and norfloxacin in 56%. These findings have important implications for the detection and treatment of bacteriuria in spinal cord injured patients.

Moxifloxacin sensitivity of respiratory pathogens in the United Kingdom

The in vitro activity of moxifloxacin and comparator agents against respiratory isolates from a range of geographically distinct centres around the United Kingdom was investigated in the following study. Clinical isolates of Streptococcus pneumoniae (n = 257), Haemophilus influenzae (n = 399) and Moraxella catarrhalis (n = 253) were obtained between March 1998 and April 1999 from nine centres in the United Kingdom. Sensitivity was determined by testing each isolate for its minimum inhibitory concentration (MIC) by agar dilution. Against Streptococcus pneumoniae moxifloxacin and grepafloxacin were the most active (MIC90 = 0.25 mg/l). Trovafloxacin and sparfloxacin were the next most active (MIC90 = 0.5 mg/l) followed by levofloxacin and ciprofloxacin. MIC90 values of the six fluoroquinolones versus H. influenzae ranged from ciprofloxacin > levofloxacin. Against M. catarrhalis the lowest MIC90 was that of grepafloxacin at 0.0625 mg/l followed by moxifloxacin, sparfloxacin, levofloxacin and ciprofloxacin. Trovafloxacin demonstrated the highest MIC90 at 0.5 mg/l. These results demonstrate that moxifloxacin has superior in vitro activity against respiratory tract pathogens than any other comparator quinolones available for clinical use.