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.

Photodynamic Antimicrobial Chemotherapy (PACT) in combination with antibiotics for treatment of Burkholderia cepacia complex infection

This study aimed to determine if Photodynamic Antimicrobial Chemotherapy (PACT) was effective in the treatment of Burkholderia cepacia complex infection and whether a synergistic effect was evident if PACT was used in combination with antibiotics. The susceptibility of both planktonic and biofilm cultures of B. cepacia complex strains to methylene blue (MB) and meso-tetra(n-methyl-4-pyridyl)porphine tetra-tosylate (TMP)-mediated PACT was determined alone and in combination with antibiotics used in the treatment of Cystic Fibrosis pulmonary infection caused by these bacteria. When B. cepacia complex strains were grown planktonically, high levels of kill of were achieved with both TMP and MB-mediated PACT with strain and photosensitizer specific differences apparent. When strains were grown in biofilm, antibiotic treatment alone was bactericidal in 17/36 (47%) strain/antibiotic combinations tested. When antibiotic treatment was combined with PACT, bactericidal activity was apparent for 33/36 (92%) strain/antibiotic combinations. No antagonism was detected between PACT and antibiotic treatment with the combination synergistic for 6/36 (17%) and indifferent for 30/36 (83%) strain/antibiotic combinations. PACT could be a viable treatment option, either alone or in combination with antibiotics for treatment of B. cepacia complex pulmonary infection.

Tobramycin Inhalation Powder™:a novel drug delivery system for treating chronic Pseudomonas aeruginosa infection in cystic fibrosis

Lung disease in cystic fibrosis (CF) is typified by the development of chronic airways infection culminating in bronchiectasis and progression to end-stage respiratory disease. Pseudomonas aeruginosa, a ubiquitous gram-negative bacteria, is the archetypical CF pathogen and is associated with an accelerated clinical decline. The development and widespread use of chronic suppressive aerosolized antibacterial therapies, in particular Tobramycin Inhalation Solution (TIS), in CF has contributed to reduced lung function decline and improved survival. However, the requirement for the aerosolization of these agents through nebulizers has been associated with increased treatment burden, reduced quality of life and remain a barrier to broader uptake. Tobramycin Inhalation Powder (TIP™) has been developed by Novartis with the express purpose of delivering the same benefits as TIS in a time-effective manner. Administered via the T-326™ (Novartis) Inhaler in four individual 28-mg capsules, TIP can be administered in a quarter of the time of traditional nebulizers and is inherently portable. In clinical studies, TIP has been shown to be safe, result in equivalent or superior reductions in P. aeruginosa sputum density and produce similar improvements in pulmonary function. TIP offers significant advantages in time saving, portability and convenience over traditional nebulized TIS with comparable clinical outcomes for individuals with CF.

Long-term flavor recognition in humans with prenatal garlic experience

The human fetus learns about its chemosensory environment and this influences its behavior at birth and during the nursing period. This study examined whether prenatal experience could influence behavior much later in life. The dietary preference of two groups of children (8- to 9-years old) was examined. Mothers of one group had consumed garlic during pregnancy, mothers of the control group had not. Children received two tests, 1 month apart, of a meal containing two portions of potato gratin, one flavored with garlic. The total amount of potato, and the percentage of garlic flavored potato, eaten was calculated and examined separately by ANOVA for factors of prenatal exposure, the child's sex, and trial. Children prenatally exposed to garlic ate significantly more garlic flavored potato and a significantly greater overall amount of potato on trial 2, compared to controls. The results demonstrate prenatal experience may affect behavior well into childhood. © 2012 Wiley Periodicals, Inc.

Prenatal and early sucking influences on dietary preference in newborn, weaning, and young adult cats

Early experiences are of potential importance in shaping long-term behavior. This study examined the relative influence of prenatal and/or early postnatal experience of chemosensory stimuli on subsequent olfactory and dietary preferences of cats as newborns, at 9-10 weeks, and at 6 months. Cats were exposed to vanillin or 4-ethylguaiacol via their mother's diet either prenatally, postnatally, perinatally (prenatal and postnatal), or experienced no exposure to the stimuli (control). Newborns were given a two-choice olfactory test between the familiar "odor" and no odor; 9-10 week olds were tested for their preference between two food treats, one flavored with the familiar stimulus and the other unflavored; at 6 months, cats were given a choice of two bowls of food, one flavored with the familiar stimulus and the other unflavored. At all ages, cats preferred the familiar, and avoided the unfamiliar, stimulus. Perinatal exposure exerted the strongest influence on preference. Prenatal exposure influenced preference at all ages and postnatal exposure exerted a stronger effect as the cat aged. We conclude that long-term chemosensory and dietary preferences of cats are influenced by prenatal and early (nursing) postnatal experience, supporting a natural and biologically relevant mechanism for the safe transmission of diet from mother to young. © The Author 2012. Published by Oxford University Press. All rights reserved.

Secretor status and Helicobacter pylori infection are independent risk factors for gastroduodenal disease

The hypothesis that non-secretors of ABO blood group antigens, a group shown to be more susceptible to certain bacterial infections, may be at greater risk of gastroduodenal disease because of increased susceptibility to Helicobacter pylori infection was investigated. Of 101 patients with symptoms of dyspepsia who were undergoing endoscopy, 32% were non-secretors (determined from Lewis blood group phenotype), 36% had endoscopically visible gastroduodenal disease (antral gastritis, gastric ulcer, erosive duodenitis, duodenal ulcer or some combination), and 58% had H pylori detected in antral biopsy specimens. Non-secretors and patients with H pylori infection were significantly more likely to have gastroduodenal disease (p = 0.02 and p = 0.002 respectively). There was, however, no significant association between secretor status and H pylori infection, logistic regression analysis confirming that these were independently associated with gastroduodenal disease. Overall, the relative risk of gastroduodenal disease for non-secretors compared with secretors was 1.9 (95% confidence intervals 1.2, 3.2). Non-secretion of ABO blood group antigens is not related to H pylori infection but is independently and significantly associated with endoscopic gastroduodenal disease. The mechanism of this remains to be explained.

Helicobacter pylori infection and dyspepsia in pregnancy

To investigate the relationship of Helicobacter pylori infection with dyspeptic symptoms in early and late pregnancy. Infection with H pylori and pregnancy outcome were also assessed.

Novel, antibacterial silicone biomaterials for the prevention of microbial adherence and infection in urinary catheters

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Morbillivirus cross-species infection:is there a risk for humans?

The World Health Organisation (WHO) has set regional elimination goals for Measles (MV) eradication to be achieved by 2020 or earlier. A major question is whether an opportunity for veterinary virus infection of humans may arise when MV is eradicated and if vaccination is discontinued. Lessons have been learned from animal to human virus transmission i.e. human immunodeficiency virus (HIV) and more recently from severe acute respiratory syndrome (SARS) and avian influenza virus infections. We are therefore alerted to the risk of zoonosis from the veterinary morbilliviruses. In this review the evidence from viral genomics, animal studies and cell culture experiments will be explored to evaluate the possibility of cross infection of humans with these viruses.

Treatment of lung infection in patients with cystic fibrosis:Current and future strategies

In patients with cystic fibrosis (CF) lung damage secondary to chronic infection is the main cause of death. Treatment of lung disease to reduce the impact of infection, inflammation and subsequent lung injury is therefore of major importance. Here we discuss the present status of antibiotic therapy for the major pathogens in CF airways, including prophylaxis against infection, eradication of early infection, suppression of chronic infection, and the treatment of infective exacerbations. We outline measures to optimize maintenance treatment for infection in the light of novel antibiotic drug formulations. We discuss new developments in culture-independent microbiological diagnostic techniques and the use of tools for monitoring the success of antibiotic treatment courses. Finally, cost-effectiveness analyses for antibiotic treatment in CF patients are discussed.

The Adult Cystic Fibrosis Airway Microbiota Is Stable over Time and Infection Type, and Highly Resilient to Antibiotic Treatment of Exacerbations

Cystic fibrosis (CF) is characterized by defective mucociliary clearance and chronic airway infection by a complex microbiota. Infection, persistent inflammation and periodic episodes of acute pulmonary exacerbation contribute to an irreversible decline in CF lung function. While the factors leading to acute exacerbations are poorly understood, antibiotic treatment can temporarily resolve pulmonary symptoms and partially restore lung function. Previous studies indicated that exacerbations may be associated with changes in microbial densities and the acquisition of new microbial species. Given the complexity of the CF microbiota, we applied massively parallel pyrosequencing to identify changes in airway microbial community structure in 23 adult CF patients during acute pulmonary exacerbation, after antibiotic treatment and during periods of stable disease. Over 350,000 sequences were generated, representing nearly 170 distinct microbial taxa. Approximately 60% of sequences obtained were from the recognized CF pathogens Pseudomonas and Burkholderia, which were detected in largely non-overlapping patient subsets. In contrast, other taxa including Prevotella, Streptococcus, Rothia and Veillonella were abundant in nearly all patient samples. Although antibiotic treatment was associated with a small decrease in species richness, there was minimal change in overall microbial community structure. Furthermore, microbial community composition was highly similar in patients during an exacerbation and when clinically stable, suggesting that exacerbations may represent intrapulmonary spread of infection rather than a change in microbial community composition. Mouthwash samples, obtained from a subset of patients, showed a nearly identical distribution of taxa as expectorated sputum, indicating that aspiration may contribute to colonization of the lower airways. Finally, we observed a strong correlation between low species richness and poor lung function. Taken together, these results indicate that the adult CF lung microbiome is largely stable through periods of exacerbation and antibiotic treatment and that short-term compositional changes in the airway microbiota do not account for CF pulmonary exacerbations.

Infection-Responsive Drug Delivery from Urinary Biomaterials Controlled by a Novel Kinetic and Thermodynamic Approach

Purpose. The pH-dependent physicochemical properties of the antimicrobial quinolone, nalidixic acid, were exploited to achieve ‘intelligent’ drug release from a potential urinary catheter coating, poly(2-hydroxyethylmethacrylate) (p(HEMA)), in direct response to the elevated pH which occurs at the onset of catheter infection.
Methods. p(HEMA) hydrogels, and reduced-hydrophilicity copolymers incorporating methyl methacrylate, were loaded with nalidixic acid by a novel, surface particulate localization method, and characterized in terms of pH-dependent drug release and microbiological activity against the common urease-producing urinary pathogen Proteus mirabilis.
Results. The pH-dependent release kinetics of surface-localized nalidixic acid were 50- and 10-fold faster at pH 9, representing the alkaline conditions induced by urease-producing urinary pathogens, compared to release at pH 5 and pH 7 respectively. Furthermore, microbiological activity against P. mirabilis was significantly enhanced after loading surface particulate nalidixic acid in comparison to p(HEMA) hydrogels conventionally loaded with dispersed drug. The more hydrophobic methyl methacrylate-containing copolymers also demonstrated this pH responsive behavior, but additionally exhibited a sustained period of zero-order release.
Conclusions. The paradigm presented here provides a system with latent, immediate infection-responsive drug release followed by prolonged zero-order antimicrobial delivery, and represents an ‘intelligent’, infection-responsive, self-sterilizing biomaterial.