Sequential antimicrobial therapy: treatment of severe lower respiratory tract infections in children

Although there have been a number of studies in adults, to date there has been little research into sequential antimicrobial therapy (SAT) in paediatric populations. The present study evaluates the impact of a SAT protocol for the treatment of severe lower respiratory tract infection in paediatric patients. The study involved 89 paediatric patients (44 control and 45 SAT). The SAT patients had a shorter length of hospital stay (4.0 versus 8.3 days), shorter duration of inpatient antimicrobial therapy (4.0 versus 7.9 days) with the period of iv therapy being reduced from a mean of 5.6 to 1.7 days. The total healthcare costs were reduced by 52%. The resolution of severe lower respiratory tract infection with a short course of iv antimicrobials, followed by conversion to oral therapy yielded clinical outcomes comparable to those achieved using longer term iv therapy. SAT proved to be an important cost-minimizing tool for realizing substantial healthcare costs savings.

A role for the enteric nervous system in the response to helminth infections

The enteric nervous system (ENS) in the gut contains a particularly high concentration of nerve cells, and effectively functions as an independent 'minibrain'. Interactions between nerve, endocrine, immune and other cell types allow the sophisticated regulation of normal gut physiology. They can also bring about a co-ordinated response to parasitic infection, possibly leading to expulsion of the parasite. In this review, Derek McKay and Ian Fairweather will consider, in brief, data pertaining to changes in the ENS following intestinal helminth infections and speculate on the role that these alterations may have in the expulsion of the parasite burden and the putative ability of the parasite to modulate these events.

Antimicrobial peptide incorporated poly(2-hydroxyethyl methacrylate) hydrogels for the prevention of Staphylococcus epidermidis-associated biomaterial infections

The effectiveness of the antimicrobial peptide maximin-4, the ultrashort peptide H-Orn-Orn-Trp-Trp-NH(2) , and the lipopeptide C(12) -Orn-Orn-Trp-Trp-NH(2) in preventing adherence of pathogens to a candidate biomaterial were tested utilizing both matrix- and immersion-loaded poly(2-hydroxyethyl methacrylate) (poly(HEMA)) hydrogels. Antiadherent properties correlated to both the concentration released and the relative antimicrobial concentrations of each compound against Staphylococcus epidermidis ATCC 35984, at each time point. Immersion-loaded samples containing C(12) -Orn-Orn-Trp-Trp-NH(2) exhibited the lowest adherence profile for all peptides studied over 1, 4, and 24 h. The results outlined in this article show that antimicrobial peptides have the potential to serve as an important weapon against biomaterial associated infections. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012.

Nasal immunization with Burkholderia multivorans outer membrane proteins and the mucosal adjuvant adamantylamide dipeptide confers efficient protection against experimental lung infections with B. multivorans and B. cenocepacia

Chronic lung infection by opportunistic pathogens, such as Pseudomonas aeruginosa and members of the Burkholderia cepacia complex, is a major cause of morbidity and mortality in patients with cystic fibrosis. Outer membrane proteins (OMPs) of gram-negative bacteria are promising vaccine antigen candidates. In this study, we evaluated the immunogenicity, protection, and cross-protection conferred by intranasal vaccination of mice with OMPs from B. multivorans plus the mucosal adjuvant adamantylamide dipeptide (AdDP). Robust mucosal and systemic immune responses were stimulated by vaccination of naive animals with OMPs from B. multivorans and B. cenocepacia plus AdDP. Using a mouse model of chronic pulmonary infection, we observed enhanced clearance of B. multivorans from the lungs of vaccinated animals, which correlated with OMP-specific secretory immunoglobulin A responses. Furthermore, OMP-immunized mice showed rapid resolution of the pulmonary infection with virtually no lung pathology after bacterial challenge with B. multivorans. In addition, we demonstrated that administration of B. multivorans OMP vaccine conferred protection against B. cenocepacia challenge in this mouse infection model, suggesting that OMPs provide cross-protection against the B. cepacia complex. Therefore, we concluded that mucosal immunity to B. multivorans elicited by intranasal vaccination with OMPs plus AdDP could prevent early steps of colonization and infection with B. multivorans and also ameliorate lung tissue damage, while eliciting cross-protection against B. cenocepacia. These results support the notion that therapies leading to increased mucosal immunity in the airways may help patients with cystic fibrosis.

Reconstitution of O-specific lipopolysaccharide expression in Burkholderia cenocepacia strain J2315, which is associated with transmissible infections in patients with cystic fibrosis

Burkholderia cenocepacia is an opportunistic bacterium that infects patients with cystic fibrosis. B. cenocepacia strains J2315, K56-2, C5424, and BC7 belong to the ET12 epidemic clone, which is transmissible among patients. We have previously shown that transposon mutants with insertions within the O antigen cluster of strain K56-2 are attenuated for survival in a rat model of lung infection. From the genomic DNA sequence of the O antigen-deficient strain J2315, we have identified an O antigen lipopolysaccharide (LPS) biosynthesis gene cluster that has an IS402 interrupting a predicted glycosyltransferase gene. A comparison with the other clonal isolates revealed that only strain K56-2, which produced O antigen and displayed serum resistance, lacked the insertion element inserted within the putative glycosyltransferase gene. We cloned the uninterrupted gene and additional flanking sequences from K56-2 and conjugated this plasmid into strains J2315, C5424, and BC7. All the exconjugants recovered the ability to form LPS O antigen. We also determined that the structure of the strain K56-2 O antigen repeat, which was absent from the LPS of strain J2315, consisted of a trisaccharide unit made of rhamnose and two N-acetylgalactosamine residues. The complexity of the gene organization of the K56-2 O antigen cluster was also investigated by reverse transcription-PCR, revealing several transcriptional units, one of which also contains genes involved in lipid A-core oligosaccharide biosynthesis.

Clinico-epidemiological features of infections caused by CTX-M type extended spectrum beta lactamase-producing Escherichia coli in hospitalised patients

A review of medical records of 45 of 53 hospitalised patients with positive cultures for CTX-M type ESBL-producing Escherichia coli between 01 January and 31 May 2004 was conducted. The mean age of the population studied was 73.1 (+/-14.6) years and the majority (55.6%) had been under the care of the internal medicine or elderly care service. In the majority (77.8%) of instances the isolate was attributed to a clinical infection rather than colonisation and the commonest clinical specimen to yield the organism was urine, which was positive in 57.8% of patients. Acquisition of the organism was categorised as nosocomial in 68.9% of patients; in this subgroup, the median duration of inpatient stay prior to recovery of the organism was 24 (range 3-240) days. Haemodialysis-dependence was the most common of the comorbidities evaluated. The mean number of antibiotics prescribed per patient in the 30 days prior to first isolation of the organism was 1.7 (range 0-4). Furthermore, the mean number of antibiotic-days exposure per patient during this period was 13.9 (range 0-48). The most frequently received class of antibiotic was beta-lactam/beta-lactamase inhibitor combinations. Of 35 infections, 26 (74.2%) were successfully treated. Overall 12 patients with infection died (34.3%); attributable mortality was presumed in seven (20%).

Trends in the epidemiology of Candida bloodstream infections in Northern Ireland between January 1984 and December 2000

Objective: To describe the epidemiology of Candida bloodstream infections (BSI) in Northern Ireland. Methods: Retrospective collation of data relating to all clinically significant BSI in a university teaching hospital, which had been recorded prospectively, between 1984 and 2000. Results: One hundred and forty five episodes of candidaemia occurred in 144 patients (of mean age 56.6 years). The contribution of Candida spp. towards all significant BSI increased from 2.00% to 2.5%. C. albicans was the most frequently isolated species, however, its incidence fell from 70% to 53% during the study period. The greatest increase in incidence was seen with C. glabrata which was the most common non-albicans species. Twenty-nine per cent of isolates occurred in patients from an intensive care unit and, surprisingly, a further 25.5% occurred in patients from a surgical service. Conclusion: There appears to be several subtle differences in the epidemiology of candidal BSI between Northern Ireland and other countries. © 2002 The British Infection Society.