The future of antimicrobial therapy in the era of antibiotic resistance in cystic fibrosis pulmonary infection

Cystic fibrosis (CF) is characterised by chronic polymicrobial airway infection and inflammation, which is the major cause of morbidity and mortality. Aggressive use of antimicrobials has been fundamental in increasing the life expectancy of CF patients in recent years. However, enhanced culture and non-culture based detection methods have identified bacteria in the CF lung not previously isolated from CF patients by routine diagnostic microbiology Coupled with increasing antimicrobial resistance, the future of antimicrobial therapy in CF respiratory infection remains challenging. New strategies are needed to address these problems and ensure improvements in life expectancy are maintained. Potential future strategies include the use of new antimicrobial agents and formulations currently in clinical trials, alternative methods of selecting appropriate therapeutic regimens, determination of the pathogenicity of species newly associated with CF and the development of new antimicrobials and adjuvants for use in clinical practice.

Infection control and meticillin-resistant Staphylococcus aureus decolonization:the perspective of nursing home staff

Infection control and meticillin-resistant Staphylococcus aureus (MRSA) in nursing homes have started to assume greater importance in practice and policy.

Evidence for chronic morbillivirus infection in the Mediterranean striped dolphin (Stenella coeruleoalba)

In the summer of 1990 an epizootic infection caused by a morbillivirus (DMV) killed several thousand striped dolphins (Stenella coeruleoalba) in the Mediterranean Sea. In 1991 and 1992 the epizootic reached Italian and Greek waters. The infection by DMV in the acute period of the epizootic caused encephalitis, pneumonia and depletion of lymph nodes. After 1990, the systemic infection apparently disappeared from the Catalonian coast, giving way to cases of chronic infection of the CNS. Dolphins that died between 1991 and May 1994 were necropsied, and investigated for lesions due to DMV, and for the presence of morbillivirus antigen in tissues. Encephalitis occurred in 6 dolphins in which DMV antigen was demonstrated in the CNS and which were without lesions or antigen in other, non-nervous tissues. Inflammatory lesions, gliosis, and DMV antigen decreased in density and amount from cerebral grey matter, through the thalamic areas to the medulla oblongata. The cerebellum was usually spared. Lesions consisted of non-suppurative encephalitis, with diffuse gliosis and glial nodules and neuronophagia, and loss of neurons. Perivascular cuffing of lymphocytes and plasma cells was present in the cerebral cortex and the white matter beneath the cortex. Multinucleate syncytia were not detected in any of the dolphins. The haemagglutinin of DMV was detected mainly in neurons in the cerebral cortical areas. There was no clear relationship between the presence and amount of DMV antigen and the density or chronicity of lesions. Viral inclusions were seen in haematoxylin and eosin stained sections in 3/6 dolphins, principally in the nucleus and the cytoplasm of neurons. In the immunoperoxidase stained sections, dense granular deposits of chromogen, similar to viral inclusions, were evident in all 6 dolphins. The change in the distribution of lesions and of DMV antigen, from systemic to localized in the CNS, and the clustering of systemic DMV infections in the first four months of the epizootic, giving rise to sporadic occurrence of local CNS infection in the subsequent four years, as well as the chronic nature of the CNS lesions, which closely resembles subacute sclerosing panencephalitis, strongly support the existence of a chronic morbillivirus infection in the striped dolphin, as a delayed consequence of the 1990 epizootic.

Fasciola hepatica in the rat:immune responses associated with the development of resistance to infection

F. hepatica infections were established in rats and immune responses were monitored during primary and challenge infections. Antibody levels peaked at 3 weeks post-primary infection and at 6 days post-challenge infection. No significant correlation was found between antibody titre and number of flukes recovered at autopsy. Immunoblotting revealed a limited number of immunogenic polypeptides. When antibodies from these reactive bands were eluted and tested by IFA they all gave identical binding patterns: on juvenile fluke sections tegumental syncytium, tegumental cells and gut cells were labelled, while on adult sections the same antibodies labelled gut cells, reproductive tissue, excretory ducts and flame cells. This suggested that these tissues shared a common epitope or range of epitopes. A pronounced eosinophilia was observed throughout the infection period studied and infected liver sections showed massive cellular infiltration. Histochemical and immunocytochemical investigation of infected liver revealed the presence of large numbers of eosinophils, neutrophils, lymphocytes and phagocytes. The implications of these findings, to an understanding of concomitant immunity in the rat are discussed.

Antibodies to the structural polypeptides of measles virus following acute infection and in SSPE

A solid-phase radioimmunoassay was used to determine the specificity of IgG antibodies from normal sera, sera and CSF from patients with SSPE for the structural polypeptides of measles virus. The polypeptide specificity of antibodies from these sources were qualitatively similar; these results indicate antigenic cross-reactivity between SSPE-derived (Mantooth) and non-SSPE-derived strains of measles virus and stimulation of antibody formation by comparable antigens.

Treatment of a cochlear implant biofilm infection: a potential role for alternative antimicrobial agents

OBJECTIVE:
This study aimed to investigate antimicrobial treatment of an infected cochlear implant, undertaken in an attempt to salvage the infected device.

METHODS:
We used the broth microdilution method to assess the susceptibility of meticillin-sensitive Staphylococcus aureus isolate, cultured from an infected cochlear implant, to common antimicrobial agents as well as to novel agents such as tea tree oil. To better simulate in vivo conditions, where bacteria grow as microcolonies encased in glycocalyx, the bactericidal activity of selected antimicrobial agents against the isolate growing in biofilm were also compared.

RESULTS:
When grown planktonically, the S aureus isolate was susceptible to 17 of the 18 antimicrobials tested. However, when grown in biofilm, it was resistant to all conventional antimicrobials. In contrast, 5 per cent tea tree oil completely eradicated the biofilm following exposure for 1 hour.

CONCLUSION:
Treatment of infected cochlear implants with novel agents such as tea tree oil could significantly improve salvage outcome.

Proteomics on porcine haptoglobin and IgG/IgA show protein species distribution and glycosylation pattern to remain similar in PCV2-SD infection

Haptoglobin (Hp) and immunoglobulins are plasma glycoproteins involved in the immune reaction of the organism after infection and/or inflammation. Porcine circovirus type 2-systemic disease (PCV2-SD), formerly known as postweaning multisystemic wasting syndrome (PMWS), is a globally spread pig disease of great economic impact. PCV2-SD affects the immunological system of pigs causing immunosuppression. The aim of this work was to characterize the Hp protein species of healthy and PCV2-SD affected pigs, as well as the protein backbone and the glycan chain composition of porcine Hp. PCV2-SD affected pigs had an increased overall Hp level, but it did not affect the ratio between Hp species. Glycoproteomic analysis of the Hp β subunits confirmed that porcine Hp is N-glycosylated and, unexpectedly, O-glycosylated, a PTM that is not found on Hp from healthy humans. The glyco-profile of porcine IgG and IgA heavy chains was also characterized; decreased levels of both proteins were found in the investigated group of PCV2-SD affected pigs. Obtained results indicate that no significant changes in the N- and O-glycosylation patterns of these major porcine plasma glycoproteins were detectable between healthy and PCV2-SD affected animals.

Common infection-related conditions and risk of lymphoid malignancies in older individuals

Background: Chronic antigenic stimulation may initiate non-Hodgkin (NHL) and Hodgkin lymphoma (HL) development. Antecedent, infection-related conditions have been associated, but evidence by lymphoproliferative subtype is limited. Methods: From the US SEER-Medicare database, 44 191 NHL, 1832 HL and 200 000 population-based controls, frequency-matched to all SEER cancer cases, were selected. Logistic regression models, adjusted for potential confounders, compared infection-related conditions in controls with HL and NHL patients and by the NHL subtypes diffuse large B-cell, T-cell, follicular and marginal zone lymphoma (MZL). Stratification by race was undertaken. Results: Respiratory tract infections were broadly associated with NHL, particularly MZL. Skin infections were associated with a 15–28% increased risk of NHL and with most NHL subtypes, particularly cellulitis with T-cell lymphoma (OR 1.36, 95%CI 1.24–1.49). Only herpes zoster remained associated with HL following Bonferroni correction (OR 1.55, 95% CI 1.28–1.87). Gastrointestinal and urinary tract infections were not strongly associated with NHL or HL. In stratified analyses by race, sinusitis, pharyngitis, bronchitis and cellulitis showed stronger associations with total NHL in blacks than whites (P<0.001). Conclusions: Infections may contribute to the aetiologic pathway and/or be markers of underlying immune modulation. Precise elucidation of these mechanisms may provide important clues for understanding how immune disturbance contributes to lymphoma.