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The widely used biocide triclosan selectively targets FabI, the NADH-dependent trans-2-enoyl-acyl carrier protein reductase, which is an important target for narrow-spectrum antimicrobial drug development. In relation to the growing concern about biocide resistance, we compared in vitro mutants and clinical isolates of Staphylococcus aureus with reduced triclosan susceptibility. Clinical isolates of S. aureus as well as laboratory-generated mutants were assayed for minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) phenotypes and genotypes related to reduced triclosan susceptibility. A potential epidemiological cut-off (ECOFF) MBC of >4mg/L was observed for triclosan in clinical isolates of S. aureus. These showed significantly lower MICs and higher MBCs than laboratory mutants. These groups of strains also had few similarities in the triclosan resistance mechanism. Molecular analysis identified novel resistance mechanisms linked to the presence of an additional sh-fabI allele derived from Staphylococcus haemolyticus. The lack of predictive value of in-vitro-selected mutations for clinical isolates indicates that laboratory tests in the present form appear to be of limited value. More importantly, detection of sh-fabI as a novel resistance mechanism with high potential for horizontal gene transfer demonstrates for the first time that a biocide could exert a selective pressure able to drive the spread of a resistance determinant in a human pathogen.

BACKGROUND: Catheter-related bloodstream infections are a serious and common complication in patients receiving home parenteral nutrition (HPN). METHODS: Prevalence of infections, type of agents, and effectiveness of antibiotic therapy were evaluated in 296 patients (133 males, 163 females; mean age 58.2 +/- 13.5 years) receiving HPN for at least 3 months, from January 1995 to December 2006. Patients underwent 99,969 (331 +/- 552; minimum 91, maximum 4353) days of catheterization, corresponding to 93,236 (311 +/- 489; minimum 52, maximum 4353) days of HPN. RESULTS: Fifty-two patients (24 males and 28 females; 35 oncological and 17 nononcological) were diagnosed with 169 infections. The overall corresponding infection rate was 2.0 per 1000 days of catheterization, with a progressive, regular decrease with time. In 30 cases, immediate central venous catheter removal was necessary. Infections were eradicated in 103 of 139 (74%) cases. As to the most common causative agent, 86 (51%) infections were due to Staphylococcus epidermidis. Of these, 64 were treated from 1995 to 2004, 57 of them (89%) successfully; 22 were treated from 2005 onward, only 7 of them (32%) successfully. CONCLUSIONS: Although the global infection rate has progressively decreased over the years, S epidermidis has shown an alarming increase in resistance to antibiotic treatment in the last 2 years, suggesting the need for strategies to prevent central venous catheter infection.

The human and bovine bacterial pathogen Streptococcus agalactiae (Group B Streptococcus, GBS) expresses a thick polysaccharide capsule that constitutes a major virulence factor and vaccine target. GBS can be classified into ten distinct serotypes differing in the chemical composition of their capsular polysaccharide. However, non-typeable strains that do not react with anti-capsular sera are frequently isolated from colonized and infected humans and cattle. To gain a comprehensive insight into the molecular basis for the loss of capsule expression in GBS, a collection of well-characterized non-typeable strains was investigated by genome sequencing. Genome based phylogenetic analysis extended to a wide population of sequenced strains confirmed the recently observed high clonality among GBS lineages mainly containing human strains, and revealed a much higher degree of diversity in the bovine population. Remarkably, non-typeable strains were equally distributed in all lineages. A number of distinct mutations in the cps operon were identified that were apparently responsible for inactivation of capsule synthesis. The most frequent genetic alterations were point mutations leading to stop codons in the cps genes, and the main target was found to be cpsE encoding the portal glycosyl trasferase of capsule biosynthesis. Complementation of strains carrying missense mutations in cpsE with a wild-type gene restored capsule expression allowing the identification of amino acid residues essential for enzyme activity.

Antibiotic treatment of infections associated with the use of indwelling medical devices in ageing and/or severely ill patients represents a significant healthcare problem due to the difficulty of treating such infections and to the various collateral effects that may be observed following the often aggressive therapy. We summarize some effects of antibiotics on the expression of virulence factors of the microorganisms which cause such infections. These effects, particularly those resulting in a stimulation of bacterial virulence, might be usefully included among the other well-known collateral effects of antibiotic therapy.

Research on implant infections requires cooperative efforts and integration between basic and clinical expertises. An international group of women scientists is acting together in this field. The main research topics of the participants of this group are described. Formation of bacterial biofilms, antibiotic resistance and production of virulence factors like adhesins and toxins are investigated. New biomaterials, coatings and drugs designed to inhibit microbial adhesion are evaluated, and infection-resistant biomaterials are under study, such as a novel heparinizable polycarbonate-urethane (Bionate) or incorporation of diamino-diamide-diol (PIME) to reduce bacterial attachment. The correlation between biofilm production and the accessory-gene-regulator (agr) is investigated in Staphylococcus aureus. The ability to form biofilm has also been shown to be one of the important virulence factors of Enterococcus faecalis, favouring colonization of inert and biological surfaces. The study of quorum sensing has led to the discovery of a quorum sensing inhibitor termed RIP that suppresses staphylococcal biofilm and infections. The immune response and the local defence mechanisms of the host against implant-associated infections, activation and infiltration of immunocompetent cells into the sites of infection have been studied in patients with implant-associated osteomyelitis. Production of monoclonal antibodies (mAbs) as possible vaccines against the staphylococcal collagen-binding MSCRAMMs is in progress.

The Istituto Superiore di Sanità (ISS, the National Institute of Health of Italy) and the Istituto dei Motori (IM) of the Consiglio Nazionale delle Ricerche (CNR, National Research Council) have carried out this study, jointly funded by the two institutes together with the Ministry of Environment. The chemical and toxicological characteristics of emissions from two urban bus engines were studied: a diesel engine fueled with both diesel oil and biodiesel blend and an equivalent spark-ignition one fuelled with compressed natural gas, operating in steady-state conditions. Regulated and unregulated pollutants, such as carcinogenic polycyclic aromatic hydrocarbons and nitrated derivatives, carbonyl compounds and light aromatic hydrocarbons were quantified. Mutagenicity of the emissions was evaluated by the Salmonella typhimurium/mammalian microsome assay. The effect of the fuels under study on the size distribution of particulate matter was also evaluated. The impact of diesel-powered transport on urban air quality, and the potential benefits for human health deriving from the use of natural gas for public transport, are discussed.

The past 2 decades have brought worrying increases in severe Streptococcus pyogenes diseases globally. To investigate and compare the epidemiological patterns of these diseases within Europe, data were collected through a European Union FP-5-funded program (Strep-EURO). Prospective population-based surveillance of severe S. pyogenes infection diagnosed during 2003 and 2004 was undertaken in 11 countries across Europe (Cyprus, the Czech Republic, Denmark, Finland, France, Germany, Greece, Italy, Romania, Sweden, and the United Kingdom) using a standardized case definition. A total of 5,522 cases were identified across the 11 countries during this period. Rates of reported infection varied, reaching 3/100,000 population in the northern European countries. Seasonal patterns of infection showed remarkable congruence between countries. The risk of infection was highest among the elderly, and rates were higher in males than in females in most countries. Skin lesions/wounds were the most common predisposing factor, reported in 25% of cases; 21% had no predisposing factors reported. Skin and soft tissue were the most common foci of infection, with 32% of patients having cellulitis and 8% necrotizing fasciitis. The overall 7-day case fatality rate was 19%; it was 44% among patients who developed streptococcal toxic shock syndrome. The findings from Strep-EURO confirm a high incidence of severe S. pyogenes disease in Europe. Furthermore, these results have identified targets for public health intervention, as well as raising awareness of severe S. pyogenes disease across Europe. Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Le emissioni autoveicolari contribuiscono in maniera significativa all’inquinamento urbano e rappresentano un serio rischio per la salute umana, tanto che la IARC (IARC, 1989) ha classificato le emissioni diesel nel gruppo 2A (probabile cancerogeno umano) e le emissioni da autoveicoli a benzina nel gruppo 2B (possibile cancerogeno umano). In particolare, i motori diesel sono tra le sorgenti principali di particelle fini nelle aree urbane. Queste particelle si depositano facilmente nel tratto respiratorio e possono fungere da iniziatori di tumori polmonari o provocare altre malattie dell’apparato respiratorio (USEPA, 2002; Health Effects Institute, 2002). Il articolato proveniente da emissioni autoveicolari è costituito da una matrice solida carboniosa sulla quale sono adsorbiti centinaia di composti tossici, molti dei quali presentano attività mutagena e/o cancerogena. Fra questi, particolare rilevanza tossicologica hanno gli idrocarburi policiclici aromatici (IPA) e i loro derivati nitrati (Nitro-IPA), la cui presenza nelle emissioni è stata correlata con il combustibile usato e con la tecnologia motoristica impiegata (Concawe, 1998; Westerholm, 1994). Poiché la maggior parte degli autobus destinati al trasporto pubblico urbano è dotata di motori diesel, l’emissione di particolato avviene in aree densamente popolate, contribuendo significativamente all’esposizione della popolazione generale. Specificamente esposte alle emissioni risultano anche le categorie dei lavoratori impiegati sulle strade a tutela della disciplina del traffico, come ad esempio gli agenti di polizia municipale e di polizia stradale.