Systemic and local antibiotic prophylaxis in the prevention of Staphylococcus epidermidis graft infection

BACKGROUND: The aim of the study was to investigate the in vivo efficacy of local and systemic antibiotic prophylaxis in the prevention of Staphylococcus (S.) epidermidis graft infection in a rat model and to evaluate the bacterial adherence to frequently used prosthetic graft materials. METHODS: Graft infections were established in the subcutaneous tissue of 120 male Wistar rats by implantation of Dacron/ePTFE grafts followed by topical inoculation with 2 × 10(7 )CFUs of clinical isolate of methicillin-resistant S. epidermidis. Each of the graft series included a control group, one contaminated group that did not receive any antibiotic prophylaxis, two contaminated groups that received systemic prophylaxis with teicoplanin or levofloxacin and two contaminated groups that received teicoplanin-soaked or levofloxacin-soaked grafts. The grafts were removed 7 days after implantation and evaluated by quantitative culture. RESULTS: There was significant bacterial growth inhibition in the groups given systemic or local prophylaxis (P < 0.05). Methicillin-resistant S. epidermidis had greater affinity to Dacron graft when compared with ePTFE graft in the untreated contaminated groups (P < 0.05). CONCLUSION: The study demonstrated that the usage of systemic or local prophylaxis and preference of ePTFE graft can be useful in reducing the risk of vascular graft infections caused by staphylococcal strains with high levels of resistance

Methicillin Resistance Alters the Biofilm Phenotype and Attenuates Virulence in Staphylococcus aureus Device-Associated Infections

Clinical isolates of Staphylococcus aureus can express biofilm phenotypes promoted by the major cell wall autolysin and the fibronectin-binding proteins or the icaADBC-encoded polysaccharide intercellular adhesin/poly-N-acetylglucosamine (PIA/PNAG). Biofilm production in methicillin-susceptible S. aureus (MSSA) strains is typically dependent on PIA/PNAG whereas methicillin-resistant isolates express an Atl/FnBP-mediated biofilm phenotype suggesting a relationship between susceptibility to β-lactam antibiotics and biofilm. By introducing the methicillin resistance gene mecA into the PNAG-producing laboratory strain 8325-4 we generated a heterogeneously resistant (HeR) strain, from which a homogeneous, high-level resistant (HoR) derivative was isolated following exposure to oxacillin. The HoR phenotype was associated with a R602H substitution in the DHHA1 domain of GdpP, a recently identified c-di-AMP phosphodiesterase with roles in resistance/tolerance to β-lactam antibiotics and cell envelope stress. Transcription of icaADBC and PNAG production were impaired in the 8325-4 HoR derivative, which instead produced a proteinaceous biofilm that was significantly inhibited by antibodies against the mecA-encoded penicillin binding protein 2a (PBP2a). Conversely excision of the SCCmec element in the MRSA strain BH1CC resulted in oxacillin susceptibility and reduced biofilm production, both of which were complemented by mecA alone. Transcriptional activity of the accessory gene regulator locus was also repressed in the 8325-4 HoR strain, which in turn was accompanied by reduced protease production and significantly reduced virulence in a mouse model of device infection. Thus, homogeneous methicillin resistance has the potential to affect agr- and icaADBC-mediated phenotypes, including altered biofilm expression and virulence, which together are consistent with the adaptation of healthcare-associated MRSA strains to the antibiotic-rich hospital environment in which they are frequently responsible for device-related infections in immuno-compromised patients

Molecular and Evolutionary Bases of Within-Patient Genotypic and Phenotypic Diversity in Escherichia coli Extraintestinal Infections

Although polymicrobial infections, caused by combinations of viruses, bacteria, fungi and parasites, are being recognised with increasing frequency, little is known about the occurrence of within-species diversity in bacterial infections and the molecular and evolutionary bases of this diversity. We used multiple approaches to study the genomic and phenotypic diversity among 226 Escherichia coli isolates from deep and closed visceral infections occurring in 19 patients. We observed genomic variability among isolates from the same site within 11 patients. This diversity was of two types, as patients were infected either by several distinct E. coli clones (4 patients) or by members of a single clone that exhibit micro-heterogeneity (11 patients); both types of diversity were present in 4 patients. A surprisingly wide continuum of antibiotic resistance, outer membrane permeability, growth rate, stress resistance, red dry and rough morphotype characteristics and virulence properties were present within the isolates of single clones in 8 of the 11 patients showing genomic micro-heterogeneity. Many of the observed phenotypic differences within clones affected the trade-off between self-preservation and nutritional competence (SPANC). We showed in 3 patients that this phenotypic variability was associated with distinct levels of RpoS in co-existing isolates. Genome mutational analysis and global proteomic comparisons in isolates from a patient revealed a star-like relationship of changes amongst clonally diverging isolates. A mathematical model demonstrated that multiple genotypes with distinct RpoS levels can co-exist as a result of the SPANC trade-off. In the cases involving infection by a single clone, we present several lines of evidence to suggest diversification during the infectious process rather than an infection by multiple isolates exhibiting a micro-heterogeneity. Our results suggest that bacteria are subject to trade-offs during an infectious process and that the observed diversity resembled results obtained in experimental evolution studies. Whatever the mechanisms leading to diversity, our results have strong medical implications in terms of the need for more extensive isolate testing before deciding on antibiotic therapies

Can better prescribing turn the tide of resistance?

In the wake of concerns about the level of antibiotic resistance, governments worldwide are pressing for reduced antibiotic use, hoping thereby to reverse resistance trends. Is success likely? The evidence is mixed, and expectations should be tempered by the growing realization that many resistant bacteria are biologically fit, making them difficult to displace. If resistance is unlikely to be reduced significantly by changing prescription practices, how can clinicians outpace increased resistance, particularly when much of 'big pharma' is abandoning antibiotic development