Antimicrobial chemotherapy

The introduction of highly active antiretroviral therapy (also known as combination therapy) has transformed the nature of HIV infection from a severe and ultimately fatal disease to that of a manageable chronic condition. HIV drugs are highly efficacious, but their use comes at ...

Objectives We examined virological outcomes, patterns of acquired HIV drug resistance (ADR), correlates of virological failure (VF) and acquired drug resistance among fisherfolk on first-line ART. Methods We enrolled 1169 adults on ART for a median duration of 6, 12, 24, 36 and ≥48 months and used a pooled VL testing approach to identify VF (VL ≥1000 copies/mL). We performed genotyping among VF cases and determined correlates of VF and ADR by logistic regression. Results The overall virological suppression rate was 91.7% and ADR was detected in 71/97 (73.2%) VF cases. The most prevalent mutations were M184V/I (53.6%) for NRTIs and K103N (39.2%) for NNRTIs. Thymidine analogue mutations were detected in 21.6% of VF cases while PI mutations were absent. A zidovudine-based ART regimen, duration on ART (≥24 months) and secondary/higher education level were significantly associated with VF. A nevirapine-based regimen [adjusted OR (aOR): 1.87; 95% CI: 0.03–0.54)] and VL ≥10000 copies/mL (a...

Objectives: Time-kill studies are commonly used in investigations of new antimicrobial agents. However, they typically provide descriptive information on pharmacodynamics. We developed a mathe- matical model to capture the relationship between microbial burden and antimicrobial agent concentrations. Methods: Time-kill studies were performed with 108 cfu/mL of Pseudomonas aeruginosa at baseline. Meropenem at 0, 0.25, 1, 4, 16 and 64 3

OBJECTIVES: To determine the stability/reversibility and mechanism of monensin adaptation in monensin-treated cattle isolates compared with reference bacterial isolates, exposed in vitro to high monensin concentrations. METHODS: We evaluated the potential for cattle-origin strains of Clostridium perfringens, Enterococcus faecium and Enterococcus faecalis exposed to monensin in vivo (in vivo monensin-exposed isolates) to maintain or achieve the ability to grow in the presence of high monensin concentrations (in vitro monensin-adapted isolates). Twenty-one consecutive subcultures of the in vitro monensin-adapted strains were performed, and monensin MICs were determined for the 3rd, 7th, 14th and 21st subcultures (subcultured isolates). SDS-PAGE and transmission electron microscopy (TEM) were used to determine protein expression and visualize extracellular morphology changes. RESULTS: Monensin-non-exposed isolates did not display monensin adaptation during in vitro monensin exposure. I...

To investigate phenotypically and genotypically the presence of MDR efflux pumps in 21 clinical isolates of Staphylococcus haemolyticus collected over a period of 10 years. MICs of different antibiotics and biocides were determined by the broth dilution method in the presence/absence of carbonyl cyanide-m-chlorophenylhydrazone (CCCP), an efflux pump inhibitor. PCR followed by sequencing was performed to detect the qac genes that encode for antiseptic resistance. Clonal relationships were determined by PFGE SmaI patterns using a standard protocol. All the isolates were resistant to gentamicin, 15 to erythromycin, 18 to ciprofloxacin, 7 to chloramphenicol and 1 to tetracycline. They showed higher susceptibility to antibiotics when they were exposed to CCCP. The MICs of ethidium bromide, SDS and benzalkonium chloride were also decreased, whereas the MIC of triclosan was decreased in only four isolates in the presence CCCP. Of the 21 isolates, qacA/B was detected in 5 isolates, smr in a...

Abstract: Salmonella is one of the leading causes of foodborne illness in countries around the world. Treatment of Salmonella infections, in both animals and humans has become more difficult with the emergence of multidrug-resistant (MDR) Salmonella strains. Foodborne infections and outbreaks with MDR Salmonella are also increasingly reported. To better monitor and control the spread of MDR Salmonella, it is important to understand the mechanisms responsible for drug resistance and how drug resistance is transmitted to ...

A previous study on 12 in vitro-selected azithromycin-resistant Legionella pneumophila lineages showed that ribosomal mutations were major macrolide resistance determinants. In addition to these mechanisms that have been well described in many species, mutations upstream of lpeAB operon, homologous to acrAB in Escherichia coli, were identified in two lineages. In this study, we investigated the role of LpeAB and of these mutations in macrolide resistance of L. pneumophila METHODS: The role of LpeAB was studied by testing the antibiotic susceptibility of WT, deleted and complemented L. pneumophila Paris strains. Translational fusion experiments using GFP as a reporter were conducted to investigate the consequences of the mutations observed in the upstream sequence of lpeAB operon. We demonstrated the involvement of LpeAB in an efflux pump responsible for a macrolide-specific reduced susceptibility of L. pneumophila Paris strain. Mutations in the upstream sequence of lpeAB operon were...

In the light of increasing drug resistance in Staphylococcus aureus, bacteriophage endolysins [peptidoglycan hydrolases (PGHs)] have been suggested as promising antimicrobial agents. The aim of this study was to determine the antimicrobial activity of nine enzymes representing unique homology groups within a diverse class of staphylococcal PGHs. PGHs were recombinantly expressed, purified and tested for staphylolytic activity in multiple in vitro assays (zymogram, turbidity reduction assay and plate lysis) and against a comprehensive set of strains (S. aureus and CoNS). PGH cut sites in the staphylococcal peptidoglycan were determined by biochemical assays (Park-Johnson and Ghuysen procedures) and MS analysis. The enzymes were tested for their ability to eradicate static S. aureus biofilms and compared for their efficacy against systemic MRSA infection in a mouse model. Despite similar modular architectures and unexpectedly conserved cleavage sites in the peptidoglycan (conferred by...

Few have heard of Orkney tweed today, but in the mid-twentieth century it was as well known as Harris Tweed, and praised for its soft and light characteristics. This article investigates the rise and fall of Orkney tweed and suggests that its decline in the 1960s can be attributed to a variety of factors, including the advent of synthetic, ready-to-wear clothing, but also problems inherent in the mixed marketing messages around the textile. While the main producers of Orkney tweed emphasized the Viking connections of the Orkney islands and their product, the fashion media and overseas customers were more comfortable with positioning Orkney tweed within a stereotypic context of Scottish romanticism, in which Orkney tweed became interchangeable—and replaceable—with all Scottish tweeds. Contemporary attempts to re-establish tweed production on the Orkney Islands have rejected both approaches, focusing instead on the ‘natural’ properties of the fabric and the production of easily portab...

The objectives of this study were to summarize antiretroviral drug concentrations in breast milk (BM) and exposure of breast-fed infants. This was a systematic review of pharmacokinetic studies of HIV-positive women taking antiretrovirals that measured drugs in BM. The quality of pharmacokinetic and laboratory methods was assessed using pre-defined criteria. Pooled ratios and 95% CIs were calculated using the generalized inverse variance method and heterogeneity was estimated by the I(2) statistic. PubMed Central, SCOPUS and LactMed databases were searched. No date or language restrictions were applied. Searches were conducted up to 10 November 2014. Clinical relevance was estimated by comparing ingested dose with the recommended therapeutic dose for each drug. Twenty-four studies were included. There was substantial variability in the clinical and laboratory methods used and in reported results. Relative to maternal plasma (MP), NRTIs accumulate in BM, with BM : MP ratios (95% CI e...