A reiterative method for calculating the early bactericidal activity of antituberculosis drugs.

Studies of early bactericidal activity (EBA) are important in the rapid evaluation of new antituberculosis drugs. Historically, these have concentrated on the log fall in the viable count in sputum during the first 48 hours of therapy. In this paper, we provide a mathematical model that suggests that the viable count in sputum follows an exponential decay curve with the equation V = S + Me(-kt) (where V is the viable count, M the population of bacteria susceptible to the test drug, S the population susceptible only to sterilizing agents, t the day of sputum collection as related to start of therapy, k the rate constant for the bacteria killed each day, and e the Napierian constant). We demonstrate that data from clinical trials fits the exponential decay model. We propose that future EBA studies should be performed by measuring daily quantitative counts for at least 5 days. We also propose that the comparison of the early bactericidal activity of antituberculosis drugs should be evaluated using the time taken to reduce the viable count by 50% (vt(50)). A further reiterative refinement following a rule set based on statistically the best fit to the exponential decay model is described that will allow investigators to identify anomalous results and thus enhance the accuracy in measuring early bactericidal activity

Leak Detection: Technology and Implementation

Ageing infrastructure and declining water resources are major concerns with a growing global population. Controlling water loss has therefore become a priority for water utilities around the world. In order to improve efficiencies, water utilities need to apply good practices in leak detection. Leak Detection: Technology and Implementation assists water utilities with the development and implementation of leak detection programs. Leak detection and repair is one of the components of controlling water loss.  In addition, techniques are discussed within this book and relevant case studies are presented. This book provides useful and practical information on leakage issues

Leak Detection: Technology and Implementation

Ageing infrastructure and declining water resources are major concerns with a growing global population. Controlling water loss has therefore become a priority for water utilities around the world. In order to improve efficiencies, water utilities need to apply good practices in leak detection. Leak Detection: Technology and Implementation assists water utilities with the development and implementation of leak detection programs. Leak detection and repair is one of the components of controlling water loss.  In addition, techniques are discussed within this book and relevant case studies are presented. This book provides useful and practical information on leakage issues

The adaptive potential during nasopharyngeal colonisation of <em>Streptococcus pneumoniae</em>

Adaptation to host defences and antimicrobials is critical for Streptococcus pneumoniae (the pneumococcus) during colonisation of the nasopharynx – its only ecological habitat. The pneumococcus is highly transformable with the genome between different strains varying widely in both gene content and genesequence. Thus, mixed strains colonising together will expand the genetic reservoir – ‘‘supragenome’’ for this highly transformable microorganism, increasing its adaptive potential.The extent of the phenotypic and genotypic diversity of strains co-colonising in the nasopharynx was determined. In contrast to most carriage studies, which characterise single colonies, a systematic analysis of up to 20 colonies per colonisation was undertaken in Tanzanian children for 12 months. The serotypewas determined by conventional serology and confirmed by DNA-based methods. The antibiotype for penicillin and co-trimoxazole was determined from the minimum inhibitory concentration determined by E-test. As representative of the genotype of strains the sequence types (STs) was determined by multilocus sequence typing (MLST).Of 61 colonisation events studied, seven (11.5%) had strains expressing multiple serotypes, with a maximum of five serotypes detected. Four colonisation events also had co-colonisation of penicillin and/or cotrimoxazole susceptible and non-susceptible pneumococci. Sequence typing revealed that 58% were unique to our cohort. Simultaneous colonisation of up to six STs with two expressing serotype 6B was seen. Re-isolation of either the same or different strains of serotype 6B was seen. Genetically related single-locus and double-locus variants were identified in our cohort that differed by multiple nucleotides.Multiple colony characterisation revealed phenotypic and genetic evidence of microevolution and a greater diversity of pneumococcal strains colonising together than previously observed, thus increasing the potential to adapt in response to the host environment during colonisation