The population of Salmonella enterica serovar Typhi (S. Typhi), the causative agent of typhoid fever, exhibits limited DNA sequence variation, which complicates efforts to rationally discriminate individual isolates. Here we utilize data from whole-genome sequences (WGS) of nearly 2,000 isolates sourced from over 60 countries to generate a robust genotyping scheme that is phylogenetically informative and compatible with a range of assays. These data show that, with the exception of the rapidly disseminating H58 subclade (now designated genotype 4.3.1), the global S. Typhi population is highly structured and includes dozens of subclades that display geographical restriction. The genotyping approach presented here can be used to interrogate local S. Typhi populations and help identify recent introductions of S. Typhi into new or previously endemic locations, providing information on their likely geographical source. This approach can be used to classify clinical isolates and provides a universal framework for further experimental investigations.

Background New approaches are urgently required to address increasing rates of gonorrhoea and the emergence and global spread of antibiotic-resistant Neisseria gonorrhoeae. Whole genome sequencing (WGS) can be applied to study transmission and track resistance. Methods We performed WGS on 1659 isolates from Brighton, UK, and 217 additional isolates from other UK locations. We included WGS data (n=196) from the USA. Estimated mutation rates, plus diversity observed within patients across anatomical sites and probable transmission pairs, were used to fit a coalescent model to determine the number of single nucleotide polymorphisms (SNPs) expected between sequences related by direct/indirect transmission, depending on the time between samples. Findings We detected extensive local transmission. 281/1061(26%) Brighton cases were indistinguishable (0 SNPs) to ≥1 previous case(s), and 786(74%) had evidence of a sampled direct or indirect Brighton source. There was evidence of sustained transmission of some lineages. We observed multiple related samples across geographic locations. Of 1273 infections in Brighton, 225(18%) were linked to another case from elsewhere in the UK, and 115(9%) to a case from the USA. Four lineages initially identified in Brighton could be linked to 70 USA sequences, including 61 from a lineage carrying the mosaic penA XXXIV associated with reduced cefixime susceptibility. Interpretation We present a WGS-based tool for genomic contact tracing of N. gonorrhoeae and demonstrate local, national and international transmission. WGS can be applied across geographical boundaries to investigate gonorrhoea transmission and to track antimicrobial resistance. Funding Oxford NIHR Health Protection Research Unit and Biomedical Research Centre.

This review examines the contribution dental prescribing makes to the selection of antibiotic resistance in bacteria of the oral flora. The antibiotics commonly used in dental prescribing in the UK are discussed, together with the problems of resistance in members of the oral flora. The antibiotic prescribing habits of general dental practitioners are then reviewed with respect to therapeutic prescriptions and those drugs that are prescribed prophylactically. Not all antibiotic prescriptions for dental problems are written by dentists; prescribing outside the dental profession is also considered. The review then considers the support available to dentists from clinical diagnostic microbiology laboratories. It concludes that better use of diagnostic services, surveillance and improvements in dental education are required now to lessen the impact of antibiotic resistance in the future.

High-level azithromycin resistance (AZM-HR), defined as a MIC of >256 mg/liter, emerged in Neisseria gonorrhoeae in the United Kingdom in 2004. To determine the mechanism of this novel phenotype, isolates from the United Kingdom that were AZM-HR (n, 19), moderately AZM resistant (MICs, 2 to 8 mg/liter) (n, 26), or sensitive (MICs, 0.12 to 0.25 mg/liter) (n, 4) were screened for methylase (erm) genes and for mutations in the mtrR promoter region, associated with efflux pump upregulation. All AZM-resistant isolates and 12 sensitive isolates were screened for mutations in domain V of each 23S rRNA allele. All AZM-HR isolates contained the A2059G mutation (Escherichia coli numbering) in three (3 isolates) or four (16 isolates) 23S rRNA alleles. Most (22/26) moderately AZM resistant isolates contained the C2611T mutation in at least 3/4 alleles. The remainder contained four wild-type alleles, as did 8/12 sensitive isolates, while one allele was mutated in the remaining four sensitive isolates. Serial passage of AZM-sensitive colonies on an erythromycin-containing medium selected AZM-HR if the parent strain already contained mutation A2059G in one 23S rRNA allele. The resultant AZM-HR strains contained four mutated alleles. Eight isolates (five moderately AZM resistant and three AZM-HR) contained mutations in the mtrR promoter. No methylase genes were detected. This is the first evidence that AZM-HR in gonococci may result from a single point mutation (A2059G) in the peptidyltransferase loop in domain V of the 23S rRNA gene. Mutation of a single allele is insufficient to confer AZM-HR, but AZM-HR can develop under selection pressure. The description of a novel resistance mechanism will aid in screening for the AZM-HR phenotype.

In our study, isolates resembling PFGE type EMRSA-16 harboured more biocide resistance genes than other types. The observed reduction in susceptibility of clinical isolates to chlorhexidine may mean that a selective pressure is being exerted by residues in the clinical environment, and highlights the importance of efficacy testing on clinical strains and good infection control practices. The development of reduced microbial susceptibility to biocides represents a serious cause for concern in the clinical environment.