John Cheesbrough

Tracing the Source of Campylobacteriosis

Campylobacter jejuni is the leading cause of bacterial gastro-enteritis in the developed world. It is thought to infect 2–3 million people a year in the US alone, at a cost to the economy in excess of US

UK epidemic Escherichia coli strains A–E, with CTX-M-15 β-lactamase, all belong to the international O25:H4-ST131 clone

4 billion. C. jejuni is a widespread zoonotic pathogen that is carried by animals farmed for meat and poultry. A connection with contaminated food is recognized, but C. jejuni is also commonly found in wild animals and water sources. Phylogenetic studies have suggested that genotypes pathogenic to humans bear greatest resemblance to non-livestock isolates. Moreover, seasonal variation in campylobacteriosis bears the hallmarks of water-borne disease, and certain outbreaks have been attributed to contamination of drinking water. As a result, the relative importance of these reservoirs to human disease is controversial. We use multilocus sequence typing to genotype 1,231 cases of C. jejuni isolated from patients in Lancashire, England. By modeling the DNA sequence evolution and zoonotic transmission of C. jejuni between host species and the environment, we assign human cases probabilistically to source populations. Our novel population genetics approach reveals that the vast majority (97%) of sporadic disease can be attributed to animals farmed for meat and poultry. Chicken and cattle are the principal sources of C. jejuni pathogenic to humans, whereas wild animal and environmental sources are responsible for just 3% of disease. Our results imply that the primary transmission route is through the food chain, and suggest that incidence could be dramatically reduced by enhanced on-farm biosecurity or preventing food-borne transmission.

Rapid Evolution and the Importance of Recombination to the Gastroenteric Pathogen Campylobacter jejuni

OBJECTIVES Uropathogenic and invasive Escherichia coli O25:H4-ST131 isolates producing CTX-M-15 extended-spectrum beta-lactamase (ESBL) enzymes have recently been shown to be disseminated across the globe. In the UK, many CTX-M-15 ESBL-producing E. coli strains have been previously defined as belonging to the epidemic strains A-E, as determined by PFGE. The present study was carried out to define the relationship between these two groups of pathogenic E. coli. METHODS Multilocus sequence typing and PFGE were used for molecular characterization of a collection of 61 ESBL-producing E. coli isolates from across the UK. RESULTS Strains A to E all belonged to the ST131 clone, further underscoring the epidemiological importance of this lineage. CONCLUSIONS The future spread of the ST131 clone, and its UK variants, should be monitored closely and the pathogenic mechanisms explaining their success should be investigated.

Major Uropathogenic Escherichia coli Strain Isolated in the Northwest of England Identified by Multilocus Sequence Typing

Responsible for the majority of bacterial gastroenteritis in the developed world, Campylobacter jejuni is a pervasive pathogen of humans and animals, but its evolution is obscure. In this paper, we exploit contemporary genetic diversity and empirical evidence to piece together the evolutionary history of C. jejuni and quantify its evolutionary potential. Our combined population genetics–phylogenetics approach reveals a surprising picture. Campylobacter jejuni is a rapidly evolving species, subject to intense purifying selection that purges 60% of novel variation, but possessing a massive evolutionary potential. The low mutation rate is offset by a large effective population size so that a mutation at any site can occur somewhere in the population within the space of a week. Recombination has a fundamental role, generating diversity at twice the rate of de novo mutation, and facilitating gene flow between C. jejuni and its sister species Campylobacter coli. We attempt to calibrate the rate of molecular evolution in C. jejuni based solely on within-species variation. The rates we obtain are up to 1,000 times faster than conventional estimates, placing the C. jejuni–C. coli split at the time of the Neolithic revolution. We weigh the plausibility of such recent bacterial evolution against alternative explanations and discuss the evidence required to settle the issue.

Population structure, virulence potential and antibiotic susceptibility of uropathogenic Escherichia coli from Northwest England

ABSTRACT A total of 88 uropathogenic Escherichia coli isolates, including 68 isolates from urine and 20 isolates from blood, were characterized by multilocus sequence typing (MLST). MLST has identified an important genetic lineage of E. coli, designated sequence type 131 (ST-131), represented by 52 of these isolates, 51 of which were resistant to extended-spectrum cephalosporins. ST-131 appears to be a drug-resistant uropathogenic strain of E. coli responsible for causing urinary tract infections and bacteremia and is widely disseminated among both community and hospital patients from different geographical areas in the northwest of England. Application of MLST has helped to define the population biology which may underpin the epidemiology of pathogenic E. coli strains. The portability of MLST allows the accurate monitoring of this antibiotic-resistant uropathogenic strain of E. coli and will enhance surveillance for this important group of organisms.

High metabolic potential may contribute to the success of ST131 uropathogenic Escherichia coli.

OBJECTIVES Multilocus sequence typing (MLST) has been used to characterize diverse pathogens, including uropathogenic Escherichia coli (UPEC). There has been significant interest in the contribution of the O25b:H4-ST131 lineage to UPEC disease, as these isolates are often highly virulent and exhibit multidrug resistance. To reveal the wider impact of sequence type (ST) 131, we have examined its contribution to the overall population structure of UPEC isolates that were not selected on the basis of virulence or antibiotic resistance. METHODS Three hundred UPEC isolates were recovered from community and hospital urine samples examined by clinical microbiology laboratories in the Northwest region of England in June 2007 and June 2009. They were characterized by susceptibility profiling, MLST and virulence gene PCR. PFGE was used to examine isolates from key clones. RESULTS The most common lineage was ST73 (16.6%) followed by ST131 (13.3%), ST69 (9%), ST95 (6.3%), ST10 (4.3%) and ST127 (3.6%). ST131 isolates were significantly more likely to exhibit high levels of antibiotic resistance (35% being CTX-M-15 PCR positive) and those of ST127 were the most widely susceptible but carried the highest number of virulence genes. Only when the CTX-M-15-O25b-positive strains were examined was a high level of virulence observed for ST131 isolates. PFGE indicated ongoing local evolution in ST131. CONCLUSIONS ST131 isolates are well established in the wider UPEC population. This clone is still evolving and we further support suggestions that it represents a real threat to health. We suggest that ST127 is a recently emerged, community-associated, virulent clone that warrants further study.

Is closure of entire wards necessary to control norovirus outbreaks in hospital? : comparing the effectiveness of two infection control strategies

ABSTRACT Uropathogenic Escherichia coli (UPEC) is the predominant cause of urinary tract infection in both hospital and community settings. The recent emergence of multidrug-resistant clones like the O25b:H4-ST131 lineage represents a significant threat to health, and numerous studies have explored the virulence potential of these organisms. Members of the ST131 clone have been described as having variable carriage of key virulence factors, and it has been suggested that additional unidentified factors contribute to virulence. Here we demonstrated that ST131 isolates have high metabolic potential and biochemical profiles that distinguish them from isolates of many other sequence types (STs). A collection of 300 UPEC isolates recovered in 2007 and 2009 in the Northwest region of England were subjected to metabolic profiling using the Vitek2 Advanced Expert System (AES). Of the 47 tests carried out, 30 gave a positive result with at least one of the 300 isolates examined. ST131 isolates demonstrated significant association with eight tests, including those for peptidase, decarboxylase, and alkalinization activity. Metabolic activity also correlated with antibiotic susceptibility profiles, with resistant organisms displaying the highest metabolic potential. This is the first comprehensive study of metabolic potential in the ST131 lineage, and we suggest that high metabolic potential may have contributed to the fitness of members of the ST131 clone, which are able to exploit the available nutrients in both the intestinal and urinary tract environments.

Multi-resistant Escherichia coli and mycotic aneurysm: two case reports

The standard approach for norovirus control in hospitals in the UK, as outlined by the Health Protection Agency guidance and implemented previously by Lancashire Teaching Hospitals, involves the early closure of affected wards. However, this has a major impact on bed-days lost and cancelled admissions. In 2008, a new strategy was introduced in the study hospital, key elements of which included closure of affected ward bays (rather than wards), installation of bay doors, enhanced cleaning, a rapid in-house molecular test and an enlarged infection control team. The impact of these changes was assessed by comparing two norovirus seasons (2007-08 and 2009-10) before and after implementation of the new strategy, expressing the contrast between seasons as a ratio (r) of expected counts in the two seasons. There was a significant decrease in the ratio of confirmed hospital outbreaks to community outbreaks (r = 0.317, P = 0.025), the number of days of restricted admissions on hospital wards per outbreak (r = 0.742, P = 0.041), and the number of hospital bed-days lost per outbreak (r = 0.344, P <0.001). However, there was no significant change in the number of patients affected per hospital outbreak (r = 1.080, P = 0.517), or the number of hospital staff affected per outbreak (r = 0.651, P = 0.105). Closure of entire wards during norovirus outbreaks is not always necessary. The changes implemented at the study hospital resulted in a significant reduction in the number of bed-days lost per outbreak, and this, together with a reduction in outbreak frequency, resulted in considerable cost savings.

Estimating incidence rates using exact or interval-censored data, with an application to hospital-acquired infections.

IntroductionMycotic aneurysms account for a small proportion of all aneurysms. Escherichia coli a gram-negative organism, is recognised as a rare cause of aortic aneurysm. We report two cases of mycotic aneurysm caused by the same strain of multi-resistant Escherichia coli. The purpose of this case report is to highlight the possibility that this strain may be associated with an increased risk of endovascular infection especially in extra-aortic sites. These aneurysms can be difficult to detect and can have serious consequences.Case presentationIn case one, the patient presented with symptoms and signs of septicaemia secondary to a urinary tract infection. Despite adequate treatment the patient continued with pyrexia and raised inflammatory markers, therefore a series of CT scans of the abdomen and thorax were performed, which revealed two intra-thoracic pseudo-aneurysms with associated haematomas. In case two, the patient also developed Escherichia coli septicaemia. On day 44 he developed a swelling on the right side of his neck. An ultrasound scan showed a pseudoaneurysm of the right common carotid artery.ConclusionsWhilst a case report cannot prove that a heightened risk exists, we suggest that it is an area worthy of further surveillance. We recommend when older patients with atheromatosis develop prolonged Escherichia coli septicaemia, the possibility of an infected aneurysm should be borne in mind.

Sepsis and a painful shoulder in a haemodialysis patient.

Health-care providers in the UK and elsewhere are required to maintain records of incidents relating to patient safety, including the date and time of each incident. However, for reporting and analysis, the resulting data are typically grouped into discrete time intervals, for example, weekly or monthly counts. The grouping represents a potential loss of information for estimating variations in incidence over time. We use a Poisson point process model to quantify this loss of information. We also suggest some diagnostic procedures for checking the goodness of fit of the Poisson model. Finally, we apply the model to the data on hospital-acquired methicillin-resistant Staphylococcus aureus infections in two hospitals in the north of England. We find that, in one of the hospitals, the estimated incidence decreased by a factor of approximately 2.3 over a 7-year period from 0.323 to 0.097 cases per day per 1000 beds, whereas in the other, the estimated incidence showed only a small and nonsignificant decrease over the same period from 0.137 to 0.131.