Publications
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McLeod M, Ahmad R, Shebl NA, et al., 2019, A whole-health-economy approach to antimicrobial stewardship: Analysis of current models and future direction, PLoS Medicine, Vol: 16, ISSN: 1549-1277
In a Policy Forum, Alison Holmes and colleagues discuss coordinated approaches to antimicrobial stewardship.
Rawson TM, Ahmad R, Toumazou C, et al., 2019, Artificial intelligence can improve decision-making in infection management, Nature Human Behaviour, Vol: 3, Pages: 543-545, ISSN: 2397-3374
Antibiotic resistance is an emerging global danger. Reaching responsible prescribing decisions requires the integration of broad and complex information. Artificial intelligence tools could support decision-making at multiple levels, but building them needs a transparent co-development approach to ensure their adoption upon implementation.
Ming D, Rawson T, Sangkaew S, et al., 2019, Connectivity of rapid-testing diagnostics and surveillance of infectious diseases (vol 97, pg 244, 2019), BULLETIN OF THE WORLD HEALTH ORGANIZATION, Vol: 97, ISSN: 0042-9686
Ming D, Rawson T, Sangkaew S, et al., 2019, Connectivity of rapid-testing diagnostics and surveillance of infectious diseases, Bulletin of the World Health Organization, Vol: 97, Pages: 242-244, ISSN: 0042-9686
The World Health Organization (WHO) developed the ASSURED criteria to describe the ideal characteristics for point-of-care testing in low-resource settings: affordable, sensitive, specific, user-friendly, rapid and robust, equipment-free and deliverable.1 These standards describe. Over the last decade, widespread adoption of point-of-care testing has led to significant changes in clinical decision-making processes. The development of compact molecular diagnostics, such as the GeneXpert® platform, have enabled short turnaround times and allowed profiling of antimicrobial resistance. Although modern assays have increased operational requirements, many devices are robust and can be operated within communities with minimal training. These new generation of rapid tests have bypassed barriers to care and enabled treatment to take place independently from central facilities. Here we describe the importance of connectivity, the automatic capture and sharing of patient healthcare data from testing, in the adoption and roll-out of rapid testing.
Phillips CJ, Gilchrist M, Cooke FJ, et al., 2019, Adherence to antibiotic guidelines and reported penicillin allergy: pooled cohort data on prescribing and allergy documentation from two English National Health Service (NHS) trusts, BMJ Open, Vol: 9, ISSN: 2044-6055
OBJECTIVE: To investigate documentation of antimicrobial allergy and to determine prescribing adherence to local antibiotic guidelines for inpatients with and without reported penicillin allergy treated for infection in a National Health Service (NHS) context. SETTING: Data were collected at two English hospital NHS trusts over two time-periods: June 2016 and February 2017. DESIGN: Cohort study. Trust 1 data were sourced from prospective point prevalence surveys. Trust 2 data were extracted retrospectively from an electronic report. PARTICIPANTS: Inpatients treated for urinary tract infection (UTI), community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP) and skin and soft tissue infection (SSTI). Data on allergy were collected, and antibiotic selection assessed for adherence to trust guidelines with differences between groups presented as adjusted ORs. RESULTS: A total of 1497 patients were included, with 2645 antibiotics orders. Patients were treated for CAP (n=495; 33.1%), UTI (407; 27.2%), HAP (330; 22%) and SSTI (265; 17.7%). There were 240 (16%) patients with penicillin allergy. Penicillin allergy was recorded as allergy (n=52; 21.7%), side effect (27; 11.3%) and no documentation (161; 67.1%). Overall, 2184 (82.6%) antibiotic orders were guideline-adherent. Adherence was greatest for those labelled penicillin allergy (453 of 517; 87.6%) versus no allergy (1731 of 2128; 81.3%) (OR 0.52 (95% CI 0.37 to 0.73) p<0.001). Guideline-adherence for CAP was higher if penicillin allergy (151 of 163; 92.6%) versus no allergy (582 of 810; 71.9%) (OR 0.20 (95% CI 0.10 to 0.37) p<0.001). There was no difference in adherence between those with and without penicillin allergy for UTI, HAP or SSTI treatment. CONCLUSIONS: A relatively high proportion of patients had a penicillin allergy and two thirds of these had no description of their allergy, which has important implications for patient safety. Patients with penicillin allergy treated for CAP
Gharbi M, Lishman H, Goudie R, et al., 2019, Antibiotic management of urinary tract infection in the elderly in primary care and its association with bloodstream infections and all-cause mortality: a population-based cohort study, BMJ, Vol: 365, ISSN: 0959-8138
OBJECTIVETo evaluate the association between severe adverse outcomes and the antibiotic treatment for urinary tract infection (UTI) diagnosed in elderly adults in primary care. DESIGNA retrospective population-based cohort study.SETTINGClinical Practice Research Datalink (2007-2015) primary care records linked to Hospital Episode Statistics and death records in England.PARTICIPANTSPatients aged≥65 years presenting to a General Practitioner (GP) with at least one diagnosis of suspected or confirmed lower UTI from November 2007 to May 2015.MAIN OUTCOME MEASURESBloodstream infection (BSI), hospital admission and all-cause mortality within 60 days following the index UTI diagnosis.RESULTSAmong 312,896 UTI episodes (157,264 unique patients), 7% did not have a record of having been prescribed antibiotics and 6% showed a delay in antibiotic prescribing. 1,539 episodes of BSI were recorded within 60 days following the initial UTI. The rate of BSI was significantly higher among those patients who were not prescribed an antibiotic (2. 9%) and those patients recorded as returning to the GP within 7 days of the initial consultation for an antibiotic prescription (2.2%), compared with those given a prescription for an antibiotic at the initial consultation (0.2%) (p=0.001). After adjustment for covariates, patients were significantly more likely to experience a BSI in the ‘deferred antibiotics’ and ‘no antibiotics’ groups compared with the ‘immediate antibiotics’ group (aOR=7.12 [95% CI 6.22 to 8.14] and aOR=8.08 [95% CI 7.12 to 9.16]).The Number Needed to Harm (NNH) for occurrence of BSI was lower (greater risk) for the ‘no antibiotics’ group (NNH=37) than for the ‘deferred antibiotics’ group (NNH=51), relative to the ‘immediate antibiotics’ group. The rate of hospital admissions was approximately double among cases with ‘no antibiotics’ (27%) and ‘deferred antibiotics’ (27%) comp
Charani E, Castro-Sanchez E, Bradley S, et al., 2019, Implementation of antibiotic stewardship in different settings - results of an international survey, Antimicrobial Resistance and Infection Control, Vol: 8, ISSN: 2047-2994
BackgroundAntibiotic stewardship interventions are being implemented across different healthcare settings. We report the findings of a global survey of healthcare professionals on the implementation of antibiotic stewardship programmes.MethodsLearners of a Massive Online Open Course (MOOC) on antibiotic stewardship were invited to complete an online survey on the core available organisational resources for stewardship. The categorical variables were analysed using chi-squared test, and Likert questions were analysed using an ordinal regression model. The p-values were considered as two-tailed. Significance was set at p-value of < 0.05.ResultsThe response rate was 55% (505/920), from 53 countries. The responders were 36% (182) doctors, 26% (130) pharmacists, 18% (89) nurses and 20% (104) other (researchers, students and members of the public). Post-graduate training in infection management and stewardship was reported by 56% of doctors compared with 43% (OR 0.59, 95%CI 0.35–1.00) nurses and 35% (OR 0.39, 95%CI 0.24–0.62) of pharmacists. Hospitals were significantly (83% in teaching hospitals, 79% in regional hospitals, p = < 0.01) more likely to have antibiotic policies, when compared to primary care. A surveillance mechanism for antibiotic consumption was reported in 58% (104/178) of teaching hospitals and 62% (98/159) of regional hospitals. Antimicrobial resistance, patient needs, policy, peer influence and specialty level culture and practices were deemed important determinants for decision-making.ConclusionPostgraduate training and support in antibiotic prescribing remains low amongst nurses and pharmacists. Whilst antibiotic policies and committees are established in most institutions, surveillance of antibiotic use is not. The impact of specialty level culture, and peer influence appears to be important factors of antibiotic prescribing.
Rodriguez-Manzano J, Moniri A, Malpartida-Cardenas K, et al., 2019, Simultaneous single-channel multiplexing and quantification of carbapenem-resistant genes using multidimensional standard curves, Analytical Chemistry, Vol: 91, Pages: 2013-2020, ISSN: 0003-2700
Multiplexing and quantification of nucleic acids, both have, in their own right, significant and extensive use in biomedical related fields. Currently, the ability to detect several nucleic acid targets in a single-reaction scales linearly with the number of targets; an expensive and time-consuming feat. Here, we propose a new methodology based on multidimensional standard curves that extends the use of real-time PCR data obtained by common qPCR instruments. By applying this novel method-ology, we achieve simultaneous single-channel multiplexing and enhanced quantification of multiple targets using only real-time amplification data. This is obtained without the need of fluorescent probes, agarose gels, melting curves or sequencing analysis. Given the importance and demand for tackling challenges in antimicrobial resistance, the proposed method is ap-plied to four of the most prominent carbapenem-resistant genes: blaOXA-48, blaNDM, blaVIM and blaKPC, which account for 97% of the UK's reported carbapenemase-producing Enterobacteriaceae.
Blandy O, Honeyford K, Gharbi M, et al., 2019, Factors that impact on the burden of Escherichia coli bacteraemia: multivariable regression analysis of 2011-2015 data from West London, Journal of Hospital Infection, Vol: 101, Pages: 120-128, ISSN: 0195-6701
BackgroundThe incidence of Escherichia coli bacteraemia in England is increasing amid concern regarding the roles of antimicrobial resistance and nosocomial acquisition on burden of disease.AimTo determine the relative contributions of hospital-onset E. coli blood stream infection and specific E. coli antimicrobial resistance patterns to the burden and severity of E. coli bacteremia in West London.MethodsPatient and antimicrobial susceptibility data were collected for all cases of E. coli bacteraemia between 2011 and 2015. Multivariable logistic regression was used to determine the association between the category of infection (hospital or community-onset) and length of stay, intensive care unit admission, and 30-day all-cause mortality.FindingsE. coli bacteraemia incidence increased by 76% during the study period, predominantly due to community-onset cases. Resistance to quinolones, third-generation cephalosporins, and aminoglycosides also increased over the study period, occurring in both community- and hospital-onset cases. Hospital-onset and non-susceptibility to either quinolones or third-generation cephalosporins were significant risk factors for prolonged length of stay, as was older age. Rates of mortality were 7% and 12% at 7 and 30 days, respectively. Older age, a higher comorbidity score, and bacteraemia caused by strains resistant to three antibiotic classes were all significant risk factors for mortality at 30 days.ConclusionMultidrug resistance, increased age, and comorbidities were the main drivers of adverse outcome. The rise in E. coli bacteraemia was predominantly driven by community-onset infections, and initiatives to prevent community-onset cases should be a major focus to reduce the quantitative burden of E. coli infection.
Otter JA, Galtelly TJ, Davies F, et al., 2019, Planning to halve Gram-negative bloodstream infection: getting to grips with healthcare-associated <i>Escherichia coli</i> bloodstream infection sources, JOURNAL OF HOSPITAL INFECTION, Vol: 101, Pages: 129-133, ISSN: 0195-6701
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Charani E, Holmes A, 2019, Antibiotic stewardship-twenty years in the making, Antibiotics, Vol: 8, ISSN: 2079-6382
In the last 20 years, efforts were made to optimize antibiotic use in hospitals across the world as a means of addressing the increasing threat of antibiotic resistance. Despite robust evidence supporting optimal practice, antibiotic decision-making remains sub-optimal in many settings, including in hospitals. Globally, resources remain a limiting factor in the implementation of antibiotic stewardship programs. In addition, antibiotic decision-making is a social process dependent on cultural and contextual factors. Cultural boundaries in healthcare and across specialties still limit the involvement of allied healthcare professionals in stewardship interventions. There is variation in the social norms and antibiotic-prescribing behaviors between specialties in hospitals. The cultural differences between specialties and healthcare professionals (1) shape the shared knowledge within and across specialties in the patient pathway, and (2) result in variation in care, thus impacting patient outcomes. Bespoke stewardship interventions that account for contextual variation in practice are necessary.
Charani E, Smith I, Skodvin B, et al., 2019, Investigating the cultural and contextual determinants of antimicrobial stewardship programmes across low-, middle- and high-income countries – a qualitative study, PLoS ONE, Vol: 14, ISSN: 1932-6203
BackgroundMost of the evidence on antimicrobial stewardship programmes (ASP) to help sustain the effectiveness of antimicrobials is generated in high income countries. We report a study investigating implementation of ASP in secondary care across low-, middle- and high-income countries. The objective of this study was to map the key contextual, including cultural, drivers of the development and implementation of ASP across different resource settings.Materials and methodsHealthcare professionals responsible for implementing ASP in hospitals in England, France, Norway, India, and Burkina Faso were invited to participate in face-to face interviews. Field notes from observations, documentary evidence, and interview transcripts were analysed using grounded theory approach. The key emerging categories were analysed iteratively using constant comparison, initial coding, going back the field for further data collection, and focused coding. Theoretical sampling was applied until the categories were saturated. Cross-validation and triangulation of the findings were achieved through the multiple data sources.Results54 participants from 24 hospitals (England 9 participants/4 hospitals; Norway 13 participants/4 hospitals; France 9 participants/7 hospitals; India 13 participants/ 7 hospitals; Burkina Faso 8 participants/2 hospitals) were interviewed. Across Norway, France and England there was consistency in ASP structures. In India and Burkina Faso there were country level heterogeneity in ASP. State support for ASP was perceived as essential in countries where it is lacking (India, Burkina Faso), and where it was present, it was perceived as a barrier (England, France). Professional boundaries are one of the key cultural determinants dictating involvement in initiatives with doctors recognised as leaders in ASP. Nurse and pharmacist involvement was limited to England. The surgical specialty was identified as most difficult to engage with in each country. Despite challenges, on
Castro-Sánchez E, Sood A, Rawson TM, et al., 2019, Forecasting implementation, adoption, and evaluation challenges for an electronic game–based antimicrobial stewardship intervention: co-design workshop with multidisciplinary stakeholders (Preprint), Publisher: JMIR Publications
Background:Serious games have been proposed to address the lack of engagement and sustainability traditionally affecting interventions aiming to improve optimal antibiotic use among hospital prescribers.Objective:The goal of the research was to forecast gaps in implementation, adoption and evaluation of game-based interventions, and co-design solutions with antimicrobial clinicians and digital and behavioral researchers.Methods:A co-development workshop with clinicians and academics in serious games, antimicrobials, and behavioral sciences was organized to open the International Summit on Serious Health Games in London, United Kingdom, in March 2018. The workshop was announced on social media and online platforms. Attendees were asked to work in small groups provided with a laptop/tablet and the latest version of the game On call: Antibiotics. A workshop leader guided open group discussions around implementation, adoption, and evaluation threats and potential solutions. Workshop summary notes were collated by an observer.Results:There were 29 participants attending the workshop. Anticipated challenges to resolve reflected implementation threats such as an inadequate organizational arrangement to scale and sustain the use of the game, requiring sufficient technical and educational support and a streamlined feedback mechanism that made best use of data arriving from the game. Adoption threats included collective perceptions that a game would be a ludic rather than professional tool and demanding efforts to integrate all available educational solutions so none are seen as inferior. Evaluation threats included the need to combine game metrics with organizational indicators such as antibiotic use, which may be difficult to enable.Conclusions:As with other technology-based interventions, deploying game-based solutions requires careful planning on how to engage and support clinicians in their use and how best to integrate the game and game outputs onto existing workflows.
Rawson T, Ming D, Gowers S, et al., 2019, Public acceptability of computer-controlled antibiotic management: an exploration of automated dosing and opportunities for implementation, Journal of Infection, Vol: 78, Pages: 75-86, ISSN: 0163-4453
Abbas M, Zingg W, Storr J, et al., 2019, Broadening the infection prevention and control network globally; 2017 Geneva IPC-think tank (part 3), Antimicrobial Resistance & Infection Control
Abbas M, Zingg W, Park BJ, et al., 2019, Technology for the prevention of antimicrobial resistance and healthcare-associated infections; 2017 Geneva IPC-Think Tank (Part 2), Antimicrobial Resistance & Infection Control
Rodriguez-Manzano J, Miscourides N, Malpartida-Cardenas K, et al., 2019, Rapid detection of <i>Klebsiella pneumoniae</i> using an auto-calibrated ISFET-array Lab-on-Chip platform, IEEE Biomedical Circuits and Systems Conference (BioCAS), Publisher: IEEE, ISSN: 2163-4025
Abbas M, Zingg W, Storr J, et al., 2019, Implementation research for the prevention of antimicrobial resistance and healthcare-associated infections; 2017 Geneva infection prevention and control (IPC)-think tank (part 1), Antimicrobial Resistance & Infection Control
Charani E, Ahmad R, Rawson TM, et al., 2018, Reply to Peiffer-Smadja, et al., Clin Infect Dis
Chatterjee A, Modarai M, Naylor N, et al., 2018, Quantifying drivers of antibiotic resistance in humans: a systematic review, The Lancet Infectious Diseases, Vol: 18, Pages: e368-e378, ISSN: 1473-3099
Mitigating the risks of antibiotic resistance requires a horizon scan linking the quality with the quantity of data reported on drivers of antibiotic resistance in humans, arising from the human, animal, and environmental reservoirs. We did a systematic review using a One Health approach to survey the key drivers of antibiotic resistance in humans. Two sets of reviewers selected 565 studies from a total of 2819 titles and abstracts identified in Embase, MEDLINE, and Scopus (2005–18), and the European Centre for Disease Prevention and Control, the US Centers for Disease Control and Prevention, and WHO (One Health data). Study quality was assessed in accordance with Cochrane recommendations. Previous antibiotic exposure, underlying disease, and invasive procedures were the risk factors with most supporting evidence identified from the 88 risk factors retrieved. The odds ratios of antibiotic resistance were primarily reported to be between 2 and 4 for these risk factors when compared with their respective controls or baseline risk groups. Food-related transmission from the animal reservoir and water-related transmission from the environmental reservoir were frequently quantified. Uniformly quantifying relationships between risk factors will help researchers to better understand the process by which antibiotic resistance arises in human infections.
Troughton R, Birgand G, Johnson AP, et al., 2018, Mapping national surveillance of surgical site infections (SSIs) to national needs and priorities: an assessment of England’s surveillance landscape, Journal of Hospital Infection, Vol: 100, Pages: 378-385, ISSN: 0195-6701
BackgroundThe rise in antimicrobial resistance has highlighted the importance of surgical site infection (SSI) prevention with effective surveillance strategies playing a key role in improving patient safety. This study maps national needs and priorities for SSI surveillance against current national surveillance activity.MethodsThis study analysed SSI surveillance in NHS hospitals in England covering 23 surgical procedures. Data collected were: (i) annual number of procedures, (ii) SSI rates from national reports, (iii) national reporting requirement (mandatory, voluntary, not offered), (iv) priority ranking from a survey of 84 English NHS hospitals, (v) excess length of stay and costs from the literature. The relationships between estimated SSI burden, national surveillance activity, and hospital-reported priorities were explored with descriptive and univariate analyses.FindingsAmong the 23 surgical categories analysed, top priority ranking by hospitals was associated only with current surveillance (r=0.76, p<0.01) and mandatory reporting (33% vs 8 and 4%, p=0.04). Percentage of hospitals undertaking surveillance, mandatory reporting, and the selection of priorities did not match SSI burden. Large bowel surgery (LBS, voluntary) and caesarean section (not offered) were the two highest contributors of total SSIs per annum, with 39,000 (38%) and 17,000 (16%) respectively, while the four orthopaedic categories (all mandatory) contributed 5,000 (5%). LBS also had the highest associated costs (£119m per annum).ConclusionCurrent surveillance and future priorities were not associated with SSI rate, volume, or cost to hospitals. The two highest contributors of SSIs and related costs have no (caesarean section) or limited (LBS) coverage by national surveillance.
Mizuno S, Iwami M, Kunisawa S, et al., 2018, Comparison of national strategies to reduce methicillin-resistant Staphylococcus aureus (MRSA) infections in Japan and England, Journal of Hospital Infection, Vol: 100, Pages: 280-298, ISSN: 0195-6701
BackgroundNational responses to healthcare-associated infections vary between high-income countries but when analysed for contextual comparability, interventions can be assessed for transferability.AimTo identify learning from country-level approaches to addressing meticillin-resistant Staphylococcus aureus (MRSA) in Japan and England.MethodsA longitudinal analysis (2000-17), comparing epidemiological trends and policy interventions. Data from 441 textual sources concerning infection prevention and control (IPC), surveillance, and antimicrobial stewardship interventions were systematically coded for: type - mandatory requirements, recommendations, or national campaigns; method - restrictive, persuasive, structural in nature; level of implementation - macro (national), meso (organisational), micro (individual) levels. Healthcare organisational structures and role of media were also assessed.FindingsIn England significant reduction has been achieved in number of reported MRSA bloodstream infections. In Japan, in spite of reductions, MRSA remains a predominant infection. Both countries face new threats in the emergence of drug-resistant Escherichia coli. England has focused on national mandatory and structural interventions, supported by a combination of outcomes-based incentives and punitive mechanisms, and multidisciplinary IPC hospital teams. Japan has focused on (non-mandatory) recommendations and primarily persuasive interventions, supported by process-based incentives, with voluntary surveillance. Areas for development in Japan include resourcing of dedicated data management support and implementation of national campaigns for healthcare professionals and the public.ConclusionPolicy interventions need to be relevant to local epidemiological trends, while acceptable within health system cultures and public expectations. Cross-national learning can help inform the right mix of interventions to create sustainable and resilient systems for future infection and econom
Kyratsis Y, Ahmad R, Iwami M, et al., 2018, A multi-level analysis of infection control in English hospitals: coerced safety culture change, Publisher: OXFORD UNIV PRESS, Pages: 180-180, ISSN: 1101-1262
Herrero P, Rawson TM, Philip A, et al., 2018, Closed-loop control for precision antimicrobial delivery: an In silico proof-of-concept, IEEE Transactions on Biomedical Engineering, Vol: 65, Pages: 2231-2236, ISSN: 0018-9294
IEEE Objective: Inappropriate dosing of patients with antibiotics is a driver of antimicrobial resistance, toxicity, and poor outcomes of therapy. In this paper, we investigate, in silico, the hypothesis that the use of a closed-loop control system could improve the attainment of pharmacokinetic-pharmacodynamic targets for antimicrobial therapy, where wide variations in target attainment have been reported. This includes patients in critical care, patients with renal disease and patients with obesity.
Aylin PP, Bou-Antoun S, Costelloe CE, et al., 2018, Age-related decline in antibiotic prescribing for uncomplicated respiratory tract infections in primary care in England following the introduction of a national financial incentive (the Quality Premium) for health commissioners to reduce use of antibiotics in the community: an interrupted time series analysis, Journal of Antimicrobial Chemotherapy, Vol: 73, Pages: 2883-2892, ISSN: 0305-7453
Objectives: To assess the impact of the 2015/16 NHS England Quality Premium (which provided a financial incentive for Clinical Commissioning Groups to reduce antibiotic prescribing in primary care) on antibiotic prescribing by General Practitioners (GPs) for respiratory tract infections (RTIs).Method: Interrupted time series analysis using monthly patient-level consultation and prescribing data obtained from the Clinical Practice Research Datalink (CPRD), between April 2011 and March 2017. The study population comprised patients consulting a GP who were diagnosed with an RTI. We assessed the rate of antibiotic prescribing in patients (both aggregate and stratified by age) with a recorded diagnosis of uncomplicated RTI, before and after the implementation of the Quality Premium.Results: Prescribing rates decreased over the six year study period, with evident seasonality. Notably, there was a 3% drop in the rate of antibiotic prescribing (equating to 14.65 prescriptions per 1,000 RTI consultations) (p<0.05) in April 2015, coinciding with the introduction of the Quality Premium. This reduction was sustained, such that after two years there was a 3% decrease in prescribing relative to that expected had the pre-intervention trend continued. There was also a concurrent 2% relative reduction in the rate of broad-spectrum antibiotic prescribing. Antibiotic prescribing for RTIs diagnosed in children showed the greatest decline with a 6% relative change two years after the intervention. Of the RTI indications studied, the greatest reductions in antibiotic prescribing were seen for patients with sore throats.Conclusions: Community prescribing of antibiotics for RTIs significantly decreased following the introduction of the Quality Premium, with the greatest reduction seen in younger patients.
Clack L, Zingg W, Saint S, et al., 2018, Implementing infection prevention practices across European hospitals: an in-depth qualitative assessment, BMJ QUALITY & SAFETY, Vol: 27, Pages: 771-780, ISSN: 2044-5415
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Abdolrasouli A, Petrou MA, Park H, et al., 2018, Surveillance for azole-resistant Aspergillus fumigatus in a centralized diagnostic mycology service, London, United Kingdom, 1998-2017, Frontiers in Microbiology, Vol: 9, ISSN: 1664-302X
Background/Objectives: Aspergillus fumigatus is the leading cause of invasive aspergillosis. Treatment is hindered by the emergence of resistance to triazole antimycotic agents. Here, we present the prevalence of triazole resistance among clinical isolates at a major centralized medical mycology laboratory in London, United Kingdom, in the period 1998–2017.Methods: A large number (n = 1469) of clinical A. fumigatus isolates from unselected clinical specimens were identified and their susceptibility against three triazoles, amphotericin B and three echinocandin agents was carried out. All isolates were identified phenotypically and antifungal susceptibility testing was carried out by using a standard broth microdilution method.Results: Retrospective surveillance (1998–2011) shows 5/1151 (0.43%) isolates were resistant to at least one of the clinically used triazole antifungal agents. Prospective surveillance (2015–2017) shows 7/356 (2.2%) isolates were resistant to at least one triazole antifungals demonstrating an increase in incidence of triazole-resistant A. fumigatus in our laboratory. Among five isolates collected from 2015 to 2017 and available for molecular testing, three harbored TR34/L98H alteration in the cyp51A gene that are associated with the acquisition of resistance in the non-patient environment.Conclusion: These data show that historically low prevalence of azole resistance may be increasing, warranting further surveillance of susceptible patients.
Jauneikaite E, Kapatai G, Davies F, et al., 2018, Serial clustering of late onset group B streptococcal infections in the neonatal unit - a genomic re-evaluation of causality, Clinical Infectious Diseases, Vol: 67, Pages: 854-860, ISSN: 1058-4838
Background. Invasive Group B streptococcus (GBS) is a major cause of serious neonatal infection. Current strategies to reduce early onset GBS disease have no impact on late onset disease (LOD). Although GBS is a normal part of the enteric microbiota in healthy term infants, LOD cases arising in the neonatal intensive care unit setting raise questions about mode of acquisition.Methods. Enhanced surveillance for any case of late onset GBS sepsis admitted to a level 3, 24-bed neonatal intensive care unit over a 2 year period was instituted following a cluster of four cases. All late onset GBS isolates were serotyped and genomes sequenced. Rectal screening of neonates for GBS was undertaken weekly. Healthcare workers and parents were not screened.Results. Over 24 months, a total of 12 late onset invasive GBS episodes were identified (incidence 0.6/1000 live births). Genomic analysis revealed that 11/12 GBS isolates (92%) were linked to at least one other LOD isolate. Four isolates from the first cluster were serotype V, resistant to macrolides and lincosamides, providing early evidence of a common source. Sequencing confirmed isolates were indistinguishable, or distinguishable by 1 SNP, from each other, and distinct from contemporary serotype V GBS. Although a common environmental source was not identified, prompt infection prevention interventions were instituted and no further serotype V GBS infections arose. Prospective surveillance identified three further clusters of LOD due to serotypes Ia, Ib, and III, leading to re-evaluation of interventions required for preventing GBS LOD. Conclusion. Acquisition routes for LOD GBS in the neonatal unit are poorly understood; such cases may not necessarily be sporadic. Within this neonatal unit, our data suggest that a single case of LOD GBS sepsis should be considered a potential nosocomial transmission event warranting prompt investigation, heightened infection prevention vigilance and action where required.
Rodriguez-Manzano J, Moniri A, Malpartida-Cardenas K, et al., 2018, Simultaneous single-channel multiplex and quantification of carbapenem-resistant genes using multidimensional standard curves
<jats:title>ABSTRACT</jats:title><jats:p>Multiplexing and absolute quantification of nucleic acids, both have, in their own right, significant and extensive use in biomedical related fields, especially in point-of-care applications. Currently, the ability to detect several nucleic acid targets in a single-reaction scales linearly with the number of targets; an expensive and time-consuming feat. Here, we propose a new methodology based on multidimensional standard curves that extends the use of real-time PCR data obtained by common qPCR instruments. By applying this novel methodology, we achieve simultaneous single-channel multiplexing and enhanced quantification of multiple targets using only real-time amplification data. This is obtained without the need of fluorescent probes, agarose gels, melting curves or sequencing analysis. Given the importance and demand for tackling challenges in antimicrobial resistance, the proposed method is applied to the four most prominent carbapenem-resistant genes:<jats:italic>bla</jats:italic><jats:sub>OXA-48</jats:sub>,<jats:italic>bla</jats:italic><jats:sub>NDM</jats:sub>,<jats:italic>bla</jats:italic><jats:sub>VIM</jats:sub>and<jats:italic>bla</jats:italic><jats:sub>KPC</jats:sub>, which account for 97% of the UK’s reported carbapenemase-producing Enterobacteriaceae.</jats:p>
Balinskaite V, Holmes A, Johnson A, et al., 2018, The Impact of a National Antimicrobial Stewardship Programmes on Antibiotic Prescribing in Primary Care in England: An Interrupted Time Series Analysis, ISQua, Publisher: OXFORD UNIV PRESS, Pages: 37-38, ISSN: 1353-4505
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