Hugo Donaldson

Waterborne Elizabethkingia meningoseptica in Adult Critical Care.

This outbreak might reflect improved diagnostic testing, indicating that E. meningoseptica is a pseudo-emerging pathogen.

Homogeneity of antimicrobial policy, yet heterogeneity of antimicrobial resistance: antimicrobial non-susceptibility among 108 717 clinical isolates from primary, secondary and tertiary care patients in London

Objectives We examined the 4 year trend in antimicrobial susceptibilities and prescribing across levels of care at two London teaching hospitals and their multisite renal unit, and for the surrounding community. Methods Laboratory and pharmacy information management systems were interrogated, with antimicrobial use and susceptibilities analysed between hospitals, within hospitals and over time. Results A total of 108 717 isolates from 71 687 patients were identified, with significant differences (at P < 0.05) in antimicrobial susceptibility between and within hospitals. Across the 4 years, rates of ESBL-/AmpC-producing Enterobacteriaceae ranged from 6.4% to 10.7% among community isolates, 17.8% to 26.9% at ward level and 25.2% to 52.5% in critical care. Significant variations were also demonstrated in glycopeptide-resistant enterococci (ward level 6.2%–17.4%; critical care 21.9%–56.3%), MRSA (ward level 18.5%–38.2%; critical care 12.5%–47.9%) and carbapenem-resistant Pseudomonas spp. (ward level 8.3%–16.9%; critical care 19.9%–53.7%). Few instances of persistently higher resistance were seen between the hospitals in equivalent cohorts, despite persistently higher antimicrobial use in Hospital 1 than Hospital 2. We found significant fluctuations in non-susceptibility year on year across the cohorts, but with few persistent trends. Conclusions The marked heterogeneity of antimicrobial susceptibilities between hospitals, within hospitals and over time demands detailed, standardized surveillance and appropriate benchmarking to identify possible drivers and effective interventions. Homogeneous antimicrobial policies are unlikely to continue to be suitable as individual hospitals join hospital networks, and policies should be tailored to local resistance rates, at least at the hospital level, and possibly with finer resolution, particularly for critical care.

Lessons for control of heroin-associated anthrax in Europe from 2009-2010 outbreak case studies, London, UK.

Serologic surveillance should be implemented to identify the prevalence of this disease in persons who inject drugs.

Carbapenemase-producing Enterobacteriaceae in the UK: a national study (EuSCAPE-UK) on prevalence, incidence, laboratory detection methods and infection control measures

Objectives To estimate UK prevalence and incidence of clinically significant carbapenemase-producing Enterobacteriaceae (CPE), and to determine epidemiological characteristics, laboratory methods and infection prevention and control (IPC) measures in acute care facilities. Methods A 6 month survey was undertaken in November 2013–April 2014 in 21 sentinel UK laboratories as part of the European Survey on Carbapenemase-Producing Enterobacteriaceae (EuSCAPE) project. Up to 10 consecutive, non-duplicate, clinically significant and carbapenem-non-susceptible isolates of Escherichia coli or Klebsiella pneumoniae were submitted to a reference laboratory. Participants answered a questionnaire on relevant laboratory methods and IPC measures. Results Of 102 isolates submitted, 89 (87%) were non-susceptible to ≥1 carbapenem, and 32 (36%) were confirmed as CPE. CPE were resistant to most antibiotics, except colistin (94% susceptible), gentamicin (63%), tigecycline (56%) and amikacin (53%). The prevalence of CPE was 0.02% (95% CI = 0.01%–0.03%). The incidence of CPE was 0.007 per 1000 patient-days (95% CI = 0.005–0.010), with north-west England the most affected region at 0.033 per 1000 patient-days (95% CI = 0.012–0.072). Recommended IPC measures were not universally followed, notably screening high-risk patients on admission (applied by 86%), using a CPE ‘flag’ on patients’ records (70%) and alerting neighbouring hospitals when transferring affected patients (only 30%). Most sites (86%) had a laboratory protocol for CPE screening, most frequently using chromogenic agar (52%) or MacConkey/CLED agars with carbapenem discs (38%). Conclusions The UK prevalence and incidence of clinically significant CPE is currently low, but these MDR bacteria affect most UK regions. Improved IPC measures, vigilance and monitoring are required.

Exploring the epidemiology of carbapenem-resistant Gram-negative bacteria in west London and the utility of routinely collected hospital microbiology data

OBJECTIVES The objective of this study was to identify carbapenem-resistant organisms using routinely collected local microbiology data and describe the epidemiology of carbapenem resistance in two London teaching hospitals. METHODS Data on inpatients infected or colonized with Gram-negative organisms between March 2009 and February 2012 were extracted. A computer algorithm was developed incorporating internationally recognized criteria to distinguish carbapenem-resistant organisms. Multivariable analysis was conducted to identify factors associated with infection or colonization with carbapenem-resistant organisms. Binomial regression was performed to detect changes in resistance trends over time. RESULTS Yearly incidence of carbapenem resistance was observed to be increasing, with significant increasing trends in Acinetobacter baumannii (47.1% in 2009-10 to 77.2% in 2011-12; P<0.001) and Enterobacter spp. (2.2% in 2009-10 to 11.5% in 2011-12; P<0.001). Single-variable and multivariable analysis demonstrated differences in the proportion of carbapenem-resistant isolates across all variables investigated, including age, sex and clinical specialty; in the latter organism-specific niches were identified. Patients in the youngest age group (16-24 years old) had the highest odds of being infected or colonized with carbapenem-resistant isolates of Escherichia coli, Klebsiella spp. or Pseudomonas aeruginosa. Furthermore, proportions of carbapenem-resistant organisms differed between the hospitals. CONCLUSIONS Carbapenem resistance is an emerging problem within the UK inpatient healthcare setting. This is not an issue confined to the Enterobacteriaceae and fine-resolution surveillance is needed to identify at-risk groups. Regular analysis of routinely collected data can provide insight into the evolving carbapenem-resistance threat, with the ability to inform efforts to prevent the spread of resistance.

Emergence and clonal spread of colistin resistance due to multiple mutational mechanisms in carbapenemase-producing Klebsiella pneumoniae in London

Carbapenemase-producing Enterobacteriaceae (CPE) are emerging worldwide, limiting therapeutic options. Mutational and plasmid-mediated mechanisms of colistin resistance have both been reported. The emergence and clonal spread of colistin resistance was analysed in 40 epidemiologically-related NDM-1 carbapenemase producing Klebsiella pneumoniae isolates identified during an outbreak in a group of London hospitals. Isolates from July 2014 to October 2015 were tested for colistin susceptibility using agar dilution, and characterised by whole genome sequencing (WGS). Colistin resistance was detected in 25/38 (65.8%) cases for which colistin susceptibility was tested. WGS found that three potential mechanisms of colistin resistance had emerged separately, two due to different mutations in mgrB, and one due to a mutation in phoQ, with onward transmission of two distinct colistin-resistant variants, resulting in two sub-clones associated with transmission at separate hospitals. A high rate of colistin resistance (66%) emerged over a 10 month period. WGS demonstrated that mutational colistin resistance emerged three times during the outbreak, with transmission of two colistin-resistant variants.

Comment on: Effects of selective digestive decontamination (SDD) on the gut resistome

Sir, We read with interest the report by Buelow et al. entitled ‘Effects of selective digestive decontamination (SDD) on the gut resistome’. The authors undertook metagenomic analyses to highlight the effect of SDD on an individual’s gut resistome. The authors eloquently describe the limitations of conventional culture techniques, especially as no resistant organisms were cultured in parallel to the molecular methods. We would like to highlight, however, the importance of phenotypic methods of identification of resistant organisms. We report two recent cases of vancomycin-dependent enterococci (VDE) isolated from rectal swabs of patients receiving SDD in an intensive care unit (ICU). These were identified as Enterococcus faecium. In our institution, all patients expected to be intubated for .48 h receive SDD consisting of 6 hourly administration of 80 mg of tobramycin, 250000 U of colistin and 1 million units of nystatin by mouth and nasogastric tube for the duration of intubation. Vancomycin (500 mg) is added to this oral and nasogastric administration due to concerns about methicillin-resistant Staphylococcus aureus (MRSA). Patient 1 was admitted to an ICU for management of quadriplegia following an episode of meningitis. He had been an inpatient for several weeks prior to his ICU admission, during which he received several courses of intravenous vancomycin. Whilst in the ICU he continued to receive vancomycin as part of SDD. VDE was isolated from a rectal screening swab on day 145 of intubation. Patient 2 was admitted for management of status epilepticus. She had not been treated with vancomycin other than as part of SDD. VDE was first isolated on day 7 of intubation. Bacterial growth occurred at vancomycin concentrations .1 mg/L, which gave the phenotypic characteristic of growth occurring only around the antibiotic disc or the MIC test strip. To our knowledge, these are the first two isolates of VDE to be reported associated with SDD. VDE were described in the UK in 1994 relating to two renal patients in separate hospitals. Since then, numerous cases of VDE have been reported including nosocomial outbreaks. VDE grow in the presence of vancomycin and are mutants of vancomycin-resistant enterococci. This phenotype results from mutations in the ddl gene leading to an inactive host D-Ala:D-Ala ligase requiring vancomycin to induce the production of peptidoglycan precursors. Although an ability to cause nosocomial infection is recognized, the clinical significance of VDE is not entirely clear. With regard to our cases, VDE was isolated on routine screening swabs and did not appear to lead to clinically significant infection. SDD is a controversial technique and is not employed in all UK ICUs. SDD regimens differ between units, often reflecting local microbiological epidemiology. Including enteral vancomycin has been shown to be effective at controlling MRSA in endemic settings. In 2013, a meta-analysis detected no relationship between the use of SDD or selective oral decontamination (SOD) and the development of antimicrobial resistance. However, the authors acknowledged the need for research over the longer term in ICUs. A recent 4 year ecological study published in JAC reported decreasing trends for resistance to third-generation cephalosporin and ciprofloxacin antibiotics. Conventional culture-based methods were used in both the aforementioned studies focusing on a small selection of resistant organisms. We welcome the study by Buelow et al. for widening the scope of antimicrobial resistance detection, via molecular techniques, highlighting the importance of mobile genetic elements in cross-species transfer of genetic resistance. Molecular techniques have limitations and our two cases demonstrate the continued need for rigorous phenotypic evaluation of organisms isolated in a diagnostic microbiology laboratory. The potential unintended consequence of SDD/SOD on antimicrobial resistance needs careful consideration. We believe that a whole gut microbiome approach is warranted rather than focusing on a narrow spectrum of politically worrisome organisms.

Neurological picture. Multiple intracranial abscesses due to Streptococcus anginosus in a previously well individual.

A 39-year-old Portuguese male was found obtunded and incontinent of urine. On admission, his Glasgow Coma Scale (GCS) score was 14/15. He had fever, left-sided facial weakness and mydriasis, and bilateral clonus. Cranial CT and MRI demonstrated multiple supra- and infra-tentorial contrast-enhancing lesions, surrounding oedema and hydrocephalus (figures 1 and 2). Chest radiography and CT revealed two right upper lobe cavitating lesions (figure 3). No ear, sinus or dentition abnormalities were detected. He had no history of intravenous drug use or significant medical history. His white cell count (WCC) was 24.8×109/l (reference range: 4.0–11.0×109/l) and C reactive protein (CRP) …

Multiple intracranial abscesses due to Streptococcus anginosus in a previously well individual

A 39-year-old Portuguese male was found obtunded and incontinent of urine. On admission, his Glasgow Coma Scale (GCS) score was 14/15. He had fever, left-sided facial weakness and mydriasis, and bilateral clonus. Cranial CT and MRI demonstrated multiple supra- and infra-tentorial contrast-enhancing lesions, surrounding oedema and hydrocephalus (figures 1 and 2). Chest radiography and CT revealed two right upper lobe cavitating lesions (figure 3). No ear, sinus or dentition abnormalities were detected. He had no history of intravenous drug use or significant medical history. His white cell count (WCC) was 24.8×109/l (reference range: 4.0–11.0×109/l) and C reactive protein (CRP) …

Surveillance for azole-resistant Aspergillus fumigatus in a centralized diagnostic mycology service, London, United Kingdom, 1998-2017

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.