OXA-1 β-lactamase and non-susceptibility to penicillin/β-lactamase inhibitor combinations among ESBL-producing Escherichia coli

Background ESBL-producing Escherichia coli have expanded globally since the turn of the century and present a major public health issue. Their in vitro susceptibility to penicillin/inhibitor combinations is variable, and clinical use of these combinations against ESBL producers remains controversial. We hypothesized that this variability related to co-production of OXA-1 penicillinase. Methods During a national study we collected 293 ESBL-producing E. coli from bacteraemias, determined MICs by BSAC agar dilution, and undertook genomic sequencing with Illumina methodology. Results The collection was dominated by ST131 (n = 188 isolates, 64.2%) and bla CTX-M-15 (present in 229 isolates, 78.2%); over half the isolates (159/293, 54.3%) were ST131 with bla CTX-M-15. bla OXA-1 was found in 149 ESBL producers (50.9%) and bla TEM-1/191 in 137 (46.8%). Irrespective of whether all isolates were considered, or ST131 alone, there were strong associations (P < 0.001) between co-carriage of bla OXA-1 and reduced susceptibility to penicillin/inhibitor combinations, whereas there was no significant association with co-carriage of bla TEM-1/191. For piperacillin/tazobactam the modal MIC rose from 2 mg/L in the absence of bla OXA-1 to 8 or 16 mg/L in its presence; for co-amoxiclav the shift was smaller, from 4 or 8 to 16 mg/L, but crossed the breakpoint. bla OXA-1 was strongly associated with co-carriage also of aac(6′)-Ib-cr, which compromises amikacin and tobramycin. Conclusions Co-carriage of OXA-1, a penicillinase with weak affinity for inhibitors, is a major correlate of resistance to piperacillin/tazobactam and co-amoxiclav in E. coli and is commonly associated with co-carriage of aac(6′)-Ib-cr, which narrows aminoglycoside options

Infection prevention and control of Clostridium difficile – a global review of guidelines, strategies, and recommendations

BACKGROUND: Clostridium difficile is the leading cause of health care–associated infections. Given the high incidence of C. difficile infection (CDI) and the lack of primary prevention through immunization, health care professionals should be aware of the most current guidance, as well as strengths and limitations of the evidence base underpinning this guidance. METHODS: We identified publicly available national or organizational guidelines related to CDI infection and prevention control (IPC) published between 2000 and 2015 and for any health care setting through an internet search using the Google search engine. We reviewed CDI–targeted IPC recommendations and describe the assessment of evidence in available guidelines. RESULTS: We identified documents from 28 countries/territories, mainly from acute care hospitals in North America, the Western Pacific, and Europe (18 countries). We identified only a few specific recommendations for long–term care facilities (LTCFs) and from countries in South America (Uruguay and Chile), South East Asia (Thailand), and none for Africa or Eastern Mediterranean. Of 10 IPC areas, antimicrobial stewardship was universally recognized as essential and supported by high quality evidence. Five other widely reported “strong” recommendations were: effective environment cleaning (including medical equipment), case isolation, use of personal protective equipment, surveillance, and education. Several unresolved and emerging issues were documented and currently available evidence was classified mainly as of mixed quality. CONCLUSION: Our review underlines the need for targeted CDI IPC guidelines in several countries and for LTCFs. International harmonisation on the assessment of the evidence for best practices is needed as well as more robust evidence to support targeted recommendations

KPC enzymes in the UK: an analysis of the first 160 cases outside the North-West region

Objectives: Klebsiella pneumoniae carbapenemases (KPCs) have been increasingly reported in the UK since 2003. We analysed patient and isolate data for KPC-positive bacteria confirmed by the national reference laboratory from UK laboratories, with the exception of the North-West England region, where the epidemiology has previously been studied, from August 2003 to August 2014. Methods: MICs were determined by BSAC agar dilution methodology. Carbapenem-resistant isolates lacking imipenem/EDTA synergy were tested by PCR for blaKPC. Multi-locus sequence typing and blaKPC sequencing was performed on a subset of isolates. Plasmid analysis was performed by transformation, PCR-based replicon typing and, in some cases, whole-plasmid sequencing. Patient data provided by the sending laboratories were reviewed. Results: Two hundred and ten KPC-producing isolates were submitted from 71 UK laboratories outside North-West England, representing 160 patients. All were Enterobacteriaceae, predominantly K. pneumoniae (82%; 172/210), and most (91%; 191/210) were obtained from hospitalised patients. Analysis of 123 isolates identified blaKPC-2 (64%; 79/123), blaKPC-3 (27%; 33/123) and blaKPC-4 (9%; 11/123). Within K. pneumoniae, clonal group (CG) sequence type (ST) 258 was dominant (64%; 54/84), however 21 unrelated STs were also identified. Plasmid analysis identified a diverse range of plasmids of at least 11 different replicon types, found in multiple STs and species. Conclusions: KPC enzymes are increasingly detected in Enterobacteriaceae in the UK outside North-West England, despite a lack of reported outbreaks. K. pneumoniae CG258 are the dominant hosts although plasmid spread also plays a significant role in dissemination of KPCs between other K. pneumoniae STs and enterobacterial species

Extended-spectrum β-lactamase-producing Escherichia coli in human-derived and foodchain-derived samples from England, Wales, and Scotland: an epidemiological surveillance and typing study

Background: Escherichia coli isolates producing extended-spectrum βlactamases (‘ESBL-E. coli’) cause >5000 bacteraemias annually in the UK. The contribution of the food chain to this challenge is debated. Methods: Selective media were used to seek ESBL-E. coli in routinely-submitted human faeces, sewage, farm slurry, and retail foodstuffs in London, East Anglia, Northwest England, Scotland and Wales. Recovered isolates were sequenced and compared with 293 bloodstream and 83 veterinary surveillance ESBL-E. coli isolates from the same regions. Findings: 10.7% (2157/20243) of human faeces contained ESBL-E. coli, rising to 17.0% (678/3995) in London. ESBL-E. coli also were frequent in sewage and present in 65.4% (104/159) of retail chicken, but rare in other meats and absent from plant-based foods. Sequence Type (ST) 131 dominated among ESBL-E. coli from human blood (188/293, 64.2%), faeces (128/360, 35.6%) and sewage (14/65, 21.5%) with STs 38 and 648 also widespread; CTX-M-15 was the predominant ESBL in these lineages. By contrast, STs 602, 23, 117 - mostly with CTX-M-1 ESBL - dominated among food and veterinary isolates, with only two ST131 organisms recovered. ST10 occurred in both animals and humans: being frequent in surveillance bovines and representing 4.2% (15/360) of human faecal isolates (but only 1% [3/293] from bacteraemias); however both human and animal ST10 isolates were diverse in serotype. Interpretation: Most human bacteraemias with ESBL-E. coli in the UK involve successful human-associated STs, particularly ST131; non-human reservoirs made little contribution to invasive human disease. Funding: NIHR Policy Research

Der Sekanten-Tangentensatz in Cayley/Klein-Ebenen vom Index O sowie dessen Dualisierung

An unified formulation (as far as possible) of the secant-tangent theorem for circles (curves of constant curvature) in CAYLEY/KLEIN-planes of index 0 is given, proved, and dualized. (orig.)SIGLEAvailable from TIB Hannover: RN 7879(9305) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Pharmacodynamic Functions: a Multiparameter Approach to the Design of Antibiotic Treatment Regimens

There is a complex quantitative relationship between the concentrations of antibiotics and the growth and death rates of bacteria. Despite this complexity, in most cases only a single pharmacodynamic parameter, the MIC of the drug, is employed for the rational development of antibiotic treatment regimens. In this report, we use a mathematical model based on a Hill function—which we call the pharmacodynamic function and which is related to previously published E(max) models—to describe the relationship between the bacterial net growth rates and the concentrations of antibiotics of five different classes: ampicillin, ciprofloxacin, tetracycline, streptomycin, and rifampin. Using Escherichia coli O18:K1:H7, we illustrate how precise estimates of the four parameters of the pharmacodynamic function can be obtained from in vitro time-kill data. We show that, in addition to their respective MICs, these antibiotics differ in the values of the other pharmacodynamic parameters. Using a computer simulation of antibiotic treatment in vivo, we demonstrate that, as a consequence of differences in pharmacodynamic parameters, such as the steepness of the Hill function and the minimum bacterial net growth rate attained at high antibiotic concentrations, there can be profound differences in the microbiological efficacy of antibiotics with identical MICs. We discuss the clinical implications and limitations of these results