Antimicrobial resistance in community and nosocomial Escherichia coli urinary tract isolates, London 2005 – 2006

<p>Abstract</p> <p>Background</p> <p><it>Escherichia coli </it>is the commonest cause of community and nosocomial urinary tract infection (UTI). Antibiotic treatment is usually empirical relying on susceptibility data from local surveillance studies. We therefore set out to determine levels of resistance to 8 commonly used antimicrobial agents amongst all urinary isolates obtained over a 12 month period.</p> <p>Methods</p> <p>Antimicrobial susceptibility to ampicillin, amoxicillin/clavulanate, cefalexin, ciprofloxacin, gentamicin, nitrofurantoin, trimethoprim and cefpodoxime was determined for 11,865 <it>E. coli </it>urinary isolates obtained from community and hospitalised patients in East London.</p> <p>Results</p> <p>Nitrofurantoin was the most active agent (94% susceptible), followed by gentamicin and cefpodoxime. High rates of resistance to ampicillin (55%) and trimethoprim (40%), often in combination were observed in both sets of isolates. Although isolates exhibiting resistance to multiple drug classes were rare, resistance to cefpodoxime, indicative of Extended spectrum β-lactamase production, was observed in 5.7% of community and 21.6% of nosocomial isolates.</p> <p>Conclusion</p> <p>With the exception of nitrofurantoin, resistance to agents commonly used as empirical oral treatments for UTI was extremely high. Levels of resistance to trimethoprim and ampicillin render them unsuitable for empirical use. Continued surveillance and investigation of other oral agents for treatment of UTI in the community is required.</p

Whiter, brighter, and more stable cellulose paper coated with antibacterial carboxymethyl starch stabilized ZnO nanoparticles

Small, carboxymethyl-starch-stabilised zinc oxide nanoparticles with a defined shape, size and morphology were prepared in situ in water at relatively low reaction temperatures using soluble carboxymethyl starch (CMS) as a combined crystallising, stabilising and solubilising agent and triethanolamine as the reducing agent. Aqueous colloidal solutions of these CMS-stabilised ZnO nanoparticles were used to deposit a coating of ZnO nanoparticles on cellulose paper by a wet-chemistry, polyelectrolyte, layer-by-layer approach using water as the only solvent. Such cellulose paper samples, coated with these CMS-stabilised ZnO nanoparticles, show higher brightness and whiteness than that of blank reference paper and are more stable to UV-radiation than the paper reference as well as demonstrating good antibacterial activity against MRSA and A. baumannii

Antifungal synergy of theaflavin and epicatechin combinations against Candida albicans

New antifungal agents are required to compensate for the increase in resistance to standard antifungal agents of Candida albicans, which is an important opportunistic fungal pathogen that causes minor infections in many individuals but very serious infections in those who are immune-compromised. In this study, combinations of theaflavin and epicatechin are investigated as potential antifungal agents and also to establish whether antifungal synergy exists between these two readily accessible and cost-effective polyphenols isolated from black and green tea. The results of disc diffusion assays showed stronger antibacterial activity of theaflavin:epicatechin combinations against C. albicans NCTC 3255 and NCTC 3179, than that of theaflavin alone. Minimum inhibitory concentrations (MICs) of 1,024 &mu;g/ml with theaflavin and 128-256 &mu;g/ml with theaflavin:epicatechin combinations were found. The fractional inhibitory concentration indexes were calculated, and the synergy between theaflavin and epicatechin against both isolates of C. albicans was confirmed. Theaflavin:epicatechin combinations show real potential for future use as a treatment for infections caused by C. albicans

In Vitro Antibacterial Activity of Curcumin-Polymyxin B Combinations against Multidrug-Resistant Bacteria Associated with Traumatic Wound Infections

Bacterial infections resulting from nonsurgical traumatic wounds can be life threatening, especially those caused by multidrug-resistant (MDR) bacteria with limited therapeutic options. The antimicrobial activity of polymyxin B (1) and curcumin (2) alone and in combination was determined versus MDR bacterial isolates associated with traumatic wound infections. Cytotoxicity assays for 1 and 2 were undertaken in keratinocyte cell lines. Minimum inhibitory concentrations of 1 were significantly reduced in the presence of 2 (3- to 10-fold reduction), with synergy observed. Time− kill assays showed the combinations produced bactericidal activity. Cytotoxicity assays indicate the toxicity of 2 was reduced in the presence of 1

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

Using natural experimental studies to guide public health action: turning the evidence-based medicine paradigm on its head.

Despite smaller effect sizes, interventions delivered at population level to prevent non-communicable diseases generally have greater reach, impact and equity than those delivered to high-risk groups. Nevertheless, how to shift population behaviour patterns in this way remains one of the greatest uncertainties for research and policy. Evidence about behaviour change interventions that are easier to evaluate tends to overshadow that for population-wide and system-wide approaches that generate and sustain healthier behaviours. Population health interventions are often implemented as natural experiments, which makes their evaluation more complex and unpredictable than a typical randomised controlled trial (RCT). We discuss the growing importance of evaluating natural experiments and their distinctive contribution to the evidence for public health policy. We contrast the established evidence-based practice pathway, in which RCTs generate 'definitive' evidence for particular interventions, with a practice-based evidence pathway in which evaluation can help adjust the compass bearing of existing policy. We propose that intervention studies should focus on reducing critical uncertainties, that non-randomised study designs should be embraced rather than tolerated and that a more nuanced approach to appraising the utility of diverse types of evidence is required. The complex evidence needed to guide public health action is not necessarily the same as that which is needed to provide an unbiased effect size estimate. The practice-based evidence pathway is neither inferior nor merely the best available when all else fails. It is often the only way to generate meaningful evidence to address critical questions about investing in population health interventions.DO, JP and NW are supported by the Medical Research Council (Unit Programme numbers MC_UU_12015/6 and MC_UU_12015/1). The paper was initially developed in the course of a visiting appointment as Thought Leader in Residence at the School of Public Health at the University of Sydney, for which the intellectual environment and financial support provided by the Prevention Research Collaboration is gratefully acknowledged. It was further developed under the auspices of the Centre for Diet and Activity Research (CEDAR), a UKCRC Public Health Research Centre of Excellence at the University of Cambridge, for which funding from the British Heart Foundation, Economic and Social Research Council, Medical Research Council, National Institute for Health Research and the Wellcome Trust, under the auspices of the United Kingdom Clinical Research Collaboration, is gratefully acknowledge

Recurrent spontaneous Escherichia coli meningitis in an adult: a case report

Objectives The aim of this study was to characterize an unusual case of spontaneous, community-acquired Escherichia coli meningitis in an adult presenting to a general hospital in Kenya, where initial clinical recovery was followed by reinfection with an MDR, hospital-acquired strain. Patient and methods An adult presented to a hospital in Kenya with meningitis symptoms. E. coli was cultured from CSF. Treatment with ceftriaxone was successful; however, the patient relapsed a few days later. E. coli was cultured from CSF and blood during the reinfection episode, though the patient died during admission. We sequenced the isolates using Illumina MiSeq and performed antimicrobial susceptibility testing, fitness and virulence assays on the bacteria. Results The E. coli isolates from the two episodes were found to be distinct: the initial strain was ST88, serotype O8 H17 while the subsequent episode was caused by an ST167, serotype O101 H5 MDR strain. The ST88 strain was susceptible to all drugs except ampicillin and amoxicillin/clavulanate while the ST167 strain was MDR, including to all β-lactam drugs due to the presence of the carbapenemase gene blaNDM-5. The hospital-acquired ST167 strain was also resistant to newer drugs such as cefiderocol and eravacycline, which are currently not available locally, and had overall lower fitness and virulence in vitro compared with the initial infecting strain. Conclusions Though less fit and virulent in vitro, the MDR strain was fatal, suggesting that host factors, rather than bacterial virulence, may have been of greater importance in this patient’s outcome

Candidate Gene Association Study in Type 2 Diabetes Indicates a Role for Genes Involved in β-Cell Function as Well as Insulin Action

Type 2 diabetes is an increasingly common, serious metabolic disorder with a substantial inherited component. It is characterised by defects in both insulin secretion and action. Progress in identification of specific genetic variants predisposing to the disease has been limited. To complement ongoing positional cloning efforts, we have undertaken a large-scale candidate gene association study. We examined 152 SNPs in 71 candidate genes for association with diabetes status and related phenotypes in 2,134 Caucasians in a case-control study and an independent quantitative trait (QT) cohort in the United Kingdom. Polymorphisms in five of 15 genes (33%) encoding molecules known to primarily influence pancreatic β-cell function—ABCC8 (sulphonylurea receptor), KCNJ11 (KIR6.2), SLC2A2 (GLUT2), HNF4A (HNF4α), and INS (insulin)—significantly altered disease risk, and in three genes, the risk allele, haplotype, or both had a biologically consistent effect on a relevant physiological trait in the QT study. We examined 35 genes predicted to have their major influence on insulin action, and three (9%)—INSR, PIK3R1, and SOS1—showed significant associations with diabetes. These results confirm the genetic complexity of Type 2 diabetes and provide evidence that common variants in genes influencing pancreatic β-cell function may make a significant contribution to the inherited component of this disease. This study additionally demonstrates that the systematic examination of panels of biological candidate genes in large, well-characterised populations can be an effective complement to positional cloning approaches. The absence of large single-gene effects and the detection of multiple small effects accentuate the need for the study of larger populations in order to reliably identify the size of effect we now expect for complex diseases

Polymyxin B‐Triggered Assembly of Peptide Hydrogels for Localized and Sustained Release of Combined Antimicrobial Therapy

Repurposing old antibiotics into more effective and safer formulations is an emergent approach to tackle the growing threat of antimicrobial resistance. Herein, a peptide hydrogel is reported for the localized and sustained release of polymyxin B (PMB), a decade-old antibiotic with increasing clinical utility for treating multidrug-resistant Gram-negative bacterial infections. The hydrogel is assembled by additing PMB solution into a rationally designed peptide amphiphile (PA) solution and its mechanical properties can be adjusted through the addition of counterions, envisioning its application in diverse infection scenarios. Sustained release of PMB from the hydrogel over a 5-day period and prolonged antimicrobial activities against Gram-negative bacteria are observed. The localized release of active PMB from the hydrogel is shown to be effective in vivo for treating Pseudomonas aeruginosa infection in the Galleria mellonella burn wound infection model, dramatically reducing the mortality from 93% to 13%. Complementary antimicrobial activity against Gram-positive Staphylococcus aureus and enhanced antimicrobial effect against the Gram-negative Acinetobacter baumannii are observed when an additional antibiotic fusidic acid is incorporated into the hydrogen network. These results demonstrate the potential of the PMB-triggered PA hydrogel as a versatile platform for the localized and sustained delivery of combined antimicrobial therapies