Archive for January, 2018

Long-term acute care hospitals.

Clinical Infectious Diseases August 1, 2009  V.49 N.3 P.438-43.     

Munoz-Price LS1.

Author information

1 simunozprice@gmail.com

Abstract

Long-term acute care hospitals (LTACHs) are health care facilities that admit complex patients with acute care needs (eg, mechanical ventilator weaning, administration of intravenous antibiotics, and complex wound care) for a mean duration of stay of 25 days. LTACHs are different than nursing homes and were initially created in the 1990s in an effort to decrease Medicare costs by facilitating prompt discharge from intensive care units of patients with difficulty weaning mechanical ventilation; however, current admission diagnoses are quite broad. Patients admitted to these facilities have multiple comorbidities and are at risk for colonization with multidrug-resistant organisms. LTACH patients have been shown to have high rates of hospital-acquired infections, including central vascular catheter-associated bloodstream infection and ventilator-associated pneumonia. In addition, LTACHs have been implicated in various regional outbreaks of multidrug-resistant organisms. This review summarizes the limited amount of scientific literature on LTACHs while highlighting their infection control problems, as well as the role LTACHs play on regional outbreaks.

abstract

https://academic.oup.com/cid/article/49/3/438/499066

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January 30, 2018 at 4:08 pm

Continued high rates of antibiotic prescribing to adults with respiratory tract infection: survey of 568 UK general practices

BMJ Journals 2014

Martin C Gulliford1, Alex Dregan1, Michael V Moore2, Mark Ashworth1, Tjeerd van Staa3,4, Gerard McCann3, Judith Charlton1, Lucy Yardley2, Paul Little2, Lisa McDermott1

Author affiliations

King’s College London, Primary Care and Public Health Sciences, London, UK

Department of Primary Care and Population Sciences, University of Southampton, Southampton, UK

Clinical Practice Research Datalink (CPRD) Division, Medicines and Healthcare Products Regulatory Agency, London, UK

Health eResearch Centre, Farr Institute for Health Informatics Research, University of Manchester, London, UK

Abstract

Objectives

Overutilisation of antibiotics may contribute to the emergence of antimicrobial drug resistance, a growing international concern. This study aimed to analyse the performance of UK general practices with respect to antibiotic prescribing for respiratory tract infections (RTIs) among young and middle-aged adults.

Setting

Data are reported for 568 UK general practices contributing to the Clinical Practice Research Datalink.

Participants

Participants were adults aged 18–59 years. Consultations were identified for acute upper RTIs including colds, cough, otitis-media, rhino-sinusitis and sore throat.

Primary and secondary outcome measures

For each consultation, we identified whether an antibiotic was prescribed. The proportion of RTI consultations with antibiotics prescribed was estimated.

Results

There were 568 general practices analysed. The median general practice prescribed antibiotics at 54% of RTI consultations. At the highest prescribing 10% of practices, antibiotics were prescribed at 69% of RTI consultations. At the lowest prescribing 10% of practices, antibiotics were prescribed at 39% RTI consultations. The median practice prescribed antibiotics at 38% of consultations for ‘colds and upper RTIs’, 48% for ‘cough and bronchitis’, 60% for ‘sore throat’, 60% for ‘otitis-media’ and 91% for ‘rhino-sinusitis’. The highest prescribing 10% of practices issued antibiotic prescriptions at 72% of consultations for ‘colds’, 67% for ‘cough’, 78% for ‘sore throat’, 90% for ‘otitis-media’ and 100% for ‘rhino-sinusitis’.

Conclusions

Most UK general practices prescribe antibiotics to young and middle-aged adults with respiratory infections at rates that are considerably in excess of what is clinically justified. This will fuel antibiotic resistance.

FULL TEXT

http://bmjopen.bmj.com/content/4/10/e006245.long

PDF

http://bmjopen.bmj.com/content/bmjopen/4/10/e006245.full.pdf

 

January 30, 2018 at 3:41 pm

Genomic epidemiology and antimicrobial resistance of Neisseria gonorrhoeae in New Zealand

Journal of Antimicrobial Chemotherapy February 2018 V.73 N.2 P.353–364  

Robyn S Lee; Torsten Seemann; Helen Heffernan; Jason C Kwong; Anders Gonçalves da Silva …

Background

Antimicrobial-resistant Neisseria gonorrhoeae is a major threat to public health. No studies to date have examined the genomic epidemiology of gonorrhoea in the Western Pacific Region, where the incidence of gonorrhoea is particularly high.

Methods

A population-level study of N. gonorrhoeae in New Zealand (October 2014 to May 2015). Comprehensive susceptibility testing and WGS data were obtained for 398 isolates. Relatedness was inferred using phylogenetic trees, and pairwise core SNPs. Mutations and genes known to be associated with resistance were identified, and correlated with phenotype.

Results

Eleven clusters were identified. In six of these clusters, >25% of isolates were from females, while in eight of them, >15% of isolates were from females. Drug resistance was common; 98%, 32% and 68% of isolates were non-susceptible to penicillin, ciprofloxacin and tetracycline, respectively. Elevated MICs to extended-spectrum cephalosporins (ESCs) were observed in 3.5% of isolates (cefixime MICs ≥ 0.12 mg/L, ceftriaxone MICs ≥ 0.06 mg/L). Only nine isolates had penA XXXIV genotypes, three of which had decreased susceptibility to ESCs (MIC = 0.12 mg/L). Azithromycin non-susceptibility was identified in 43 isolates (10.8%); two of these isolates had 23S mutations (C2611T, 4/4 alleles), while all had mutations in mtrR or its promoter.

Conclusions

The high proportion of females in clusters suggests transmission is not exclusively among MSM in New Zealand; re-assessment of risk factors for transmission may be warranted in this context. As elevated MICs of ESCs and/or azithromycin were found in closely related strains, targeted public health interventions to halt transmission are urgently needed.

abstract

https://academic.oup.com/jac/article/73/2/353/4647718

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January 28, 2018 at 7:40 pm

Prospective evaluation of a continuous infusion vancomycin dosing nomogram in critically ill patients undergoing continuous venovenous haemofiltration

Journal of Antimicrobial Chemotherapy January 2018 V.73 N.1 P.199–203    

EDITOR’S CHOICE

Jonathan H Sin; Kelly Newman; Ramy H Elshaboury; D Dante Yeh; Marc A de Moya

Objectives

The most optimal method of attaining therapeutic vancomycin concentrations during continuous venovenous haemofiltration (CVVH) remains unclear. Studies have shown continuous infusion vancomycin (CIV) achieves target concentrations more rapidly and consistently when compared with intermittent infusion. Positive correlations between CVVH intensity and vancomycin clearance (CLvanc) have been noted. This study is the first to evaluate a CIV regimen in patients undergoing CVVH that incorporates weight-based CVVH intensity (mL/kg/h) into the dosing nomogram.

Methods

This was a prospective, observational study of patients undergoing CVVH and receiving CIV based on the nomogram. The primary outcome was achievement of a therapeutic vancomycin concentration (15–25 mg/L) at 24 h. Secondary outcomes included the achievement of therapeutic concentrations at 48 and 72 h.

Results

The nomogram was analysed in 52 critically ill adults. Vancomycin concentrations were therapeutic in 43/52 patients (82.7%) at 24 h. Of the nine patients who were not therapeutic at 24 h, seven were supratherapeutic and two were subtherapeutic. The mean (SD) concentration was 20.1 (4.2)  mg/L at 24 h, 20.7 (3.7) mg/L at 48 h and 21.9 (3.5)  mg/L at 72 h. Patients with CVVH intensity >20 mL/kg/h experienced higher CLvanc at 24 h compared with patients with CVVH intensity <20 mL/kg/h (3.1 versus 2.6 L/h; P = 0.013).

Conclusions

By incorporating CVVH intensity into the CIV dosing nomogram, the majority of patients achieved therapeutic concentrations at 24 h and maintained them within range at 48 and 72 h. Additional studies are required to validate this nomogram before widespread implementation may be considered.

abstract

https://academic.oup.com/jac/article/73/1/199/4457942

 

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January 28, 2018 at 7:39 pm

Long-lasting successful dissemination of resistance to oxazolidinones in MDR Staphylococcus epidermidis clinical isolates in a tertiary care hospital in France

Journal of Antimicrobial Chemotherapy January 2018 V.73 N.1 P.41–51    

Laurent Dortet; Philippe Glaser; Najiby Kassis-Chikhani; Delphine Girlich; Philippe Ichai …

Objectives

Patient- and procedure-related changes in modern medicine have turned CoNS into one of the major nosocomial pathogens. Treatments of CoNS infections are challenging owing to the large proportion of MDR strains and oxazolidinones often remain the last active antimicrobial molecules. Here, we have investigated a long-lasting outbreak (2010–13) due to methicillin- and linezolid-resistant (LR) CoNS (n = 168), involving 72 carriers and 49 infected patients.

Methods

Antimicrobial susceptibilities were tested by the disc diffusion method and MICs were determined by broth microdilution or Etest. The clonal relationship of LR Staphylococcus epidermidis (LRSE) was first determined using a semi-automated repetitive element palindromic PCR (rep-PCR) method. Then, WGS was performed on all cfr-positive LRSE (n = 30) and LRSE isolates representative of each rep-PCR-defined clone (n = 17). Self-transferability of cfr-carrying plasmids was analysed by filter-mating experiments.

Results

This outbreak was caused by the dissemination of three clones (ST2, ST5 and ST22) of LRSE. In these clones, linezolid resistance was caused by (i) mutations in the chromosome-located genes encoding the 23S RNA and L3 and L4 ribosomal proteins, but also by (ii) the dissemination of two different self-conjugative plasmids carrying the cfr gene encoding a 23S RNA methylase. By monitoring linezolid prescriptions in two neighbouring hospitals, we highlighted that the spread of LR-CoNS was strongly associated with linezolid use.

Conclusions

Physicians should be aware that plasmid-encoded linezolid resistance has started to disseminate among CoNS and that rational use of oxazolidinones is critical to preserve these molecules as efficient treatment options for MDR Gram-positive pathogens.

abstract

https://academic.oup.com/jac/article/73/1/41/4582307

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January 28, 2018 at 7:38 pm

Comparative efficacy and safety of treatment options for MDR and XDR Acinetobacter baumannii infections: a systematic review and network meta-analysis

Journal of Antimicrobial Chemotherapy January 2018 V.73 N.1 P.22–32     

EDITOR’S CHOICE

Kirati Kengkla; Khachen Kongpakwattana; Surasak Saokaew; Anucha Apisarnthanarak; Nathorn Chaiyakunapruk

Objectives

To comprehensively compare and rank the efficacy and safety of available treatment options for patients with MDR and XDR Acinetobacter baumannii (AB) infection.

Methods

We searched PubMed, Embase and the Cochrane register of trials systematically for studies that examined treatment options for patients with MDR- and XDR-AB infections until April 2016. Network meta-analysis (NMA) was performed to estimate the risk ratio (RR) and 95% CI from both direct and indirect evidence. Primary outcomes were clinical cure and microbiological cure. Secondary outcomes were all-cause mortality and nephrotoxic and non-nephrotoxic adverse events.

Results

A total of 29 studies with 2529 patients (median age 60 years; 65% male; median APACHE II score 19.0) were included. Although there were no statistically significant differences between treatment options, triple therapy with colistin, sulbactam and tigecycline had the highest clinical cure rate. Colistin in combination with sulbactam was associated with a significantly higher microbiological cure rate compared with colistin in combination with tigecycline (RR 1.23; 95% CI 1.03–1.47) and colistin monotherapy (RR 1.21; 95% CI 1.06–1.38). No significant differences in all-cause mortality were noted between treatment options. Tigecycline-based therapy also appeared less effective for achieving a microbiological cure and is not appropriate for treating bloodstream MDR- and XDR-AB infections.

Conclusions

Combination therapy of colistin with sulbactam demonstrates superiority in terms of microbiological cure with a safety profile similar to that of colistin monotherapy. Thus, our findings support the use of this combination as a treatment for MDR- and XDR-AB infections.

abstract

https://academic.oup.com/jac/article/73/1/22/4563557

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January 28, 2018 at 7:37 pm

Population Pharmacokinetic Analysis of Cefiderocol, a Parenteral Siderophore Cephalosporin, in Healthy Subjects, Subjects with Various Degrees of Renal Function, and Patients with Complicated Urinary Tract Infection or Acute Uncomplicated Pyelonephritis

Agents and Chemotherapy February 2018 V.62 N.2

Nao Kawaguchi, Takayuki Katsube, Roger Echols and Toshihiro Wajima

aProject Management Department, Shionogi & Co., Ltd., Osaka, Japan

bInfectious Disease Drug Development Consulting, LLC, Easton, Connecticut, USA

Cefiderocol, a novel parenteral siderophore cephalosporin, exhibits potent efficacy against most Gram-negative bacteria, including carbapenem-resistant strains.

The aim of this study was to perform a population pharmacokinetic (PK) analysis based on plasma cefiderocol concentrations in healthy subjects, subjects with various degrees of renal function, and patients with complicated urinary tract infection (cUTI) or acute uncomplicated pyelonephritis (AUP) caused by Gram-negative pathogens and to calculate the fraction of the time during the dosing interval where the free drug concentration in plasma exceeds the MIC (fTMIC).

Population PK models were developed with three renal function markers, body surface area-adjusted estimated glomerular filtration rate (eGFR), absolute eGFR, and creatinine clearance, on the basis of 2,571 plasma concentrations from 91 subjects without infection and 238 patients with infection.

The population PK models with each renal function marker adequately described the plasma cefiderocol concentrations. Clear relationships of total clearance (CL) to all renal function markers were observed.

Body weight and disease status (with or without infection) were also significant covariates. The CL in patients with infection was 26% higher than that in subjects without infection.

The fTMIC values were more than 75% in all patients (and were 100% in most patients), suggesting that a sufficient exposure to cefiderocol was provided by the tested dose regimens (2 g every 8 h as the standard dose regimen) for the treatment of cUTI or AUP caused by Gram-negative pathogens.

abstract

http://aac.asm.org/content/62/2/e01391-17.abstract?etoc

PDF

http://aac.asm.org/content/62/2/e01391-17.full.pdf+html

 

January 27, 2018 at 3:12 pm

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