Search

Antimicrobial-resistant Enterobacterales carriage and the coronavirus disease 2019 (COVID-19) lockdown measures may impact the incidence all-cause mortality rate among nursing home residents. To determine the all-cause mortality rate in the presence/absence of antimicrobial-resistant Enterobacterales carriage and the incidence all-cause mortality rate before and during COVID-19 pandemic lockdown, this prospective closed-cohort study was conducted at various types of nursing homes in Bangkok, Thailand, from June 2020 to December 2021. The elderly residents included 142 participants (aged ≥60 years) living in nursing homes ≥3 months, who did not have terminal illnesses. Time-to-event analyses with Cox proportional hazards models and stratified log-rank tests were used. The all-cause mortality rate was 18%, and the incidence all-cause mortality rate was 0.59/1000 person-days in residents who had antimicrobial-resistant Enterobacterales carriage at baseline. Meanwhile, the incidence all-cause mortality rate among noncarriage was 0.17/1000 person-days. The mortality incidence rate of carriage was three times higher than residents who were noncarriage without statistical significance (HR 3.2; 95% CI 0.74, 13.83). Residents in nonprofit nursing homes had a higher mortality rate than those in for-profit nursing homes (OR 9.24; 95% CI 2.14, 39.86). The incidence mortality rate during and before lockdown were 0.62 and 0.30, respectively. Effective infection-control policies akin to hospital-based systems should be endorsed in all types of nursing homes. To limit the interruption of long-term chronic care, COVID-19 prevention should be individualized to nursing homes.

Background: Randomized clinical trials (RCTs) in hospital-acquired and ventilator-associated bacterial pneumonia (HABP and VABP, respectively) are important for the evaluation of new antimicrobials. However, the heterogeneity in endpoints used in RCTs evaluating treatment of HABP/VABP may puzzle clinicians. The aim of this work was to reach a consensus on clinical endpoints to consider in future clinical trials evaluating antimicrobial treatment efficacy for HABP/VABP. Methods: Twenty-six international experts from intensive care, infectious diseases, and the pharmaceutical industry were polled using the Delphi method. Results: The panel recommended a hierarchical composite endpoint including, by priority order, (1) survival at day 28, (2) mechanical ventilation-free days through day 28, and (3) clinical cure between study days 7 and 10 for VABP; and (1) survival (day 28) and (2) clinical cure (days 7-10) for HABP. Clinical cure was defined as the combination of resolution of signs and symptoms present at enrollment and improvement or lack of progression of radiological signs. More than 70% of the experts agreed to assess survival and mechanical ventilation-free days though day 28, and clinical cure between day 7 and day 10 after treatment initiation. Finally, the hierarchical order of endpoint components was reached after 3 Delphi rounds (72% agreement). Conclusions: We provide a multinational expert consensus on separate hierarchical composite endpoints for VABP and HABP, and on a definition of clinical cure that could be considered for use in future HABP/VABP clinical trials. © 2019 The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

The polymyxin antibiotics colistin (polymyxin E) and polymyxin B became available in the 1950s and thus did not undergo contemporary drug development procedures. Their clinical use has recently resurged, assuming an important role as salvage therapy for otherwise untreatable gram-negative infections. Since their reintroduction into the clinic, significant confusion remains due to the existence of several different conventions used to describe doses of the polymyxins, differences in their formulations, outdated product information, and uncertainties about susceptibility testing that has led to lack of clarity on how to optimally utilize and dose colistin and polymyxin B. We report consensus therapeutic guidelines for agent selection and dosing of the polymyxin antibiotics for optimal use in adult patients, as endorsed by the American College of Clinical Pharmacy (ACCP), Infectious Diseases Society of America (IDSA), International Society of Anti-Infective Pharmacology (ISAP), Society for Critical Care Medicine (SCCM), and Society of Infectious Diseases Pharmacists (SIDP). The European Society for Clinical Microbiology and Infectious Diseases (ESCMID) endorses this document as a consensus statement. The overall conclusions in the document are endorsed by the European Committee on Antimicrobial Susceptibility Testing (EUCAST). We established a diverse international expert panel to make therapeutic recommendations regarding the pharmacokinetic and pharmacodynamic properties of the drugs and pharmacokinetic targets, polymyxin agent selection, dosing, dosage adjustment and monitoring of colistin and polymyxin B, use of polymyxin-based combination therapy, intrathecal therapy, inhalation therapy, toxicity, and prevention of renal failure. The treatment guidelines provide the first ever consensus recommendations for colistin and polymyxin B therapy that are intended to guide optimal clinical use. © 2019 Pharmacotherapy Publications, Inc.

Contains fulltext : 193452.pdf (Publisher’s version ) (Open Access) Background: This study was conducted as part of the Driving Reinvestment in Research and Development and Responsible Antibiotic Use (DRIVE-AB) project and aimed to develop generic quality indicators (QIs) for responsible antibiotic use in the inpatient setting. Methods: A RAND-modified Delphi method was applied. First, QIs were identified by a systematic review. A complementary search was performed on web sites of relevant organizations. Duplicates were removed and disease and patient-specific QIs were combined into generic indicators. The relevance of these QIs was appraised by a multidisciplinary international stakeholder panel through two questionnaires and an in-between consensus meeting. Results: The systematic review retrieved 70 potential generic QIs. The QIs were appraised by 25 international stakeholders with diverse backgrounds (medical community, public health, patients, antibiotic research and development, regulators, governments). Ultimately, 51 QIs were selected in consensus. QIs with the highest relevance score included: (i) an antibiotic plan should be documented in the medical record at the start of the antibiotic treatment; (ii) the results of bacteriological susceptibility testing should be documented in the medical record; (iii) the local guidelines should correspond to the national guidelines but should be adapted based on local resistance patterns; (iv) an antibiotic stewardship programme should be in place at the healthcare facility; and (v) allergy status should be taken into account when antibiotics are prescribed. Conclusions: This systematic and stepwise method combining evidence from literature and stakeholder opinion led to multidisciplinary international consensus on generic inpatient QIs that can be used globally to assess the quality of antibiotic use.

Contains fulltext : 193591.pdf (Publisher’s version ) (Open Access) Background: Quantifying antibiotic use is an essential element of antibiotic stewardship since it allows comparison between different settings and time windows, and measurement of the impact of interventions. However, quantity metrics (QMs) and methods have not been standardized. Objectives: To propose a set of QMs for antibiotic use in inpatients (IQMs) that are accepted globally by professionals in a range of disciplines. The study was conducted within the Driving Reinvestment in Research and Development and Responsible Antibiotic Use (DRIVE-AB) project. Methods: A systematic literature review using MEDLINE identified articles on measuring inpatient antibiotic use, published up to 29 January 2015. A consensually selected list of national and international web sites was screened for additional IQMs. IQMs were classified according to the type of numerator used and presented to a multidisciplinary panel of stakeholders. A RAND-modified Delphi consensus procedure, which consisted of two online questionnaires and a face-to-face meeting, was performed. Results: The systematic literature review and web site search identified 168 eligible articles from which an initial list of 20 IQMs, composed of 20 different numerators and associated denominators was developed. The consensus procedure resulted in a final set of 12 IQMs. Among this final set, DDDs per 100(0) patient-days and days of therapy per patient-days were most frequently found in the review. The panel recommended that antibiotic use should be expressed in at least two metrics simultaneously. Conclusions: Our consensus procedure identified a set of IQMs that we propose as an evidence-based global standard.

Improved understanding of pathogens that cause sepsis would aid management and antimicrobial selection. In this study, we aimed to identify the causative pathogens of sepsis in southeast Asia.In this multinational multicentre cross-sectional study of community-acquired sepsis and severe sepsis, we prospectively recruited children (age ≥30 days and18 years) and adults (age ≥18 years) at 13 public hospitals in Indonesia (n=3), Thailand (n=4), and Vietnam (n=6). Hospitalised patients with suspected or documented community-acquired infection, with at least three diagnostic criteria for sepsis according to the Surviving Sepsis Campaign 2012, and within 24 h of admission were enrolled. Blood from every patient, and nasopharyngeal swab, urine, stool, and cerebrospinal fluid, if indicated, were collected for reference diagnostic tests to identify causative pathogens. We report causative pathogens of sepsis and 28-day mortality. We also estimate mortality associated with enrolment with severe sepsis. This study was registered with ClinicalTrials.gov, number NCT02157259.From Dec 16, 2013, to Dec 14, 2015, 4736 patients were screened and 1578 patients (763 children and 815 adults) were enrolled. Dengue viruses (n=122 [8%]), Leptospira spp (n=95 [6%]), rickettsial pathogens (n=96 [6%]), Escherichia coli (n=76 [5%]), and influenza viruses (n=65 [4%]) were commonly identified in both age groups; whereas Plasmodium spp (n=12 [1%]) and Salmonella enterica serovar Typhi (n=3 [0·2%]) were rarely observed. Emerging pathogens identified included hantaviruses (n=28 [2%]), non-typhoidal Salmonella spp (n=21 [1%]), Streptococcus suis (n=18 [1%]), Acinetobacter spp (n=12 [1%]), and Burkholderia pseudomallei (n=5 [1%]). 28-day mortality occurred in 14 (2%) of 731 children with known statuses and 108 (13%) of 804 adults. Severe sepsis was identified on enrolment in 194 (28%) of 731 children and 546 (68%) of 804 adults, and was associated with increased mortality (adjusted odds ratio 5·3, 95% CI 2·7-10·4; p0·001).Sepsis in southeast Asia is caused by a wide range of known and emerging pathogens, and is associated with substantial mortality.National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institutes of Health, USA, and Wellcome Trust, UK.

Acute kidney injury (AKI) occurs in a substantial proportion of critically ill patients receiving intravenous colistin. In the pharmacokinetic/toxicodynamic analysis reported here, the relationship of the occurrence of AKI to exposure to colistin and a number of potential patient factors was explored in 153 critically ill patients, none of whom were receiving renal replacement therapy. Tree-based modeling revealed that the rates of AKI were substantially higher when the average steady-state plasma colistin concentration was greater than ∼2 mg/liter. Copyright © 2017 American Society for Microbiology. All Rights Reserved.

Random peptide libraries displayed by bacteriophage T7 and M13 were employed to identify mimotopes from 4 monoclonal antibodies (MAbs) specific to Burkholderia pseudomallei. Insert DNA sequences of bound phages selected from four rounds of panning with each MAb revealed peptide sequences corresponding to B. pseudomallei K96243 hypothetical protein BPSL2046, hypothetical protein BpseP_02000035, B. pseudomallei K96243 hypothetical protein BPSS0784, B. pseudomallei 1710b hypothetical protein BURPS1710b_1104, and B. cenocepacia H12424 TonB-dependent siderophore receptor, all located at the outer membrane. The immune responses from all selected phagotopes were significantly higher than that of lipopolysaccharide. The study demonstrates the feasibility of identifying mimotopes through screening of phage-displayed random peptide libraries with B. pseudomallei MAbs.

Background. The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) have approved updated dose recommendations for intravenous colistin in patients with various degrees of renal function. We assessed the recommendations in relation to their ability to achieve clinically relevant plasma colistin concentrations. Methods. Pharmacokinetic data from 162 adult critically ill patients (creatinine clearance range, 5.4-211 mL/min) were used to determine the average steady-state plasma colistin concentration (Css,avg) that would be achieved if each patient received the FDA or EMA dose. Target attainment rates for FDA- and EMA-approved daily doses to achieve colistin Css,avg of ≥0.5, ≥1, ≥2, and ≥4 mg/L were determined for each creatinine clearance category (≥80 mL/min, 50 to

The results of a surveillance study conducted by the International Nosocomial Infection Control Consortium (INICC) from January 2004 through December 2009 in 422 intensive care units (ICUs) of 36 countries in Latin America, Asia, Africa, and Europe are reported. During the 6-year study period, using Centers for Disease Control and Prevention (CDC) National Healthcare Safety Network (NHSN; formerly the National Nosocomial Infection Surveillance system [NNIS]) definitions for device-associated health care-associated infections, we gathered prospective data from 313,008 patients hospitalized in the consortium's ICUs for an aggregate of 2,194,897 ICU bed-days. Despite the fact that the use of devices in the developing countries' ICUs was remarkably similar to that reported in US ICUs in the CDC's NHSN, rates of device-associated nosocomial infection were significantly higher in the ICUs of the INICC hospitals; the pooled rate of central line-associated bloodstream infection in the INICC ICUs of 6.8 per 1,000 central line-days was more than 3-fold higher than the 2.0 per 1,000 central line-days reported in comparable US ICUs. The overall rate of ventilator-associated pneumonia also was far higher (15.8 vs 3.3 per 1,000 ventilator-days), as was the rate of catheter-associated urinary tract infection (6.3 vs. 3.3 per 1,000 catheter-days). Notably, the frequencies of resistance of Pseudomonas aeruginosa isolates to imipenem (47.2% vs 23.0%), Klebsiella pneumoniae isolates to ceftazidime (76.3% vs 27.1%), Escherichia coli isolates to ceftazidime (66.7% vs 8.1%), Staphylococcus aureus isolates to methicillin (84.4% vs 56.8%), were also higher in the consortium's ICUs, and the crude unadjusted excess mortalities of device-related infections ranged from 7.3% (for catheter-associated urinary tract infection) to 15.2% (for ventilator-associated pneumonia). Copyright © 2012 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.